Persistent Liver Biochemistry Abnormalities Are More Common in Older Patients and those With Cholestatic Drug Induced Liver Injury

Robert J. Fontana, Paul H. Hayashi, Huiman Barnhart, David E. Kleiner, K. Rajender Reddy, Naga Chalasani, William M. Lee, Andrew Stolz, Thomas Phillips, Jose Serrano, Paul B. Watkins

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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.Am J Gastroenterol advance online publication, 8 September 2015; doi:10.1038/ajg.2015.283.

Original languageEnglish (US)
JournalAmerican Journal of Gastroenterology
DOIs
StatePublished - Oct 1 2015

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ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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Fontana, R. J., Hayashi, P. H., Barnhart, H., Kleiner, D. E., Reddy, K. R., Chalasani, N., Lee, W. M., Stolz, A., Phillips, T., Serrano, J., & Watkins, P. B. (2015). Persistent Liver Biochemistry Abnormalities Are More Common in Older Patients and those With Cholestatic Drug Induced Liver Injury. American Journal of Gastroenterology. https://doi.org/10.1038/ajg.2015.283