自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征的临床及病理学特征分析

Clinical and pathological features of autoimmune hepatitis-primary biliary cholangitis overlap syndrome versus autoimmune hepatitis

目的自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征(AIH-PBC OS)的诊断仍然是目前尚未解决的难点,对AIH-PBC OS与AIH的临床与病理特征进行比较分析,以加强对AIH-PBC OS的认识,提高AIH-PBC OS的早期诊断率。方法前瞻性收集2015年1月20日-2016年11月28日于四川大学华西医院就诊且经肝穿刺确诊的AIH-PBC OS患者(50例)和单纯AIH患者(57例)的临床特征、生化免疫学指标、自身抗体和肝组织病理学表现等方面,比较AIH-PBC OS与AIH的不同特点。实验室指标等计量资料2组间比较采用非参数秩和检验;临床特征、肝组织病理学表现等计数资料2组间比较采用χ~2检验。结果AIH-PBC OS组发病年龄低于AIH组(Z=-1.975,P=0.048),男女性别比无明显差异。AIH-PBC OS患者较AIH患者更易出现瘙痒症状(22.0%vs 7.0%,χ~2=4.960,P=0.026)。AIH-PBC OS组ALP、GGT和IgM水平以及AMA的阳性率均高于AIH组(Z=-6.250、-4.789、-5.407、χ~2=26.811,P值均<0.001),而血清ALT、AST和IgG的水平则低于AIH组(Z=-2.916、-3.381、-2.285,P=0.004、0.001、0.022)。肝穿刺活组织检查AIH-PBC OS组患者胆管损伤、胆管缺失、肉芽肿样病变和胆汁淤积的发生率均高于AIH组(χ~2=25.612、15.953、6.490、10.042,P<0.001、<0.001、0.001、0.002)。结论 AIH-PBC OS虽然同时具备AIH和PBC的特点,但并非AIH与PBC的简单叠加。瘙痒,ALP、GGT、IgM水平显著升高,AMA阳性,病理学表现出的炎症性胆管病变和胆汁淤积均对AIH-PBC OS的诊断有提示作用。由于AIH-PBC OS的肝脏炎症损伤程度和自身免疫异常程度总体可能较AIH轻,故在AIH-PBC OS诊断时应考虑适当放宽巴黎标准中ALT、IgG的水平,以防因漏诊而影响治疗方案的选择和患者预后。

Objective To investigate the clinical and pathological features of autoimmune hepatitis（AIH）-primary biliary cholangitis（PBC） overlap syndrome（AIH-PBC OS） versus AIH,since it is still difficult to diagnose AIH-PBC OS in clinical practice,and to enhance the knowledge of AIH-PBC OS and improve its early diagnostic rate.Methods A prospective study was performed for the clinical data,biochemical and immunological markers,autoantibody,and liver pathology of 50 patients with AIH-PBC OS confirmed by liver biopsy who visited West China Hospital,Sichuan University,from January 20,2015 to November 28,2016 and 57 patients with AIH alone,in order to compare the features of AIH-PBC OS and AIH.Continuous data such as laboratory markers were expressed as median M（inter-quartile range） and the nonparametric rank sum test was used for comparison of these data between two groups;categorical data including clinical features、histopathological manifestations were expressed as rates and the chi-square test was used for comparison of these data between two groups.Results The AIH-PBC OS group had a significantly lower age of onset than the AIH group（Z=-1.975,P=0.048）,while there was no significant difference in male/female sex ratio between the two groups.The AIH-PBC OS group had a significantly higher proportion of patients with pruritus than the AIH group（22.0% vs 7.0%,χ^2=4.960,P=0.026）.Compared with the AIH group,the AIH-PBC OS group had significantly higher levels of alkaline phosphatase（ALP）,gamma-glutamyl transpeptidase（GGT）,and immunoglobulin M（IgM）（Z=-6.250,-4.789,and-5.407,all P〈0.001）,a significantly higher positive rate of antimitochondrial antibody（AMA）（χ^2=26.811,P〈0.001）,and significantly lower serum levels of alanine aminotransferase（ALT）,aspartate aminotransferase,and immunoglobulin G（IgG）（Z=-2.916,-3.381,and-2.285,P=0.004,0.001,and 0.022）.The AIH-PBC OS group had significantly higher incidence rates of bile duct injury,bile duct loss,granulomatous disease,and cholestasis than the AIH group（χ-2=25.612,15.953,6.490,and 10.042,P〈0.001,0.001,0.001,and 0.002）.Conclusion Although AIH-PBC OS has the features of both AIH and PBC,it is not a simple overlap between AIH and PBC.Pruritus,significant increases in the levels of ALP,GGT,and IgM,positive AMA,and inflammatory bile duct disease and cholestasis may have implications for the diagnos of AIH-PBC OS.Since AIH-PBC OS may have milder liver inflammatory injury and autoimmune abnormalities than AIH,the levels of ALT and IgG in Paris criteria can be broadened during the diagnosis of AIH-PBC OS,in order to prevent missed diagnosis and avoid affecting the selection of treatment regimen and patients＇ prognosis.