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

Harshad Devarbhavi, Rajvir Singh, Mallikarjun Patil, Keyur Sheth, Channagiri Krishnamurthy Adarsh, Girisha Balaraju

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

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. Methods: Single center analysis of consecutive cases of anti-TB DILI following combination anti-TB drugs exposure from 1997-2011. Results: 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 2months. 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%. Conclusions: 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%.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume28
Issue number1
DOIs
Publication statusPublished - 01-01-2013

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Hepatology

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