自身免疫性肝病临床病理特征分析28例

目的:探讨并比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(AIH-PBC CS)的临床、生化、影象学以及组织学特征.方法:收集在我院自身免疫性肝病住院患者28例,其中v型AIH 13例、PBC 6例和AIH-PBCOS9例,回顾性分析患者临床资料.结果:AIH-PBC OS患者血清谷草转氨酶(AST)和γ-球蛋白(GLO)水平(分别为和)均明显高于AIH和PBC患者(132.67±35.05 vs 81.15±39.26,55.17±24.38;44.33±8.92 vs 34.23±9.89,33.17±6.79,均P＜0.05),而碱性磷酸酶(ALP)和γ-谷氨酰转肽酶(GGT)水平明显高于AIH患者(218.11±107.79 vs 106.85±91.57;280.33±133.51 vs 82.07±36.67,均P＜0.05),低于PBC患者(245.83±88.60,315.67±160.01,均P＜0.05).AIH-PBC OS和PBC患者的IgM水平均明显高于AIH患者(793.00±528.57 vs127.33±30.14;538.50±349.43 vs 127.33±30.14,均P＜0.05),而AIH-PBC OS患者的IgG水平明显高于PBC患者(2036.00±457.03 vs1121.25±313.8,P＜0.05).AIH-PBC OS患者界面性肝炎和破坏性胆管炎的发生率分别为88.9%和66.7%.腹部BUS提示三者常伴有脾大和腹腔淋巴结肿大.结论:AIH和PBC是典型的分别选择性损伤肝细胞及肝内小胆管的自身免疫性肝病,AIH-PBC OS同时具有AIH和PBC的临床病理学特征,与PBC相比,AIH-PBC OS更倾向于AIH.     

自身免疫性肝病相关自身抗体谱的检测和临床意义

自身免疫性肝病(autoimmune liver disease,A I L D)是一组因为肝脏免疫耐受机制失衡引起的肝细胞或胆管上皮细胞的慢性损伤性炎症,是肝硬化和肝功能障碍的常见原因之一.利用间接免疫荧光法(indirect immunofluorescence,IIF)和抗原特异性检测方法,进行自身抗体的筛查和确认,是AILD病因学诊断的重要方法.新的靶抗原的发现和鉴定丰富了AILD自身抗体谱的组成,也拓展了自身抗体检测的临床应用范围.作为生物标记物,自身抗体的临床意义不仅体现在自身免疫性疾病的诊断上,在反映疾病活动性和严重程度、评价病情演进过程、疗效监测和预后判断等方面也发挥着越来越重要的作用.     

自身免疫性肝病研究进展

在影响肝脏的三种自身免疫性疾病中，肝细胞是自身免疫性肝炎（AIH）中自身抗体的攻击靶（即肝细胞受损），原发性胆汁性肝硬化（PBC）是小胆管受损，原发性硬化性胆管炎（PSC）主要是大胆管破坏，它们被看作是复杂性疾病，发病机理包括遗传因素和环境因素。[第一段]     

自身免疫性肝病的回顾性研究

目的 提高对自身免疫性肝病的认识,以利于早期诊断、早期治疗.方法 回顾性对81例自身免疫性肝病患者进行诊断,比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及其重叠综合征(OS)的临床、血液化学及病理特点.结果 81例患者中,女性占91.4%;总体误诊率为45.7%,OS漏诊率为96.7%,初始诊断为肝硬化者60.5%(49/81),其中37%(30/81)为失代偿期肝硬化.AIH组18.2%(6/33)以急性肝功能衰竭发病,明显高于PBC、OS组,3组患者症状、体征基本一致,AIH、OS组患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及抗核抗体(ANA)阳性率明显高于PBC组(Z=6.411,P=0.041;Z=7.980,P=0.019;X2=11.951,P=0.003),PBC、OS组患者血清门冬氨酸氨基转移酶(GGT)、碱性磷酸酶(ALP)、总胆固醇、载脂蛋白B水平及抗线粒体抗体(AMA)阳性率明显高于AIH组(Z=37.327,P=0.000;Z=12.929,P=0.002;Z=16.722,P=0.000;Z=6.695,P=0.035;X2=31.219,P=0.000).结论 自身免疫性肝病误诊率高.AIH、OS患者氨基转移酶升高明显,ANA阳性率高,PBC、OS患者GGT、ALP升高明显,血脂代谢障碍,AMA阳性率高.     

