Biopsy

[Guest guest]

virus lives at least 4 days outside body

From: bob Larson <bobList@...>

Subject: RE: Re: biopsy

Hepatitis C

Date: Sunday, April 5, 2009, 11:01 AM

it takes an exchange of blood. contaminated medical, dental, tattoo,

piercing, injection drug outfit sharing, sometimes shared razors or

toothbrushes, possible kissing if both have bleeding gum problems, very slim

through non-violent vaginal sex, but anal is a significant risk. anyway

that blood can get into blood. stomach acid kills it. it won't live

outside in the air for long... but i forget how long.

> Re: biopsy

>

> During a routine physical, my doctor decided to do a

> hepatitis blood test because I had been complaining about a

> cough that I had. The test came back positive for 'hepatitis

> c'. I am scheduled for a liver biopsy at the end of the

> month. I have been upset about this since being told that I

> have 'hep c'. I just started a new job in July and trying not

> to take time off from work. What other ways can 'hep c' be

> contracted aside from sex and blood transfusion?

>

[Guest guest]

Thanks your information on Hepatitis C,I got Hepatitis C from a Blood tranfusion

in 1978.

I was on interferon in 1996-1997,it didn't help I don't any energy,I stay

depress and I am

losing my teeth.I am 65 years old with advance stage of Cirrhosis.I have been on

Milk

Thistle,Noni Juice,Dandelion,Triple Magnesium Complex,High Potency

Softgel(without iron)

Vitamin & Mineral Supplement,and Tri-Fiber Complex.I never did drugs,or drink.

                                                                            

Bettie

 

Prayer has the power to change mountains into highways.

Pray as if everything Depended on God;act as if everything depended on you.

From: hdhepper1 <grisley6315@ charter.net>

Subject: Re: biopsy

Hepatitis Csupportgr oupgroups (DOT) com

Date: Sunday, April 5, 2009, 2:04 AM

THE DECISION TO DO TREATMENT IS ALWAYS THE PATIENTS!! I did not mean to imply

that EVERYONE must do treatment. Check with your local library and find " The Hep

C Help Book " by Misha Cohen and Dr. Gish. They compare Traditional Chinese

Medicine(TAM) and western treatments. They also dicsuss how TAM will help manage

the side effects of the patient who chooses western meds so they can stay on

treatment longer. A good diet and a healthy life will increase a persons chance

of keeping the virus managable. Misha Cohen, author of " Chicken Soup for Chinese

Medicine " , has stated in two conferences I attended that " No herbal treatment

will eradicate the hepatitis C vitus " .

> >

> >

> > From: Angelo <tommybad238@ ...>

> > Subject: biopsy

> > Hepatitis Csupportgr oupgroups (DOT) com

> > Date: Friday, April 3, 2009, 10:29 PM

> >

> >

> >

> >

> >

> >

> > there's always the possibility that the needle hits cancer and cancer cells

> > can in the process escape into the system and metastasize leading to big

> > trouble. slim but possible. it happens with prostate biopsies

> >  

> >  

> >  

> > Can you show me some scientific proof of this happening? This reminds me

othe the rumors that go around saying once the cancer cells hit air they

multiply rapidly or something like that. maybe I'm wrong.

> >

> >

[Guest guest]

Thanks your information on Hepatitis C,I got Hepatitis C from a Blood tranfusion

in 1978.

I was on interferon in 1996-1997,it didn't help I don't any energy,I stay

depress and I am

losing my teeth.I am 65 years old with advance stage of Cirrhosis.I have been on

Milk

Thistle,Noni Juice,Dandelion,Triple Magnesium Complex,High Potency

Softgel(without iron)

Vitamin & Mineral Supplement,and Tri-Fiber Complex.I never did drugs,or drink.

                                                                            

Bettie

 

Prayer has the power to change mountains into highways.

Pray as if everything Depended on God;act as if everything depended on you.

From: hdhepper1 <grisley6315@ charter.net>

Subject: Re: biopsy

Hepatitis Csupportgr oupgroups (DOT) com

Date: Sunday, April 5, 2009, 2:04 AM

THE DECISION TO DO TREATMENT IS ALWAYS THE PATIENTS!! I did not mean to imply

that EVERYONE must do treatment. Check with your local library and find " The Hep

C Help Book " by Misha Cohen and Dr. Gish. They compare Traditional Chinese

Medicine(TAM) and western treatments. They also dicsuss how TAM will help manage

the side effects of the patient who chooses western meds so they can stay on

treatment longer. A good diet and a healthy life will increase a persons chance

of keeping the virus managable. Misha Cohen, author of " Chicken Soup for Chinese

Medicine " , has stated in two conferences I attended that " No herbal treatment

will eradicate the hepatitis C vitus " .

> >

> >

> > From: Angelo <tommybad238@ ...>

> > Subject: biopsy

> > Hepatitis Csupportgr oupgroups (DOT) com

> > Date: Friday, April 3, 2009, 10:29 PM

> >

> >

> >

> >

> >

> >

> > there's always the possibility that the needle hits cancer and cancer cells

> > can in the process escape into the system and metastasize leading to big

> > trouble. slim but possible. it happens with prostate biopsies

> >  

> >  

> >  

> > Can you show me some scientific proof of this happening? This reminds me

othe the rumors that go around saying once the cancer cells hit air they

multiply rapidly or something like that. maybe I'm wrong.

> >

> >

[Guest guest]

bettie,hoping you feel better by the grace of God. i'm about to go to bed and i

will add u to my prayer. it seems as i get older life feels more complicated

than ever before,hmmm. im thinking ive had hep about 14 yrs. i cryed for a month

straight after hearing the news. its going on 2 months now that ive known...i

quit smoking about 5 months ago also so im not smoking but it runs threw my mind

alot lately. i will continue to fight the nicademon

 

hope you are doing ok,i did some surfing and found that bananas are a natural

anti'depressant,try to eat one in the morning when you get up and at lunch

time and one at nite, 3 aday...and see how that helps you let me know ok,give

it about a week,before you see results! god bless and be good to yourself your

friend debbie

 

From: hdhepper1 <grisley6315@ charter.net>

Subject: Re: biopsy

Hepatitis Csupportgr oupgroups (DOT) com

Date: Sunday, April 5, 2009, 2:04 AM

THE DECISION TO DO TREATMENT IS ALWAYS THE PATIENTS!! I did not mean to imply

that EVERYONE must do treatment. Check with your local library and find " The Hep

C Help Book " by Misha Cohen and Dr. Gish. They compare Traditional Chinese

Medicine(TAM) and western treatments. They also dicsuss how TAM will help manage

the side effects of the patient who chooses western meds so they can stay on

treatment longer. A good diet and a healthy life will increase a persons chance

of keeping the virus managable. Misha Cohen, author of " Chicken Soup for Chinese

Medicine " , has stated in two conferences I attended that " No herbal treatment

will eradicate the hepatitis C vitus " .

> >

> >

> > From: Angelo <tommybad238@ ...>

> > Subject: biopsy

> > Hepatitis Csupportgr oupgroups (DOT) com

> > Date: Friday, April 3, 2009, 10:29 PM

> >

> >

> >

> >

> >

> >

> > there's always the possibility that the needle hits cancer and cancer cells

> > can in the process escape into the system and metastasize leading to big

> > trouble. slim but possible. it happens with prostate biopsies

> >  

> >  

> >  

> > Can you show me some scientific proof of this happening? This reminds me

othe the rumors that go around saying once the cancer cells hit air they

multiply rapidly or something like that. maybe I'm wrong.

