中国西部自身免疫性肝病患者自身抗体的分布特征

目的: 探讨中国西部自身免疫性肝病患者中相关自身抗体的存在状况及特征.方法: 57例自身免疫性肝病患者分为3组: 自身免疫性肝炎(AIH)12例、原发性胆汁性肝硬化(PBC)32例、原发性硬化性胆管炎(PSC)13例.用间接免疫荧光法检测抗核抗体(ANA)、平滑肌抗体(SMA)、抗肝肾微粒抗体1型抗体(anti-LKM1)、抗线粒体抗体(AMA)和抗中性粒细胞胞质抗体(ANCA),Western blot检测抗肝细胞胞溶质抗原1型抗体(anti-LC1)、抗可溶性肝抗原/肝胰抗原抗体(anti-SLA/LP)、抗肝肾微粒抗体1型(anti-LKM1)、 AMA-M2亚型等多种肝抗原自身抗体.结果: 57例中ANA、AMA、M-2、pANCA阳性率在组间有统计学差异(P<0.01).PBC中AMA、M-2阳性检出率均为100%, PSC中pANCA阳性检出率为53.8%, Fisher精确检验在α'=0.002水准与其他各组比较有统计学差异.AIH与PBC的ANA阳性率分别为100%和50%,Fisher精确检验在α'=0.002水准二者无统计学意义,与其他各组比较有明显差异.在AIH组SMA阳性率为25%,LKM-1、LC-1、SLA/LP阳性率均为8.3%, 与其他组无统计学意义,可能与病例少有关.PBC中分别有1例患者ANA、SMA以及ANA、LKM-1同时阳性, PSC中有1例ANA、SLA/LP同时阳性,此3例患者结合性别、生化、自身抗体等资料符合AIH诊断条件;AIH中有1例M-2阳性综合各项资料符合PBC(重叠综合征).结论: 肝抗原自身抗体、ANA、AMA及M-2亚型的检测有助于自身免疫性肝病的诊断.对肝炎病毒血清标志物阴性的肝功能异常者应该行肝抗原自身抗体检测协助诊断.     

肝抗原自身抗体在自身免疫性肝病诊断中的意义

目的 探讨肝抗原自身抗体在自身免疫性肝病患者血清中的阳性率。方法 将患者分为3组：①自身免疫性肝病组，包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)，原发性硬化性胆管炎(PSC)。②各类病毒性肝炎组；③不明原因肝损伤组。分别用间接免疫荧光法、免疫印迹法检测肝抗原(SAL/LP、LKM-1、LC-1、AMA-M2)自身抗体。结果 抗SLP／LP抗体在AIH患者血清中阳性率为46．4％，明显高于LKM-1(13．3％)、LC-1(0．O％)及AMA-M2(13．3％)抗体，并且在病毒性肝炎患者血清中呈阴性反应。抗AMA-M2抗体在PBC患者血清中阳性率达95．0％。不明原因肝损伤组患者中有10．0％的AMA-M2抗体阳性。结论 抗SLA/LP抗体对AIH具有特异性，肝抗原自身抗体的检测将有助于自身免疫性肝病患者的诊断及治疗。     

肝病患者自身抗体特征性的研究

目的：观察抗肝抗原自身抗体在我国不同类型肝病患者中的存在状况；探讨自身免疫性肝脏疾病的自身抗体特征。方法：间接免疫荧光法初筛1412例肝功能异常血清，从中选择28例：①自身免疫性肝病组42例：初步诊断为AIH18例、PBC21例、PSC3例。②HAV组23例；③DBV组70例；④HCV组33例；⑤非甲—非戊型肝炎组60例。结合Western blot、酶免疫条带技术等分别检测ANA、AMA、SMA、LKM—1、LC—1、SLA/LP和AMA-M2亚型、dsDNA及ENA类多种抗体。结果：1412例中诊断AIH、PBC和PSC者分别为送检标本的12．7‰，14．9‰和2．1‰。28例血清中2例LKM—1阳性和2例SLA／LP阳性；按AIH的分型标准，自身免疫性肝病组属于I型AIH者14例(78％)，Ⅱ型2例(11％)，Ⅲ型2例(11％)；AIH患者ANA抗体未见特定的荧光类型。PBC患者AMA和M2全部阳性；其ANA以核膜型为主(7／14)。NonA—E组4例AMA和M2阳性，3例SMA高滴度阳性，4例出现SS-A、SS-B或dsDNA等抗体。结论：三型自身免疫性肝炎在中国都存在，肝抗原自身抗体和ANA及AMA的分型检测有助于自身免疫性肝病的诊断与治疗；少数非甲—非戊型肝炎应考虑自身免疫性肝病诊断。     

