Outcomes and Predictors of Mortality in Patients With Drug-Induced Liver Injury at a Tertiary Hospital in South India: A Single-Centre Experience

Abstract

Introduction: Drug-induced liver injury (DILI) is an important cause of acute liver failure with significant morbidity and mortality. The outcome of DILI varies widely according to the drug implicated and the type of liver injury. Owing to the heterogeneous nature of liver injury, knowledge on clinical course and prognosis of DILI is limited. We had undertaken this study to determine the clinical characteristics, outcomes, and predictors of mortality in patients with DILI.

Materials and methods: This prospective study was conducted from January 2015 through December 2018. We analyzed the drugs implicated, clinical course, and the outcome. Causality assessment was performed by using Roussel Uclaf Causality Assessment Method scoring. Patients were followed for 6 months until recovery/death or liver transplantation.

Results: There were 133 cases with DILI. The mean age was 47.6 years, and 51.9% of them were men. Drugs causing DILI were antitubercular drugs (37.5%) followed by neuropsychiatric drugs (16.5%), antibiotics/antifungals (12%), complementary and alternative medicine (10.5%), immunomodulatory/chemotherapeutic drugs (10.5%), and nonsteroidal antiinflammatory drugs (7.5%). Eighty-two (61.6%) patients were classified as hepatocellular, 30 (22.5%) as mixed and 21 (15.7%) as cholestatic type of injury. There was no significant difference in the mortality and morbidity between the three types of liver injury. There were 18 deaths (13.5%), of which antitubercular drugs constituted the majority (55.5%) followed by neuropsychiatric drugs (27.7%) and complementary and alternative medicine (16.6%). Based on receiver operating characteristic curve analysis, model for end-stage liver disease (MELD) score >28, mean international normalized ratio (INR) >1.97, mean bilirubin level >15.6 mg/dl, and creatinine level >1.35 mg/dl were associated with mortality.

Conclusion: Although DILI is uncommon, it has significant morbidity and mortality. Antitubercular drugs were the most common cause for DILI and DILI-related mortality in our study. Variables such as MELD, INR, bilirubin, albumin, and creatinine help in predicting severity of liver injury and may help in triaging the patient for referral for liver transplantation.

Keywords: ALF, Acute liver failure; ALP, Alkaline phosphatase; ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; ATT, Antitubercular therapy; BMI, Body mass index; CAM, Complementary and alternative medicine; DILI; DILI, Drug induced liver injury; DOTS, Directly observed therapy short course; DRESS, Drug reaction with eosinophilia and systemic symptoms; Hb, Hemoglobin; INR, International normalized ratio; LFT, Liver function test; MELD, Model for end stage liver disease; MRCP, Magnetic resonance cholangio pancreatography; NSAID, Non-steroidal anti-inflammatory drugs; PT, Prothrombin time; RBS, Random blood sugar; RUCAM, Roussel Uclaf Causality Assessment Method; SD, Standard deviation; ULN, Upper limit normal; WBC, White blood cell; antitubercular drugs; complementary and alternative medicine (CAM); mortality.

Figure 1

ROC curve for predicting mortality in patients with DILI (MELD > 28, creatinine > 1.35 mg/dl, mean INR > 1.975, mean bilirubin > 15.65 mg/dl). ROC: receiver operating characteristic; DILI: drug-induced liver injury; MELD: model for end-stage liver disease; INR: international normalized ratio.