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  • Review Article
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Management of acute HCV infection in the era of direct-acting antiviral therapy

Nature Reviews Gastroenterology & Hepatology volume 15, pages 412–424 (2018)Cite this article

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Abstract

The management of acute HCV infection has not been standardized following the availability of direct-acting antiviral agents (DAAs) for chronic HCV infection, and substantial uncertainty exists regarding the optimal treatment regimen and duration. Despite the lack of direct evidence, the 2016 American Association for the Study of Liver Diseases (AASLD)–Infectious Diseases Society of America (IDSA) guidelines supported “the same regimens for acute HCV as recommended for chronic HCV infection … owing to high efficacy and safety”, whereas the 2016 European Association for the Study of the Liver (EASL) guidelines recommended sofosbuvir–ledipasvir, sofosbuvir–velpatasvir or sofosbuvir plus daclatasvir for 8 weeks in acute HCV infection, with a longer duration of 12 weeks recommended for those infected with HIV and/or baseline HCV RNA levels >1,000,000 IU/ml. This Review outlines the epidemiology, natural history and diagnosis of acute HCV infection and provides contemporary information on DAAs for acute and recent HCV infection. The Review also discusses the 2016 AASLD–IDSA and EASL recommendations for acute HCV infection management in light of available evidence and highlights key differences in study populations and design that influence interpretation. We focus on populations at high risk of HCV transmission and acquisition, including people who inject drugs and HIV-positive men who have sex with men, and highlight the potential effects of diagnosis and treatment of acute HCV infection in contributing to HCV elimination.

Key points

  • In 2015, an estimated 1.75 million new HCV infections occurred worldwide, with injection drug use and unsafe health-care practices being the predominant modes of transmission.

  • Access to HCV care, education and treatment for people at high risk of onward transmission, including those with acute and recent HCV infection, should be a priority.

  • Monitoring HCV RNA levels for between 4 and 12 weeks following diagnosis of acute infection provides an opportunity to assess for spontaneous clearance without compromising outcome.

  • The role of (ultra-)short duration direct-acting antiviral agents in recent HCV infection is under investigation; pending the results of large trials, treatment is recommended with the same regimens as for chronic HCV infection.

  • Screening of at-risk populations (at least annually) is recommended to improve diagnosis and treatment of acute HCV infection.

  • Early detection and re-treatment of HCV reinfection, along with education and harm reduction, should be incorporated into the individual-level and population-level HCV response.

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Fig. 1: Viral kinetics in acute HCV infection.
Fig. 2: Efficacy of shortened duration direct-acting antiviral agent therapy in acute and recent HCV genotype 1 infection.

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Acknowledgements

The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. The content is solely the responsibility of the authors. B.H., J.G., G.J.D. and G.V.M. are supported through the Australian National Health and Medical Research Council Fellowships (Early Career Fellowship (B.H.), Career Development Fellowships (J.G. and G.V.M.) and Practitioner Fellowship (G.J.D.)).

Review criteria

Data for this Review were identified by searches of PubMed and Google Scholar up to 24 October 2017 using the terms “acute hepatitis C”, “acute HCV”, “recent hepatitis C”, “recent HCV”, “early hepatitis C” and “early HCV” in combination with the roots “epidemi*”, “diagnos*” “natural history”, “spontaneous clear*”, “HIV”, “men-who-have-sex-with-men”, “men who have sex with men”, “MSM”, “inject drug*”, “injecting drug*”, “drug inject*”, “drug use*”, “PWID”, “treat*”, “direct acting antiviral*”, “direct-acting antiviral*”, “DAA”, “interferon free”, “interferon-free”, “IFN free” and “IFNfree”. No language or date restrictions were specified. The references of identified articles were manually searched for further relevant papers. Key abstracts at international meetings were also considered. ClinicalTrials.gov was searched for studies in progress.

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Authors and Affiliations

  1. Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW, Sydney, NSW, Australia

    Marianne Martinello, Behzad Hajarizadeh, Jason Grebely, Gregory J. Dore & Gail V. Matthews

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  1. Marianne Martinello
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  2. Behzad Hajarizadeh
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  3. Jason Grebely
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  4. Gregory J. Dore
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  5. Gail V. Matthews
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Contributions

All authors contributed equally to the Review.

Corresponding author

Correspondence to Marianne Martinello.

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Competing interests

M.M. has received speaker payments from AbbVie. J.G. is a consultant and/or adviser and has received research grants from AbbVie, Bristol-Myers Squibb, Gilead and Merck. G.J.D. is an advisory board member and has received honoraria from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck and Roche, has received research grant funding from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Janssen, Merck, Roche and Vertex and has received travel sponsorship from Bristol-Myers Squibb, Gilead, Janssen, Merck and Roche. G.V.M. has received research funding, advisory board payments and speaker payments from Gilead and research funding and speaker payments from Janssen. B.H. declares no competing interests.

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Martinello, M., Hajarizadeh, B., Grebely, J. et al. Management of acute HCV infection in the era of direct-acting antiviral therapy. Nat Rev Gastroenterol Hepatol 15, 412–424 (2018). https://doi.org/10.1038/s41575-018-0026-5

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