自身免疫性肝炎合并自身免疫性疾病的特征研究

目的 比较自身免疫性肝炎（AIH）合并原发性胆汁性胆管炎（PBC）或部分肝外自身免疫性疾病（autoimmune disease）患者与单纯AIH患者临床特点及并发症，为改善AIH患者的诊治提供参考。方法 收集1999年8月~2019年8月我院收治的AIH患者149例，根据合并症分为无合并病的AIH组（68例）、AIH合并PBC组（AIH-PBC 组，41例）及AIH合并肝外自身免疫性疾病组（AIH-肝外组，40例），比较三组临床特点、并发症、肝纤维化/肝硬化进展情况。结果 ①AIH-PBC 组及AIH-肝外组年龄低于AIH组，差异有统计学意义（P＜0.05）；三组性别比较，差异无统计学意义（P＞0.05）。②三组共有的临床症状为瘙痒、黄疸、乏力、食欲不振及腹部不适，其中AIH-PBC组瘙痒症状患者多于AIH组、AIH-肝外组，差异有统计学意义（P＜0.05）；三组黄疸、乏力、食欲不振及腹部不适比较，差异无统计学意义（P＞0.05）。③AIH-PBC 组ALT低于AIH组及AIH-肝外组，ALP、GGT高于AIH组及AIH-肝外组，差异有统计学意义（P＜0.05）；AIH-肝外组的AST、DBIL高于AIH组及AIH-PBC 组，差异有统计学意义（P＜0.05）；AIH-肝外组IgG水平高于AIH组及AIH-PBC 组，差异有统计学意义（P＜0.05）。④三组ANA、ASMA、SLA、LKM-1阳性率比较，差异无统计学意义（P＞0.05）；AIH-PBC组AMA、AMA-M2 阳性率高于AIH组、AIH-肝外组，差异有统计学意义（P＜0.05）。⑤三组均以界面性肝炎和淋巴细胞浸润表现居多，其中AIH-PBC组胆管病变、胆汁淤积高于AIH组，差异有统计学意义（P＜0.05）。⑥三组并发症主要包括食管胃底静脉曲张/破裂出血、腹水、肝性脑病、肝癌、肝移植，组间比较，差异无统计学意义（P＞0.05）。⑦三组肝纤维化/肝硬化发生率比较，差异无统计学意义（P＞0.05）；但AIH-PBC组2~5年肝纤维化/肝硬化进展率高于AIH组及AIH-肝外组，差异有统计学意义（P＜0.05）。结论 合并PBC的AIH患者比单纯AIH患者诊断年龄早，肝脏炎症反应轻、胆管病变重；比AIH及合并肝外自身免疫性疾病更易出现瘙痒、胆汁淤积更重、胆管损伤更严重，且肝纤维化/肝硬化速度更快。AMA、AMA-M2可作为AIH合并PBC的鉴别指标。另外，AIH合并肝外自身免疫性疾病常存在肝功能损害，IgG对其具有提示意义。

Study on the Characteristics of Autoimmune Hepatitis Combined with Autoimmune Diseases

Objective To compare the clinical characteristics and complications of patients with autoimmune hepatitis (AIH) with primary biliary cholangitis (PBC) or some extrahepatic autoimmune disease and patients with AIH alone, to provide a reference for improving the diagnosis and treatment of patients with AIH. Methods A total of 149 AIH patients admitted in our hospital from August 1999 to August 2019 were collected and divided into AIH group without complications (68 cases), AIH combined with PBC group (AIH-PBC group, 41 cases), and AIH according to comorbidities. The extrahepatic autoimmune disease group (AIH-extrahepatic group, 40 cases) was combined, and the clinical characteristics, complications, and liver fibrosis/cirrhosis progress were compared among the three groups.Results ①The age of AIH-PBC group and AIH-extrahepatic group was lower than AIH group, the difference was statistically significant (P<0.05); there was no statistically significant difference between the three groups (P>0.05). ②The clinical symptoms common to the three groups were pruritus, jaundice, fatigue, loss of appetite, and abdominal discomfort. Among the patients in the AIH-PBC group, there were more pruritus symptoms than in the AIH and AIH-extrahepatic groups,the difference was statistically significant (P<0.05);There was no significant difference in jaundice, fatigue, loss of appetite and abdominal discomfort among the three groups (P>0.05). ③AIH-PBC group had lower ALT than AIH group and AIH-extrahepatic group, ALP and GGT were higher than AIH group and AIH-extrahepatic group, the difference was statistically significant (P<0.05); AST and DBIL of AIH-extrahepatic group compared with AIH group and AIH-PBC group, the difference was statistically significant (P<0.05); AIH-extrahepatic group IgG levels were higher than AIH group and AIH-PBC group, the difference was statistically significant (P<0.05). ④ There was no significant difference in the positive rates of ANA, ASMA, SLA, and LKM-1 in the three groups (P>0.05). The positive rates of AMA and AMA-M2 in the AIH-PBC group were higher than those in the AIH and AIH-extrahepatic groups,the difference was statistically significant (P<0.05). ⑤The three groups were mostly manifested by interfacial hepatitis and lymphocyte infiltration. The bile duct lesions and cholestasis in the AIH-PBC group were higher than those in the AIH group,the differences were statistically significant (P<0.05). ⑥Complications in the three groups mainly included esophageal gastric fundus varices / rupture bleeding, ascites, hepatic encephalopathy, liver cancer, and liver transplantation,there was no significant difference between the groups (P>0.05).⑦There was no significant difference in the incidence of liver fibrosis / cirrhosis in the three groups (P>0.05); however, the progression rate of liver fibrosis / cirrhosis in the AIH-PBC group was higher than that of the AIH group and AIH-extrahepatic in 2 to 5 years,the difference was statistically significant (P<0.05).Conclusion Patients with AIH who have PBC are diagnosed earlier than patients with AIH alone. They have mild liver inflammation and severe bile duct lesions. They are more prone to pruritus, hepatic cholestasis, more severe bile duct injury, and hepatic fibrosis than AIH and patients with extrahepatic autoimmune diseases/cirrhosis is faster. AMA and AMA-M2 can be used as identification indicators for AIH combined with PBC. In addition, AIH with extrahepatic autoimmune diseases often has liver damage, and IgG has implications for it.