Treatment of chronic hepatitis C: Anticipated impact of resistance in patients treated with protease inhibitors

被引：7

作者：

Kronenberger B. ^{[1
]}

Zeuzem S. ^{[1
]}

机构：

[1] Zentrum der Inneren Medizin, Medizinische Klinik 1, 60590 Frankfurt am Main

来源：

Current Gastroenterology Reports | 2009年 / 11卷 / 1期

关键词：

Sustained Virologic Response; Sustained Virologic Response Rate; Telaprevir; Boceprevir; Peginterferon Alfa;

D O I：

10.1007/s11894-009-0003-9

中图分类号：

学科分类号：

摘要：

A main target of specifically targeted antiviral therapy for hepatitis C (STAT-C) is the NS3-protease, which has key functions in the hepatitis C virus (HCV) replication cycle. HCV/NS3-protease inhibitors have shown high antiviral activity in vitro and in patients with chronic hepatitis C. Protease-resistant HCV variants occurred rapidly in patients receiving protease-inhibitor monotherapy. The development of resistance can be best explained by selection of preexisting resistant variants, which grow out under selective pressure. Numerous mutations associated with resistance were identified. Clinical trials showed that protease-resistant strains are sensitive to interferon and that a triple combination of protease inhibitors, peginterferon, and ribavirin may improve the sustained virologic response rate compared with standard peginterferon/ribavirin combination therapy. Overall, it can be anticipated that successful treatment with protease inhibitors will require either combination therapy with peginterferon/ribavirin or a combination of STAT-C compounds with distinct modes of action and resistance patterns. © Springer Science+Business Media, LLC 2009.

引用

页码：15 / 21

页数：6

共 25 条

[1]

Lohmann V., Korner F., Koch J., Et al., Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line, Science, 285, pp. 110-113, (1999)

[2]

Kim J.L., Morgenstern K.A., Lin C., Et al., Crystal structure of the hepatitis C virus NS3 protease domain complexed with a synthetic NS4A cofactor peptide, Cell, 87, pp. 343-355, (1996)

[3]

Lamarre D., Anderson P.C., Bailey M., Et al., An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus, Nature, 426, pp. 186-189, (2003)

[4]

Meylan E., Curran J., Hofmann K., Et al., Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus, Nature, 437, pp. 1167-1172, (2005)

[5]

Li K., Foy E., Ferreon J.C., Et al., Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF, Proc Natl Acad Sci U S A, 102, pp. 2992-2997, (2005)

[6]

Hinrichsen H., Benhamou Y., Wedemeyer H., Et al., Shortterm antiviral efficacy of BILN 2061, a hepatitis C virus serine protease inhibitor, in hepatitis C genotype 1 patients, Gastroenterology, 127, pp. 1347-1355, (2004)

[7]

Sarrazin C., Rouzier R., Wagner F., Et al., SCH 503034, a novel hepatitis C virus protease inhibitor, plus pegylated interferon alpha-2b for genotype 1 nonresponders, Gastroenterology, 132, pp. 1270-1278, (2007)

[8]

Reesink H.W., Zeuzem S., Weegink C.J., Et al., Rapid decline of viral RNA in hepatitis C patients treated with VX-950: A phase Ib, placebo-controlled, randomized study, Gastroenterology, 131, pp. 997-1002, (2006)

[9]

Soriano V., Perelson A.S., Zoulim F., Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses?, J Antimicrob Chemother, 62, pp. 1-4, (2008)

[10]

Lin C., Lin K., Luong Y.P., Et al., In vitro resistance studies of hepatitis C virus serine protease inhibitors, VX-950 and BILN 2061: Structural analysis indicates different resistance mechanisms, J Biol Chem, 279, pp. 17508-17514, (2004)

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