Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury


  • Ethics approval: The study was approved by Institution Ethical Review Board.
  • Author contributions: HD: Concept and design, acquisition of data, analysis and interpretation of data, statistical analysis, drafting and critical revision of the manuscript, study supervision. MP, KS, CKA: Acquisition of data, study supervision, drafting and critical revision of the manuscript. RS: Interpretation of data, statistical analysis, drafting and critical revision of the manuscript. Final approval of the manuscript: All authors


Professor Harshad Devarbhavi, Department of Gastroenterology, St. John's Medical College Hospital, Sarjapur Road, Bangalore, Karnataka 560034, India. Email: harshad.devarbhavi@gmail.com


Background and Aim

Worldwide anti-tuberculosis (TB) drug-induced liver disease (DILI) is an important cause of hepatotoxicity, and drug-induced acute liver failure (ALF). Reported series on anti-TB DILI are limited by a mix of cases with mild transaminase elevation or adaptation. Our aim was to analyze the clinical features, laboratory characteristics, outcome, and determine predictors of 90-day mortality.


Single center analysis of consecutive cases of anti-TB DILI following combination anti-TB drugs exposure from 1997–2011.


Of the 269 patients, 191 (71%) experienced jaundice and 69 (25.7%) accounted for ALF. The mean age and treatment duration was 41.3 years and 1.9 months, respectively; males constituted 55.7%. DILI occurred throughout the course of treatment; three-quarters occurred within the first 2 months. HIV infection was present in 21 (7.8%). The 90-day mortality was 22.7%. DILI accompanied by jaundice (n = 191), encephalopathy (n = 69) or ascites (n = 69) resulted in mortality in 30%, 69.6% and 50.7%, respectively (P < 0.001). Age, gender, transaminase levels, HIV or hepatitis B surface antigen (HBsAg) status did not influence survival. Treatment duration, encephalopathy, ascites, bilirubin, serum albumin, international normalized ratio (INR), serum creatinine and leukocyte count were associated with mortality (P < 0.001). Multivariate logistic regression model for mortality, incorporating encephalopathy, albumin, bilirubin, INR, and creatinine yielded a C-statistic of 97%.


Anti-TB DILI occurs throughout treatment duration progressing to ALF in a quarter of patients. The overall mortality is 22.7%, which is higher when accompanied by jaundice, ascites or encephalopathy. An anti-TB DILI model, incorporating bilirubin, INR, encephalopathy, serum creatinine and albumin predicted mortality with C-statistic of 97%.