Hepatitis C virus: A time for decisions. Who should be treated and when?

Abstract

Cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) regardless of the etiology of cirrhosis. Compared to individuals who are anti-hepatitis C virus (HCV) seronegative, anti-HCV seropositive individuals have a greater mortality from both hepatic as well as nonhepatic disease processes. The aim of this paper is do describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. The newly developed direct acting antiviral (DAA) therapies are associated with greater rates of drug compliance, fewer adverse effects, and appear not to be limited by the presence of a variety of factors that adversely affect the outcome of interferon-based therapies. Because of the cost of the current DAA, their use has been severely rationed by insurers as well as state and federal agencies to those with advanced fibrotic liver disease (Metavir fibrosis stage F3-F4). The rationale for such rationing is that many of those recognized as having the disease progress slowly over many years and will not develop advanced liver disease manifested as chronic hepatitis C, cirrhosis, and experience any of the multiple complications of liver disease to include HCC. This mitigation has a short sided view of the cost of treatment of hepatitis C related disease processes and ignores the long-term expenses of hepatitis C treatment consisting of the cost of treatment of hepatitis C, the management of cirrhosis with or without decompensation as well as the cost of treatment of HCC and liver transplantation. We believe that treatment should include all HCV infected patients including those with stage F0-F2 fibrosis with or without evidence of coexisting liver disease. Specifically, interferon (IFN)-free regimens with the current effective DAAs without liver staging requirements and including those without evidence of hepatic diseases but having recognized extrahepatic manifestations of HCV infection is projected to be the most cost-effective approach for treating HCV in all of its varied presentations. Early rather than later therapy of HCV infected individuals would be even more efficacious than waiting particularly if it includes all cases from F0-F4 hepatic disease. Timely therapy will reduce the number of individuals developing advanced liver disease, reduce the cost of treating these cases and more importantly, reduce the lifetime cost of treatment of those with any form of HCV related disease as well as HCV associated all - cause mortality. Importantly, HCV treatment regimens without any restrictions would result in a substantial reduction in health care expenditure and simultaneously reduce the number of infected individuals who are infecting others.

Keywords: Hepatitis C virus, Direct acting antivirals, Cirrhosis of the liver, Timing of treatment

Core tip: This study presents the burden of hepatitis C virus (HCV) infection. Current guidelines limit treatment to those with advanced liver disease (Metavir F-3 or F-4 fibrosis). This represents a small fraction of those infected having the worse prognosis. They are unlikely to infect others. In contrast, the much larger group F-0 to F-2 is the vectors for additional infections. The plague of HCV can only be eliminated if the larger groups that infect others are treated. The cost of treating this larger population is expensive but much less expensive than treating only those with advanced fibrosis in the long run.