Risk of drug-induced liver injury in chronic hepatitis C and tuberculosis co- infection: a systematic review and meta- analysis

Purpose Antituberculosis drug-induced liver injury (ATLI) is a common and serious adverse drug reaction of tuberculosis treatment. The impact of ATLI in patients with chronic hepatitis C is unclear. The aim of this study is to evaluate the prevalence of DILI in patients with and without HCV and assess its impact in the prevalence of ATLI. Methods The preferred reporting items for systematic reviews and meta-analyses standards were followed, and the protocol was registered in PROSPERO. In this study, PubMed, Web of Sciences, EMBASE, the Cochrane Library were searched from inception to 21 May 2024. We performed a systematic review and meta-analysis of studies of the papers relevant to compare the prevalence of anti-tuberculosis drug-induced liver injury in patients with and without chronic hepatitis C. Subgroup analyses were predefined for DILI severity (mild/moderate/severe), diagnostic criteria (ALT > 3ULN vs. >5ULN), anti-TB regimens (3-drug vs. 4-drug), HCV definition (antibody vs. RNA positivity), and study design (prospective vs. retrospective). Results Thirteen studies comprising a total of 3,174 patients met the inclusion criteria and were included in the final analysis. Of these, 727 patients had HCV-TB co-infection, while 2,447 presented with active TB infection without HCV. The overall prevalence of DILI in patients with HCV-TB was 15.54% and 8.54% in patients without HCV(OR = 3.50, 95% CI 2.48-4.94,I 2 = 20%), which revealed that the prevalence of DILI was significantly higher in those with HCV infection than those without HCV infection. The meta-analysis indicated that TB patients with hepatitis C virus (HCV) infection had a higher risk of mild DILI compared to those without HCV infection (Relative Risk [RR] = 3.13, 95% CI 1.77-5.52, I²=0%). Additionally, TB patients with HCV infection were at a greater risk of moderate DILI than those without HCV infection (RR = 3.71, 95% CI 1.58-8.75, I²=33%), and they also had a higher risk of severe DILI (RR = 2.33, 95% CI 0.82-6.61, I²=31%). Subgroup analysis revealed that TB patients with HCV infection had a higher risk of anti-tuberculosis drug-induced liver injury (ATDILI) than those without HCV, using both a strict definition of DILI (alanine aminotransferase [ALT] > 5 times the upper limit of normal [ULN], Odds Ratio [OR] = 4.13, 95% CI: 2.76-6.17, I²=0%) and a loose definition of DILI (ALT > 3 ULN, OR = 3.16, 95% CI: 1.41-7.05, I²=58%). This was observed in patients receiving standard four-drug combination anti-TB therapy (OR = 3.38, 95% CI: 2.01-5.69, I²=47%) and three-drug combination anti-TB therapy (OR = 3.01, 95% CI: 1.50-6.05, I²=0%). The definition of HCV infection was associated with the risk of DILI; when HCV infection was defined by a positive hepatitis C antibody, the OR was 3.35 (95% CI: 2.23-5.03, I²=30%). When HCV infection was defined by a positive HCV RNA, the OR increased to 4.59 (95% CI: 2.17-9.69, I²=0%). Furthermore, the risk was examined in retrospective studies (OR 3.31, 95% CI: 2.10-5.20, I²=36%) and in prospective studies (OR 4.39, 95% CI: 2.36-8.16, I²=0%). Conclusion This meta-analysis suggests that the prevalence of DILI in patients with HCV is higher than in those without HCV. Routine HCV screening before the initiation of TB therapy is critically important for the early identification of HCV-TB co-infection, enabling clinicians to modify TB and HCV treatment and management to mitigate the risks of DILI. Close follow-up and regular liver test monitoring are indispensable for the treatment of TB in chronic hepatitis C carriers.