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 journalArticle

31 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

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Chemical and Drug Induced Liver Injury
Tuberculosis
Mortality
International Normalized Ratio
Acute Liver Failure
Brain Diseases
Jaundice
Ascites
Kernicterus
Creatinine
Transaminases
Serum Albumin
Logistic Models
Diagnosis-Related Groups
Therapeutics
Hepatitis B Surface Antigens
Leukocyte Count
Bilirubin
Pharmaceutical Preparations
HIV Infections

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Hepatology

Cite this

Devarbhavi, Harshad ; Singh, Rajvir ; Patil, Mallikarjun ; Sheth, Keyur ; Adarsh, Channagiri Krishnamurthy ; Balaraju, Girisha. / Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury. In: Journal of Gastroenterology and Hepatology (Australia). 2013 ; Vol. 28, No. 1. pp. 161-167.
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Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury. / Devarbhavi, Harshad; Singh, Rajvir; Patil, Mallikarjun; Sheth, Keyur; Adarsh, Channagiri Krishnamurthy; Balaraju, Girisha.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 28, No. 1, 01.01.2013, p. 161-167.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury

AU - Devarbhavi, Harshad

AU - Singh, Rajvir

AU - Patil, Mallikarjun

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AU - Adarsh, Channagiri Krishnamurthy

AU - Balaraju, Girisha

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N2 - 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%.

AB - 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%.

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