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Observational Study
. 2014 Jul;147(1):96-108.e4.
doi: 10.1053/j.gastro.2014.03.045. Epub 2014 Mar 27.

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

Robert J Fontana  1 , Paul H Hayashi  2 , Jiezhun Gu  3 , K Rajender Reddy  4 , Huiman Barnhart  3 , Paul B Watkins  2 , Jose Serrano  5 , William M Lee  6 , Naga Chalasani  7 , Andrew Stolz  8 , Timothy Davern  9 , Jayant A Talwakar  10 ; DILIN Network
Affiliations
Observational Study

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

Robert J Fontana et al. Gastroenterology. 2014 Jul.

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.

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Conflict of interest statement

Conflicts of interest

These authors disclose the following: Robert J. Fontana has received research support from Vertex Pharmaceuticals and Gilead; he has also served as a consultant to Tibotec, Merck, and GlaxoSmithKline in the past year. K. Rajender Reddy has received research support from Merck, Gilead, Abbvie, Bristol-MyersSquibb, Janssen, Ikaria, and Genfit and served as an advisor to Merck, Genetech-Roche, Gilead, BMS, Vertex, Janssen, Idenix, and Abbvie. William M. Lee received research support from BI, BMS, Anadys, Gilead, Vertex, Merck, Roche and has consulted for Lilly, Novartis, and GSK. Naga Chalasani has served as a consultant to Merck, Aegerion, BMS, Abbvie, Lilly, and Salix during the past 12 months and received financial compensation from these entities. He has received research support from Intercept, Cumberland, Gilead, Enterome, and Takeda. The remaining authors disclose no conflicts.

Figures

Figure 1
Figure 1
Overview of the study population. *One subject died after liver transplant
Figure 2
Figure 2
Kaplan–Meier Survival curves for time to each of the three early outcomes
See this image and copyright information in PMC

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