Hepatitis C and risk of tuberculosis amongst United States veterans: a national cohort study

Background Tuberculosis (TB) and hepatitis C virus (HCV) infections share many risk factors and settings. We sought to determine and compare the incidence of TB amongst HCV-positive and negative individuals in a large national cohort of United States veterans, controlling for multiple confounders. Methods We conducted a retrospective-cohort study using data from The Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES) between 2001 and 2024 among United States veterans in care in the Veterans Affairs (VA) healthcare system. HCV-positive veterans were matched to HCV-negative veterans by age, sex, race/ethnicity, and VA enrollment year; veterans with TB diagnosed before the index HCV test, solid organ transplant history, and missing liver fibrosis score (FIB-4) or income data were excluded. Findings The primary outcomes were incident TB, defined as a new diagnosis recorded in the electronic health record after the index HCV antibody test date. We also determined the risk of TB among HCV patients treated with and without sustained virologic response. In weighted multivariable analysis controlling for age, sex, income, fibrosis, smoking, homelessness, substance, alcohol, HIV, and other comorbidities, untreated HCV infection remained the greatest risk factor for TB (adjusted hazard ratio [aHR]: 1.67; 95% CI: 1.58-1.77) compared to HCV-negative individuals. Treated individuals with sustained virologic response (SVR) also had an increased TB risk (aHR: 1.26; 95% CI: 1.19-1.33), though less than untreated HCV. Treated individuals without SVR had a slightly lower TB risk (aHR: 1.56; 95% CI: 1.37-1.77), comparable to untreated HCV. Individuals with spontaneous viral clearance had similar risk for TB as treated individuals with SVR. (aHR: 1.28; 95% CI: 1.20-1.37). Interpretation Our findings suggest people with HCV are at increased risk of tuberculosis, with decreasing risk among those successfully treated. This supports the need for comprehensive TB screening in individuals with HCV and the provision of early treatment for HCV with monitoring. Funding This work was supported by resources and the use of facilities at the Veterans Health Administration (VA) Pittsburgh Healthcare System, and the central data repositories maintained by the VA Information Resource Center, including the National Patient Care Database, Decisions Support System Database, and Pharmacy Benefits Management Database.