In This Article Expand or collapse the "in this article" section Hepatitis C

  • Introduction
  • General Overviews
  • Epidemiology
  • Historical Breakthroughs for the Development of Antiviral Therapies
  • Impact of Antiviral Treatment
  • Treatment of Acute Hepatitis C Virus Infection
  • Hepatitic C Vaccine

Public Health Hepatitis C
Benjamin Maasoumy, Markus Cornberg
  • LAST REVIEWED: 14 October 2016
  • LAST MODIFIED: 28 October 2014
  • DOI: 10.1093/obo/9780199756797-0142


The hepatitis C virus (HCV) is an uncoated, single-stranded, positive-sense ribonucleic acid (RNA) virus that belongs to the group of Flaviviridae. HCV infection is transmitted between humans mainly via direct blood contact. Therefore, intravenous drug users belong to a high-risk population. Before identification in the late 1980s and the subsequent routine testing of blood products, blood transfusions were an import route of transmission. Here, the introduction of assays to detect antibodies to hepatitis C virus (anti-HCV assays) was a milestone in the prevention of new infections. In the early 21st century more than 185 million people worldwide have been exposed to HCV. Acute HCV infection may be associated with nonspecific symptoms, such as fatigue or abdominal discomfort, while only 20 percent of patients develop jaundice. Fulminant hepatitis C is a rare event. However, the majority of patients remain asymptomatic and thus may not be diagnosed during the acute phase. HCV infection is a self-limited disease in only 10–50 percent of patients, whereas more than half develop chronic infection. Chronic HCV infection is a major reason for the increasing incidence of liver cirrhosis and hepatocellular carcinoma (HCC) in most Western countries. Approximately 15–50 percent of patients with chronic hepatitis C develop liver cirrhosis at some point, approximately 16 percent within twenty years. The progression rate depends on cofactors, such as obesity, older age, alcohol, and coinfections. As soon as HCV-related fibrosis progresses to cirrhosis, the risk of HCC increases to approximately 2–4 percent per year. Successful eradication of the virus through sufficient antiviral treatment can prevent many of these cases and significantly improves the liver-related outcome as well as all-cause mortality. In the acute phase of the infection, monotherapy with pegylated-interferon alfa (Peg-IFN alfa) leads to a sustained virological response (SVR) in up to 90 percent. In chronic HCV infection a dual combination consisting of Peg-IFN alfa and the nucleoside ribavirin (RBV) has been the standard of care in the early 21st century for a long time. Whereas approximately 70 percent of patients infected with genotype 2 or 3 achieve SVR, this regimen cures less than half of patients with genotype 1. In 2011 the protease inhibitors (PIs) boceprevir (BOC) and telaprevir (TLV) were approved for treatment of chronic HCV genotype 1 infection and lead to a significant increase of SVR rates (up to 88 percent under optimal conditions). Still, treatment remained challenging in previous Peg-IFN/RBV null responders, in particular those with liver cirrhosis, in which SVR rates do not exceed 15 percent. In addition, both drugs are accompanied by significant side effects. Both PIs belong to a generation of HCV-specific compounds, so-called direct-acting antivirals (DAA). More recently, a second wave of DAAs has been approved, including the macrocyclic PI simeprevir (SMV) and the NS5B polymerase inhibitor sofosbuvir (SOF). The approval of SOF allowed patients to be treated without IFN for the first time. SOF/RBV dual therapy is highly effective in the majority of genotype 2 and many genotype 3 patients. Several other DAAs are close to coming on the market. Published studies suggest that through a combination of different DAAs belonging to different DAA classes, highly effective IFN-free regimens may become possible for all known HCV genotypes, with cure rates exceeding 90 percent. This article contains a selection of reviews, textbooks, and original papers concerning a variety of hepatitis C, including HCV epidemiology, diagnosis, the natural history, and current and future treatment options in the early 21st century as well as efforts to generate an efficient HCV vaccine.

General Overviews

The selected citations all provide an overview of hepatitis C. European Association for the Study of the Liver 2014 and Ghany, et al. 2009 contain expert recommendations for the optimal management of the disease. They are very useful not only as a guide in clinical practice, but also as an introduction to the field of hepatitis C. The guidelines’ sponsoring organizations (the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases, respectively) decided to offer frequent online updates on this rapidly changing field. Both texts are the result of systematic review by the leading experts in the field and may be considered reference works. Janssen and Craxi 2012, a collection of important reviews, also puts forward a very practical approach to specific aspects of the field. Mauss, et al. 2014 covers the whole range of topics and is updated yearly. A shorter but still very comprehensive source is Tillmann and McHutchison 2012, which includes plenty of helpful figures and tables.

  • European Association for the Study of the Liver. 2014. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 60.2: 392–420.

    DOI: 10.1016/j.jhep.2013.11.003

    This is a well-structured, practical guide for the management of HCV patients. The key publications related to HCV have been considered for this publication. Recommendations for treatment with some newer direct-acting antivirals (DAAs) are not yet included but available in the updated online version of the recommendations.

  • Ghany, M. G., D. B. Strader, D. L. Thomas, and L. B. Seeff. 2009. Diagnosis, management, and treatment of hepatitis C: An update. Hepatology 49.4: 1335–1374.

    DOI: 10.1002/hep.22759

    This state-of-the-art guide by the American Association for the Study of Liver Diseases gives recommendations for management of the disease. Although somewhat outdated, an update is available online covering the usage of direct-acting antivirals (DAA).

  • Janssen, H., and A. Craxi, eds. 2012. Special issue: Chronic hepatitis C: Diagnosis and treatment. Best Practice and Research Clinical Gastroenterology 26.4: 369–548.

    This issue contains fourteen reviews concerning the epidemiology, natural history, diagnosis, and treatment of chronic hepatitis C. At the end of each review, the most important practical implications are summarized as bullet points.

  • Mauss, S., T. Berg, J. Rockstroh, C. Sarrazin, and H. Wedemeyer, eds. 2014. 2014 Flying Publisher short guide to hepatitis C. Flying Publisher.

    A German project, written by several experts in the field of viral hepatitis, this comprehensive guide covers the whole field of hepatitis C. Includes chapters on future treatment of DAAs. The section on management of chronic hepatitis C is evidence based and reflects current guidelines. Updated yearly.

  • Tillmann, H. L., and J. G. McHutchison. 2012. Hepatitis C. In Zakim and Boyer`s hepatology: A textbook of liver disease. Edited by T. D. Boyer, M. P. Manns, and A. J. Sanyal, 564–604. Philadelphia: Saunders/Elsevier.

    An outstanding book chapter that gives a comprehensive overview of HCV. Has a very useful table with suggestions for the management of side effects of interferon (IFN) treatment and a nice figure with recommendations for patient monitoring during treatment.

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