Altered expressions of circulating microRNAs 122 and 192 during antitubercular drug induced liver injury indicating their role as potential biomarkers

Abstract

Drug induced liver toxicity is a serious health complication leading to high mortality rates and post marketing withdrawal of drugs. Although considered to be the gold standard biomarkers; aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase have been found to have specificities beyond liver, therefore more specific and predictive markers for the detection of antitubercular drug mediated liver damage are required. Unfortunately, the effectiveness of currently used first line antitubercular drugs namely isoniazid, rifampicin, pyrazinamide is often accompanied with liver injury, impeding the cure of patients. Keeping in view, the prognostic and diagnostic applications of microRNAs in various diseases, we tried to assess the importance of microRNAs 122 and 192 in antitubercular drug associated liver injuries. The study included subjects having tuberculosis of any type with antitubercular drug induced liver injury; naïve or newly diagnosed tuberculosis patients, tuberculosis patients on drugs not having toxicity and healthy controls. Observations from this study revealed that expression levels of miR-122 and miR-192 were significantly decreased in the serum of antitubercular drug induced liver injury patients only. Therefore, these microRNAs or the pathways associated with them can be used as a tool to predict or cure antitubercular drug associated liver injury in future.

Analysis of serum microRNA‐122 in a randomized controlled trial of N‐acetylcysteine for treatment of antituberculosis drug‐induced liver injury

“…In both these participants, miR-122 concentrations increased considerably from baseline, by 15-and 20-fold, respectively. A recent Indian study by Bakshi et al found miR-122 expression to be 75% lower in participants with AT-DILI compared to healthy controls,24 but miR-122 was only sampled at enrolment and participants had less severe DILI than in our study, with a median ALT of 120 U/L. Despite these differences, the reason for the conflicting results is unclear and requires further exploration.…”

Novel Clinical Biomarkers for Drug-Induced Liver Injury

“…South American (43) (Santos et al, 2019) MiR-122, miR-192 South Asian (50) (Bakshi et al, 2021) Non-genetic…”

“…Recently, the serum level of miR-122 and miR-192 in Indian subjects was measured. Compared to the healthy control, naive tuberculosis patients and anti-TB tolerant subjects, serum level of both miR-122 and miR-192 was decreased significantly in the DILI subjects (Bakshi et al, 2021), providing evidence for selecting microRNA as potential biomarkers for anti-TB-induced hepatotoxicity. However, studies on the clinical associations of microRNAs and DILI induced by anti-TB drugs are rarely reported, further investigations are needed.…”

Immune regulation and emerging roles of noncoding RNAs in Mycobacterium tuberculosis infection

“…During anti-TB treatment, drug-induced liver injury (DILI) is the most common severe adverse drug response, with an approximate incidence of 2%–28% ( 206 ). miR-122 and miR-192 are significantly decreased in the serum of TB patients with DILI and could be used to predict this serious complication in TB ( 207 ). Likewise, another study revealed the value of upregulated circMARS in identifying TB patients suffering from anti-TB drug-induced liver injury (ADLI), with an AUC of 0.80 ( 208 ).…”