HCV Coinfection Linked to Higher Rates of Drug-Induced Liver Injury in TB

8 December 2025

The higher prevalence of TB drug-induced liver injury in patients with vs without hepatitis C virus (HCV) coinfection highlights the importance of routine HCV screening prior to treatment initiation.

The prevalence of drug–induced liver injury (DILI) in patients undergoing TB therapy appears to be higher in those with vs without chronic hepatitis C virus (HCV) infection, according to findings published in BMC Infectious Diseases.

Although hepatotoxicity is a well-recognized complication of first-line TB regimens, the extent to which HCV coinfection contributes to DILI has remained uncertain. To address this evidence gap, researchers conducted a systematic review and meta-analysis of adults with and without chronic HCV infection receiving standard TB therapy.

Data for the analysis were sourced from prospective and retrospective observational cohorts and case-control studies. The criteria for DILI definition were based on biochemical thresholds, most commonly alanine aminotransferase levels of more than 3 or 5 times the upper limit of normal, while HCV infection was identified via anti-HCV antibody testing or HCV RNA positivity. Thirteen studies, comprising 3174 patients, met inclusion criteria for the review. Overall, 727 individuals had HCV-TB coinfection and 2447 had TB infection alone.

Across all studies, the prevalence of DILI during TB therapy was significantly higher in patients with HCV (15.54%) than in those without HCV (15.54% vs 8.54%; odds ratio [OR], 3.50; 95% CI, 2.48-4.94; I², 20%). The researchers observed consistent findings when restricting the analysis to cohort studies (pooled risk ratio [RR], 2.71; 95% CI, 2.08-3.54).

Six studies reported severity-stratified outcomes. Compared with patients with TB infection alone, those with HCV coinfection had higher risk of developing mild (RR, 3.13; 95% CI, 1.77-5.52; I², 0%) and moderate DILI (RR, 3.71; 95% CI, 1.58-8.75; I², 33%). Although the risk for severe DILI trended higher among adults with HCV-TB coinfection, it did not reach statistical significance (RR, 2.33; 95% CI, 0.82-6.61).

Subgroup analyses demonstrated that the elevated risk persisted regardless of DILI definition, treatment regimen (3-drug vs standard 4-drug combinations), and study design. Of studies in which HCV was confirmed by RNA positivity, the reported effect size was higher (OR, 4.59; 95% CI, 2.17-9.69) when compared with those in which disease was confirmed by antibody testing alone (OR, 3.35; 95% CI, 2.23-5.03), suggesting active viral replication may confer greater susceptibility.

According to the researchers, routine HCV screening before the initiation of TB therapy may enable earlier identification of coinfection and inform individualized treatment decisions, including closer laboratory monitoring or selection of less hepatotoxic regimens. They also emphasized regular liver function testing remains essential throughout therapy, particularly in resource-limited settings where TB burden is high and HCV frequently remains undiagnosed.

Study limitations include variations in DILI definitions, insufficient data on HCV treatment status and viral load, and potential confounding from unmeasured coinfections.

“The implementation of routine HCV screening in newly diagnosed tuberculosis cases is not only epidemiologically meaningful but also represents a critical risk mitigation measure,” the researchers concluded.

By Hibah Khaja, PharmD

Reference:

Wei X, Cai R, Wu X, et al. Risk of drug-induced liver injury in chronic hepatitis C and tuberculosis co- infection: a systematic review and meta-analysis. BMC Infect Dis. Published online November 13, 2025. doi:10.1186/s12879-025-12005-y

 

Source: Infectious Disease Advisor