European Journal of Epidemiology

, Volume 31, Issue 6, pp 625–633 | Cite as

Mediation effect of hepatitis B and C on mortality

  • Yen-Tsung HuangEmail author
  • Joshua R. Freeman
  • Hwai-I Yang
  • Jessica Liu
  • Mei-Hsuan Lee
  • Chien-Jen Chen


Hepatitis B (HBV) and C (HCV) viruses cause many liver diseases. To move beyond statistical interaction, we aimed to assess the coordinated effect of the two viruses on mortality using mediation analyses. A prospective cohort study of 3837 residents in Taiwan examined participants seropositive for hepatitis B, of which 181 subjects (4.7 %) were co-infected by HCV and 589 died during follow-up. Mediation analyses for cause-specific mortality were performed using Cox proportional hazards model. Follow-up HBV viral load was inversely correlated with baseline HCV viral load (r2 = −0.074; P < 0.001). For HCV serum viral load increasing from 800 to 404,000 IU/mL (minimum to median) at baseline, the effect of HCV mediated through HBV viral load decreased the all-cause mortality with a hazard ratio (HR) of 0.89 (95 % confidence interval (CI) 0.85, 0.94; P < 0.001), and the effect independent of HBV viral load had an opposite HR of 1.25 (95 % CI 0.98, 1.60; P = 0.08). The protective mediation effects of HCV viral load through HBV DNA level were observed in mortality from causes specific to liver-related diseases and liver cancer, but not in that from non-liver-related diseases. Our findings suggest a suppressive effect of HCV on mortality mediated through decreasing HBV viral load.


Mediation analyses Hepatitis B virus Hepatitis C virus Mortality Viral load Viral interaction 



NIH/NCI R03 CA182937-02, NIH/NIA R01 AG048825-01 and Salomon Research Fund at Brown University.

Supplementary material

10654_2016_118_MOESM1_ESM.docx (173 kb)
Supplementary material 1 (DOCX 175 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Yen-Tsung Huang
    • 1
    Email author
  • Joshua R. Freeman
    • 2
  • Hwai-I Yang
    • 3
  • Jessica Liu
    • 3
  • Mei-Hsuan Lee
    • 4
  • Chien-Jen Chen
    • 3
  1. 1.Departments of Epidemiology and BiostatisticsBrown UniversityProvidenceUSA
  2. 2.Department of EpidemiologyBrown UniversityProvidenceUSA
  3. 3.Genomics Research CenterAcademia SinicaTaipeiTaiwan
  4. 4.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan

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