不同肝病患者抗肝抗原自身抗体的研究

目的：观察我国不同类型肝病患者中几种抗肝抗原自身抗体的存在状况；探讨自身免疫性肝脏疾病的自身抗体特征。方法：由1412例标本中选择230例肝功能异常患者分为5组：①自身免疫性肝病组42例：自身免疫性肝炎（AIH）18例、原发性胆汁性肝硬化（PBC）21例、原发性硬化性胆管炎（PSC）3例。②HAV组23例；③HBV组70例；④HCV组35例；⑤非甲-戊型肝炎组60例。用间接免疫荧光、Western blot、酶免疫条带技术等分别检测抗核抗体（ANA）、抗线粒体抗体（AMA）、平滑肌抗体（SMA）、肝肾微粒抗体I型（LKM-1）、肝细胞胞溶质抗原I型（LC-1）、可溶性肝抗原（SLA）/肝胰抗原（LP）和AMA-M2亚型，以及SS-A、SS-B、dsDNA等多种抗体。结果：1412例中诊断AIH、PBC和PSC者分别为送检标本的1.27%，1.49%和0.21%。230例血清中2例LKM-1阳性和2例SLA/LP阳性，分别见于AIH和HCV感染者。PBC患者AMA和M2全部阳性；其ANA以核膜型为主（7/14）；AIH患者ANA抗体未见特定的荧光类型，而抗-Actin仅见于AIH者。非甲-戊组4例AMA和M2阳性，3例SMA高滴度阳性，4例出现SS-A、SS-B或dsDNA等抗体。结论：肝抗原抗体和ANA及AMA分型的检测有助于自身免疫性肝端正和重叠多种免疫性肝病的诊断；非甲-戊型肝炎诊断时应考虑自身免疫性疾病。     

161例自身免疫性肝病患者相关自身抗体检测的临床研究

目的探讨自身抗体检测对自身免疫性肝病(AILD)诊断的临床意义。方法 161例自身免疫性肝病[其中自身免疫性肝炎(AIH)68例、原发性胆汁性肝硬化(PBC)41例和原发性硬化性胆管炎(PSC)52例]、276例病毒性肝炎患者和50例健康体检者采用间接免疫荧光法(IIF)检测抗核抗体(ANA)、抗中性粒细胞胞浆抗体(ANCA)、抗平滑肌抗体(SMA)和抗线粒体抗体(AMA)等自身抗体,采用酶联免疫吸附法(ELISA)检测抗MPO抗体,并对其结果进行回顾性分析。结果 161例AILD检测ANA、ANCA、SMA、抗MPO抗体及AMA结果显示其阳性率分别为42.9%、46.6%、29.2%、30.1%、42.2%,与病毒性肝炎及对照组比较,均P<0.01。各种肝病对自身抗体的检测结果显示AIH较高;AIH中ANCA及p-ANCA检出率与其他肝病组及对照组相比,除PSC外P<0.01,有非常显著意义。结论肝病相关自身抗体的联合检测对自身免疫性肝病的检出、诊断、鉴别诊断、临床分型有重要临床价值,对提高自身免疫性肝病在临床上同病毒性肝炎鉴别诊断和指导治疗有着非常重要的意义。     

