Hepatitis C overview
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Hepatitis C |
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Diagnosis |
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Treatment |
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Hepatitis C overview On the Web |
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American Roentgen Ray Society Images of Hepatitis C overview |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Yazan Daaboul; Serge Korjian
Overview
Hepatitis C virus (HCV) is a single-stranded RNA virus that causes liver injury. Initially discovered in 1989, HCV was found to be a bloodborne infection that tends to persist into a chronic state in the majority of cases. Although the exact pathogenesis and life cycle of HCV are poorly understood, it has been demonstrated that impaired innate and adaptive immunity to acute HCV may contribute to the development of chronic infection. While the transfusion of blood and blood products along with injectable therapy were considered the most common risk factors for HCV in the past, the use of injectable illicit drugs is currently the most important risk factor. In the absence of treatment, chronic HCV leads to liver cirrhosis several years after the initial infection, a course complicated by decompensated liver failure or hepatocellular carcinoma. Other extra-hepatic manifestations are also common. Specific patient populations should be screened for HCV first using HCV serological testing, or rarely directly by measuring HCV RNA in patients who have had previous HCV exposure, treatment-induced clearance, or immunosuppression. The diagnosis is made when anti-HCV and HCV RNA both demonstrate positive results. Measures to slow the progression of liver disease, such as vaccines against other diseases and awareness against the use of alcohol or drugs that injure the liver should be taken following diagnosis. Classically, interferon (IFN) therapy was used to treat HCV, followed by the use of ribavirin. More recently, protease inhibitors emerged as effective drugs of choice for HCV infection.
Pathophysiology
Hepatitis C virus (HCV) is a member of the genus Hepacivirus that belongs to the Flaviviridae family. It is an enveloped, single-stranded RNA virus that measures approximately 60 nm in diameter. The virus enters the cell using E1 and E2 envelope proteins. HCV RNA acts as template for the production of new proteins by translational, co-translational, and post-translational processes. These mechanisms lead to the synthesis of 10 proteins, 3 of which are structural and 7 of which are non-structural. In isolated acute HCV infection, the host immune system causes secretion of interferon-alpha and activation of natural killer cells, along with proper activation of adaptive immune cells. Chronic HCV is characterized by the impairment of these mechanisms. Eventually, chronic HCV infection leads to local inflammation and fibrogenesis causing hepatic injury and cirrhosis. Hepatocellular carcinoma, a known complication of chronic HCV infection, arises in cases of cirrhosis; the role of oncogenic proteins of HCV in the pathogenesis of hepatocellular carcinoma is yet to be elucidated.
Treatment
The treatment of hepatitis C has changed dramatically over the past decade. Whereas relatively new protease inhibitors telaprevir and boceprevir were added to the regular regimen of IFN and ribavirin in 2011 to treat patients with genotype 1 HCV, newer oral agents sofosbuvir and simeprevir have demonstrated greater efficacy in viral clearance along with a better safety profile. New guidelines from the AASLD and the IDSA have recommended the use of these oral agents (particularly sofosbuvir) as first line agents in the treatment of chronic HCV in both relapsers and treatment-naive patients.