Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury.
OBJECTIVE
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.
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Robert J
RJ
Fontana
University of North Carolina, Chapel Hill, North Carolina, USA.
Paul H
PH
Hayashi
Duke Clinical Research Institute, Durham, North Carolina, USA.
Huiman
H
Barnhart
National Cancer Institute, Bethesda, Maryland, USA.
David E
DE
Kleiner
Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennysylvania, USA.
K Rajender
KR
Reddy
Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
Naga
N
Chalasani
Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
William M
WM
Lee
University of Southern California, Los Angeles, California, USA.
Andrew
A
Stolz
Duke Clinical Research Institute, Durham, North Carolina, USA.
Thomas
T
Phillips
Liver Disease Research Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland, USA.
Jose
J
Serrano
University of North Carolina, Chapel Hill, North Carolina, USA.
Paul B
PB
Watkins
D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000469:Alkaline Phosphatase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood* / Q000473:pathology; D002779:Cholestasis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006505:Hepatitis / Q000097:blood* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies
D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase