title: Mediation effect of hepatitis B and C on mortality.
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 (r(2) = -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.
authors.affiliation: Departments of Epidemiology and Biostatistics, Brown University, 121 South Main Street, Providence, RI, 02912, USA. Yen-Tsung_Huang@brown.edu.
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.affiliation: Department of Epidemiology, Brown University, 121 South Main Street, Providence, RI, 02912, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Freeman
authors.affiliation: Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, Taiwan.
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.affiliation: Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, Taiwan.
authors.forename: Jessica
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, 201 Shih-Pai Road, Section 2, Peitou, Taipei, Taiwan.
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D060085:Coinfection / Q000150:complications* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications* / Q000401:mortality / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification*; D006526:Hepatitis C / Q000150:complications* / Q000401:mortality / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D019562:Viral Load
chemical_list: D006514:Hepatitis B Surface Antigens
keywords: Hepatitis B virus; Hepatitis C virus; Mediation analyses; Mortality; Viral interaction; Viral load