Commentary: Treatment of hepatitis C-related cirrhosis in the era of direct-acting anti-virals
Journal
Alimentary Pharmacology and Therapeutics
Journal Volume
39
Journal Issue
12
Pages
1427-1428
Date Issued
2014
Author(s)
Wong V.W.-S.
Abstract
Chronic hepatitis C is the leading cause of cirrhosis and hepatocellular carcinoma in the Western world. While patients with cirrhosis and/or liver decompensation have the strongest need to eradicate hepatitis C virus (HCV), treatment in such patients is not easy. First, cirrhotic patients have poorer response to treatment. For example, only 33% of patients with genotype 1/4 infection and cirrhosis can achieve sustained virological response to peginterferon and ribavirin.1 Second, cirrhotic patients are more prone to the side effects of treatment. As a result, many patients with advanced disease are left untreated.2, 3 With the registration of the first-generation direct-acting anti-virals (DAAs) boceprevir and telaprevir in 2011, it is now possible to achieve higher SVR rates of 60–70% in treatment-naïve patients and prior nonresponders with genotype 1 infection.4 Hepatologists hope that these two agents may also benefit patients with established cirrhosis. Boceprevir and telaprevir are protease inhibitors targeting HCV replication. Although effective, these drugs have to be administered together with peginterferon and ribavirin and therefore result in even more side effects. Furthermore, patients with cirrhosis and liver decompensation are underrepresented in the registration trials, so it is important to evaluate the efficacy and tolerability of triple therapy in this patient group. Recently, Saxena et al. reported a multicentre study of 160 US cirrhotic patients receiving triple therapy, 75 of whom having Child-Pugh score ≥6.5 Undetectable HCV RNA 12 weeks after the cessation of treatment (SVR12) was achieved in 54% of the patients with compensated cirrhosis and 35% of those with mild decompensation (P = 0.02). Among patients with decompensation, over half required reduction in peginterferon and/or ribavirin dose; 45% had premature discontinuation of treatment; 24% needed hospitalisation, and 52% had increased liver decompensation. The findings are similar to the experience of the French compassionate programme, which showed that low platelet count ≤100 000/mm3 and serum albumin <35 g/L were associated with an unacceptably side effect profile with triple therapy.6 At this moment, triple therapy should be restricted to noncirrhotic patients and those with compensated cirrhosis. However, the future is bright. New DAAs as interferon-free regimens offer the opportunity to treat patients infected with different HCV genotypes, with decompensation and even prevent reinfection after liver transplantation.7 This will ultimately broaden treatment indications and benefit those in greatest need for treatment. Declaration of personal interests: VWW has served as an advisory board member and speaker for Gilead. He has also served as a consultant for Merck. CJL has served as an advisory board member and speaker for Gilead and Merck. Declaration of funding interests: None.
Other Subjects
boceprevir; peginterferon; ribavirin; telaprevir; virus RNA; antiviral therapy; decompensated liver cirrhosis; drug efficacy; drug tolerability; hepatitis C; Hepatitis C virus genotype 1; hospitalization; human; liver cirrhosis; note; priority journal; reinfection; treatment indication; treatment outcome; treatment response; virus replication; Antiviral Agents; Female; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male
Publisher
Blackwell Publishing Ltd
Type
note