> >

> >

[Guest guest]

bettie,hoping you feel better by the grace of God. i'm about to go to bed and i

will add u to my prayer. it seems as i get older life feels more complicated

than ever before,hmmm. im thinking ive had hep about 14 yrs. i cryed for a month

straight after hearing the news. its going on 2 months now that ive known...i

quit smoking about 5 months ago also so im not smoking but it runs threw my mind

alot lately. i will continue to fight the nicademon

 

hope you are doing ok,i did some surfing and found that bananas are a natural

anti'depressant,try to eat one in the morning when you get up and at lunch

time and one at nite, 3 aday...and see how that helps you let me know ok,give

it about a week,before you see results! god bless and be good to yourself your

friend debbie

 

From: hdhepper1 <grisley6315@ charter.net>

Subject: Re: biopsy

Hepatitis Csupportgr oupgroups (DOT) com

Date: Sunday, April 5, 2009, 2:04 AM

THE DECISION TO DO TREATMENT IS ALWAYS THE PATIENTS!! I did not mean to imply

that EVERYONE must do treatment. Check with your local library and find " The Hep

C Help Book " by Misha Cohen and Dr. Gish. They compare Traditional Chinese

Medicine(TAM) and western treatments. They also dicsuss how TAM will help manage

the side effects of the patient who chooses western meds so they can stay on

treatment longer. A good diet and a healthy life will increase a persons chance

of keeping the virus managable. Misha Cohen, author of " Chicken Soup for Chinese

Medicine " , has stated in two conferences I attended that " No herbal treatment

will eradicate the hepatitis C vitus " .

> >

> >

> > From: Angelo <tommybad238@ ...>

> > Subject: biopsy

> > Hepatitis Csupportgr oupgroups (DOT) com

> > Date: Friday, April 3, 2009, 10:29 PM

> >

> >

> >

> >

> >

> >

> > there's always the possibility that the needle hits cancer and cancer cells

> > can in the process escape into the system and metastasize leading to big

> > trouble. slim but possible. it happens with prostate biopsies

> >  

> >  

> >  

> > Can you show me some scientific proof of this happening? This reminds me

othe the rumors that go around saying once the cancer cells hit air they

multiply rapidly or something like that. maybe I'm wrong.

> >

> >

[Guest guest]

Hi Marie

Keeping everything crossed for you - and I will look forward to

those results. I use Silica 2500 plus. This is the cheapest place to buy

them online http://www.bodyexchange.co.uk/Skin,+Nails+%252526+Hair/Kordel's+Silica+2500+Plus+90+Tabs.html

.. I could prize off the metal top from a beer bottle with these nails )

Luv - Sheila

Hi Sheila and all just to let you know i had my

biopsy done on Monday evening just a small piece of skin taken and a stitch put

in i will get results in December will keep you informed how things go. I read

about you taking Silica i have terrible problems with my finger nails they rip

off half way down the nail sometimes really sore how much do you have to take ?

and were can i buy them ? Marie.

No virus

found in this incoming message.

Checked by AVG - www.avg.com

Version: 8.5.424 / Virus Database: 270.14.48/2479 - Release Date: 11/03/09

19:38:00

[Guest guest]

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health.dir./group/ /links/Biopsy_VS_Fibrosure_blood_test_001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301@...>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000@...>009 - VCHepC <VCHepC >; Hepatitis C <Hepatitis C >; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy (SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy. Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs. Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

Thanks Don I knew you would have the answer.

From: Christ <ludichrist2000@...> Sent: Tue, May 4, 2010 7:17:42 PMSubject: Re: [ ] biopsy

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health. dir.groups. / group/HepCWebWar riors/links/ Biopsy_VS_ Fibrosure_ blood_test_ 001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000>009 - VCHepC <VCHepCgroups (DOT) com>; Hepatitis C <Hepatitis C@gro ups.com>; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy (SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy. Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs. Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

I had two biopsies with no side effects at all and I had two ultrasounds with no effects at all. But I have here and elswhere heard about complications and recurring problems from a biopsy and not an ultrasound. So, should one get a biopsy, which is a more complicated procedure. Maybe. Should one get an ultrasound? Absolutely! The ultrasound will show inflamation, scarring, fatty infiltration, suspicious spots, tumors, and other visible images of the liver, and nearby organs, but it does not show the actual virus. Most good doctors can tell the extent of viral damage, or otherwise, by a visual inspection of all labs and the patient without having to do a biopsy. The support group I belong to which provides free medical care and treatment does not require either. The doctor is a very good one who

specializes in Hep C treatment and he relies on all the other emperical data but not a biopsy and ultrasound. We have an 85% success rate of treatment (40+ patients). The key seems to be helping patients get through treatment by whatever means they need. I know this sounds to hard to believe, but it's true. As for me, I have not been fortunate enough to get on this treament program yet. We have a very long waiting list, which is based on urgency. I hope to one day go through it again, and maybe be rid of this dragon once and for all. Randy O Website-- SuncoastHepCFriends.OrgForum -- Suncoast HepC Friends ForumFrom: Beth Frey <bethfrey42301@...> Sent: Tue, May 4, 2010 9:11:11 PMSubject: Re: [ ] biopsy

Thanks Don I knew you would have the answer.

From: Christ <ludichrist2000> Sent: Tue, May 4, 2010 7:17:42 PMSubject: Re: [ ] biopsy

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health. dir.groups. / group/HepCWebWar riors/links/ Biopsy_VS_ Fibrosure_ blood_test_ 001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000>009 - VCHepC <VCHepCgroups (DOT) com>; Hepatitis C <Hepatitis C@gro ups.com>; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with

genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new

challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard

therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy

(SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups

receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based

on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy.

Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs.

Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

My doctor used the ultrasound as a location finder for where to do the biopsy.... or at least that's what he told me.. the ultrasound was done right before the biopsy.TeriFrom: Randy <randyowe@...> Sent: Tue, May 4, 2010 9:56:04 PMSubject: Re: [ ] biopsy

I had two biopsies with no side effects at all and I had two ultrasounds with no effects at all. But I have here and elswhere heard about complications and recurring problems from a biopsy and not an ultrasound. So, should one get a biopsy, which is a more complicated procedure. Maybe. Should one get an ultrasound? Absolutely! The ultrasound will show inflamation, scarring, fatty infiltration, suspicious spots, tumors, and other visible images of the liver, and nearby organs, but it does not show the actual virus. Most good doctors can tell the extent of viral damage, or otherwise, by a visual inspection of all labs and the patient without having to do a biopsy. The support group I belong to which provides free medical care and treatment does not require either. The doctor is a very good one who

specializes in Hep C treatment and he relies on all the other emperical data but not a biopsy and ultrasound. We have an 85% success rate of treatment (40+ patients). The key seems to be helping patients get through treatment by whatever means they need. I know this sounds to hard to believe, but it's true. As for me, I have not been fortunate enough to get on this treament program yet. We have a very long waiting list, which is based on urgency. I hope to one day go through it again, and maybe be rid of this dragon once and for all. Randy O Website-- SuncoastHepCFriends .OrgForum -- Suncoast HepC Friends ForumFrom: Beth Frey <bethfrey42301> Sent: Tue, May 4, 2010 9:11:11 PMSubject: Re: [ ] biopsy

Thanks Don I knew you would have the answer.

