Date Published: September 13, 2019
Publisher: Public Library of Science
Author(s): Yen-Chieh Lee, Jiun-Ling Wang, Yaa-Hui Dong, Hsi-Chieh Chen, Li-Chiu Wu, Chia-Hsuin Chang, Amit Singal
Abstract: BackgroundInfection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk.Methods and findingsIn this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005–2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12–1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88–1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93–1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73–0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04–0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs).ConclusionsIn this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.
Partial Text: Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis and generally results in liver cirrhosis and subsequent hepatocellular carcinoma after decades of exposure . HCV infects 130 to 210 million people worldwide, and 75% to 85% of them are persistently infected after initial exposure to the virus . Taiwan, as a hyperendemic area for chronic liver disease, has the highest prevalence rate for HCV infection in Northeast Asia . The HCV seroprevalence in Taiwan, according to an earlier nationwide community-based survey, varies greatly among cities (ranging from 1.6% to 19.6%), and iatrogenic factors are reported to be the major routes of transmission .
In this community-based cohort study of volunteers participating in a health screening program, the presence of a NC-HCV infection conferred a greater risk for hospitalization for overall infections, including sepsis and different infection syndromes, particularly among those over age 50. In contrast, no increased risk for infection-related hospitalization was observed in the NC-HBV and NBNC groups with moderate to markedly elevated ALT levels, most of whom had alcoholic or fatty liver disease.