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

DILIN Investigators

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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.

Original languageEnglish (US)
Pages (from-to)1450-1459
Number of pages10
JournalThe American Journal of Gastroenterology
Volume110
Issue number10
DOIs
StatePublished - Oct 1 2015

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Chemical and Drug Induced Liver Injury
Biochemistry
Liver
Wounds and Injuries
Alkaline Phosphatase
Cholestasis
Fatty Liver
Chronic Hepatitis
Aspartate Aminotransferases
Serum
Alanine Transaminase
Disease Progression
Liver Diseases
Multivariate Analysis

ASJC Scopus subject areas

  • Gastroenterology

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

In: The American Journal of Gastroenterology, Vol. 110, No. 10, 01.10.2015, p. 1450-1459.

Research output: Contribution to journalArticle

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title = "Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury",
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.",
author = "{DILIN Investigators} and Fontana, {Robert J.} and Hayashi, {Paul H.} and Huiman Barnhart and Kleiner, {David E.} and Reddy, {K. Rajender} and Naga Chalasani and Lee, {William M.} and Andrew Stolz and Thomas Phillips and Jose Serrano and Watkins, {Paul B.}",
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AU - DILIN Investigators

AU - Fontana, Robert J.

AU - Hayashi, Paul H.

AU - Barnhart, Huiman

AU - Kleiner, David E.

AU - Reddy, K. Rajender

AU - Chalasani, Naga

AU - Lee, William M.

AU - Stolz, Andrew

AU - Phillips, Thomas

AU - Serrano, Jose

AU - Watkins, Paul B.

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N2 - 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.

AB - 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.

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