Association between Hepatitis C Virus Infection and Esophageal Cancer: An Asian Nationwide Population-Based Cohort Study

Abstract

Background: Hepatitis C virus (HCV) infection causes many extrahepatic cancers, and whether HCV infection is associated with esophageal cancer development remains inconclusive. Methods: A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database (TNHIRD) was conducted. Results: From 2003 to 2012, of 11,895,993 patients, three 1:1:1 propensity score-matched cohorts, including HCV-treated (interferon-based therapy ≧6 months, n = 9047), HCV-untreated (n = 9047), and HCV-uninfected cohorts (n = 9047), were enrolled. The HCV-untreated cohort had the highest 9-year cumulative incidence of esophageal cancer among the three cohorts (0.174%; 95% confidence interval (CI): 0.068-0.395) (p = 0.0292). However, no difference in cumulative incidences was identified between the HCV-treated (0.019%; 0.002-0.109%) and HCV-uninfected cohorts (0.035%; 0.007-0.133%) (p = 0.5964). The multivariate analysis showed that HCV positivity (hazard ratio (HR): 5.1, 95% CI HR: 1.39-18.51) and male sex (HR: 8.897; 95% CI HR: 1.194-66.323) were independently associated with the development of esophageal cancer. Of the three cohorts, the HCV-untreated cohort had the highest cumulative incidence of overall mortality at 9 years (21.459%, 95% CI: 18.599-24.460) (p < 0.0001), and the HCV-treated (12.422%, 95% CI: 8.653-16.905%) and HCV-uninfected cohorts (5.545%, 95% CI: 4.225-7.108%) yielded indifferent cumulative mortality incidences (p = 0.1234). Conclusions: Although HCV positivity and male sex were independent factors associated with esophageal cancer development, whether HCV infection is the true culprit or a bystander for developing esophageal cancer remains to be further investigated. Interferon-based anti-HCV therapy might attenuate esophageal risk and decrease overall mortality in HCV-infected patients.

Keywords: HCV; esophageal cancer; interferon; male; mortality.

Figure 1

Flow chart of TNHIRD study subjects’ selection. TNHIRD: Taiwan National Health Insurance Research Database; HCV: hepatitis C virus; Peg-IFN: pegylated interferon; PS: propensity score.

Figure 2

Cumulative incidence of esophageal cancers among the three TNHIRD cohorts, including HCV-treated, HCV-untreated, and HCV-uninfected cohorts.

Figure 3

Forest plot of factors associated with incident esophageal cancers in the two TNHIRD cohorts, including HCV-positive and HCV-negative cohorts. neg: Negative; HR: hazards ratio; CI: confidence interval; LCL: lower confidence limit; HCL: higher confidence limit; HCV: hepatitis C virus; COPD: Chronic obstructive pulmonary disease; ESRD:end stage renal disease; DM: diabetes.