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Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C

Nature Reviews Gastroenterology & Hepatology volume 8, pages 212–223 (2011)Cite this article

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Abstract

HCV infects approximately 2–3% of the global population and is a leading cause of end-stage liver disease and hepatocellular carcinoma. Treatment of HCV infection with Peg-IFN in combination with ribavirin can eradicate HCV infection in 40–90% of patients; however, a major barrier to treatment uptake and delivery is the association of this therapy with frequent and, at times, serious adverse effects. Recognition and effective management of these adverse effects are critical components of the successful treatment of chronic HCV infection. In clinical trials, approximately 10–15% of patients discontinue Peg-IFN and ribavirin therapy due to adverse effects; however, in clinical practice, the rate of treatment discontinuation has been reported to be substantially higher. The off-target effect of Peg-IFN and ribavirin impacts most, if not all, organ systems; the most common adverse effects are hematologic, dermatologic, neurologic, immunologic, gastrointestinal, pulmonary, cardiovascular, and ocular. Regional and global variability exists in the nature of these adverse effects and the strategies employed to ameliorate their impact. This article provides a comprehensive literature review that systematically describes the adverse effects of Peg-IFN-α and ribavirin on various organ systems and, more importantly, recommends consensus approaches to managing those effects.

Key Points

  • The standard of care for chronic HCV infection is combination treatment with Peg-IFN-α and ribavirin

  • Potential adverse events associated with Peg-IFN-α and ribavirin therapy impact most, if not all, organ systems and symptoms range from mild to severe in intensity and frequency

  • Ineffective management of adverse events can lead to decreased patient quality of life during therapy, decreased treatment adherence, and decreased effectiveness of treatment

  • A consensus approach to the management of treatment-emergent adverse events can help to reduce the likelihood of dose reduction or treatment discontinuation thereby improving treatment outcomes

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Figure 1: An overview of the main organ systems affected by and potential adverse events associated with Peg-IFN-α and ribavirin treatment for HCV infection.
Figure 2: Time course of onset and changes in relative severity of several common Peg-IFN-α and ribavirin treatment-related adverse events.
Figure 3: Decision tree summarizing the management of hematological adverse events associated with Peg-IFN-α and ribavirin treatment.
Figure 4: Decision tree outlining a timeline for monitoring Peg-IFN-α and ribavirin treatment-emergent depression symptoms and their severity.
Figure 5: Decision tree summarizing the management of thyroid adverse events associated with Peg-IFN-α treatment.

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Acknowledgements

This study was completed through the International Conquer C Coalition (I-C3). The I-C3 is an international, interdisciplinary group of physicians involved in the treatment and care of patients infected with HCV with the goal of increasing the understanding of the epidemiology, diagnosis, side effect management, and treatment options for hepatitis C. The work presented here is the result of the practical guidelines for side effects management workgroup. We are indebted to all I-C3 members for their contributions and comments. The authors would also like to acknowledge editorial assistance provided by S. Glomb-Reinmund, Science First LLC, who provided the following assistance: coordination of workgroup interactive writing process, copy edit of manuscript, manuscript formatting to journal specification, construction of manuscript reference database and reference formatting to journal specification (references were selected by authors), table formatting, figure formatting, and administrative assistance in obtaining author competing interests, affiliations, and biographies. Funding was provided through an unrestricted educational grant provided by Merck; the sponsor did not participate in the writing of any aspect of this paper and had no influence on its content.

Author information

Authors and Affiliations

  1. Viral Hepatitis Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Mark S. Sulkowski

  2. Department of Medicine, Division of Infectious Diseases, Ottawa Hospital, General Campus, Ottawa, ON, Canada

    Curtis Cooper

  3. Department of Medicine, Kaposi Mór Teaching Hospital, Kaposvár, Hungary

    Bela Hunyady

  4. Beijing Friendship Hospital, Xuanwu District,, Beijing, China

    Jidong Jia

  5. Russian Peoples' Friendship University of Medicine, Moscow, Russia

    Pavel Ogurtsov

  6. Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

    Markus Peck-Radosavljevic

  7. Liver Institute of Virginia and Bon Secours Virginia Health System, VA, USA

    Mitchell L. Shiffman

  8. Hepatology Institute, University of Ankara, Ankara, Turkey

    Cihan Yurdaydin

  9. Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway

    Olav Dalgard

Authors
  1. Mark S. Sulkowski
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  2. Curtis Cooper
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  3. Bela Hunyady
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  4. Jidong Jia
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  5. Pavel Ogurtsov
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  6. Markus Peck-Radosavljevic
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  7. Mitchell L. Shiffman
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  8. Cihan Yurdaydin
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  9. Olav Dalgard
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Contributions

M. S. Sulkowski, P. Ogurtsov, M. Peck-Radosavljevic, M. L. Shiffman and O. Dalgard contributed equally to all aspects of the article. B. Hunyady contributed substantially to the discussion of content, writing and review/editing of the manuscript before submission. J. Jia researched data for the article, contributed substantially to the discussion of content, and review/editing of the manuscript before submission. C. Yurdaydin contributed substantially to the discussion of content, and review/editing of the manuscript before submission.

Corresponding author

Correspondence to Mark S. Sulkowski.

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Competing interests

M. S. Sulkowski is a Consultant for and has received grant/research support from Merck and Roche/Genentech. J.-D. Jia is a Consultant for, is on the Speakers Bureau of, and has received grant/research support from Bristol-Myers Squibb, GlaxoSmithKline, MSD, Novartis and Roche. M. Peck-Radosavljevic is a Consultant for, is on the Speakers Bureau of, and has received grant/research support from MPD, Roche and Merck/Schering Plough. M. Shiffman is a Consultant, is on the Speakers Bureau of, and has received grant/research support from Bristol-Myers Squibb/Zymogenetics, Merck, Roche/Genentech. He is also a Consultant and has received grant/research support from Romark. C. Yurdaydin is on the Speakers Bureau of Merck and Roche. O. Dalgard is a Consultant and has received grant/research support from Hoffman-La Roche and Merck. He is also a Consultant for Janssen Cilag. The other authors declare no competing interests.

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Sulkowski, M., Cooper, C., Hunyady, B. et al. Management of adverse effects of Peg-IFN and ribavirin therapy for hepatitis C. Nat Rev Gastroenterol Hepatol 8, 212–223 (2011). https://doi.org/10.1038/nrgastro.2011.21

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