Pegylated interferon plus ribavirin for chronic hepatitis C: the role of combination therapy today, tomorrow and in the future.
Approximately 123 million people worldwide are infected with hepatitis C virus (HCV). The majority of those infected with the virus develop chronic progressive liver disease that over time can result in cirrhosis, end-stage liver disease, hepatocellular carcinoma and death. The goal of treatment is viral eradication. The recognised standard of care for chronic hepatitis C is the combination of pegylated interferon plus ribavirin, which has been shown to be effective in treatment-naïve patients, including those with persistently normal ALT levels, and in patients with HIV-HCV coinfection. Two pegylated interferons are commercially available, both of which have distinct pharmacokinetic properties that necessitate different dosing strategies. With the standard of care, overall virological response rates have exceeded 50% in randomised, multinational phase III studies. Viral response rates are heterogenous and are influenced by a range of viral and host-specific factors. By far, the most important factors influencing treatment outcomes are HCV genotype and baseline HCV RNA level. Customisation of therapy based on baseline factors is recommended in treatment guidelines in order to maximise cure rates. Pegylated interferon plus ribavirin has been shown to be effective and safe in patients with HIV-HCV coinfection and is now recommended in this important and growing subpopulation. Ongoing efforts to improve treatment outcomes are focused on dynamic customisation of therapy based on the on-treatment response to therapy. Treatment of nonresponders to previous interferon-based therapies is an important area under investigation. Although several promising oral agents have been identified and are currently in clinical development, it seems likely that pegylated interferon will remain the backbone of therapy for years to come.
Department of Internal Medicine IV, Medical University of Vienna, Vienna, Austria. peter.ferenci@meduniwien.ac.at
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D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005544:Forecasting; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a