Treatment of Hepatitis C Virus Infection -- What Is on the Horizon (or Even Closer)?

Heiner Wedemeyer, MD; Michael P. Manns, MD

Disclosures

May 03, 2004

In This Article

Introduction

Treatment of hepatitis C virus (HCV) infection significantly improved between the years 1995 and 2002. The introduction of interferon alfa plus ribavirin combination therapy and the development of pegylated interferons have led to an impressive increase in the achievement of virologic treatment responses from less than 10% to more than 50% of cases.[1] Subsequently, the 2002 National Institutes of Health (NIH) consensus conference on the management of hepatitis C gave clear treatment guidelines for individuals with chronic hepatitis C.[2] According to these guidelines, patients infected with HCV genotype 1 should receive pegylated interferon in combination with ribavirin for 48 weeks, whereas 24 weeks of combination therapy was considered to be sufficient for treatment of HCV genotype 2 and 3 infection.[3,4,5] However, for more than 2 years now, clinicians have been awaiting the arrival of new agents, with the goal of further improving treatment. Such new drug development is especially warranted for patients infected with the difficult-to-treat HCV genotype 1, for patients who have not responded to a previous course of interferon-based therapies, and for individuals with contraindications for either interferon alfa and/or ribavirin. Furthermore, we have to consider that the current standard therapy for hepatitis C may be associated with severe side effects and is associated with significant costs, making only a minority of patients eligible for treatment.[6] Thus, what can the clinician tell his patients if they ask about new drugs in the pipeline? When can clinicians expect these alternative treatments? What will be their efficacy?

Strategies to optimize the use of approved drugs include:

  • Longer treatment with pegylated interferon and ribavirin in patients showing a delayed clearance during therapy;

  • Shorter treatment than 24 weeks in patients infected with HCV genotypes 2 and 3;

  • Early prediction of nonresponse to avoid unnecessary treatment;

  • Individualization of pegylated interferon and ribavirin treatment duration dependent on viral kinetics;

  • Pegylated interferon monotherapy to prevent fibrosis progression and hepatocellular carcinoma development (HALT-C; EPIC trials);

  • Ribavirin monotherapy to prevent fibrosis progression and hepatocellular carcinoma development;

  • Selection of immunosuppressive agents based on antiviral effects (?);

  • Addition of a third drug (amantadine; histamine dihydrochloride; tymosin alpha); and

  • Synergistic effects of interferon alfa and interferon gamma.

Several alternative treatment strategies are currently being explored, and some very promising new data were presented during the 39th annual meeting of the European Association for the Study of the Liver (EASL), which convened this year in Berlin, Germany, April 14-18. Some of these new approaches may already have consequences for the management of HCV patients in the very near future, while others will most likely not transition into routine clinical routine practice even within the next 5 years.

New drugs against hepatitis C include:

  • Drugs with a lower incidence of hemolytic anemia than ribavirin;

  • Alternative IMPDH inhibitors;

  • Inhibition of apoptosis;

  • HCV enzyme inhibitors;

  • Molecular-based approaches (ribozymes, antisense oligonucleotides); and

  • Anti-HCV antibodies to prevent HCV reinfection after liver transplantation.

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