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

Abstract

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,

Acute Liver Failure: Indian Perspective

“…Recently, the INDILI has reported the prospectively collected information from 2013 to 2018, which provides the details on their methods of diagnosis (based on criteria adopted by international DIII expert group and causality assessment by Roussel Uclaf Causality Assessment Method model), etiology, clinical presentation, outcome, and prognostic markers in Indian patients with DILI (n = 1288). 5 In this study, the most frequent causes of DILI in chronological sequence were combination ATDs (46.4%), CAMs (13.9%), antiepileptic drugs (AEDs; 8.1%), non-ATD antimicrobials (6.5%), antimetabolites (3.8%), antiretroviral drugs (ARTs; 3.5%), NSAIDs (2.6%), hormones (2.5%), and statins (1.4%). About 10% of the patients with DILI had or progressed to ALF, and among these patients with ALF (n = 124), the most frequent etiology was ATDs (63%), CAMs (12.1%), AEDs (8.1%), other drugs used for central nervous system disorders (3.2%), Dapsone (2.4%), ARTs (3.2%), and infrequently other drugs (chemotherapeutic agents, hormones, methotrexate, NSAIDs, and statins: 5%).…”

“…The INDILI also found CAMs and ASMs to be the second most common cause of DILI and drug-induced ALF. 5 An Official Learning Resource of AASLD Copyright 2020, Elsevier.…”

“…Data were collected from various tertiary care centers all over India in a predesigned case record form and sent to St. John's Medical College Hospital, Bangalore, which was the nodal center for the INDILI. Recently, the INDILI has reported the prospectively collected information from 2013 to 2018, which provides the details on their methods of diagnosis (based on criteria adopted by international DIII expert group and causality assessment by Roussel Uclaf Causality Assessment Method model), etiology, clinical presentation, outcome, and prognostic markers in Indian patients with DILI (n = 1288) 5 . In this study, the most frequent causes of DILI in chronological sequence were combination ATDs (46.4%), CAMs (13.9%), antiepileptic drugs (AEDs; 8.1%), non‐ATD antimicrobials (6.5%), antimetabolites (3.8%), antiretroviral drugs (ARTs; 3.5%), NSAIDs (2.6%), hormones (2.5%), and statins (1.4%).…”

“…However, those with ALF had a female predominance. Even though the exact CAM responsible for DILI could not be specified in the earlier study, the possibility of types of CAM in India is discussed in the following section 5 …”

Drug‐Induced Liver Injury Unique to India

“…Although the true incidence of DILI in India is unknown, it is likely to be higher than in the Western countries. The idiosyncratic form of DILI constitutes ~99% of all DILI cases in India, and intrinsic DILI as it occurs in acetaminophen/paracetamol hepatotoxicity accounts for <1% of cases 1 . Intrinsic hepatotoxicity such as from rodenticide toxicity (yellow phosphorus poisoning) is a much more common cause of acute liver failure (ALF) in India than acetaminophen/paracetamol hepatotoxicity 2 …”