From: Christ <ludichrist2000> Sent: Tue, May 4, 2010 7:17:42 PMSubject: Re: [ ] biopsy

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health. dir.groups. / group/HepCWebWar riors/links/ Biopsy_VS_ Fibrosure_ blood_test_ 001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000>009 - VCHepC <VCHepCgroups (DOT) com>; Hepatitis C <Hepatitis C@gro ups.com>; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with

genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new

challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard

therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy

(SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups

receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based

on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy.

Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs.

Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

Teri, Yes, they use an ultrasound to guide the probe into your liver when they perform a biopsy. However, a "UR" "upper right quadrant" ultrasound is performed in a clinic on a table just like they do when a pregnant women gets one done. The smear the KY all over your abdomen and wiggle the "thingamajigy" over your stomach and side. You can actually watch the monitor as it is done. Randy O Website-- SuncoastHepCFriends.OrgForum -- Suncoast HepC Friends ForumFrom: Teri Gottlieb <theresagottlieb@...> Sent: Wed, May 5, 2010 4:02:13 AMSubject: Re: [ ] biopsy

My doctor used the ultrasound as a location finder for where to do the biopsy.... or at least that's what he told me.. the ultrasound was done right before the biopsy.TeriFrom: Randy <randyowe (DOT) com> Sent: Tue, May 4, 2010 9:56:04 PMSubject:

Re: [ ] biopsy

I had two biopsies with no side effects at all and I had two ultrasounds with no effects at all. But I have here and elswhere heard about complications and recurring problems from a biopsy and not an ultrasound. So, should one get a biopsy, which is a more complicated procedure. Maybe. Should one get an ultrasound? Absolutely! The ultrasound will show inflamation, scarring, fatty infiltration, suspicious spots, tumors, and other visible images of the liver, and nearby organs, but it does not show the actual virus. Most good doctors can tell the extent of viral damage, or otherwise, by a visual inspection of all labs and the patient without having to do a biopsy. The support group I belong to which provides free medical care and treatment does not require either. The doctor is a very good one who

specializes in Hep C treatment and he relies on all the other emperical data but not a biopsy and ultrasound. We have an 85% success rate of treatment (40+ patients). The key seems to be helping patients get through treatment by whatever means they need. I know this sounds to hard to believe, but it's true. As for me, I have not been fortunate enough to get on this treament program yet. We have a very long waiting list, which is based on urgency. I hope to one day go through it again, and maybe be rid of this dragon once and for all. Randy O Website-- SuncoastHepCFriends .OrgForum -- Suncoast HepC Friends ForumFrom: Beth Frey <bethfrey42301> Sent: Tue, May 4, 2010 9:11:11 PMSubject: Re: [ ] biopsy

Thanks Don I knew you would have the answer.

From: Christ <ludichrist2000> Sent: Tue, May 4, 2010 7:17:42 PMSubject: Re: [ ] biopsy

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health. dir.groups. / group/HepCWebWar riors/links/ Biopsy_VS_ Fibrosure_ blood_test_ 001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000>009 - VCHepC <VCHepCgroups (DOT) com>; Hepatitis C <Hepatitis C@gro ups.com>; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with

genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new

challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard

therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy

(SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups

receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based

on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy.

Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs.

Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

Same thing here Teri - both times. So it's a Radiologist working with the surgeon on the biopsy. That's what was supposed to happen for the procedure on my liver tumours too. Only, guess in the end, surgeon decided to go right in.Gloria

My doctor used the ultrasound as a location finder for where to do the biopsy.... or at least that's what he told me.. the ultrasound was done right before the biopsy.TeriFrom: Randy <randyowe (DOT) com> Sent: Tue, May 4, 2010 9:56:04 PMSubject:

Re: [ ] biopsy

I had two biopsies with no side effects at all and I had two ultrasounds with no effects at all. But I have here and elswhere heard about complications and recurring problems from a biopsy and not an ultrasound. So, should one get a biopsy, which is a more complicated procedure. Maybe. Should one get an ultrasound? Absolutely! The ultrasound will show inflamation, scarring, fatty infiltration, suspicious spots, tumors, and other visible images of the liver, and nearby organs, but it does not show the actual virus. Most good doctors can tell the extent of viral damage, or otherwise, by a visual inspection of all labs and the patient without having to do a biopsy. The support group I belong to which provides free medical care and treatment does not require either. The doctor is a very good one who

specializes in Hep C treatment and he relies on all the other emperical data but not a biopsy and ultrasound. We have an 85% success rate of treatment (40+ patients). The key seems to be helping patients get through treatment by whatever means they need. I know this sounds to hard to believe, but it's true. As for me, I have not been fortunate enough to get on this treament program yet. We have a very long waiting list, which is based on urgency. I hope to one day go through it again, and maybe be rid of this dragon once and for all. Randy O Website-- SuncoastHepCFriends .OrgForum -- Suncoast HepC Friends ForumFrom: Beth Frey <bethfrey42301> Sent: Tue, May 4, 2010 9:11:11 PMSubject: Re: [ ] biopsy

Thanks Don I knew you would have the answer.

From: Christ <ludichrist2000> Sent: Tue, May 4, 2010 7:17:42 PMSubject: Re: [ ] biopsy

Hi Beth

Biopsy is probably the surest way to determine what state your liver is in, but there is some risk, although very low.

Most biopsys are performed, and life goes on.

Biopsys are very fast, and usually do not hurt.

Many folks here have had liver biopsys. I have not.

But having said that, there are other non-invasive methods, that carry no risk.

Your doctor may prefer one method over another, or your personal case may require a certain proceedure.

Click on this link for the HCV Links LIbrary folder: 008 - Biopsy - Fibrosure blood test - methacetin breath test (MBT) - FibroSCAN [transient elastography test]

http://health. dir.groups. / group/HepCWebWar riors/links/ Biopsy_VS_ Fibrosure_ blood_test_ 001247284498/

I hope this info will help you with some of your questions.

love

don in ks

From: Beth Frey <bethfrey42301>Subject: [ ] biopsy Date: Tuesday, May 4, 2010, 6:55 PM

what is the take on biopsy to the blood hcv fibrosoe panel. My gastro said it is acurate and safer. What has anyone else heard

From: Christ <ludichrist2000>009 - VCHepC <VCHepCgroups (DOT) com>; Hepatitis C <Hepatitis C@gro ups.com>; WebWarriors grp < >Sent: Tue, May 4, 2010 6:49:37 PMSubject: [ ] New Therapies in Hepatitis C Virus/Protease Inhibitors

New Therapies in Hepatitis C Virus/Protease Inhibitors

New Medication to Treat Hepatitis C / ann GromischHepatitis C is a contagious liver disease which is spread by contact with blood that is contaminated with the hepatitis C virus. Most cases of acute hepatitis C or HCV advance to chronic HCV. This increases the risk of developing advanced liver disease which is the leading cause of liver cancer. People with HCV are grouped into genotypes, which are subgroups of the virus and are determined by duration

of infection, age, viral load, and degree of liver inflammation and tissue scarring. The current standard treatment for HCV is pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). This treatment is effective in about 40 to 50 percent of people with

genotype-1 and 80

percent of individuals classified as genotype-2 and 3. In the United States, most people with HCV are genotype-1. An article in the May 2010 issue of Current Opinions in Gastroenterology announces the current trial of new medication which promise higher cure rates for HCV genotype-1 patients.The introduction of a first generation protease inhibitor is hoped to have a higher response rate in new HCV patients as well as HCV patients who have received prior treatment. This new type of medication, STAT-C, or specifically targeted antiviral therapy, would be added to the combination therapy of PEG-IFN and RBV. STAT-C targets the enzymes which cause the replication of the hepatitis C virus. The hope is for higher cure rates and reduced time of treatment. There is concern regarding relapse rates and side effects. In clinical trials, the relapse rate was the lowest for patients who received 24 weeks of treatment with the three drugs followed by 24 weeks of

treatment with the current standard treatment.Additional clinical trials are investigating the combination of oral antiviral drugs, protease inhibitors, and polymerase inhibitors. The aim is to develop an effective interferon free regime. About 50 to 60 percent of HIV-infected individuals cannot tolerate interferon.Approval of the first generation protease inhibitor and testing of interferon free treatments is expected in 2011.Sources: Current Opinion in Gastroenterology, May 2010- volume 26- issue 3

Article In Full

From Current Opinion in GastroenterologyNew Therapies in the Management of Hepatitis C Virus J. s; R.

