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Meta-analysis: mortality and serious adverse events of peginterferon plus ribavirin therapy for chronic hepatitis C

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy is the current standard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events (SAEs) and mortality from a single study is rather difficult because of the infrequency of such events. The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample, and to assess the relationship between SAEs and mortality rates and therapeutic characteristics.

Methods

A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of PEG-IFN/RBV therapy. We calculated the crude mortality and SAE rates with 95 % confidence intervals (CIs).

Results

Eighty studies with 153 treatment arms that included 27569 patients were enrolled (14401 patients treated with Peg-IFN alpha-2a/RBV and 13168 with Peg-IFN alpha-2b/RBV). All-cause and treatment-related deaths were observed in 50 (0.18 %; 95 % confidence interval [CI] 0.13–0.24 %) and sixteen (0.058 %; 95 % CI 0.033–0.094 %) patients, respectively. The crude SAE rate was 7.08 % (95 % CI 6.75–7.41 %). Subgroup analysis revealed higher SAE rates in patients receiving PEG-IFN alpha-2a than in those with PEG-IFN alpha-2b (7.45 vs. 6.74 %), and higher SAE rates with higher doses than with the lower doses in PEG-IFN-2a and 2b (11.94 vs. 6.99 %, 7.10 vs. 5.05 %, respectively), and with extended duration (>48 weeks) than with standard duration (48 weeks) (15.5 vs. 6.67 %) in PEG-IFN alpha-2a.

Conclusion

The mortality rate during PEG-IFN/RBV therapy was acceptably low, but the rate of SAEs was not negligible in a treatment for a benign disease, and the rate was affected by treatment regimens.

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Abbreviations

CI:

Confidence interval

HCV:

Hepatitis C virus

HCC:

Hepatocellular carcinoma

PEG-IFN:

Pegylated interferon

RCT:

Randomized controlled trial

RBV:

Ribavirin

SAE:

Serious adverse event

SVR:

Sustained virological response

WHO:

World Health Organization

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Conflict of interest

Kazuhiko Koike has served as a speaker for MSD and Chugai Pharmaceutical Co., Ltd., and has received research funding from MSD and Chugai Pharmaceutical Co., Ltd.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Tatsuya Minami, Takahiro Kishikawa, Masaya Sato, Ryosuke Tateishi, Haruhiko Yoshida & Kazuhiko Koike

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  1. Tatsuya Minami
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  2. Takahiro Kishikawa
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  3. Masaya Sato
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  4. Ryosuke Tateishi
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Correspondence to Ryosuke Tateishi.

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Minami, T., Kishikawa, T., Sato, M. et al. Meta-analysis: mortality and serious adverse events of peginterferon plus ribavirin therapy for chronic hepatitis C. J Gastroenterol 48, 254–268 (2013). https://doi.org/10.1007/s00535-012-0631-y

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