Re: Being candid about Candida ...Response to Lori and Taru-Mari

March 28, 2009

Dear Lori and Taru-Mari;

Sorry that the information contained in the abstracts is often so technical.

There's not much I can do about this except try to answer any questions that may

arise.

The term " stenosis " means a narrowing, and therefore means the same as a

" stricture " [the German group seems to prefer the term " stenosis " whereas in the

U.S. the term " stricture " is more often used]. So, both " stenosis " and

" stricture " mean narrowing of the bile-duct.

The term " dominant stenosis " or " dominant stricture " means a narrowing of the

main bile duct (the common bile duct) coming out of the liver, and/or a

narrowing of one or both of the main left and right branches from the common

bile duct inside the liver. Dr. Stiehl has his own very strict definition of a

" dominant stenosis " , and this is:

" A dominant stenosis was defined as a stenosis with a diameter of less than 1.5

mm of the common duct or less than 1.0 mm of a hepatic duct (within 2 cm of the

bifurcation) "

The term " bifurcation " refers to the branch point where the right and left

hepatic ducts join to form the main bile duct (common bile duct) that comes out

of the liver.

The above definition is from an earlier paper in which Dr. Stiehl's group first

documented Candida infections in PSC patients:

Kulaksiz H, Rudolph G, Kloeters-Plachky P, Sauer P, Geiss H, Stiehl A (2006)

Biliary candida infections in primary sclerosing cholangitis. J. Hepatol. 45:

711-716.

http://www.ncbi.nlm.nih.gov/pubmed/16979779

In this paper they note: " Candida disappeared spontaneously in 2/7 patients,

cleared after antifungal treatment in 2, and persisted in 3 patients. Patients

with biliary Candida had more severe cholangitis with higher CRP and serum

bilirubin compared to those without Candida infection. "

CRP means C-reactive protein, which is often used as a measure of inflammation.

In the full text of this paper they describe some of the antifungal treatments

attempted in these patients (Candida is a yeast which is a form of fungus):

" Three of the 8 patients with biliary Candida infection had clinical signs of

cholangitis and marked cholestasis and in addition to antibiotic treatment also

received antifungal treatment. One of these was treated with fluconazole,

Candida persisted despite treatment

and he died due to a cholangio-carcinoma after 2 months. The other two patients

were treated with caspofungine and Candida disappeared; in one of them the fungi

recurred after ending of treatment whereas

one patient had permanent clearance of the fungi. In the patient with permanent

clearance of Candida, cholestasis improved markedly and serum bilirubin

decreased from 8.8 to 2.2 mg/dl. By contrast, in the

patient with Candida recurrence cholestasis improved little and serum bilirubin

decreased only from 12.1 to 8.6 mg/dl. Both patients are scheduled for liver

transplantation. "

" Of the 5 patients not treated for fungal infection, in two Candida cleared

spontaneously, two continued to have Candida in bile and one patient was

transplanted. The two patients with Candida in their control bile have clinical

cholangitis with elevated CRP and serum bilirubin and currently are treated for

their fungal infection.

Apart from the fact that patients with Candida in bile belonged to the group of

patients with more severe cholestasis and higher serum bilirubin we did not find

any clinical signs which would be characteristic for this subgroup of patients. "

The abstract I posted yesterday is obviously a follow-up to this 2006 paper, and

they now come to the conclusion that the presence of Candida in bile IS a risk

factor for disease progression ( " Candida in bile is associated with a poor

prognosis and these patients need liver transplantation relatively soon " ). I

think you got this point (!!) but the " why " of this is more difficult to answer.

As I posted above, the Candida infections do not seem to be controlled in all

patients when treated with antifungal medications, such as fluconazole or

caspofungine, and it may be possible that the shorter time to transplantation in

patients with Candida infection is associated with poor response to these

antifungal therapies?

However, because I have not yet seen the full text of this article (my

subscription to J. Hepatol. has expired), I can't really comment much further on

this point. If anyone has a subscription to J. Hepatol. and can share this

recent paper, that would be much appreciated.

The abstract concludes that presence of a dominant stricture is a risk factor

for reduced survival free of liver transplantation ( " Survival free of liver

transplantation in patients without dominant stenosis at 18 years was 73.1% and

of patients with dominant stenosis was 25.0% (p=0.011) " ). This means there is an

approximately 3-fold higher risk of dying or needing a transplant in those

patients with a dominant stricture (compared to those without a dominant

stricture) during the 18-year period that these patients have been monitored.

The abstract concludes that bacteria in bile does not affect the risk for

survival free of transplantation provided that these infections are treated with

antibiotics and if dominant strictures are opened with endoscopic procedures

such as balloon dilatation during ERCP ( " Bacteria in bile do not worsen the

outcome if dominant stenoses are opened endoscopically and infection is

adequately treated with antibiotics. " ) What the abstract is NOT saying here is

that outcomes would probably be much worse if dominant strictures were not

opened endoscopically, and if bacterial infections were left untreated.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

March 28, 2009

Dave,

Thank you so much for your response. I really appreciate it. It takes a lot of time and thought to explain as you have and in so much detail. I am going to study some more on Candida so I can learn how to take it out of your system. Looks like the medicines they used in the study do not work well. I wonder if there is another way perhaps naturally?

