3 New HCV Abstracts

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Hepatology. 2011 Mar 3. doi: 10.1002/hep.24262. [Epub ahead of print]

Treatment failure and resistance with direct acting antiviral drugs against

hepatitis C virus.

Pawlotsky JM.

National Reference Center for Viral Hepatitis B, C and Delta, Department of

Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM

U955, Créteil, France. jean-michel.pawlotsky@....

Abstract

Current treatment of chronic hepatitis C virus infection is based on the

combination of pegylated interferon-α and ribavirin. The recent development of

direct-acting antiviral molecules active on hepatitis C virus, together with in

vitro and in vivo studies showing that these drugs may lead to the selection of

resistant viruses if administered alone, has raised concerns that resistance may

undermine therapy based on direct acting antivirals. A new standard-of-care

treatment will soon be available for both treatment-naïve and -experienced

patients infected with hepatitis C virus genotype 1, based on a triple

combination of pegylated interferon-α, ribavirin and a protease inhibitor,

either telaprevir or boceprevir. With this therapy, most failures to eradicate

infection in treatment-adherent patients are due to an inadequate response to

pegylated interferon-α and ribavirin, in the context of a low genetic barrier

to resistance of first-generation protease inhibitors. This article reviews

patterns of resistance to hepatitis C virus direct acting antiviral drugs in

development, the mechanisms underlying treatment failure when these drugs are

combined with pegylated interferon-α and ribavirin, the consequences of

treatment failure, and possible means of optimizing therapies using direct

acting antivirals in the future. (HEPATOLOGY 2011.).Copyright © 2011 American

Association for the Study of Liver Diseases.

PMID: 21374691 [PubMed - as supplied by publisher]

Hepatology. 2011 Mar 3. doi: 10.1002/hep.24262. [Epub ahead of print]

Treatment failure and resistance with direct acting antiviral drugs against

hepatitis C virus.

Pawlotsky JM.

National Reference Center for Viral Hepatitis B, C and Delta, Department of

Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM

U955, Créteil, France. jean-michel.pawlotsky@....

Abstract

Current treatment of chronic hepatitis C virus infection is based on the

combination of pegylated interferon-α and ribavirin. The recent development of

direct-acting antiviral molecules active on hepatitis C virus, together with in

vitro and in vivo studies showing that these drugs may lead to the selection of

resistant viruses if administered alone, has raised concerns that resistance may

undermine therapy based on direct acting antivirals. A new standard-of-care

treatment will soon be available for both treatment-naïve and -experienced

patients infected with hepatitis C virus genotype 1, based on a triple

combination of pegylated interferon-α, ribavirin and a protease inhibitor,

either telaprevir or boceprevir. With this therapy, most failures to eradicate

infection in treatment-adherent patients are due to an inadequate response to

pegylated interferon-α and ribavirin, in the context of a low genetic barrier

to resistance of first-generation protease inhibitors. This article reviews

patterns of resistance to hepatitis C virus direct acting antiviral drugs in

development, the mechanisms underlying treatment failure when these drugs are

combined with pegylated interferon-α and ribavirin, the consequences of

treatment failure, and possible means of optimizing therapies using direct

acting antivirals in the future. (HEPATOLOGY 2011.).Copyright © 2011 American

Association for the Study of Liver Diseases.

PMID: 21374691 [PubMed - as supplied by publisher]

Related citations

15.

Hepatology. 2011 Mar 3. doi: 10.1002/hep.24257. [Epub ahead of print]

Occult and previous hepatitis B virus infection are not associated with

hepatocellular carcinoma in us patients with chronic hepatitis C.

Lok AS, Everhart JE, Di Bisceglie AM, Kim HY, Hussain M, TR; the HALT-C

Trial Group.

Division of Gastroenterology, Department of Internal Medicine, University of

Michigan Medical School, Ann Arbor, MI. ASLok@....

Abstract

BACKGROUND & AIM: Previous studies have suggested that prior exposure to

hepatitis B virus (HBV) infection may increase the risk of development of

hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. The aim of

this study was to compare the prevalence of previous or occult HBV infection in

a cohort of HBsAg-negative patients with histologically advanced chronic

hepatitis C in the United States who did or did not develop HCC.

METHODS: Stored sera from 91 patients with HCC and 182 matched controls who

participated in the HALTC Trial were tested for anti-HBc, anti-HBs and HBV DNA.

Frozen liver samples from 28 HCC cases and 55 controls were tested for HBV DNA

by real-time PCR.

RESULTS: Anti-HBc (as a marker of previous HBV infection) was present in the

serum of 41.8% HCC cases and 45.6% controls (P=0.54); anti-HBc alone was present

in 16.5% of HCC cases and 24.7% of controls. HBV DNA was detected in the serum

of only one control subject and no patient with HCC. HBV DNA (as a marker of

occult HBV infection) was detected in the liver of 10.7% HCC cases and 23.6%

controls (P=0.18).

CONCLUSION: Although almost half the patients in the HALT-C Trial had

serological evidence of previous HBV infection there was no difference in

prevalence of anti-HBc in serum or HBV DNA in liver between patients who did or

did not develop HCC. In the United States, neither previous nor occult HBV

infection is an important factor in HCC development among patients with advanced

chronic hepatitis C. (HEPATOLOGY2011.).Copyright © 2011 American Association

for the Study of Liver Diseases.

PMID: 21374690 [PubMed - as supplied by publisher]