自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床特征及诊疗分析

Clinical Feature and Treatment of Autoimmune Hepatitis-primary Biliary Cirrhosis Overlap Syndrome

目的探讨自身免疫性肝炎(AIH)-原发性胆汁性肝硬化(PBC)重叠综合征的临床特征、治疗方法及疗效。方法从我院2005年1月—2011年1月收治的287例自身免疫性肝病患者中筛选出AIH-PBC患者42例,30例患者接受熊去氧胆酸(UDCA)联合泼尼松治疗;12例患者接受UDCA、泼尼松和硫唑嘌呤联合治疗。回顾分析其一般资料、血清生化及免疫指标、影像学检查及肝组织学病理检查。结果 (1)42例AIH-PBC重叠综合征患者中,女36例,男6例;平均发病年龄为(58.1±6.9)岁。患者均出现食欲不振、关节肌肉酸痛、腹胀等临床症状,28.57%(12/42)的患者出现乏力,19.05%(8/42)出现皮肤瘙痒,7.14%(3/42)出现消化道出血;均出现双下肢水肿、腹腔积液、肝脾肿大等临床体征,45.24%(19/42)的患者出现黄疸。(2)所有患者血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、总胆红素(TBiL)水平均高于参考值,83.33%(35/42)的患者球蛋白(GLO)或免疫球蛋白G(IgG)水平升高,38.10%(16/42)免疫球蛋白M(IgM)水平升高,97.62%(41/42)抗核抗体(ANA)阳性,92.86%(39/42)抗线粒体抗体(AMA)和(或)AMA-M2阳性,7.14%(3/42)抗平滑肌抗体(SMA)阳性。(3)52.38%(22/42)的患者合并干燥综合征,4.76%(2/42)合并肺纤维化,14.29%(6/42)合并结节性甲状腺肿大,11.90%(6/42)合并腰椎和(或)肋骨骨折。42.86%(18/42)的患者出现汇管区浆细胞浸润,14.29%(6/42)出现玫瑰花结样改变,9.52%(4/42)出现胆管炎或肉芽肿,11.90%(5/42)出现小胆管增生、小叶间胆管消失,40.48%(17/42)出现肝细胞胆汁淤积,35.71%(15/42)出现汇管区纤维组织增生、假小叶形成。(4)所有患者病情缓解率为61.90%(26/42),病情进展率为28.57%(12/42),不完全应答率为28.57%(12/42),复发率为11.90(5/42),治疗失败率为9.52%(4/42)。结论 AIH-PBC重叠综合征表现出AIH和PBC的双重特征,但又不完全是二者的重叠。UDCA联合糖皮质激素治疗可明显改善患者AIH-PBC生化指标,延缓患者病情进展,提高患者生存率,缓解率也较高。

Objective To observe the clinical and pathological features and treatment of autoimmune hepatitis-primary biliary cirrhosis overlap syndrome（AIH-PBC）.Methods A total of 42 AIH-PBC patients were screened out from 287 ATH patients in the Third People′s Hospital of Yunnan from January 2005 to January 2011,30 of whom were given UDCA combined with prednisone,12 given UDCA,prednisone and azathioprine.General data,serum biochemical and immunological indicators and liver pathological examination were analyzed retrospectively.Results In 42 ATH-PBC patients,36 females,6 males,average onset age was（58.1±6.9）years old.All patients presented with inappetence,articular muscular soreness,abdominal distension and other clinical symptoms.28.57%（12/42）patients had hypodynamia,19.05%（8/42）had itch of skin,7.14%（3/42） had alimentary tract hemorrhage;All had edema of both lower extremities,seroperitoneum,splenohepatomegalia and other clinical signs,45.24%（19/42）had jaundice.The serum levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphatase（ALP）,γ-glutamyl transpeptidase（GGT）and total bilirubin（TBiL）increased in different degrees in 42 AIH-PBC patients.Globulin of immunoglobulin G（IgG） increased in 83.33%（35/42）,immunoglobulin M（IgM）increased in 38.10%（16/42）.The positive rates of antinuclear antibody（ANA）,anti-mitochondrial antibody（AMA）and anti-smooth muscle antibody（SMA）were 97.62%,92.86%,7.14%,respectively.52.38% patients combined with sicca syndrome,4.76% with pulmonary fibrosis,14.29% with nodular goiter,11.90% with fractures of lumbar vertebrae and（or）rib.42.86% patients had plasma cell infiltration of portal area,14.29% had rosette-like change,9.52% had cholangitis or granuloma,11.90% had small bile duct proliferation,interlobular bile duct disappearance,40.48% had cholestatic liver cells,35.71% had fibroplasia of portal area and pseudolobules formation.The remission rates of all patients were 61.90%,progression rate was 28.57%,incomplete response rate 28.57%,recurrence rate 11.90%,treatment failure rate 9.25%.Conclusion AIH-PBC overlap syndrome showed double features of both AIH and PBC but not absolutely overlapping.UDCA combined glucocorticoids therapy in AIH-PBC treatment can significantly improve patients′blood biochemical indexes,delay disease progression,improve survival rate and remission rate.