Authors and DisclosuresAbstract and IntroductionAbstractPurpose of review The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat. This article will discuss the most promising up-to-date hepatitis C virus antiviral therapies in clinical investigation as well as the associated clinical trial results.Recent findings First generation protease inhibitors will offer higher sustained viral response rates for both naive (70–80%) and treatment-experienc ed (40–50%) populations when added to standard pegylated interferon and ribavirin. However, these dramatic gains will be partially offset by new

challenges

with viral resistance and increased adverse events.Summary There are currently a number of drugs under investigation that target the enzymes involved in hepatitis C virus replication. Year 2011 should bring the approval of the first generation of protease inhibitors that will offer higher cure rates for genotype 1 patients and open the door for the eventual testing of interferon-free regimens.IntroductionHepatitis C virus (HCV) infection is a global problem with an estimated prevalence of 1.6% in the United States.[1,2] The majority of patients acutely infected with HCV become chronically infected, which increases the risk of developing further complications associated with advanced liver disease. HCV-related end-stage liver disease is a leading cause of hepatocellular carcinoma and the most common indication for liver transplantation in the United States.[3] Current standard

therapy

for HCV includes pegylated interferon (PEG-IFN) in combination with ribavirin (RBV), and this combination is effective in approximately 40–50% of genotype 1-infected patients and 80% of genotype 2-infected and 3-infected patients.[4, 5] Unfortunately, the majority of HCV patients in the United States are infected with genotype 1.[6] The relatively low response rate in treating genotype 1-infected patients, in combination with the long treatment durations and adverse side effect profile has led to a relatively small minority of patients opting for treatment. However, the introduction of specifically targeted antiviral therapy (STAT-C) is now on the horizon with anticipated higher cure rates and the potential for shorter treatment duration. Approval of the first STAT-C compounds is expected by mid-2011 and many patients are being 'warehoused' in anticipation.

Protease Inhibitors: Higher Sustained Viral Response, Shorter Duration, Resistance EmergenceGiven the advancement of our understanding of the HCV life cycle over the past decade, there are a number of drugs under investigation that target the enzymes involved in HCV replication. The class of drugs furthest along in development is the inhibitors of the HCV serine protease NS3-NS4A.[7] Two protease inhibitors have now completed phase II testing and have yielded some consistent early lessons. For naive, genotype 1 patients, higher cure rates and shorter duration of therapy can be expected, but partially offset by new issues of resistance and increased adverse events. The recently published Protease Inhibition for Viral Evaluation (PROVE 1 and 2, evaluating telaprevir, TVR)[8••,9••] and Serine Protease Inhibitor Therapy

(SPRINT-1,

evaluating boceprevir, BOC)[10••] studies evaluated protease inhibitors in combination with PEG-IFN/RBV in genotype 1, naive patients. In PROVE 1, TVR was dosed at 750 mg every 8 h for 12 weeks in combination with PEG-IFN and RBV followed by an additional 12 weeks, or 36 weeks of standard of care (SOC). The sustained viral response (SVR) rate in SOC was 41%, compared with 61% (P = 0.02) in the 24 week treatment group and 67% (P = 0.002) in the 48 week treatment group. Relapse rates were highest in the control group (23%) compared with the 24 week (2%) and 48 week TVR treatment group (6%). However, more patients discontinued therapy in the TVR treatment groups secondary to adverse side effects, with rash being the most common reason for discontinuation.[8••] In the PROVE 2 trial, shorter duration treatment was explored with treatment groups

receiving

triple therapy (TVR + PEG-IFN/RBV) for only 12 weeks (with and without RBV) compared with an additional 12 weeks of SOC. SVR was 46% in the control group, compared with 36% in the non-RBV group (P = 0.20), 60% in the 12 week triple therapy TVR group (P = 0.12) and 69% in the 24 week triple therapy TVR group (P = 0.004). Relapse rates were highest in the non-RBV-treated group (48%) compared with the control group (22%), 12 week triple therapy group (30%) and 24 week triple therapy group (14%). Rash again occurred more commonly in the TVR treatment groups than in the control group[9••] (Fig. 1).Figure 1.Sustained viral response data in naive patients treated with telaprevirPROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response

From PROVE 1 and 2, it appears that TVR has the ability to help overcome negative host and viral factors. A recent pooled analysis[11•] looked at a subgroup of patients with characteristics associated with low virologic response. The overall SVR for the pooled TVR treatment groups was 65 vs. 44% in the control group (P < href="javascript: newshowcontent( ">[12•] treatment-naive, genotype 1 patients (N = 161) were administered triple therapy for 12 weeks with the subsequent PEG-IFN/RBV treatment duration determined using a response-guided strategy. Patients who achieved rapid virologic response (RVR) received a total of 24 weeks of therapy and those who did not have an RVR continued PEG-IFN/RBV to week 48. The SVR rates in this study ranged from 81 to 85%, higher than those observed in the phase II PROVE trials. This study clearly suggests that response-guided therapy based

on RVR

at week 4 may optimize SVR and provides a useful guide for determining which patients should be treated for 24 vs. 48 weeks.

BOC is another oral NS3-NS4A protease inhibitor with potent antiviral activity. The final results from the HCV SPRINT-1 study have been reported in which HCV genotype 1 patients were randomly assigned to receive different combinations of PEG-IFN, RBV (400–1400 mg/day) and BOC (800 mg three times daily). The treatment regimens included a control group treated with 48 weeks of SOC compared to five BOC treatment regimens (4 weeks of PEG-IFN/RBV lead-in followed by triple therapy for 24 or 44 weeks; triple therapy for 28 or 48 weeks; triple therapy, but with low-dose RBV for 48 weeks). The following SVR rates were reported: control group, 38%; triple therapy 28 weeks, 55%; triple therapy 48 weeks, 67%; lead-in group 28 weeks, 56%; lead-in group 48 weeks, 75%; and low-dose RBV group, 36%. It should be noted that up to 50% of patients were treated with erythropoietin in this trial, highlighting the increased rates of anemia with BOC.

Higher rates of discontinuation secondary to adverse side effects and viral breakthrough occurred in the BOC treatment groups compared with the control group. Of note, the highest reported viral breakthrough was seen in the low-dose RBV group.[10••]

Ribavirin is Required to Maximize Sustained Viral Response with Protease Inhibitors and Limit Resistance

As highlighted above, early phase II studies show strong evidence for the need of RBV in STAT-C drug regimens. Patients who did not receive RBV in the PROVE trials and those with low-dose RBV (400–1000 mg) in the SPRINT-1 trial had increased viral breakthrough, higher relapse and lower SVR. These data strongly indicate that standard-dose RBV is required to optimize response to these first generation protease inhibitors via a reduction in the development of resistance/breakthr ough (Fig. 2).

