Recent Advances in Hepatitis C: Highlights from the 2010 AASLD Meeting.

4 Gastroenterology & Hepatology volume 7, issue 1, Supplement 1 January 2011 did not attain SVR with peginterferon and ribavirin were re-treated with telaprevir plus peginterferon and ribavirin; re-treatment with this triple combination was significantly more effective than re-treating with peginterferon and ribavirin alone.7 The other widely studied protease inhibitor, boceprevir, has also demonstrated efficacy in several trials. The SPRINT-1 study was a randomized, open-label, phase II trial evaluating the safety and efficacy of boceprevir plus peginterferon and ribavirin in treatment-naïve patients with genotype 1 HCV infection.8 In the first part of this study, 520 patients were randomized to receive either a combination of peginterferon and ribavirin alone or 1 of 4 regimens containing boceprevir in addition to peginterferon and ribavirin. Part 2 of this study evaluated the feasibility of using peginterferon with a lower dose of ribavirin, which could help to reduce the risk of anemia-related complications. This study found that all boceprevir-containing regimens were significantly superior to peginterferon and ribavirin alone, with SVR rates of 54–75% versus 38%, respectively, but lower doses of ribavirin were not as effective as full-dose ribavirin with peginterferon and boceprevir. In 2008, Schiff and colleagues reported on the activity of boceprevir plus peginterferon and ribavirin in select treatment-experienced patients with genotype 1 HCV infection, in particular those with some initial response to peginterferon and ribavirin.9 In patients who had failed treatment with peginterferon and ribavirin, the combination of peginterferon, ribavirin, and boceprevir was associated with an SVR rate of 14%. In this dose-ranging study, no patients received the full treatment duration of boceprevir (>24 weeks) at the 800-mg dose that is used today. Lower doses of boceprevir were found to be less effective and associated with more resistance, which supported the use of the higher, 800-mg dose. Early response to therapy, defined as undetectable HCV RNA levels within 5 weeks, was a major predictor of SVR. Another recent area of interest has been the exploration of how genetics influence response to treatment. Individuals of European ancestry are more likely than those of African ancestry to attain SVR with peginterferon and ribavirin, and genetic studies have revealed that approximately half of this difference is explained by a polymorphism near the interleukin (IL)-28B gene, which encodes interferon-λ3. 10,11 Thus, recent studies have focused on Hepatitis C virus (HCV) infection is a common blood-borne infection that can result in serious long-term consequences, including cirrhosis, hepatocellular carcinoma (HCC), liver failure, and the need for liver transplantation. Approximately 4.1 million individuals in the United States test positive for anti-HCV antibodies, and 3.2 million individuals have chronic HCV infection.1 The goal of treatment for chronic HCV infection is to achieve sustained virologic response (SVR), defined as undetectable HCV RNA levels 6 months after completing treatment. Attaining SVR has been shown to be durable (ie, equivalent to cure), to slow disease progression, and to reduce mortality. Currently, standard treatment for HCV infection is combination therapy with peginterferon α-2a or -2b and ribavirin; this treatment is associated with SVR rates of approximately 54–63% in previously untreated patients.2-4 Response to and duration of treatment varies by genotype. In patients with genotype 2 or 3 HCV infection, a 24-week course of peginterferon and ribavirin induces SVR in nearly 80% of patients.5 In contrast, patients with genotypes 1 and 4 typically require at least 48 weeks of treatment, and most (50–60%) do not attain SVR. Since at least half of genotype 1 patients do not achieve SVR with peginterferon and ribavirin, alternative treatments continue to be tested. In recent years, researchers have developed therapeutic agents that directly target HCV. The direct-acting antivirals (DAAs) that have been most widely studied are the protease inhibitors, telaprevir and boceprevir, which inhibit the HCV enzymes NS3/NS4 and NS3, respectively, causing a disruption of HCV replication. Telaprevir has demonstrated significant efficacy in combination with peginterferon and ribavirin in several large trials. The PROVE1 study evaluated the addition of telaprevir to peginterferon and ribavirin in patients with genotype 1 HCV infection. SVR rates were 41% in patients receiving the combination of peginterferon and ribavirin alone, 61% in patients receiving telaprevir for 12 weeks plus peginterferon and ribavirin for 24 weeks, and 67% in patients receiving telaprevir for 12 weeks plus peginterferon and ribavirin for 48 weeks (P=.02 and P=.002, respectively). 6 The PROVE3 study demonstrated the efficacy of telaprevir in patients with previously treated genotype 1 HCV infection. In this study, patients who Introduction R e C e n t A D v A n C e S i n H e pA t i t i S C Gastroenterology & Hepatology volume 7, issue 1, Supplement 1 January 2011 5 assessing the role of IL-28B polymorphisms in determining response to therapy with these new agents. Finally, recent studies have investigated how to best apply these new agents, either by using them in combination with other therapies, optimizing treatment durations and regimens in different patient populations, and/or identifying factors associated with response to therapy. The results of such studies were presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), which was held October 29–November 2, 2010, in Boston, Massachusetts. Highlights of several key studies are presented in the following pages.