In a recent study published in Scientific Reports, a group of researchers evaluated the effectiveness and safety of herbs and alternative medicines in preventing liver injury induced by anti-tuberculosis (anti-TB) drugs.
Study: Systematic review and network meta-analysis of efficacy and safety of interventions for preventing anti-tuberculosis drug induced liver injury. Image Credit: SewCreamStudio/Shutterstock.com
Background
Tuberculosis (TB) treatment, typically involving rifampicin, isoniazid, pyrazinamide, and ethambutol, poses a risk of hepatotoxicity, potentially leading to less effective treatment options and multidrug-resistant TB ( MDR TB).
This hepatotoxicity, or anti-TB drug-induced liver injury (anti-TB DILI), is often related to increased production of toxic metabolites. While antioxidants and anti-inflammatory agents like Silymarin, N-Acetyl Cysteine (NAC), Curcuma longa, Tinospora cordifolia, and L-carnitine show potential in mitigating this risk, there is no established preventive medication.
Further research is necessary to identify the most effective herbal and alternative medicines for preventing anti-TB DILI, as the current understanding of their efficacy and safety is incomplete.
About the study
The researchers extensively searched several databases, including Scopus, Embase, PubMed, and others, without restrictions on time or language, focusing on randomized controlled trials (RCTs) related to the subject. They also performed hand searches to ensure comprehensive coverage.
The present study selection criteria were specific, such as only RCTs with new case TB patients were considered, focusing on those examining the effects of herbal or alternative medicines on anti-TB DILI.
Exclusions were made for observational studies, reviews, animal and in vitro studies, and studies with insufficient or inaccessible data. Two researchers independently selected studies, with disagreements resolved through consultation with the third.
Quality assessment was rigorously conducted using the revised Cochrane Risk of Bias Tool. The primary outcome was the efficacy of interventions, measured by the incidence of hepatotoxicity, while secondary outcomes included liver function tests and adverse events.
Statistical analyses involved pairwise meta-analysis and network meta-analysis (NMA), using a random-effects model and considering factors like study duration and criteria for anti-TB DILI.
The NMA allowed for a comprehensive comparison of treatments and ranking of their efficacy. Subgroup analyses were conducted based on study characteristics, and sensitivity analyses were performed to ensure vitality. A comparison-adjusted funnel plot was used to detect small-study effects, and all analyses considered a significance level of P-value < 0.05.
Study results
In the present study, 2,507 articles were initially sourced from electronic databases and other resources, including 14 relevant studies published between 2008 and 2021. It involved 3,423 TB patients from various Asian countries, and the studies, all parallel RCTs, varied in size and had follow-up periods ranging from 2 to 24 weeks.
They predominantly investigated silymarin's effectiveness among other herbal medicines in new TB patients treated with standard regimens.
The age range of the participants was broad, and the majority were male. The study focused on a variety of interventions for preventing hepatitis induced by TB medication.
These included combinations of Turmeric extract and Tinospora cordifolia, NAC, Silymarin and its derivatives, L-carnitine, Bicyclol, various Chinese herbal medicines, Glucuronolactone, Glutathione, Vitamins A and D, Poly-herbal formulations, and Garlic tablets. These interventions were administered at the onset of TB treatment, typically oral, and continued for 2 to 24 weeks.
Quality assessments indicated a generally low risk of bias in most studies. Network maps created for primary and secondary outcomes showed a range of interventions being compared, with no significant inconsistencies or transitivity violations noted.
Primary outcomes focused on the occurrence of anti-TB DILI and NMA findings, consistent with pairwise meta-analysis, revealed that Turmeric plus Tinospora cordifolia extract and NAC significantly reduced the incidence of anti-TB DILI compared to placebo.
Turmeric plus Tinospora cordifolia also showed superiority over other interventions except NAC. However, Silymarin, despite being widely used, did not significantly reduce the incidence of anti-TB DILI compared to placebo.
Secondary outcomes looked at liver function test levels, including Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), and Total bilirubin (Tbil). While pairwise meta-analysis found significant reductions in AST levels with some interventions, these results were not mirrored in the NMA.
Only the poly-herbal preparation showed a significant reduction in ALP and Tbil levels compared to placebo, with Vitamin D also beneficial in reducing total bilirubin levels.
Regarding safety, six studies reported adverse events, predominantly gastrointestinal side effects, but no serious adverse events were noted.
Subgroup analysis for secondary outcomes at week 4 showed that NAC, Vitamin D, and Poly-herbal preparations were more effective than placebo in reducing AST and ALT levels, with Poly-herbal preparation and Vitamin D also significantly reducing ALP and Tbil levels, respectively.
Sensitivity analyses using fixed-effect models aligned with the main findings, and no evidence of small-study effects was observed.
Understanding metabolic alterations and immune dysfunction in acute-on-chronic liver failure