Figure 2.Importance of ribavirin in combination with protease inhibitors PROVE, Protease Inhibition for Viral Evaluation; SVR, sustained viral response.

It is also clear that the initial rapid drop in HCV viral levels on protease combination therapy is due to inhibition of wild-type virus that then leads to the 'uncovering' of preexisting resistant variants. The continued replication of these variants can then lead to a virologic breakthrough. Resistant variants are present in most patients at very low frequencies (<1%)>

Protease Inhibitors: Hope for NonrespondersAn initial phase II trial with BOC-containing regimens in previous HCV genotype 1 nonresponders to SOC was not encouraging (SVR 14%), though in retrospect inadequate BOC dosing regimens were being used.[13] Since this early experience, a number of studies are starting to suggest reasonable response rates for the treatment-experienc ed population. In PROVE 3,[14••] treatment-experienc ed patients were randomized to one of four treatment arms (SOC for 48 weeks; TVR + PEG-IFN/RBV for 12 weeks, then SOC for an additional 12 weeks; TVR + PEG-IFN/RBV for 24 weeks, then SOC for an additional 24 weeks; or TVR + PEG-IFN for 24 weeks). SVR rates were 38–39% among previous nonresponders who received TVR-based triple therapy.

Relapse rates were

lowest among patients who received 24 weeks of triple therapy followed by 24 weeks of standard therapy (13 vs. 30–53% for other treatment arms). An important factor to consider in interpreting the results of the PROVE 3 trial is the stringent stopping rule established for TVR therapy. Because of concerns for high rates of resistance with incomplete viral suppression, patients in PROVE 3 discontinued TVR if HCV RNA remained detectable (>30 IU/ml) at week 4. It is now apparent that patients with declining but detectable HCV RNA at week 4 continue to experience HCV RNA reductions during treatment with TVR-containing regimens and have a high likelihood of achieving SVR with a total of 48 weeks of therapy. A hint of anticipated SVR with this response-guided approach to retreatment has now been reported from study 107 (patients in PROVE studies who did not achieve SVR in control group were retreated with triple therapy for 12 weeks followed by either 12

or 36 weeks of consolidation PEG-IFN/RBV) . SVR rate for this well characterized population was 57% among prior nonresponders.[15]

Of interest, a similar SVR rate was seen in 'lead-in, null responders' from the SPRINT-1 trial. Kwo et al. conducted a retrospective analysis of SVR rates among patients who received 24 or 44 weeks of BOC and PEG-IFN/RBV following a 4-week lead-in period of PEG-IFN/RBV therapy. Among patients with a null response to the 4-week lead-in treatment period (<>

Lead-in viral decline and relationship to sustained viral response HCV, hepatitis C virus.

Polymerase Inhibitors: Unique Genetic Barrier to Resistance for NucleosidesMultiple agents targeting the HCV RNA-dependent polymerase inhibitor, which is critical for viral replication, are also currently in trials. One of the most advanced of these polymerase inhibitors is RG7128, a nucleoside analogue. RG7128 showed potent antiviral activity as monotherapy in HCV genotype 1 patients who had failed prior standard therapy,[16] as well as in combination with PEG-IFN/RBV. [17,18] It also has been shown to have a similar safety profile as standard therapy with PEG-IFN/RBV and has demonstrated significant antiviral potency regardless of race, ethnicity or genotype.[17–19] Thus far, viral resistance has not been seen in any clinical trials with RG7128,[16,18] which suggests that the nucleoside class may offer a higher genetic barrier to viral resistance than the protease class of inhibitors.[ 20•]Another

nucleoside polymerase inhibitor, R1626, also showed potent HCV antiviral activity (virus negative at 48 weeks) when combined with PEG-IFN/RBV compared with the control group (84 vs. 65%, respectively) . This trial also showed the importance of RBV in combination therapy as the end of treatment responses were less in the non-RBV groups compared with the control group. However, the development of this drug has been halted due to unacceptable rates of hematologic abnormalities, highlighted by lymphopenia. [21] Other second generation nucleotide polymerase inhibitors are in the early stages of development, such as PSI-7851 and IDX184, and have shown encouraging antiviral activity.[22, 23] PSI-7851 has demonstrated dose-dependent HCV RNA reductions over 3 days of dosing, and patients receiving the 400-mg dose achieved a mean HCV RNA decrease of 1.95 log10 IU/ml. Population sequencing did not identify any evidence of treatment-emergent drug resistance and no

patients discontinued treatment early.[22] Dose-dependent decreases in HCV RNA were also observed during the 3-day IDX184 dosing period with mean reductions ranging from 0.47 to 0.74 log10 IU/ml.[23]In addition to the nucleoside RNA-polymerase inhibitors, nonnucleoside HCV RNA-polymerase inhibitors are also showing promise in early HCV trials. Nonnucleoside inhibitors such as GS-9190, filibuvir, BI207127, VCH-916, VCH-222, MK-3281 and ABT-333 have shown potent antiviral activity for patients with genotype 1 HCV infections and generally have been well tolerated in early clinical studies.[24–31] Even though the early results have shown promise, the genetic barrier to resistance for this class appears to be low, similar to the protease class.Interferon-free Regimens

Given the continued need for PEG-IFN and full-dose RBV, there are many HCV-infected groups that may not benefit from the initial approval of STAT-C agents, including decompensated cirrhosis, renal failure, posttransplant and the IFN-intolerant group (which may consist of as many as 50–60% of all HCV-infected patients). Thus, what is desperately needed is the development of IFN-free regimens, that is, combination of small molecules similar to HIV therapy. A novel study called INFORM-1, the first dual combination clinical trial with oral antivirals in HCV patients, is ongoing and evaluates the safety and combined antiviral activity of RG7227, a protease inhibitor and RG7128, a polymerase inhibitor, in 14 days of combination therapy in treatment-naive patients infected with HCV genotype 1. The initial cohorts of this study were reported and appear to lay the foundation for more aggressive and prolonged non-IFN trial designs.

Patients

receiving this combination for 14 days experienced a median reduction in viral levels of 4.8–5.2 log IU in the higher doses tested and this combination was equally effective in both naive and previous nonresponder patients. No treatment-related serious adverse events, dose reductions, drug–drug interactions or discontinuations were reported.[32••] Given these encouraging data, many other trials are now beginning to explore combinations of STAT-C agents in the absence of PEG-IFN and/or RBV. Lastly, other strategies to improve the tolerability of IFN and RBV with new analogues of IFN and RBV are also being investigated. [33•,34•,35•,36]Conclusion

In summary, potent viral suppression and shortened duration of therapy have been shown in clinical trials with the addition of protease inhibitors to standard therapy. Although there is optimism surrounding the new STAT-C agents in the treatment of HCV, there is also a concern on how resistance and new adverse events will impact future therapy. It also appears that the platform exists to begin to explore non-IFN-containing regimens, which would be an enormous step forward to accessing a large proportion of infected patients. The future looks encouraging for the clinician treating HCV, and more importantly, for the patients infected with HCV.http://www.medscape .com/viewarticle /720695_7

http://www.empowher .com/news/ herarticle/ 2010/05/03/ new-medication- treat-hepatitis- c

http://Hepatitis Cne wdrugs.blogspot. com/2010/ 05/new-therapies -in-hepatitis- c.html

[Guest guest]

Debbie Good luck and best wishes to you tommorrow. Beth

From: sparkles43d <sparkles43d@...>Subject: [ ] Biopsy Date: Sunday, September 19, 2010, 5:49 PM

My biopsy is tomorrow. I check-in at @ 8am. I'm not nervous this time around cuz I know what I'll be going thru. Barring no complications I should be home by early to mid-afternoon. The worst thing I find after the biopsy has been done is the shoulder pain till they take the weight off the needle site. Debbie

[Guest guest]

??? I sure don't recall any shoulder pain from any weight of the needle. In fact, I was laying pretty much flat on my back during the whole procedure.Anyway, wishing you a good biopsy tomorrow.Gloria

My biopsy is tomorrow. I check-in at @ 8am. I'm not nervous this time around cuz I know what I'll be going thru. Barring no complications I should be home by early to mid-afternoon. The worst thing I find after the biopsy has been done is the shoulder pain till they take the weight off the needle site.

Debbie

[Guest guest]

Thanks Gloria.I think I was on my back the entire time too and after wards back

in the recovery area where they monitor you for a while the spot where they

stick the needle in they place a 10 lb weight for the pressure so you are less

likely to bleed out and while the pressure from the weight is applied; that gave

me pain in the right shoulder. Some people don't experience the shoulder pain.

>

> ??? I sure don't recall any shoulder pain from any weight of the needle. In

> fact, I was laying pretty much flat on my back during the whole procedure.

>

> Anyway, wishing you a good biopsy tomorrow.

>

> Gloria

>

>

>

>

> ________________________________

>

>

> My biopsy is tomorrow. I check-in at @ 8am. I'm not nervous this time around

cuz

> I know what I'll be going thru. Barring no complications I should be home by

> early to mid-afternoon. The worst thing I find after the biopsy has been done

is

> the shoulder pain till they take the weight off the needle site.

>

>

> Debbie

>

[Guest guest]

Thanks Beth. I'll sail right thru it.

Debbie

>

>

> From: sparkles43d <sparkles43d@...>

> Subject: [ ] Biopsy

>

> Date: Sunday, September 19, 2010, 5:49 PM

>

>

>  

>

>

>

> My biopsy is tomorrow. I check-in at @ 8am. I'm not nervous this time around

cuz I know what I'll be going thru. Barring no complications I should be home by

early to mid-afternoon. The worst thing I find after the biopsy has been done is

the shoulder pain till they take the weight off the needle site.

>

> Debbie

>

[Guest guest]

Sanita,Welcome to the group.. hopefully we can answer all of your questions for you and help you along in your walk with Hep C. You can have Hep C for years and years without your liver function tests showing any changes. It's only after a significant amount of damage has been done that your liver functions studies will show a change. The test for the genotype will tell you what kind of Hep C you have and let the doctor know what the treatment length will be. Not everyone goes thru treatment, it's a personal choice.. that is unless you have significant damage. In my case, when I found out I had Hep C, I had been infected for 24 years. Lots of damage had been done, my liver function studies were way off.. the

biopsy showed 25 years worth of damage... (My biopsy was done many months after my diagnosis.. hence the time difference) I contracted the virus thru a blood transfusion. I received 5 units of untested blood in 1980. The biopsy will clearly show if your liver is being impacted by the Hep C. You will also hear a viral load number... This is the number of Hep C viruses that are in that specific sample of blood. This number can change daily. It is only important when you are starting treatment and going thru treatment. The biopsy has minimal side effects but it is a most important tool in not only the treatment but in knowing the progression of your Hep C. The procedure itself is pretty quick and I don't remember any pain... actually I barely remember the procedure. That's not because my memory is horrible but because you are given some medication to help keep you calm and it pretty much

makes it all rather easy. I was in and out of the hospital in less than 3 hours. That's from walking in the door to being in my car on the way home. There can be some residual pain afterward for a few hours but they send you home with pain meds just in case or at least my doctor did. The fact that you are starting to feel tired can indicate that the Hep C virus is running rampant in your system. I too was feeling tired (among other things) when I was diagnosed. At the time of my biopsy I was told that if I didn't start treatment I would need to be placed on the liver transplant list within 6 months... I was also told I would die waiting for a liver. For me the choice was obvious. I went thru 48 weeks of treatment and cleared the virus. You have no idea what a relief it is to know that you've cleared all of the Hep C replicates from your system. For me it was the only option.. for

you it may be different.There are people on this groups that are treating and those that are not treating for whatever their reasons are... some are taking a holistic approach, some have explored natural remedies and diet changes, some are unable to treat at this time due to medical complications. We have a pretty well rounded group here and you can get all sorts of information on different approaches to treatment.. Only you and your doctor can decide which option is the best for you. One thing to remember is that more people die with the Hep C virus than from it. It is so slow moving that a lot of people can go without treating it. In my case, I would have been dead before my 50th birthday. I have a family and I didn't want them to deal with my death this early on so I decided to treat. Actually my family decided I was going thru treatment. It was, for me, the best thing I ever did for

myself... Feel free to ask any questions... you have found a safe place. Welcome.Hugs,Teri MOVE ON. It's just a chapter in the past, but don't close the book. Just turn the page.From: Sanita <sanitafl@...> Sent: Tue, October 12, 2010 10:24:43 AMSubject: [ ] Biopsy

Hrelo, my first post. Am going to find out genotype soon. I know Dr Zhang in new york chinese medicine was effective for a friend for 15 years. About biopsy. Are there side effects with this? I kow the scar tissue shows only on biopsy, this is why I am told I NEED IT BUT what if I can keep my levels in check? I know I have had it 30 years but recently feel tired ,.....

[Guest guest]

Sanita,Welcome to the group.. hopefully we can answer all of your questions for you and help you along in your walk with Hep C. You can have Hep C for years and years without your liver function tests showing any changes. It's only after a significant amount of damage has been done that your liver functions studies will show a change. The test for the genotype will tell you what kind of Hep C you have and let the doctor know what the treatment length will be. Not everyone goes thru treatment, it's a personal choice.. that is unless you have significant damage. In my case, when I found out I had Hep C, I had been infected for 24 years. Lots of damage had been done, my liver function studies were way off.. the

biopsy showed 25 years worth of damage... (My biopsy was done many months after my diagnosis.. hence the time difference) I contracted the virus thru a blood transfusion. I received 5 units of untested blood in 1980. The biopsy will clearly show if your liver is being impacted by the Hep C. You will also hear a viral load number... This is the number of Hep C viruses that are in that specific sample of blood. This number can change daily. It is only important when you are starting treatment and going thru treatment. The biopsy has minimal side effects but it is a most important tool in not only the treatment but in knowing the progression of your Hep C. The procedure itself is pretty quick and I don't remember any pain... actually I barely remember the procedure. That's not because my memory is horrible but because you are given some medication to help keep you calm and it pretty much

makes it all rather easy. I was in and out of the hospital in less than 3 hours. That's from walking in the door to being in my car on the way home. There can be some residual pain afterward for a few hours but they send you home with pain meds just in case or at least my doctor did. The fact that you are starting to feel tired can indicate that the Hep C virus is running rampant in your system. I too was feeling tired (among other things) when I was diagnosed. At the time of my biopsy I was told that if I didn't start treatment I would need to be placed on the liver transplant list within 6 months... I was also told I would die waiting for a liver. For me the choice was obvious. I went thru 48 weeks of treatment and cleared the virus. You have no idea what a relief it is to know that you've cleared all of the Hep C replicates from your system. For me it was the only option.. for

