107例自身免疫性肝炎及其重叠综合征患者的临床分析

Clinical features of 107 autoimmune hepatitis patients and 30 of them with AIH-primary biliary cirrhosis overlap syndrome

目的分析自身免疫性肝炎（AIH）77例及其重叠综合征患者30例的临床表现、免疫学及生物化学特点及其治疗方案。方法164例自身免疫性肝病患者中，AIH患者77例和AIH胆汁性肝硬化（PBC）重叠综合征患者30例，分析患者的临床特点、生物化学及组织学变化和治疗应答反应等。结果AIH患者的发病年龄高峰在50岁左右，肝功能生物化学检查结果显示为肝炎样异常，丙种球蛋白和免疫球蛋白G均明显高于正常。74％的患者抗核抗体阳性，32％的患者抗平滑肌抗体阳性，52％的患者伴发了肝外自身免疫性疾病。肝组织病理变化以界面性肝炎为主（65％），在中、重度患者则出现小叶性肝炎、玫瑰花结样改变、桥接样坏死等。AIHPBC重叠综合征患者血清ALT、AST、Y谷氨酰转移酶、碱性磷酸酶和抗核抗体、抗线粒体抗体（AMA）／AMA—M2阳性率较高，组织学检查往往还伴有胆管的病变。60例AIH患者接受免疫抑制剂强的松龙联合硫唑嘌呤治疗第1年时，AIH治疗患者达完全缓解者42例（70％），其中26例持续缓解，16例复发（激素减量至≤10mg／d或停药后），10例部分缓解，8例无应答。持续缓解者的AST、ALT、免疫球蛋白G、丙种球蛋白及血总胆红素水平均显著低于非持续缓解者（34例，P值均〈0．05），此类患者撤除了硫唑嘌呤，单用激素的剂量均可维持在5～10mg／d。AIH—PBC重叠综合征组经联合熊去氧胆酸治疗后除碱性磷酸酶和Y谷氨酰转移酶外，其余肝功能指标（ALT、AST、总胆红素）亦明显改善（P值均〈0．01）。结论AIH及AIH—PBC重叠综合征在临床上并不少见，诊断需综合临床、生物化学、免疫学和病理学等检测结果。AIH患者联合应用糖皮质激素、硫唑嘌呤达持续缓解者，可改为单用小剂量激素治疗。AIHPBC患者加用熊去氧胆酸治疗，亦可获得较好的疗效。

Objective In order to provide a reliable basis for the diagnosis and treatment of autoimmune hepatitis （AIH） and its overlap syndrome, we investigated the clinical, immunological characteristics of and the therapeutic methods for AIH and AIH-primary biliary cirrhosis （PBC） overlap syndrome. Methods One hundred seven patients （77 with AIH and 30 with AIH-PBC overlap syndrome） were enrolled in the study. Their clinical manifestations, serum liver function tests （LFTs） findings, serum immunoglobulins, liver histopathological changes and their responsiveness to the therapies were investigated. Results The age distribution of AIH patients showed a single peak during their fifties and their main clinical manifestations were malaise, abdominal distension, anorexia and jaundice. Serum gamma globulin and IgG were significantly higher than their normal levels. 74% of the patients were positive for anti-nuclear antibody （ANA）, 32% of the patients were positive for anti-smooth muscle antibody （AMA）, and over 50% of the patients suffered from concurrent extrahepatic autoimmune diseases. The main histological changes in the liver biopsies were interface hepatitis （65%）, lobular hepatitis and rosette formation of liver cells. Bridging necrosis was observed in severe AIH cases. In the AIH-PBC overlap syndrome patients, the levels of serum ALT, AST, GGT, ALP and incidences of ANA and AMA/AMA-M2 were all significantly higher than those of the AIH group. After treating AIH patients with prednisolone and azathioprine （Aza）, complete response was seen in 42 cases （70%）, sustained response was seen in 26 cases （43%）. Sixteen cases had relapses after the withdrawal of the treatment or prednisolone dosage was reduced lower than 10 mg/d. The cases having normal serum ALT, AST, γ -globulin and IgG levels after treatment were still responding to the reduced prednisolone dosage of 5-10 mg/d without azathioprine added. After combination with ursodeoxycholic acid （UDCA） treatment, the liver function tests （AST, ALT, TBil） of AIH-PBC overlap syndrome patients also significantly improved compared to those before the treatment （P 〈 0.01）. Conclusion AIH and AIH-PBC overlap syndrome are not rare in our clinics. Their diagnoses should be based on the clinical presentations, biochemical and immunological indices and liver histological changes. In AIH cases, once their AST, ALT, V -globuline and IgG levels return to normal, the prednisolone dosage can be maintained at 5-10 mg/d and Aza can even be withdrawn. Good improvement for patients with AIH-PBC overlap syndrome can be obtained with UDCA and immunosuppression treatment.