自身免疫性肝病患者自身抗体检测及临床意义

目的 探讨自身免疫性肝病患者血清中出现的自身抗体等免疫学指标及临床意义.方法 对3 500例肝功能反复异常的患者采用间接免疫荧光法检测抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA).并对AMAM2型及抗可溶性肝抗原/肝胰抗原(抗SLA/LP)、抗肝肾微粒体抗体Ⅰ型(抗LKM-1)和抗肝特异性胞浆抗原Ⅰ型抗体(抗LC-1)等肝脏疾病相关的自身抗体进行检测.结果 3 500例患者中,自身免疫性肝炎患者29例,检出率为0.83%,其中符合Ⅰ型、Ⅱ型、Ⅲ型自身免疫性肝炎的比例占72.4%、10.3%和17.2%.原发性胆汁性肝硬化(PBC)患者58例,检出率为1.65%,血清中AMAM2型抗体阳性率为93.1%,其中19例AMAM2阳性患者进行肝穿病理检查时12例(63.7%)患者病理提示符合PBC诊断.结论 每种自身免疫性肝病都具有特征性自身抗体谱,注重自身抗体检测对明确诊断及鉴别诊断自身免疫性肝病具有重要的临床意义.     

抗Ro-52抗体在自身免疫性肝病中的检测

目的 探讨抗Ro-52抗体对自身免疫性肝病(autoimmune liver disease,AILD)的临床意义.方法 对采用免疫印迹法检测抗Ro-52抗体的115例AILD患者的临床资料进行回顾性分析,比较抗Ro-52阳性和阴性MLD患者肝功和免疫学指标,对可能有相关性的血清学指标进行诊断试验一致性评价.结果 抗Ro-52抗体在自身免疫性肝炎(autoimmune hepatitis,AIH)(37例)、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)(57例)、MH/PBC重叠综合征组(21例)的阳性率分别为32.43%、24.56%、33.33%,差异无统计学意义(x2=0.949,P>0.05).抗可溶性肝抗原/肝胰抗原抗体(anti-soluble liver antigen/liver-pancreas,anti-SLA/LP)在抗Ro-52阳性AIH组频率(58.33%)高于阴性组(16.00%)(x2=6.955,P<0.05),抗SLA/LP抗体在抗R0-52阳性AIH/PBC重叠综合征组频率(85.71%)高于阴性组(28.57%)(x2=6.109,P<0.05).抗Ro-52抗体和抗SLA/LP抗体结果有一致性(κ=0.466,P<0.05).AIH/PBC重叠综合征组抗Ro-52阳性患者IgG水平高于阴性患者(t=2.508,P<0.05).结论 抗Ro-52抗体在AIH、PBC和MH/PBC重叠综合征中的分布没有差别;抗Ro-52抗体与抗SLA/LP抗体检测结果有一致性;抗Ro-52抗体阳性MH/PBC重叠综合征患者IgG水平高于抗体阴性者.     

多种自身抗体联合检测对自身免疫性肝病的诊断价值

目的：分析各种肝病患者多种自身抗体的检出率,探讨其对自身免疫性肝病（autoimmune liver diseases,ALD）的诊断价值。方法：根据临床诊断将患者分为ALD组（n=96）、病毒性肝炎组（n=135,包括75例乙型肝炎,65例丙型肝炎）,另取62例健康体检者作为健康对照组（n=62）;其中,ALD组又分为自身免疫性肝炎组（AIH组,n=36）、原发性胆汁性肝硬化组（PBC组,n=58）、原发性硬化性胆管炎组（PSC组,n=2）。用间接免疫荧光法检测上述各组的抗核抗体（antinuclear antibodies,ANA）、抗平滑肌抗体（anti-smooth muscle antibodies,ASMA）、抗线粒体抗体（antimitochondrial ant-ibodies,AMA）;用Western印迹法检测抗肝肾微粒体Ⅰ型抗体（anti liver-kidney microsomal antibody Type 1,LKM-1）和抗线粒体Ⅱ型抗体（subtype of AMA,AMA-M2）、抗可溶性肝抗原/胰抗原抗体（soluble liver antigen/liver pancreas,SLA/LP）、抗肝细胞溶质抗原Ⅰ型抗体（antihepatocyte cytosol antigen Type 1,LC-1）。结果：AIH组ANA阳性率（69.4%）和PBC组ANA阳性率（87.9%）显著高于病毒性肝炎组（37.3%）和健康对照组（4.8%）（均P〈0.01）;AIH组ASMA,LKM-1,SLA/LP,LC-1阳性率（44.4%,11.1%,2.8%,8.3%）显著高于病毒性肝炎组（1.3%,1.7%,0,0）和健康对照组（均P〈0.01）;PBC组AMA-M2阳性率（91.3%）显著高于病毒性肝炎组（1.3%）和健康对照组（0）（均P〈0.01）。结论：联合检测ANA,ASMA,LKM-1,SLA/LP,LC-1和AMA-M2等自身抗体可提高ALD诊断的灵敏性和特异性,且对ALD分型、诊疗具有重要意义。     

