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

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, while eosinophils and granulomas were found more often in those with milder injury. In summary, 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.

Assessing liver injury associated with antimycotics: Concise literature review and clues from data mining of the FAERS database

“…Because DILI is a diagnosis of exclusion, selected elements of the medical history, laboratory tests, and previous reports were proposed to improve causality assessment [13] . The role of liver biopsy is still controversial, especially histological features and their relationship with biochemical parameters, although a systematic approach has been recently proposed as a foundation to correlate DILI pathology with its causality and outcome [14] . Efforts have been also directed to identify a list of essential elements (minimum requirements) when submitting case reports for publication [15] .…”

Drug idiosyncrasy due to pirfenidone presenting as acute liver failure: Case report and mini‐review of the literature

“…Liver biopsy is also considered where continued use of the drug is expected or liver functions remain altered beyond 180 days 8. Liver biopsy findings are generally classified into one of the 18 patterns described 19. It is important to note that none of the findings are diagnostic for DILI.…”

“…It is important to note that none of the findings are diagnostic for DILI. A study from the DILI Network19 reported the most common patterns of DILI as acute (21%); chronic hepatitis (14%), acute (9%), and chronic cholestasis (10%); and CS hepatitis (29%). The patients with HC presentation had more severe inflammation, necrosis, and apoptosis and more frequent lobular disarray, rosette formation, and hemorrhage than those with CS presentation.…”

“…The patients with CS‐DILI had more bile plugs and duct paucity. Severe or fatal DILI has been shown to have higher degrees of necrosis, fibrosis, ductular reaction, and microvesicular steatosis, whereas granulomas and eosinophils were more common in mild DILI 19. Recently, a study attempted to differentiate DILI from AIH on histology 20.…”

Hepatotoxicity Induced by High Dose of Methylprednisolone Therapy in a Patient with Multiple Sclerosis: A Case Report and Brief Review of Literature

“…In acute liver failure, the major cause is drug-induced liver injury which is the one of significant causes of liver disease with high morbidity and mortality, and it is important that any patient who has jaundice or altered liver function tests should be questioned carefully about the exposure of any drugs or chemicals used, although there is no specific tests that exists of drug-induced liver injury and the diagnosis is to performed by exclusion [2] so the challenge factor of this condition is the diagnosis of the disease. Steroids are usually considered to be safe drugs that do not cause drug induced liver injury, and even they are the treatment choice of autoimmune hepatitis, but the literatures about steroids showed are not entirely safe to liver injury and they have occasionally linked to severe hepatotoxicity, although methylprednisolone-induced hepatotoxicity cases are rare but persist on repeated administration and they lead to the poor outcome [3].…”