The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients

Harshad Devarbhavi, Tarun Joseph, Nanjegowda Sunil Kumar, Chetan Rathi, Varghese Thomas, Shivaram Prasad Singh, Prabha Sawant, Ashish Goel, Chundamannil E. Eapen, Prakash Rai, Anil Arora, Venkatakrishnan Leelakrishnan, Gayathri Gopalakrishnan, Vishnu Vardhan Reddy, Rajvir Singh, Bhabadev Goswami, Jayanthi Venkataraman, Girisha Balaraju, Mallikarjun Patil, Rakesh PatelSunil Taneja, Abraham Koshy, Padaki Nagaraja Rao, Shiv Kumar Sarin, Pravin Rathi, Radhakrishna Dhiman, Ajay K. Duseja, Joy Vargese, Ajay Kumar Jain, Manav Wadhawan, Piyush Ranjan, Dheeraj Karanth, Panchapakesan Ganesh, Sandeep Nijhawan, Gopal Krishna Dhali, Channagiri K. Adarsh, Ajay Jhaveri, Aabha Nagral, Prasanna Rao, Shalimar

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Background: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. Methods: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. Results: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. 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%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. Conclusion: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalJournal of Clinical and Experimental Hepatology
Issue number3
Publication statusPublished - 01-05-2021

All Science Journal Classification (ASJC) codes

  • Hepatology


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