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Mediation effect of hepatitis B and C on mortality

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Abstract

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.

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Acknowledgments

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

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Authors and Affiliations

  1. Departments of Epidemiology and Biostatistics, Brown University, 121 South Main Street, Providence, RI, 02912, USA

    Yen-Tsung Huang

  2. Department of Epidemiology, Brown University, 121 South Main Street, Providence, RI, 02912, USA

    Joshua R. Freeman

  3. Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, Taiwan

    Hwai-I Yang, Jessica Liu & Chien-Jen Chen

  4. Institute of Clinical Medicine, National Yang-Ming University, 201 Shih-Pai Road, Section 2, Peitou, Taipei, Taiwan

    Mei-Hsuan Lee

Authors
  1. Yen-Tsung Huang
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  2. Joshua R. Freeman
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  3. Hwai-I Yang
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  4. Jessica Liu
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  5. Mei-Hsuan Lee
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Correspondence to Yen-Tsung Huang.

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Huang, YT., Freeman, J.R., Yang, HI. et al. Mediation effect of hepatitis B and C on mortality. Eur J Epidemiol 31, 625–633 (2016). https://doi.org/10.1007/s10654-016-0118-x

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  • DOI: https://doi.org/10.1007/s10654-016-0118-x

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