2148例肝病患者血清抗核抗体谱结果分析

目的 探讨肝病患者血清抗核抗体谱(ANAs)分布情况.方法 回顾性分析2020年8月至2021年4月在首都医科大学附属北京地坛医院就诊的2148例门诊或住院的肝病患者,应用免疫印迹法检测血清ANAs.结果 2148例肝病患者中,ANAs阳性683例,阳性率31.80％,特异性自身抗体阳性率>10％的抗体有抗Ro-52抗体(25％)、抗AMA-M2抗体(14％)、抗SSA抗体(11％).不同病因所致肝脏疾病均可出现ANAs阳性,免疫性、药物性、混杂因素、其他、病毒性、酒精性、脂肪性肝病和不明原因肝功能异常组ANAs阳性率依次为74.87％、36.37％、36.02％、30.36％、27.63％、27.21％、25.56％和20.67％.自身免疫性肝病组ANAs阳性率(74.87％)高于其余病因组,不明原因肝功能异常组ANAs阳性率(20.67％)低于免疫性、药物性、混杂因素、其他、病毒性肝病组,差异均具有统计学意义(P<0.05).药物性、混杂因素、其他肝病与病毒性肝病组阳性率差异无统计学意义(P>0.05).酒精性肝病、脂肪肝与不明原因肝功能异常阳性率差异无统计学意义(P>0.05).自身免疫性肝病抗SSA抗体(16.23％)、抗SSB抗体(8.90％)、抗CENP-B抗体(20.94％)、抗Ro-52抗体(37.70％)、抗AMA-M2抗体(47.12％)阳性率高于其余病因组,差异具有统计学意义(P<0.01).结论 抗核抗体谱检测对不同病因肝病患者的诊断和鉴别诊断具有一定价值.     

自身免疫性肝炎和乙型肝炎患者自身抗体检测及对比分析

目的:检测分析自身免疫性肝炎(AIH)与乙型肝炎(HB)患者血清自身抗体特点及诊断应用价值。方法:采用间接免疫荧光法检测AIH组(n=43)和HB组(n=100)血清抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体(AMA)及抗中性粒细胞胞浆抗体(pANCA、cANCA),比较两组自身抗体检出率、ANA滴度、荧光模型及肝功能和免疫球蛋白。结果:AIH组自身抗体以ANA、SMA为主,阳性率分别为93.02和67.44%,两种抗体同时阳性的检出率为55.80%,AMA及pANCA、cANCA的检出率分别为13.95%和6.97%、2.32%;而HB组只检测出16例(16.0%)ANA,无一例SMA阳性。AIH组ANA以高滴度(≥1:320)抗体为主,荧光核型主要以核仁、核膜型为主,丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)及IgG含量明显高于HB组。HB组ANA以低滴度(≤1:100)抗体为主,荧光核型以颗粒型所占比例较高。结论:检测AIH和HB患者自身抗体相关指征对提高诊断准确性,制定治疗方案有重要作用。     

The hepatitic/cholestatic "overlap" syndrome: an Italian experience

BACKGROUND: Patients with hepatitic and cholestatic autoimmune liver disease ("overlap syndrome") represent a diagnostic and therapeutic challenge. AIM: To evaluate the prevalence of the "hepatitic/cholestatic overlap" in a large series of consecutive patients with cholestatic autoimmune liver disease. METHODS: We re-evaluated the diagnosis of 235 patients with autoimmune liver disease, including 70 with type 1 autoimmune hepatitis (AIH), 142 with primary biliary cirrhosis (PBC), and 23 with primary sclerosing cholangitis (PSC), using the revised International Autoimmune Hepatitis Group (IAIHG) scoring system. Anti-mitochondrial, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, perinuclear anti-neutrophil nuclear and anti-soluble liver antigen antibodies were evaluated in each patient. RESULTS: Ten patients (3 with a previous diagnosis of PBC and 7 of PSC) scored as "probable" or "definite" AIH. These patients did not have a specific autoantibody profile. CONCLUSIONS: Among patients with PBC, the occurrence of a PBC/AIH overlapping syndrome is rare (2.1%), whereas among patients with PSC an overlap between PSC and AIH is frequent (30.4%). Whether patients with the hepatitic/cholestatic overlap syndrome would benefit from a combination therapy with immunosuppression and ursodeoxycholic acid remains to be established.     

