Mediation Analysis of Hepatitis B and C in Relation to Hepatocellular Carcinoma Risk
Menée à Taïwan à partir de données portant sur 3 851 participants, cette étude de cohorte prospective évalue l'association entre une infection conjointe par les virus de l'hépatite B et de l'hépatite C et le risque de carcinome hépatocellulaire (278 cas)
Background: Hepatitis B and C viruses are well-established risk factors for hepatocellular carcinoma (HCC) but their coordinated etiologic mechanism remains unclear. We aimed to assess the mediation effect of the two viruses on HCC risk. Methods: We conducted a prospective cohort study in Taiwan (R.E.V.E.A.L.-Hepatitis B Virus study), which included 3,851 participants seropositive for hepatitis B surface antigen and 278 incident HCC cases. Serum samples at enrollment or follow-up were tested for seromarkers and viral load of hepatitis B (HBV) and C (HCV). Mediation analyses for HCC risk were performed using Cox proportional hazards and linear regression models. Results: Among participants with chronic hepatitis B, the direct effect of anti-HCV serostatus (positive vs. negative) independent of HBV viral load was associated with increased risk of HCC with a hazard ratio (HR) of 2.5 (95% confidence interval [CI] = 1.7, 3.6), and the indirect effect mediated through suppressing HBV viral load decreased the HCC risk with an HR of 0.75 (95% CI = 0.67, 0.84). Opposite effects led to an attenuated marginal effect with an HR of 1.7 (95% CI = 1.2, 2.5). For an increase in HCV viral load from 800 to 404,000 IU/ml (minimum to median viral level), the HRs were 1.6 (95% CI = 1.2, 2.0) for the direct effect, 0.78 (95% CI = 0.72, 0.85) for the indirect effect, and 1.1 (95% CI = 0.89, 1.5) for the marginal effect. Conclusion: The results support a suppressive effect of HCV on HCC risk mediated through HBV viral load and an adverse direct effect. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.