Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations

David E. Kleiner, Naga P. Chalasani, William M. Lee, Robert J. Fontana, Herbert L. Bonkovsky, Paul B. Watkins, Paul H. Hayashi, Timothy J. Davern, Victor Navarro, Rajender Reddy, Jayant A. Talwalkar, Andrew Stolz, Jiezhun Gu, Huiman Barnhart, Jay H. Hoofnagle

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.

Original languageEnglish (US)
Pages (from-to)661-670
Number of pages10
JournalHepatology
Volume59
Issue number2
DOIs
StatePublished - Feb 2014

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Chemical and Drug Induced Liver Injury
Liver
Wounds and Injuries
Histology
Cholestasis
Necrosis
Biopsy
Rosette Formation
Chronic Hepatitis
Bile Ducts
Granuloma
Eosinophils
Causality
Hepatitis
Observational Studies
Fibrosis
Prospective Studies
Apoptosis
Pathology
Hemorrhage

ASJC Scopus subject areas

  • Hepatology

Cite this

Kleiner, D. E., Chalasani, N. P., Lee, W. M., Fontana, R. J., Bonkovsky, H. L., Watkins, P. B., ... Hoofnagle, J. H. (2014). Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations. Hepatology, 59(2), 661-670. https://doi.org/10.1002/hep.26709

Hepatic histological findings in suspected drug-induced liver injury : Systematic evaluation and clinical associations. / Kleiner, David E.; Chalasani, Naga P.; Lee, William M.; Fontana, Robert J.; Bonkovsky, Herbert L.; Watkins, Paul B.; Hayashi, Paul H.; Davern, Timothy J.; Navarro, Victor; Reddy, Rajender; Talwalkar, Jayant A.; Stolz, Andrew; Gu, Jiezhun; Barnhart, Huiman; Hoofnagle, Jay H.

In: Hepatology, Vol. 59, No. 2, 02.2014, p. 661-670.

Research output: Contribution to journalArticle

Kleiner, DE, Chalasani, NP, Lee, WM, Fontana, RJ, Bonkovsky, HL, Watkins, PB, Hayashi, PH, Davern, TJ, Navarro, V, Reddy, R, Talwalkar, JA, Stolz, A, Gu, J, Barnhart, H & Hoofnagle, JH 2014, 'Hepatic histological findings in suspected drug-induced liver injury: Systematic evaluation and clinical associations', Hepatology, vol. 59, no. 2, pp. 661-670. https://doi.org/10.1002/hep.26709
Kleiner, David E. ; Chalasani, Naga P. ; Lee, William M. ; Fontana, Robert J. ; Bonkovsky, Herbert L. ; Watkins, Paul B. ; Hayashi, Paul H. ; Davern, Timothy J. ; Navarro, Victor ; Reddy, Rajender ; Talwalkar, Jayant A. ; Stolz, Andrew ; Gu, Jiezhun ; Barnhart, Huiman ; Hoofnagle, Jay H. / Hepatic histological findings in suspected drug-induced liver injury : Systematic evaluation and clinical associations. In: Hepatology. 2014 ; Vol. 59, No. 2. pp. 661-670.
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AU - Chalasani, Naga P.

AU - Lee, William M.

AU - Fontana, Robert J.

AU - Bonkovsky, Herbert L.

AU - Watkins, Paul B.

AU - Hayashi, Paul H.

AU - Davern, Timothy J.

AU - Navarro, Victor

AU - Reddy, Rajender

AU - Talwalkar, Jayant A.

AU - Stolz, Andrew

AU - Gu, Jiezhun

AU - Barnhart, Huiman

AU - Hoofnagle, Jay H.

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N2 - Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.

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