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Am J Gastroenterol. 2015 Oct;110(10):1450-9. doi: 10.1038/ajg.2015.283. Epub 2015 Sep 8.

Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury.

Author information

1
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
2
University of North Carolina, Chapel Hill, North Carolina, USA.
3
Duke Clinical Research Institute, Durham, North Carolina, USA.
4
National Cancer Institute, Bethesda, Maryland, USA.
5
Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennysylvania, USA.
6
Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
7
Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
8
University of Southern California, Los Angeles, California, USA.
9
Liver Disease Research Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, USA.

Abstract

OBJECTIVES:

The long-term outcomes of patients with drug induced liver injury (DILI) are not well described. The aim of this study was to determine the frequency and severity of persistent liver biochemistry abnormalities in DILI patients followed over 2 years.

METHODS:

Subjects with evidence of liver injury at 6 months after DILI onset were offered a month 12 and 24 study visit.

RESULTS:

Amongst the 99 patients with definite, probable, or very likely DILI and available laboratory data at 12 months after DILI onset, 74 (75%) had persistent liver injury (persisters) defined as a serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) or an alkaline phosphatase >ULN, while 25 (25%) had resolved liver injury (resolvers). On multivariate analysis, month 12 persisters were significantly older (52.6 vs. 43.7 years, P=0.01) and more likely to have a cholestatic lab profile at DILI onset (54 vs. 20%, P<0.01) than resolvers. The month 12 persisters also had significantly poorer SF-36 physical summary scores at DILI onset and throughout follow-up compared with the resolvers (P<0.01). Amongst the 17 subjects with a liver biopsy obtained at a median of 387 days after DILI onset, 9 had chronic cholestasis, 3 had steatohepatitis, and 3 had chronic hepatitis.

CONCLUSIONS:

In all, 75% of subjects with liver injury at 6 months after DILI onset have laboratory evidence of persistent liver injury during prolonged follow-up. Higher serum alkaline phosphatase levels at presentation and older patient age were independent predictors of persistent liver injury. Subjects with persistent liver injury at 12 months after DILI onset should be carefully monitored and assessed for liver disease progression.

Comment in

PMID:
26346867
PMCID:
PMC4784423
DOI:
10.1038/ajg.2015.283
[Indexed for MEDLINE]
Free PMC Article

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