you it may be different.There are people on this groups that are treating and those that are not treating for whatever their reasons are... some are taking a holistic approach, some have explored natural remedies and diet changes, some are unable to treat at this time due to medical complications. We have a pretty well rounded group here and you can get all sorts of information on different approaches to treatment.. Only you and your doctor can decide which option is the best for you. One thing to remember is that more people die with the Hep C virus than from it. It is so slow moving that a lot of people can go without treating it. In my case, I would have been dead before my 50th birthday. I have a family and I didn't want them to deal with my death this early on so I decided to treat. Actually my family decided I was going thru treatment. It was, for me, the best thing I ever did for

myself... Feel free to ask any questions... you have found a safe place. Welcome.Hugs,Teri MOVE ON. It's just a chapter in the past, but don't close the book. Just turn the page.From: Sanita <sanitafl@...> Sent: Tue, October 12, 2010 10:24:43 AMSubject: [ ] Biopsy

Hrelo, my first post. Am going to find out genotype soon. I know Dr Zhang in new york chinese medicine was effective for a friend for 15 years. About biopsy. Are there side effects with this? I kow the scar tissue shows only on biopsy, this is why I am told I NEED IT BUT what if I can keep my levels in check? I know I have had it 30 years but recently feel tired ,.....

[Guest guest]

SantaI think you asked if there was a side affect from the liver biopsy? Not really, if you feel it at all, it lasts for 2 seconds. A liver biopsy is the best procedure to actually learn how much damage has been done already. Liver Enzyme tests and even a viral count are just simply numbers compared to what a biopsy can tell the Doctors. Gloria

Hrelo, my first post. Am going to find out genotype soon. I know Dr Zhang in new york chinese medicine was effective for a friend for 15 years. About biopsy. Are there side effects with this? I kow the scar tissue shows only on biopsy, this is why I am told I NEED IT BUT what if I can keep my levels in check? I know I have had it 30 years but recently feel tired ,.....

[Guest guest]

Donna,

I will do more research but I will tell you that if it WERE cancer they would

have told you. I think its considered a thickening of the cells in the mucosa

with the possibility of cell changes. It can be indicitve of a pre cancerous

situation but doesn't mean that cancer will ever occur.

Look at Barrett's, its a pre cancerous condition that rarely turns into cancer.

I don't know the statistics, but from what all the surgeons told me they usually

just monitor Barrett's and control the acid.

I will look for more info and I am also saying prayers for your peace of mind

this weekend while you await your results.

cara

>

> I received records from my local hospital today that I had when I first

developed symptoms back in 2008.

>

>

> Dr. Sayuk in St. Louis didn't mention anything to me about this.

>

>

> Re: Surgical Pathology report Dated: 4/2/2008

>

> Diagnosis comment:

>

> The specimen consists of a strip of hyperplastic squamous epithelium.

>

> Diagnosis:

>

> Hyperplastic squamous epithelium.

>

>

> What does that mean? Is this implications of cancer?

>

> Donna

>

[Guest guest]

BettyI think that is one of the most horrible liver biopsy's I've ever heard about. It makes me angry to realize that they can do pain free biopsies and they just don't take the time. After I was frozen right down to the liver, I couldn't have cared less how many times they wanted to get a sample. Now that I do know that they can be painless, you can bet that I'll never have another one without thorough freezing.Geez - I want to get up and slug the Dr. that did that to you! He/She was masochistic. Anybody that is looking in here and hasn't had a biopsy. Be absolutely firm with the Dr. that is doing it, that you want to be frozen right to the

liver. The liver itself has no nerves, so what it actually hurting is the fact that they didn't freeze far enough down.Gloria

To All, IDK what is medically correct but I can only tell u my experience with the liver biopsy, well they froze the area at the ribcage and did the ultrasound to show them where to stab me, and then the did just that litterally stabbed me, they then walk over to a table and came back and said WE HAVE TO DO IT AGAIN (OMG) they didnt get enought the first time, i cried, AND THE DR LEANED OVER ME AND STABBED ME AGAIN but this time harder to go deeper, I screamed something stupid at him and told him he was mean, because it didnt hurt as much the first time (DAH).In the end all I could do was accept that this was the beginning of a long painfull process that I couln't change. I am so afraid of them wanting to repeat the biopsy at some point, IDK if I can do that one again personnally. Betty

From: Gloria <gadamscan@...> Sent: Sun, January 23, 2011 12:16:04 AMSubject: Re: [ ] Re: Don/Labs

Owwweeee unless the Dr. was good to you and froze you right down to the liver. Then, it wouldn't matter how many times they wanted to stick me.

I got stuck twice.

On Sat, Jan 22, 2011 at 10:30 PM, Gloria <gadamscan@...> wrote:

Truthfully, I thought they were taking 3 little pieces; but, its guided and supposed to show the Dr. where to stick that needle. I certainly never had that needle stuck in me twice on the same test. If they had done that on my first biopsy, I think I would have hit that Dr. Now, the biopsy in early 2009 was like a Sunday picnic. That Dr. froze me and my expanded belly right down to the liver.Gloria

Nope Don she is right.. that's why they usually, usually stick you twice. Once the scarring starts the blood flow is obstructed a bit to that area... scarring tends to happen in groupings.

On Sat, Jan 22, 2011 at 9:32 PM, Christ <ludichrist2000@...> wrote:

Hi Debbie

Im not sure that this is true.

Granted Im not a doctor, but it makes sence to me that the scaring would be evenly distributed throughout the liver.

Maybe someone else knows.

love

don in ks

From: debbiecurwick <debbiecurwick@...>Subject: [ ] Re: Don/Labs Date: Saturday, January 22, 2011, 9:29 PM

The biopsy is done with a hollow needle that goes into the liver and takes a small amount. Some parts of the liver may not have as much scarring as another place would, so if they happen to get a sample from an area that isn't as scarred it would give you a false reading so to speak. Does that make sense to you ? My hepatologist at the UW thinks that is what happened in my case.Debbie> >

> Don,> > > > Question for you. You've yet to have a liver biopsy done, Right. You say you're labs are staying in the normal range. Well my labs have been in the normal range and look at the condition of my liver. Cirrhosis compensated stage. What is keeping you from having a liver biopsy if you haven't had one done yet. Mine went from grade 1 stage 1 to grade 3 stage 4 cirrhosis in just 2 yrs. Unless when they did my first biopsy they got the sample from an area that didn't show as much damage. Who knows. So how can you say your liver is not doing bad. Labs don't always tell the whole story. I can attest to that.> > > > Debbie> > > >>------------------------------------

[Guest guest]

I saw a video on youtube once where they can do a liver biopsy like a MRI that is painless. It should thinks in colors, it was great to see, and I though why is this not the standard!it was research, but I think it was from Stanford if I remember, I will look for the video again.On Jan 23, 2011, at 1:30 PM, Gloria wrote:

BettyI think that is one of the most horrible liver biopsy's I've ever heard about. It makes me angry to realize that they can do pain free biopsies and they just don't take the time. After I was frozen right down to the liver, I couldn't have cared less how many times they wanted to get a sample. Now that I do know that they can be painless, you can bet that I'll never have another one without thorough freezing.Geez - I want to get up and slug the Dr. that did that to you! He/She was masochistic. Anybody that is looking in here and hasn't had a biopsy. Be absolutely firm with the Dr. that is doing it, that you want to be frozen right to the

liver. The liver itself has no nerves, so what it actually hurting is the fact that they didn't freeze far enough down.Gloria

