Is the Prophylactic Use of Hepatoprotectants Necessary in Anti-Tuberculosis Treatment?

Abstract

Background: Liver injury is one of the serious side effects of anti-tuberculosis (TB) drugs. It is controversial whether hepatoprotectant prophylaxis is efficient and safe in anti-TB treatment, so we aimed to assess the efficacy and safety of hepatoprotectant prophylaxis in patients who had received anti-TB treatment.

Methods: PubMed, the Cochrane library, Embase, Ovid, Springer link, Wiley, Elsevier, Web of Science, and the Karger Online Journal were systematically searched prior to April 2016 for articles related to hepatoprotectant prophylaxis in the treatment of TB. A meta-analysis was conducted to estimate the effect of hepatoprotective agents on liver function and adverse events (AEs) in patients who had received anti-TB drugs. The primary outcomes were changes in alanine transaminase (ALT) and aspartate transaminase (AST) levels. The other outcomes were drug-induced liver injury (DILI) and AEs.

Results: In our review, 6 trials that involved 1,227 patients were included. Our analysis indicated that hepatoprotective agents exerted protective effects on liver function in patients who had received anti-TB drugs (weighted mean difference, WMD = -7.81, 95% CI [-12.26, -3.37], p = 0.0006 [ALT]; WMD = -7.07, 95% CI [-11.43, -2.72], p = 0.001 [AST]) in any age group. However, in the subgroup analysis of treatment duration, the use of hepatoprotective agents was not associated with significant changes in ALT and AST levels after 2 weeks of treatment and exhibited a positive effect on liver function after 4 weeks of treatment. Moreover, the use of hepatoprotectants significantly decreased the number of DILI cases (risk ratio, RR 0.50, 95% CI [0.34-0.73], p = 0.0004). However, the use of hepatoprotectants led to similar AEs in the control groups (RR 1.07, 95% CI [0.82-1.39], p = 0.62).

Conclusions: The use of hepatoprotective drugs may prevent liver injury in patients who are receiving anti-TB drugs without any significant AEs 4 weeks after the initiation of hepatoprotective medication.

Keywords: Anti-tuberculosis drugs; Efficacy; Hepatoprotectant; Liver injury; Prophylaxis; Safety.