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

Click here

To: Sent: Saturday, March 28, 2009 1:35:24 PMSubject: Re: Being candid about Candida ...Response to Lori and Taru-Mari

Dear Lori and Taru-Mari;Sorry that the information contained in the abstracts is often so technical. There's not much I can do about this except try to answer any questions that may arise.The term "stenosis" means a narrowing, and therefore means the same as a "stricture" [the German group seems to prefer the term "stenosis" whereas in the U.S. the term "stricture" is more often used]. So, both "stenosis" and "stricture" mean narrowing of the bile-duct.The term "dominant stenosis" or "dominant stricture" means a narrowing of the main bile duct (the common bile duct) coming out of the liver, and/or a narrowing of one or both of the main left and right branches from the common bile duct inside the liver. Dr. Stiehl has his own very strict definition of a "dominant stenosis", and this is:"A dominant stenosis was defined as a stenosis with a diameter of less than 1.5 mm of the common duct or less than 1.0 mm of a hepatic

duct (within 2 cm of the bifurcation) "The term "bifurcation" refers to the branch point where the right and left hepatic ducts join to form the main bile duct (common bile duct) that comes out of the liver.The above definition is from an earlier paper in which Dr. Stiehl's group first documented Candida infections in PSC patients:Kulaksiz H, Rudolph G, Kloeters-Plachky P, Sauer P, Geiss H, Stiehl A (2006) Biliary candida infections in primary sclerosing cholangitis. J. Hepatol. 45: 711-716. http://www.ncbi. nlm.nih.gov/ pubmed/16979779In this paper they note: "Candida disappeared spontaneously in 2/7 patients, cleared after antifungal treatment in 2, and persisted in 3 patients. Patients with biliary Candida had more severe cholangitis with higher CRP and serum bilirubin compared to those without Candida infection." CRP means

C-reactive protein, which is often used as a measure of inflammation.In the full text of this paper they describe some of the antifungal treatments attempted in these patients (Candida is a yeast which is a form of fungus):"Three of the 8 patients with biliary Candida infection had clinical signs of cholangitis and marked cholestasis and in addition to antibiotic treatment also received antifungal treatment. One of these was treated with fluconazole, Candida persisted despite treatmentand he died due to a cholangio-carcinoma after 2 months. The other two patients were treated with caspofungine and Candida disappeared; in one of them the fungi recurred after ending of treatment whereasone patient had permanent clearance of the fungi. In the patient with permanent clearance of Candida, cholestasis improved markedly and serum bilirubin decreased from 8.8 to 2.2 mg/dl. By contrast, in thepatient with Candida recurrence

cholestasis improved little and serum bilirubin decreased only from 12.1 to 8.6 mg/dl. Both patients are scheduled for liver transplantation. ""Of the 5 patients not treated for fungal infection, in two Candida cleared spontaneously, two continued to have Candida in bile and one patient was transplanted. The two patients with Candida in their control bile have clinical cholangitis with elevated CRP and serum bilirubin and currently are treated for their fungal infection.Apart from the fact that patients with Candida in bile belonged to the group of patients with more severe cholestasis and higher serum bilirubin we did not find any clinical signs which would be characteristic for this subgroup of patients."The abstract I posted yesterday is obviously a follow-up to this 2006 paper, and they now come to the conclusion that the presence of Candida in bile IS a risk factor for disease progression ("Candida in bile is associated with a

poor prognosis and these patients need liver transplantation relatively soon"). I think you got this point (!!) but the "why" of this is more difficult to answer. As I posted above, the Candida infections do not seem to be controlled in all patients when treated with antifungal medications, such as fluconazole or caspofungine, and it may be possible that the shorter time to transplantation in patients with Candida infection is associated with poor response to these antifungal therapies?However, because I have not yet seen the full text of this article (my subscription to J. Hepatol. has expired), I can't really comment much further on this point. If anyone has a subscription to J. Hepatol. and can share this recent paper, that would be much appreciated.The abstract concludes that presence of a dominant stricture is a risk factor for reduced survival free of liver transplantation ("Survival free of liver transplantation in patients

without dominant stenosis at 18 years was 73.1% and of patients with dominant stenosis was 25.0% (p=0.011)"). This means there is an approximately 3-fold higher risk of dying or needing a transplant in those patients with a dominant stricture (compared to those without a dominant stricture) during the 18-year period that these patients have been monitored.The abstract concludes that bacteria in bile does not affect the risk for survival free of transplantation provided that these infections are treated with antibiotics and if dominant strictures are opened with endoscopic procedures such as balloon dilatation during ERCP ("Bacteria in bile do not worsen the outcome if dominant stenoses are opened endoscopically and infection is adequately treated with antibiotics. ") What the abstract is NOT saying here is that outcomes would probably be much worse if dominant strictures were not opened endoscopically, and if bacterial infections were left

untreated.Best regards,Dave (father of (23); PSC 07/03; UC 08/03)

March 28, 2009