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Original Article
Frequency, clinical presentation, and outcomes of drug-induced liver injury after liver transplantation†‡
Article first published online: 12 JUL 2012
DOI: 10.1002/lt.23424
Copyright © 2012 American Association for the Study of Liver Diseases
Additional Information
How to Cite
Sembera, S., Lammert, C., Talwalkar, J. A., Sanderson, S. O., Poterucha, J. J., Hay, J. E., Wiesner, R. H., Gores, G. J., Rosen, C. B., Heimbach, J. K. and Charlton, M. R. (2012), Frequency, clinical presentation, and outcomes of drug-induced liver injury after liver transplantation. Liver Transpl, 18: 803–810. doi: 10.1002/lt.23424
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Stepan Sembera and Jayant A. Talwalkar were guarantors of the integrity of the entire study and contributed to the acquisition of data or the analysis and interpretation of data, the literature research, and the statistical analysis. Jayant A. Talwalkar contributed to the study concepts and design. All the authors contributed to the drafting of the manuscript or the revision of the manuscript for important intellectual content as well as the editing of the manuscript, and all the authors approved the final version of the submitted manuscript.
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This study was supported in part by grant U01 DK082992 from the National Institutes of Health (to Jayant A. Talwalkar).
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Telephone: 507-284-4823; FAX: 507-284-0538
Publication History
- Issue published online: 12 JUL 2012
- Article first published online: 12 JUL 2012
- Accepted manuscript online: 5 MAR 2012 12:19AM EST
- Manuscript Accepted: 21 FEB 2012
- Manuscript Received: 18 JUL 2011
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. Liver Transpl, 2012. © 2012 AASLD.