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Update of the Management and Treatment of Hepatitis C Viral Infection, 2012: Introduction

for Health Care Providers

Introduction

The prevalence of chronic hepatitis C virus (HCV) infection is approximately 1.3% in the United States population and 4% in veterans who use Department of Veterans Affairs (VA) medical services (1, 2) . More than 165,000 veterans with HCV currently receive care within the Veterans Health Administration, of whom more than 5,000 such patients die annually (3) . The natural history of chronic HCV is variable, with cirrhosis eventually developing in 30-40% of individuals unless the virus is eradicated with therapy (4, 5, 6) . Advanced liver disease due to HCV is now the leading indication for liver transplantation in the United States and Europe. In addition, hepatocellular carcinoma (HCC), a frequently lethal complication of HCV-associated cirrhosis, has increased eight-fold among HCV-infected veterans receiving VA care between 2000 and 2008 (3) .

The consequences of HCV infection constitute a significant disease burden and demonstrate a need for effective medical care. Successful treatment of HCV with interferon (IFN)-based regimens can result in viral eradication, which has been associated with a reduced incidence of hepatic decompensation and HCC in addition to prolonged survival (7, 8, 9) . Sustained virologic response (SVR), defined as undetectable levels of HCV RNA at least 24 weeks after completion of therapy, is the primary endpoint of successful therapy, and is associated with durable clearance of virus in more than 98% of cases (10) .

All patients with chronic HCV are potential candidates for antiviral therapy. Patients most likely to benefit from antiviral treatment include those at risk for progressive liver disease and those with diminished quality of life secondary to their viral infection. Medical care providers should discuss the natural history of HCV infection, the risks and benefits of antiviral therapy, and steps that can be taken to minimize liver damage with every HCV-infected patient. It is crucial that individuals in whom treatment is deferred are re-evaluated for treatment candidacy as their comorbid conditions are effectively managed.

In 2011, the standard of care for many patients with HCV genotype 1 infection became a combination of an oral protease inhibitor (PI), boceprevir (BOC) or telaprevir (TVR), along with pegylated IFN (PegIFN) and ribavirin (RBV). BOC and TVR represent a new era of therapy, as they are the first commercially available hepatitis C direct-acting antiviral (DAA) agents, which directly inhibit viral replication. In clinical trials of HCV genotype 1-infected patients receiving PegIFN and RBV, combined with BOC or TVR, SVR was achieved in 63-75% of treatment naive patients, in 69-88% of PegIFN and RBV relapsers, and in up to 33% of PegIFN and RBV nonresponders (11, 12, 13, 14) . Triple therapy is associated with more side effects and requires closer patient follow-up than treatment with PegIFN and RBV alone. Increased hematological toxicity from triple therapy may lead to increased utilization of growth factors, which will further strain medical resources in healthcare systems. Additionally, BOC and TVR carry the risk of inducing HCV resistance mutations, and it is likely that cross-resistance to future generations of PIs will develop in some patients who do not achieve SVR (15) . Extensive patient monitoring for virologic response and counseling on adherence will be necessary to minimize the development of resistant variants. With the approval of HCV PIs, providers will need to identify candidates who require immediate treatment, as well as those who can wait another 4-6 years for the likely availability of IFN-free regimens. Future IFN-free regimens may include oral second generation PIs, polymerase inhibitors, HCV nonstructural protein 5a inhibitors, and combinations of these drugs (16) .

The following treatment recommendations summarize the current best practices in the management of hepatitis C, including the use of PegIFN, RBV, and BOC- or TVR-containing regimens. These recommendations are based on an extensive review of published data; the American Association for the Study of Liver Diseases Practice Guidelines: Diagnosis, Management and Treatment of Hepatitis C (2009); An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection (2011); CDC; FDA, and NIH recommendations; as well as input from thought leaders involved in the care of veterans with HCV infection (17, 18, 19, 20) . Recommendations were developed using systematic weighting and grading of the quality of evidence according to criteria used by the American Association for the Study of Liver Diseases 2009 Practice Guidelines (Table 1) (18) . Limited data that are currently available only in abstract form also have been included when the data are derived from prospective randomized, controlled trials. Each author participated in the preparation and review of the draft recommendations, and agreed with the consensus statements reflected in the final document. Feedback from external peer reviewers was obtained. The final recommendations were reviewed and endorsed by: the VA Hepatitis C Resource Centers, the VA HCV Technical Advisory Group, the VA Gastrointestinal Field Advisory Committee, and the National Hepatitis C Program Office. Additional resources pertaining to the care of the HCV-infected patient developed by the VA Hepatitis C Resource Centers are available on this site on the Publications and Products page.

RECOMMENDATION

  1. All patients with chronic HCV infection should be evaluated for HCV antiviral treatment. (Class IIa, Level B).
Table 1. Grading system for recommendations adapted from the AASLD Practice Guidelines for the Diagnosis, Management, and Treatment of Hepatitis C
Description
AASLD, American Association for the Study of Liver Diseases; RCT, randomized, controlled trials.
Classification
Class IConditions for which there is evidence and/or general agreement that a given diagnostic evaluation procedure or treatment is beneficial, useful, and effective
Class IIConditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a diagnostic evaluation, procedure, or treatment
Class IIaWeight of evidence/opinion is in favor of usefulness/efficacy Class IIb Usefulness/efficacy is less well established by evidence/opinion
Class IIbUsefulness/efficacy is less well established by evidence/opinion
IIIConditions for which there is evidence and/or general agreement that a diagnostic evaluation procedure/treatment is not useful/effective, and in some cases, may be harmful
Level of evidence
Level AData derived from multiple RCT or meta-analyses
Level BData derived from a single randomized trial, or nonrandomized studies
Level COnly consensus opinion of experts, case studies, or standard-of-care