Impact of Interferon-Based Therapy on Hepatitis C-Associated Rheumatic Diseases: A Nationwide Population-Based Cohort Study

Abstract

Whether hepatitis C virus (HCV) infection-associated risk of rheumatic diseases is reversed by anti-HCV therapy remain elusive. A nationwide population-based cohort study of the Taiwan National Health Insurance Research Database was conducted. Of 19,298,735 subjects, 3 cohorts (1:4:4, propensity score-matched), including HCV-treated (6919 HCV-infected subjects with interferon and ribavirin therapy ≥ 6 months), HCV-untreated (n = 27,676) and HCV-uninfected (n = 27,676) cohorts, were enrolled and followed (2003-2015). The HCV-uninfected cohort had the lowest cumulative incidence of rheumatic diseases (95% confidence interval (CI): 8.416-10.734%), while HCV-treated (12.417-17.704%) and HCV-untreated (13.585-16.479%) cohorts showed no difference in the cumulative incidences. Multivariate analyses showed that HCV infection (95% CI hazard ratio (HR): 1.54-1.765), female sex (1.57-1.789), age ≥ 49 years (1.091-1.257), Charlson comorbidity index ≥ 1 (1.075-1.245), liver cirrhosis (0.655-0.916), chronic obstruction pulmonary disease (1.130-1.360), end-stage renal disease (0.553-0.98), diabetes mellitus (0.834-0.991) and dyslipidemia (1.102-1.304) were associated with incident rheumatic diseases. Among the 3 cohorts, the untreated cohort had the highest cumulative incidence of overall mortality, while the treated and un-infected cohorts had indifferent mortalities. Conclusions: HCV infection, baseline demographics and comorbidities were associated with rheumatic diseases. Although HCV-associated risk of rheumatic diseases might not be reversed by interferon-based therapy, which reduced the overall mortality in HCV-infected patients.

Keywords: HCV; interferon; mortality; rheumatic.

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 incidences of rheumatic diseases among the 3 TNHIRD cohorts including HCV-treated, HCV-untreated and HCV-uninfected cohorts. TNHIRD: Taiwan National Health Insurance Research Database; HCV: hepatitis C virus.

Figure 3

Forrest plot of factors associated with incident rheumatic diseases in the 2 TNHIRD cohorts: HCV-positive (untreated) and HCV-negative (combination of treated and uninfected) cohorts. TNHIRD: Taiwan National Health Insurance Research Database; HR: hazards ratio; LCL: lower confidence interval limit; HCL: higher confidence interval limit; HCV: hepatitis C virus; CCI: Charlson Comorbidity Index score; COPD: Chronic obstructive pulmonary disease; ESRD: end-stage renal disease; DM: diabetes mellitus; NAFLD: Nonalcoholic fatty liver disease; ALD: alcoholic liver disease.