Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset

Robert J. Fontana, Paul H. Hayashi, Jiezhun Gu, K. Rajender Reddy, Huiman Barnhart, Paul B. Watkins, Jose Serrano, William M. Lee, Naga Chalasani, Andrew Stolz, Timothy Davern, Jayant A. Talwakar

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.

Original languageEnglish
JournalGastroenterology
Volume147
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Chemical and Drug Induced Liver Injury
Morbidity
Mortality
Liver
Liver Transplantation
Wounds and Injuries
Chronic Drug-Induced Liver Injury
Confidence Intervals
Pruritus
Serum
Alanine Transaminase
Platelet Count
Bilirubin
Serum Albumin
African Americans
Lung Diseases
Multicenter Studies
Alkaline Phosphatase
Comorbidity
Heart Diseases

Keywords

  • Acute Liver Failure
  • Causality
  • Hepatotoxicity
  • Transplantation

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Fontana, R. J., Hayashi, P. H., Gu, J., Reddy, K. R., Barnhart, H., Watkins, P. B., ... Talwakar, J. A. (2014). Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology, 147(1). https://doi.org/10.1053/j.gastro.2014.03.045

Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. / Fontana, Robert J.; Hayashi, Paul H.; Gu, Jiezhun; Reddy, K. Rajender; Barnhart, Huiman; Watkins, Paul B.; Serrano, Jose; Lee, William M.; Chalasani, Naga; Stolz, Andrew; Davern, Timothy; Talwakar, Jayant A.

In: Gastroenterology, Vol. 147, No. 1, 2014.

Research output: Contribution to journalArticle

Fontana, RJ, Hayashi, PH, Gu, J, Reddy, KR, Barnhart, H, Watkins, PB, Serrano, J, Lee, WM, Chalasani, N, Stolz, A, Davern, T & Talwakar, JA 2014, 'Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset', Gastroenterology, vol. 147, no. 1. https://doi.org/10.1053/j.gastro.2014.03.045
Fontana, Robert J. ; Hayashi, Paul H. ; Gu, Jiezhun ; Reddy, K. Rajender ; Barnhart, Huiman ; Watkins, Paul B. ; Serrano, Jose ; Lee, William M. ; Chalasani, Naga ; Stolz, Andrew ; Davern, Timothy ; Talwakar, Jayant A. / Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. In: Gastroenterology. 2014 ; Vol. 147, No. 1.
@article{b3ec38d4b6d9458e942e55c68336f3a9,
title = "Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset",
abstract = "Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5{\%} were female and 59.1{\%} required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5{\%}; 95{\%} confidence interval [CI], 3.0{\%}-6.1{\%}) and 32 died (5{\%}; 95{\%} CI, 3.2{\%}-6.5{\%}); 53{\%} of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9{\%} of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.",
keywords = "Acute Liver Failure, Causality, Hepatotoxicity, Transplantation",
author = "Fontana, {Robert J.} and Hayashi, {Paul H.} and Jiezhun Gu and Reddy, {K. Rajender} and Huiman Barnhart and Watkins, {Paul B.} and Jose Serrano and Lee, {William M.} and Naga Chalasani and Andrew Stolz and Timothy Davern and Talwakar, {Jayant A.}",
year = "2014",
doi = "10.1053/j.gastro.2014.03.045",
language = "English",
volume = "147",
journal = "Gastroenterology",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "1",

}

TY - JOUR

T1 - Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset

AU - Fontana, Robert J.

AU - Hayashi, Paul H.

AU - Gu, Jiezhun

AU - Reddy, K. Rajender

AU - Barnhart, Huiman

AU - Watkins, Paul B.

AU - Serrano, Jose

AU - Lee, William M.

AU - Chalasani, Naga

AU - Stolz, Andrew

AU - Davern, Timothy

AU - Talwakar, Jayant A.

PY - 2014

Y1 - 2014

N2 - Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.

AB - Background & Aims Little is known about the incidence of drug-induced liver injury (DILI) and risk factors for adverse outcomes. We evaluated short-term outcomes of a large cohort of patients with DILI enrolled in an ongoing multicenter prospective study. Methods Data were collected from 660 adults with definite, highly likely, or probable DILI. Regression methods were used to identify risk factors for early liver-related death or liver transplantation and chronic liver injury. Results Patients' median age was 51.4 years; 59.5% were female and 59.1% required hospitalization. Within 6 months of DILI onset, 30 patients received liver transplants (4.5%; 95% confidence interval [CI], 3.0%-6.1%) and 32 died (5%; 95% CI, 3.2%-6.5%); 53% of the deaths were liver related. Asian race, absence of itching, lung disease, low serum albumin levels, low platelet counts, and high serum levels of alanine aminotransferase and total bilirubin at presentation were independent risk factors for reduced times to liver-related death or liver transplantation (C-statistic = 0.87). At 6 months after DILI onset, 18.9% of the 598 evaluable subjects had persistent liver damage. African-American race, higher serum levels of alkaline phosphatase, and prior heart disease or malignancy requiring treatment were independent risk factors for chronic DILI (C-statistic = 0.71). Conclusions Nearly 1 in 10 patients die or undergo liver transplantation within 6 months of DILI onset and nearly 1 in 5 of the remaining patients have evidence of persistent liver injury at 6 months. The profile of liver injury at presentation, initial severity, patient's race, and medical comorbidities are important determinants of the likelihood of death/transplantation or persistent liver injury within 6 months.

KW - Acute Liver Failure

KW - Causality

KW - Hepatotoxicity

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=84901777524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901777524&partnerID=8YFLogxK

U2 - 10.1053/j.gastro.2014.03.045

DO - 10.1053/j.gastro.2014.03.045

M3 - Article

C2 - 24681128

AN - SCOPUS:84901777524

VL - 147

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

IS - 1

ER -