Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH vs. DILI. Biopsies from patients with clinically well-characterized DILI (n=35, including 19 hepatocellular injury [HC] and 16 cholestatic/mixed injury [CS]) and AIH (n=28) were evaluated for Ishak scores, prominent inflammatory cell types in portal and intra-acinar areas, presence or absence of emperipolesis, rosette formation and cholestasis in a blinded fashion by 4 experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but full agreement on final diagnosis among the 4 pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis and portal inflammation were present in all the evaluated cases but were more severe in AIH (p<0.05) than DILI (HC). Portal and intra-acinar plasma cells, rosette formation, and emperiopolesis were features that favored AIH (p<0.02). A model combining portal inflammation, portal plasma cells, intra-acinar lymphocytes and eosinophils, rosette formation, and canalicular cholestasis yielded an area under the ROC curve (AUC) of 0.90 in predicting DILI (HC) vs. AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS) (p≤0.05). The 4 AIH-favoring features listed above were consistently more prevalent in AIH while portal neutrophils and intracellular (hepatocellular) cholestasis were more prevalent in DILI (CS) (p<0.02). The combination of portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular (hepatocellular) cholestasis yielded an AUC of 0.91 in predicting DILI (CS) vs. AIH. Conclusion While overlap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists can use the pattern of injury to suggest the correct diagnosis.

Drug-induced liver injury (DILI) patients who do not resolve their liver damage during the first year should be considered chronic DILI patients. Risk factors for DILI chronicity are older age, dyslipidemia and severity of the acute episode. Chronic DILI is not a very common condition; normally featuring mild liver profile abnormalities and not being an important clinical problem, with the exception of a small number of cases of early onset cirrhosis.

MR imaging is a useful and noninvasive diagnostic tool for quantification of hepatic iron concentration.

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on behalf of the Spanish Group for the Study of Drug-Induced Liver Disease Individual vulnerability to drug-induced liver injury (DILI) might result from deficiencies in the detoxification process, which determines the level of exposure to the reactive metabolite. We evaluated whether a genetically determined reduction in the ability to detoxify electrophilic compounds, such as that expected among individuals with glutathione S-transferase (GST) null genotypes, might play a role in determining the risk for DILI and its clinical expression. Genomic DNA from 154 patients (74 men, 80 women; mean age, 53 years) with a diagnosis of DILI as assessed with the Council for International Organizations of Medical Science scale and 250 sexand age-matched healthy controls were analyzed. A multiplex polymerase chain reaction-based method was used to detect GSTM1 and GSTT1 gene deletions. Carriers of double GSTT1-M1 null genotypes had a 2.70-fold increased risk of developing DILI compared with noncarriers (odds ratio 2.70, 95% confidence interval 1.45-5.03; P ‫؍‬ 0.003). The odds ratio for DILI patients receiving antibacterials, and NSAIDs were 3.52 (P ‫؍‬ 0.002), and 5.61 (P ‫؍‬ 0.001), respectively. Patients with amoxicillin-clavulanate hepatotoxicity (n ‫؍‬ 32) had a 2.81-fold increased risk (P ‫؍‬ 0.037). Patients classified by the combined GSTT1 and GSTM1 null genotypes did not differ with regard to the type of injury, clinical presentation, or outcome, except for the predominance of women in the combined null genotype (P < 0.001). Conclusion: The doublenull genotype for GSTT1 and GSTM1 might play a role in determining the susceptibility to develop DILI, as a general mechanism that occurs regardless of the type of drug involved, and predominantly in women. (HEPATOLOGY 2008;48:588-596.) I diosyncratic drug-induced liver injury (DILI) is a clinical challenge due to the rarity of its diagnosis and the lack of a gold standard, which makes determination of causality difficult. 1 Efforts to enhance the identification of adverse hepatic reactions and to obtain reliable information are being made in the setting of collaborative networks. 2,3 In spite of these efforts, the genetic and environmental factors that appear