Clinical Drug Investigation

, Volume 39, Issue 9, pp 835–846 | Cite as

Bayesian Network Meta-Analysis for Assessing Adverse Effects of Anti-hepatitis B Drugs

  • Yi Shen
  • Yulong Jia
  • Jie Zhou
  • Juling JiEmail author
  • Pengcheng XunEmail author
Systematic Review


Background and Objective

Oral nucleoside/nucleotide analogues (NAs) have been advocated for chronic hepatitis B (CHB) treatment with good efficacy. However, less attention has been put on their adverse events. Therefore, a Bayesian network meta-analysis (NMA) was performed to evaluate the relative safety of five NAs (lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir disoproxil fumarate) in CHB treatment among adults.


Eligible randomized clinical trials (RCTs) and prospective cohort studies were systematically and thoroughly searched until May 1, 2019. Poisson-prior-based Bayesian NMA was performed to synthesize both direct and indirect evidence with reporting hazard ratios (HRs) and 95% credible intervals (CrIs) for serious adverse events (SAEs) and hepatic/renal impairments.


Thirty-three RCTs and 11 prospective cohort studies were identified. As to SAEs, no statistically significant difference was found of any comparison among five NAs. In terms of hepatotoxicity, lamivudine was safer than telbivudine (HR 0.45; 95% CrI 0.21, 0.85), and entecavir increased the risk by 102% (entecavir vs lamivudine: HR 2.02; 95% CrI 1.19, 3.27).


The findings from this large NMA could influence clinical practice, and the methodological framework of this study could provide evidence-based support to analyze sparse safety data in the field.


Author Contributions

Concept and design: YS, YLJ, JLJ, PCX. Statistical analysis: YLJ, JZ. Methodology: YLJ, JZ. Validation: YS, YLJ, JLJ, PCX. Writing—original draft: YS, YLJ, JZ. Writing—critical review and editing: YS, JLJ, PCX. All authors approved the final version of the manuscript.

Compliance with Ethical Standards


No sources of funding were received for this article.

Conflict of interest

Yi Shen, Yulong Jia, Jie Zhou, Juling Ji, Pengcheng Xun have no conflicts of interest that are directly relevant to the content of this article.

Supplementary material

40261_2019_802_MOESM1_ESM.tiff (16.8 mb)
Supplementary material 1 (TIFF 17250 kb)
40261_2019_802_MOESM2_ESM.pdf (382 kb)
Supplementary material 2 (PDF 381 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Epidemiology and Medical Statistics, School of Public HealthNantong UniversityNantongChina
  2. 2.Medical School of Nantong UniversityNantongChina
  3. 3.Department of Epidemiology and Biostatistics, School of Public Health-BloomingtonIndiana UniversityBloomingtonUSA

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