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Gastroenterology. 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.

Author information

1
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. Electronic address: rfontana@med.umich.edu.
2
University of North Carolina, Chapel Hill, North Carolina.
3
Duke Clinical Research Institute, Durham, North Carolina.
4
Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania.
5
Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
6
Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas.
7
Department of Medicine, Indiana University, Indianapolis, Indiana.
8
University of Southern California, Los Angeles, California.
9
California Pacific Medical Center, San Francisco, California.
10
Mayo Clinic, Rochester, Minnesota.

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

PMID:
24681128
PMCID:
PMC4285559
DOI:
10.1053/j.gastro.2014.03.045
[Indexed for MEDLINE]
Free PMC Article

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