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Hepatitis C virus infection


Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage, which might result in liver cirrhosis and hepatocellular carcinoma. Globally, between 64 and 103 million people are chronically infected. Major risk factors for this blood-borne virus infection are unsafe injection drug use and unsterile medical procedures (iatrogenic infections) in countries with high HCV prevalence. Diagnostic procedures include serum HCV antibody testing, HCV RNA measurement, viral genotype and subtype determination and, lately, assessment of resistance-associated substitutions. Various direct-acting antiviral agents (DAAs) have become available, which target three proteins involved in crucial steps of the HCV life cycle: the NS3/4A protease, the NS5A protein and the RNA-dependent RNA polymerase NS5B protein. Combination of two or three of these DAAs can cure (defined as a sustained virological response 12 weeks after treatment) HCV infection in >90% of patients, including populations that have been difficult to treat in the past. As long as a prophylactic vaccine is not available, the HCV pandemic has to be controlled by treatment-as-prevention strategies, effective screening programmes and global access to treatment.

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Figure 1: Milestones in HCV research and management.
Figure 2: HCV prevalence.
Figure 3: HCV genotype distribution.
Figure 4: HCV life cycle.
Figure 5: Diagnostic algorithm for HCV infection.


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The authors thank S. Hardtke and P. Solbach, Hannover Medical School, Hannover, Germany, for editorial assistance and M. Cornberg, Hannover Medical School for helpful discussions.

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Introduction (M.P.M.); Epidemiology (H.R.); Mechanisms/pathophysiology (J.-M.P.); Diagnosis, screening and prevention (J.-M.P. and M.B.); Management (M.P.M., E.G. and N.T.); Quality of life (Z.Y.); Outlook (M.P.M.); Overview of Primer (M.P.M.).

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Correspondence to Michael P. Manns.

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Competing interests

M.P.M. has received research grants and or served as an adviser for Roche, Bristol-Myers Squibb (BMS), Gilead, Boehringer Ingelheim, Novartis, Merck, Janssen, GlaxoSmithKline (GSK), Biotest and AbbVie. M.B. has served as a speaker and/or adviser of AbbVie, Gilead, Janssen, Merck and BMS. E.G. has served as an adviser for Roche, Gilead, Janssen, Novira, AbbVie, Novartis, Achillion, Merck and Alios. J.-M.P. has received research grants from Gilead Sciences and AbbVie. He has served as an adviser for AbbVie, BMS, Gilead, Janssen and Merck. H.R. has received research funds from Gilead and AbbVie. N.T. has received research grants and/or served as an adviser for Gilead, Cocrystal Pharma, BMS, AbbVie, Merck and Echosens North America Inc. She received royalty from UpToDate and is involved in continuing medical education and the development of educational material for CCO Hepatitis, Practice Point Communications and Focus Medical Communications. Z.Y. has received research funds from Gilead, BMS and AbbVie and is a consultant or an adviser to BMS, Gilead, GSK, Intercept and Tobira.

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Manns, M., Buti, M., Gane, E. et al. Hepatitis C virus infection. Nat Rev Dis Primers 3, 17006 (2017).

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