Evidence based observations suggest that there is a geographic variation in the etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI). The author of the present prospective trial performed a study of DILI in India, from 2013 to 2018. They reviewed and concluded the causes, clinical features, outcomes and predictors of mortality.

The researchers recruited patients with DILI with the help of international DILI expert working group criteria and Roussel Uclaf causality assessment method. These patients were further followed up to 3 months from onset of DILI or until death. Multivariate logistics regression was used to assess predictors of non-survival.

The outcome suggested that among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Other presenting symptoms included skin reaction, ascites, and encephalopathy (HE), which were reported in 19.5%, 16.4%, and 10% respectively. Among all participated patients, 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in patients with concomitant feature of HE, 17.6% in patients who fulfilled Hys law, and 16.6% in those who developed jaundice. The main causative factors were combination anti-TB drugs (ATD) (46.4%), complementary and alternative medicines (CAM) (13.9%), anti-epileptic drugs (AED) (8.1%), non-ATD antimicrobials (6.5%), anti-metabolites (3.8%), anti-retroviral drugs (ART) (3.5%), NSAID (2.6%), hormones (2.5%), and statins (1.4%). 

The predictors of non-survival as assessed by univariate analysis recognized ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score, transaminases, and anti-TB drugs. Out of which, serum creatinine, INR, HE, and ascites were remarkably correlated to mortality on multivariate analysis. ROC showed a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. Moreover, DILI was linked to more than 50 different agents and mortality was variable by drug class; 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics.

Thus, it can be concluded that ATD, CAM, AED, anti-metabolites and ART are the leading causes for the majority of patients of DILI in India. The findings suggested that 3-month mortality was approximately 12% and Hys law, presence of jaundice or MELD were regarded as predictors of mortality.

Source: Devarbhavi H, Joseph T, Nanjegowda SK, et al. The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients. Journal of Clinical and Experimental Hepatology. 2020. Available at: https://www.jcehepatology.com/article/S0973-6883(20)30175-4/fulltext