Journal of Gastroenterology

, Volume 48, Issue 2, pp 254–268

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

  • Tatsuya Minami
  • Takahiro Kishikawa
  • Masaya Sato
  • Ryosuke Tateishi
  • Haruhiko Yoshida
  • Kazuhiko Koike
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-012-0631-y

Cite this article as:
Minami, T., Kishikawa, T., Sato, M. et al. J Gastroenterol (2013) 48: 254. doi:10.1007/s00535-012-0631-y



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.


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).


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.


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.


PeginterferonRibavirinHepatitis CMortalityAdverse eventSystematic review



Confidence interval


Hepatitis C virus


Hepatocellular carcinoma


Pegylated interferon


Randomized controlled trial




Serious adverse event


Sustained virological response


World Health Organization

Supplementary material

535_2012_631_MOESM1_ESM.docx (22 kb)
Supplementary Table 1 (DOCX 22 kb)

Copyright information

© Springer 2012

Authors and Affiliations

  • Tatsuya Minami
    • 1
  • Takahiro Kishikawa
    • 1
  • Masaya Sato
    • 1
  • Ryosuke Tateishi
    • 1
  • Haruhiko Yoshida
    • 1
  • Kazuhiko Koike
    • 1
  1. 1.Department of Gastroenterology, Graduate School of MedicineThe University of TokyoTokyoJapan