The Use of Liver Biopsy Evaluation in Discrimination of Idiopathic Autoimmune Hepatitis Versus Drug-Induced Liver Injury

The Use of Liver Biopsy Evaluation in Discrimination of Idiopathic Autoimmune Hepatitis Versus Drug-Induced Liver Injury
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DOI:
10.1002/hep.24481
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发表时间:
2011-09-01
期刊:
影响因子:
13.5
通讯作者:
Bjoernsson, Einar
Bjoernsson, Einar
中科院分区:
医学1区
文献类型:
--
作者:
Suzuki, Ayako;Brunt, Elizabeth M.;Bjoernsson, Einar

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区分药物性肝损伤(DILI)与特发性自身免疫性肝炎(AIH)可能具有挑战性。我们进行了标准化的组织学评估,以探索区分AIH与DILI的潜在标志。由4名经验丰富的肝脏病理学家以盲法对临床特征良好的DILI [n = 35,包括19例肝细胞损伤(HC)和16例胆汁淤积/混合性损伤(CS)]和AIH(n = 28)患者的活检进行Ishak评分、门静脉和腺泡内区域的显著炎性细胞类型、是否存在栓塞、玫瑰花结形成和胆汁淤积进行评价。65%的病例组织学诊断与临床诊断一致,但只有46%的病例在四位病理学家之间的最终诊断完全一致。界面性肝炎、局灶性坏死和门静脉炎症在所有评估病例中均存在,但AIH比DILI(HC)更严重(P < 0.05)。门静脉和腺泡内浆细胞、玫瑰花结形成和空泡形成是AIH的特征(P < 0.02)。结合门静脉炎症、门静脉浆细胞、腺泡内淋巴细胞和嗜酸性粒细胞、玫瑰花结形成和小管胆汁淤积的模型在预测DILI(HC)与AIH时的受试者工作特征曲线下面积(AUROC)为0.90。AIH组各项Ishak炎症评分均高于DILI(CS)组(P < 0.05)。上述四种AIH有利特征在AIH中更为普遍,而门静脉中性粒细胞和细胞内胆汁淤积在DILI(CS)中更为普遍(P < 0.02)。门静脉炎症、纤维化、门静脉嗜中性粒细胞和浆细胞以及细胞内(肝细胞)胆汁淤积的组合在预测DILI(CS)与AIH方面的AUC为0.91。结论:虽然AIH和DILI的组织学表现存在重叠,但存在足够的差异,因此病理学家可以使用损伤模式来建议正确的诊断。(肝脏学2011;54:931-939)
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 versus 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, the presence or absence of emperipolesis, rosette formation, and cholestasis in a blinded fashion by four experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but agreement on final diagnosis among the four pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis, and portal inflammation were present in all 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 receiver operating characteristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS) (P < 0.05). The four AIH-favoring features listed above were consistently more prevalent in AIH, whereas 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) versus AIH. Conclusion: Although an 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. (HEPATOLOGY 2011;54:931-939)