The Hepatitic/Cholestatic "Overlap" Syndrome: An Italian Experience

Background: Patients with hepatitic and cholestatic autoimmune liver disease ("overlap syndrome") represent a diagnostic and therapeutic challenge. Aim: To evaluate the prevalence of the "hepatitic/cholestatic overlap" in a large series of consecutive patients with cholestatic autoimmune liver disease. Methods: We re-evaluated the diagnosis of 235 patients with autoimmune liver disease, including 70 with type 1 autoimmune hepatitis (AIH), 142 with primary biliary cirrhosis (PBC), and 23 with primary sclerosing cholangitis (PSC), using the revised International Autoimmune Hepatitis Group (IAIHG) scoring system. Anti-mitochondrial, anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, perinuclear anti-neutrophil nuclear and anti-soluble liver antigen antibodies were evaluated in each patient. Results: Ten patients (3 with a previous diagnosis of PBC and 7 of PSC) scored as "probable" or "definite" AIH. These patients did not have a specific autoantibody profile. Conclusions: Among patients with PBC, the occurrence of a PBC/AIH overlapping syndrome is rare (2.1%), whereas among patients with PSC an overlap between PSC and AIH is frequent (30.4%). Whether patients with the hepatitic/cholestatic overlap syndrome would benefit from a combination therapy with immunosuppression and ursodeoxycholic acid remains to be established.     

Role of liver biopsy in autoimmune liver disease

This article will review histological aspects of three chronic liver diseases – autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) – in which autoimmune mechanisms are thought to be involved. The changing role of liver biopsy in the diagnosis and management of patients with autoimmune liver disease will also be discussed. In the case of autoimmune hepatitis, histological assessments remain important in establishing a diagnosis, identifying prognostic features and monitoring therapeutic responses. By contrast, for many patients with PBC and PSC a diagnosis can now be made on the basis of biochemical, serological and/or radiological findings alone and histological confirmation may not be required. Liver biopsy can still be used to assess disease severity in such cases and remains important in establishing a diagnosis in patients with atypical features (e.g. AMA-negative PBC or the small-duct variant of PSC). Liver biopsy is also increasingly used in the assessment of patients suspected to have “overlap syndromes” involving AIH and PBC or PSC.     

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。     

IgA Anti-b2GPI Antibodies in Patients with Autoimmune Liver Diseases

INTRODUCTION: Recently, we reported a high prevalence of immunoglobulin G and/or immunoglobulin M anticardiolipin antibodies (aCL) in patients with autoimmune liver diseases, namely, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), which were independent of the respective isotypes of antibodies against beta2-glycoprotein I (anti-b2GPI). Immunoglobulin A (IgA) aCL and IgA anti-b2GPI are the least studied of the three specific isotypes either in antiphospholipid syndrome (APS) or in other conditions. METHODS: Therefore, we investigated the prevalence and clinical significance of IgA anti-b2GPI and IgA aCL by enzyme-linked immunosorbent assays in another set of Caucasian patients with autoimmune liver diseases (59 AIH, 96 PBC, and 37 PSC). The disease controls group consisted of 50 hepatitis C virus (HCV) patients, 50 hepatitis B virus (HBV), 30 alcoholic liver disease (ALD), 30 non-alcoholic steatohepatitis (NASH), and 110 healthy controls. RESULTS AND DISCUSSION: IgA anti-b2GPI prevalence was higher in AIH (50.8%) compared to PBC (p = 0.005), PSC (p = 0.008), NASH (p = 0.004), ALD (p = 0.01), and HCV (p = 0.002). The titers were also significantly higher in AIH compared to any other group of the study. IgA aCL prevalence was higher in AIH (33.9%) compared to PBC (p = 0.005), PSC (p = 0.014), NASH (p = 0.001), ALD (p = 0.004), and HCV (p < 0.001). IgA anti-b2GPI or IgA aCL were not associated with APS features in patients with liver autoimmunity. Of note, IgA anti-b2GPI and IgA aCL were associated with clinical and biochemical markers of disease severity in AIH and PBC. We demonstrated a high prevalence and high titers of IgA anti-b2GPI in patients with AIH compared to any other liver disease of the study. CONCLUSION: IgA anti-b2GPI and IgA aCL were associated with the severity and biochemical activity of AIH and PBC, but long-term prospective studies are needed to address whether this new finding is of clinical importance in AIH and PBC patients.     

Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases

Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0.05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease.     

Autoimmune hepatitis in primary Sjogren's syndrome: pathological study of the livers and labial salivary glands in 17 patients with primary Sjogren's syndrome

Although primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy, the involvement of liver has been reported. Because no study focusing on autoimmune hepatitis (AIH) in pSS has been published, the purpose of the present study was to perform a clinical and histological examination of the liver, focusing on AIH, in 17 pSS patients. The patients had liver enzyme abnormalities without hepatitis virus infection. In all cases, biopsied livers were examined, and in 10 cases biopsied labial salivary glands were also examined histologically. Based on the authors' diagnostic criteria for AIH in pSS, the liver diseases consisted of AIH (eight cases, 47%), primary biliary cirrhosis (PBC; six cases, 35%), non-specified chronic hepatitis (two cases, 12%) and acute hepatitis (one case, 6%). Lymphoplasmacytic infiltrate, with predominancy of CD3(+) T cells, was noted in both the liver and salivary glands in the patients with AIH. The patients with AIH with severe interface hepatitis had a good response to immunosuppressive therapy. The comparison of liver histology between the PBC with pSS group and the PBC without pSS group showed that the incidence of lymphoid non-suppurative cholangitis was higher in PBC with pSS. In conclusion, the present study offers new information on the relatively common occurrence, diagnostic criteria and treatment effects of AIH in pSS.     

Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes

Knowledge of concomitant autoimmune liver diseases (AILD) is more detailed in primary Sjögren’s syndrome (pSS) compared to systemic lupus erythematosus (SLE). Herein, the prevalence of autoantibodies associated with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) was investigated in stored sera from patients with SLE (n = 280) and pSS (n = 114). Antibodies against mitochondria (AMA), liver–kidney microsomal (LKM) antigen, smooth muscle (SMA) and anti‐nuclear antibodies (ANA) were analysed with immunofluorescence microscopy. In addition, AILD‐associated autoantibodies were tested with immunoblot. Prior to sampling, eight SLE (2·9%) and three pSS (2·6%) cases were diagnosed with AILD. Among SLE‐cases without known AILD (n = 272), 26 (9·6%) had PBC‐associated autoantibodies, 15 (5·5%) AIH‐associated autoantibodies (excluding ANA) and one serological overlap. Most subjects with PBC‐associated autoantibodies had liver enzymes within reference limits (22 of 27, 81%) or mild laboratory cholestasis (two of 27, 7·4%), while one fulfilled the diagnostic PBC‐criteria. AMA‐M2 detected by immunoblot was the most common PBC‐associated autoantibody in SLE (20 of 272, 7·4%). The prevalence of SMA (4·4%) was comparable with a healthy reference population, but associated with elevated liver enzymes in four of 12 (25%), none meeting AIH‐criteria. The patient with combined AIH/PBC‐serology had liver enzymes within reference limits. Among pSS cases without known AILD (n = 111), nine (8·1%) had PBC‐associated, 12 (10·8%) AIH‐associated autoantibodies and two overlapped. PBC‐associated autoantibodies were found as frequently in SLE as in pSS but were, with few exceptions, not associated with laboratory signs of liver disease. Overall, AILD‐associated autoantibodies were predominantly detected by immunoblot and no significant difference in liver enzymes was found between AILD autoantibody‐negative and ‐positive patients.