药物诱导的自身免疫性肝炎的临床和病理特点

Clinical and histopathologic features of drug-induced autoimmune hepatitis

【摘要】目的分析药物诱导的自身免疫性肝炎（DI—AIH）患者的临床和病理特点。方法回顾性分析2008年1月至2011年6月接受肝活组织检查、发病前明确有药物服用史的DI—AIH患者5例，收集其基本资料，包括性别、年龄、发病和服药情况、临床表现、治疗经过和随访情况。收集其实验室检查结果，主要指标为总胆红素、直接胆红素、ALT、AST、ALP、GGT、球蛋白、γ-球蛋白百分比、白蛋白、嗜酸粒细胞、抗核抗体、抗线粒体抗体、抗平滑肌抗体，并进行肝损伤分型。患者的肝组织切片行HE染色和网状纤维染色后观察其病理变化。对DI—A1H患者进行自身免疫性肝炎（AIH）评分。结果5例DI—AIH患者皆为女性，平均年龄为（48．0±7．5）岁，发病前均服用过中药或其制剂，纳差和乏力是最常见的临床症状。实验室检查结果中以ALT[-（795．0±467．4）U／L]、AST[-（730．4±451．5）U／L]、总胆红素[（80．3±64．1）μmol／L]、直接胆红素[（65．2±58．0）μmol／L]升高为主。1例患者抗核抗体阳性。1例患者存在药物性肝损伤，肝细胞点灶状坏死，肝组织嗜酸粒细胞浸润，肝细胞微泡型空泡变性。所有患者皆有界面性肝炎，汇管区淋巴细胞浸润或淋巴细胞一浆细胞浸润，病变部位相邻肝细胞呈玫瑰花结样结构。所有患者均接受糖皮质激素治疗，停药随访期间均未再出现肝功能异常。结论DI—AIH患者的临床表现、实验室检查结果和病理检查结果缺乏特异性。

Objective To analyze the clinical and histological features of drug-induced autoimmune hepatitis （DI-AIH）. Methods From January 2008 to June 2011, five patients with auto-immune hepatitis （AIH）, having a definitive history of medicine taking prior to the onset of disease and accepted liver biopsy were retrospectively analyzed. The general information was collected, which included gender, age, onset of the disease, medication, clinical manifestations, treatment and follow-up. The laboratory findings were also collected, which included total bilirubin （TBil）, direct bilirubin （DBil）, alanine transaminase （ALT）, aspartate transaminase （AST）, alkaline phosphatase （ALP）, gamma glutamyl transpeptidase （GGT）, globulin, y-globulin percentage, albumin （Alb）, eosinophils, antinuclear antibodies, anti- mitochondrial antibodies, anti-smooth muscle antibodies and the type of live injury. The liver tissue sections of patients were stained with hematoxylin-eosinstaining （HE） and reticular fiber staining and then pathological changes were observed. Patients with DI-AIH were scored with AIH scoring scale. Results All five patients with DI-AIH were female, average age was 48.0±7.5. Prior to the onset of disease, all patients had taken Chinese traditional medicine. Anorexia and fatigue were the most common clinical symptoms. Among laboratory findings, the level of ALT （（795.0±467.4） U/L）, AST （（730.4±51.5） U/L）, TBil （（80. 3± 64. 1 ） μmol/L） and DBil （ （65. 2 ± 58. 0） μmol/L） significantly increased. One patient was antinuclear antibody positive. One patient had drug-induced liver injury, pathological features were spotty necrosis of liver cells, liver tissue eosinophil infiltration and liver cell microbubble type degeneration. All the patients had interface hepatitis, periportal infiltration of lymphocytes or lymphocytes-plasma cells, liver cells adjacent to lesion showed rosette-like structure. All the patients received glucocorticoid treatment. After glucocorticoid withdrawal, the liver function was normal during the follow-up period. Conclusion There are no specificity of clinical manifestations, laboratory findings and histological features in patients with DI-AIH.