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

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 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%. 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%.