To All, IDK what is medically correct but I can only tell u my experience with the liver biopsy, well they froze the area at the ribcage and did the ultrasound to show them where to stab me, and then the did just that litterally stabbed me, they then walk over to a table and came back and said WE HAVE TO DO IT AGAIN (OMG) they didnt get enought the first time, i cried, AND THE DR LEANED OVER ME AND STABBED ME AGAIN but this time harder to go deeper, I screamed something stupid at him and told him he was mean, because it didnt hurt as much the first time (DAH).In the end all I could do was accept that this was the beginning of a long painfull process that I couln't change. I am so afraid of them wanting to repeat the biopsy at some point, IDK if I can do that one again personnally. Betty

From: Gloria <gadamscan@...> Sent: Sun, January 23, 2011 12:16:04 AMSubject: Re: [ ] Re: Don/Labs

Owwweeee unless the Dr. was good to you and froze you right down to the liver. Then, it wouldn't matter how many times they wanted to stick me.

I got stuck twice.

On Sat, Jan 22, 2011 at 10:30 PM, Gloria <gadamscan@...> wrote:

Truthfully, I thought they were taking 3 little pieces; but, its guided and supposed to show the Dr. where to stick that needle. I certainly never had that needle stuck in me twice on the same test. If they had done that on my first biopsy, I think I would have hit that Dr. Now, the biopsy in early 2009 was like a Sunday picnic. That Dr. froze me and my expanded belly right down to the liver.Gloria

Nope Don she is right.. that's why they usually, usually stick you twice. Once the scarring starts the blood flow is obstructed a bit to that area... scarring tends to happen in groupings.

On Sat, Jan 22, 2011 at 9:32 PM, Christ <ludichrist2000@...> wrote:

Hi Debbie

Im not sure that this is true.

Granted Im not a doctor, but it makes sence to me that the scaring would be evenly distributed throughout the liver.

Maybe someone else knows.

love

don in ks

From: debbiecurwick <debbiecurwick@...>Subject: [ ] Re: Don/Labs Date: Saturday, January 22, 2011, 9:29 PM

The biopsy is done with a hollow needle that goes into the liver and takes a small amount. Some parts of the liver may not have as much scarring as another place would, so if they happen to get a sample from an area that isn't as scarred it would give you a false reading so to speak. Does that make sense to you ? My hepatologist at the UW thinks that is what happened in my case.Debbie> >

> Don,> > > > Question for you. You've yet to have a liver biopsy done, Right. You say you're labs are staying in the normal range. Well my labs have been in the normal range and look at the condition of my liver. Cirrhosis compensated stage. What is keeping you from having a liver biopsy if you haven't had one done yet. Mine went from grade 1 stage 1 to grade 3 stage 4 cirrhosis in just 2 yrs. Unless when they did my first biopsy they got the sample from an area that didn't show as much damage. Who knows. So how can you say your liver is not doing bad. Labs don't always tell the whole story. I can attest to that.> > > > Debbie> > > >>------------------------------------

[Guest guest]

betty,OMG, can't they give you laughing gas, like at the doctors, your still awake, but kinda out of it. It sounds ridiculous, honestly. I mean it's 2011, they can't think of a way to make it painless. I don't understand why you have to be awake?? For what reason. I did once get one of those big needles in my belly when I was pregnant for down syndrome, but I don't remember it hurting?? I think I was so scared that i didn't feel it. I feel for you. I do. I don't know if I could do it. You are very brave. but to the woman who gave child birth with no meds, BRAVO!! I am sure it feels like that, something you never forget. I am afraid of getting it. So i

don'tSharonHep C victimFrom: Betty Himes <stayhungryforlife@...> Sent: Sun, January 23, 2011 11:33:29 AMSubject: Re: [ ] Biopsy

To All, IDK what is medically correct but I can only tell u my experience with the liver biopsy, well they froze the area at the ribcage and did the ultrasound to show them where to stab me, and then the did just that litterally stabbed me, they then walk over to a table and came back and said WE HAVE TO DO IT AGAIN (OMG) they didnt get enought the first time, i cried, AND THE DR LEANED OVER ME AND STABBED ME AGAIN but this time harder to go deeper, I screamed something stupid at him and told him he was mean, because it didnt hurt as much the first time (DAH).In the end all I could do was accept that this was the beginning of a long painfull process that I couln't change. I am so afraid of them wanting to repeat the biopsy at some point, IDK if I can do that one again personnally. Betty

From: Gloria <gadamscan@...> Sent: Sun, January 23, 2011 12:16:04 AMSubject: Re: [ ] Re: Don/Labs

Owwweeee unless the Dr. was good to you and froze you right down to the liver. Then, it wouldn't matter how many times they wanted to stick me.

I got stuck twice.

On Sat, Jan 22, 2011 at 10:30 PM, Gloria <gadamscan@...> wrote:

Truthfully, I thought they were taking 3 little pieces; but, its guided and supposed to show the Dr. where to stick that needle. I certainly never had that needle stuck in me twice on the same test. If they had done that on my first biopsy, I think I would have hit that Dr. Now, the biopsy in early 2009 was like a Sunday picnic. That Dr. froze me and my expanded belly right down to the liver.Gloria

Nope Don she is right.. that's why they usually, usually stick you twice. Once the scarring starts the blood flow is obstructed a bit to that area... scarring tends to happen in groupings.

On Sat, Jan 22, 2011 at 9:32 PM, Christ <ludichrist2000@...> wrote:

Hi Debbie

Im not sure that this is true.

Granted Im not a doctor, but it makes sence to me that the scaring would be evenly distributed throughout the liver.

Maybe someone else knows.

love

don in ks

From: debbiecurwick <debbiecurwick@...>Subject: [ ] Re: Don/Labs Date: Saturday, January 22, 2011, 9:29 PM

The biopsy is done with a hollow needle that goes into the liver and takes a small amount. Some parts of the liver may not have as much scarring as another place would, so if they happen to get a sample from an area that isn't as scarred it would give you a false reading so to speak. Does that make sense to you ? My hepatologist at the UW thinks that is what happened in my case.Debbie> >

> Don,> > > > Question for you. You've yet to have a liver biopsy done, Right. You say you're labs are staying in the normal range. Well my labs have been in the normal range and look at the condition of my liver. Cirrhosis compensated stage. What is keeping you from having a liver biopsy if you haven't had one done yet. Mine went from grade 1 stage 1 to grade 3 stage 4 cirrhosis in just 2 yrs. Unless when they did my first biopsy they got the sample from an area that didn't show as much damage. Who knows. So how can you say your liver is not doing bad. Labs don't always tell the whole story. I can attest to that.> > > > Debbie> > > >>------------------------------------

[Guest guest]

Hi,

Today, the surgeon called and told me I do not have cancer. However, I do have

Sjogren's Syndrome. He is also an ENT specialist as well. He told me to use

sugar-free lemon drops and drink 8 glasses of water each day for the dry mouth.

For the dry eye, I will be using lubricating eye drops.

Thanks for all your support.

Alice from Flushing

[Guest guest]

Great news Alice - Thank God our prayers are answered. I too have dry

mouth and dry eyes. There are mouth washes that lubricate the mouth.

I am very happy for you! God bless - Vivian CA