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Frequency, clinical presentation, and outcomes of drug-induced liver injury after liver transplantation.

Abstract
Drug-induced liver injury (DILI) is increasingly being recognized as a common cause of acute hepatitis. The clinical impact of DILI after liver transplantation (LT) is not known. The aim of this study was to describe the frequency, clinical presentation, and outcomes of DILI in LT recipients. LT recipients with possible DILI were identified with electronic pathology records and clinical note database retrieval tools. Diagnostic criteria were applied to identify cases of DILI. Twenty-nine of 1689 LT recipients (1.7%) were identified with DILI. The mean age was 52 years, and 52% were women. The major indications for LT were primary sclerosing cholangitis (28%), cholangiocarcinoma (14%), and hepatocellular carcinoma (14%). The severity of DILI was mild or moderate in 92% of the cases. Nausea or diarrhea (31%), jaundice (24%), and pruritus (10%) were the most common symptoms at the time of diagnosis. The mean biochemistry values were as follows: alanine aminotransferase, 204 ± 263 U/L; aspartate aminotransferase, 108 ± 237 U/L; alkaline phosphatase, 469 ± 689 U/L; and total bilirubin, 1.9 ± 10.3 mg/dL. The median duration of medication use until the diagnosis of DILI was 57 days, and the major agent classes were antibiotics (48%), immunosuppressive agents (14%), and antihyperlipidemic drugs (7%). Trimethoprim-sulfamethoxazole was the most common implicated agent (n = 11). Serum liver enzymes improved within a median time of 34 days (range = 5-246 days) after drug withdrawal. Hepatic retransplantation or death did not occur. Among the 50 cases with possible DILI explained by other causes, 13 individuals (26%) had no alternative diagnosis despite histological findings compatible with DILI. In conclusion, DILI is a rare yet underrecognized event among LT recipients. The majority of cases are not clinically severe, and they resolve after drug cessation without hepatic retransplantation or death.
AuthorsStepan Sembera, Craig Lammert, Jayant A Talwalkar, Schuyler O Sanderson, John J Poterucha, J Eileen Hay, Russell H Wiesner, Gregory J Gores, Charles B Rosen, Julie K Heimbach, Michael R Charlton
JournalLiver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (Liver Transpl) Vol. 18 Issue 7 Pg. 803-10 (Jul 2012) ISSN: 1527-6473 [Electronic] United States
PMID22389256 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2012 American Association for the Study of Liver Diseases.
Topics
  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Chemical and Drug Induced Liver Injury (diagnosis, therapy)
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Liver (drug effects, pathology)
  • Liver Transplantation (methods)
  • Male
  • Middle Aged
  • Reoperation
  • Tissue Donors
  • Treatment Outcome

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