190例自身免疫性肝病临床特征分析

目的 比较分析自身免疫性肝炎、原发性胆汁性肝硬化和重叠综合征的临床特征.方法 回顾性分析自身免疫性肝炎、原发性胆汁性肝硬化和重叠综合征患者的临床症状、体征、生化检查、免疫球蛋白、自身抗体、肝脏组织学等检查.结果 3组均以女性患者多见,以乏力、黄疸、瘙痒、脾大等为主要临床表现;3组患者白蛋白水平均下降,以原发性胆汁性肝硬化组下降最明显(P＜0.05);3组患者总胆红素、直接胆红素、丙氨酸氨基转移酶、天门冬氨酸氨基转氨酶、碱性磷酸酶和γ-谷酰转移酶均有升高,以重叠综合征升高最明显(P＜0.05).结论 自身免疫性肝病患者的临床特征可能对早期诊断有重要意义;肝功能总胆红素、直接胆红素、丙氨酸氨基转移酶、天门冬氨酸氨基转氨酶、碱性磷酸酶和T-谷酰转移酶等指标升高明显者需警惕重叠综合征的存在.     

自身免疫性肝病自身抗体研究进展

自身免疫性肝病（ALD）是一组免疫介导的肝脏损伤,根据其临床表现、生化、免疫学、影像学和组织病理学特点,可简单分为以肝炎为主型,即自身免疫性肝炎（AIH）和以胆系损害及胆汁淤积为主型,即原发性胆汁性肝硬化（PBC）、原发性硬化性胆管炎（PSC）。此外,还有这三种疾病中任意两者之间的重叠综合征（overlap syndromes）,主要以AIH—PBC重叠综合征多见。由于我国肝炎和肝硬化多因肝炎病毒,尤其是乙型肝炎病毒引起,故过去认为ALD较少见。     

自身免疫性肝病重叠综合征的现状

自身免疫性肝病(autoimmune liver disease,A I L D)包括自身免疫性肝炎(a u t o i m m u n e hepatitis,AIH)、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC).AILD重叠综合征(overlap syndrome,OS)是指患者同时兼具AIH和PBC或PSC两种疾病的临床表现、生物化学、血清学、组织学以及影像学特征的一种罕见疾病状态.AILD OS主要分为AIH-PBC OS和AIH-PSC OS.前者多见于成人,后者多见于儿童.OS若无治疗,最终可致肝硬化或肝衰竭.高剂量熊去氧胆酸(ursodeoxycholic acid)与免疫抑制剂类固醇和/或硫唑嘌呤(azathioprine)联合使用通常被用于治疗AIH-PBC OS和AIH-PSC OS.目前,肝移植仍是治疗终末期OS患者的唯一有效方法.     

加强对自身免疫性肝病重叠综合征的认识

随着自身免疫性肝病研究的不断深入,发现许多自身免疫性肝病同时具有或随后表现出其他自身免疫性肝病的特征,临床上称为自身免疫性肝病重叠综合征.由于发病率越来越高以及本组疾病的病因不明、临床表现多样、诊断标准及治疗终点等诸多方面均有待于进一步探讨,因而加强对本组疾病的探索具有重要的意义.     

自身免疫性肝病临床与病理研究

目的分析自身免疫性肝病临床、病理特点,探讨早期诊断、治疗方法。方法１９９６—１９９８年收治６２例自身免疫性肝病,比较原发性胆汁性肝硬化（ＰＢＣ）、自身免疫性肝炎（ＡＩＨ）的临床症状、体征、生物化学指标及病理特征。结果自身免疫性肝病中ＰＢＣ占５９．６８％, ＡＩＨ ４０．３２％。自身免疫性肝病中８３．８％是中老年女性,男女之比１∶１０,而ＡＩＨ　１∶５,发病年龄平均３５岁。ＰＢＣ中血循环自身免疫抗体阳性率８５．２９％,ＡＩＨ　７８．９５％。在阳性病例中 ＡＭＡ, ＡＭＡ－Ｍ２阳性率 １００％, ＡＮＡ阳性率 ８０％,血清免疫球蛋白异常, ＰＢＣ　ＩｇＭ增高占８０％, ＡＩＨＩｇＧ增高占８２．２５％, Ｐ值＜０．０５和Ｐ值＜ ０．０２５。 ＰＢＣ肝脏活组织病理显示,胆管炎和胆管增生、炎症、损伤或三者共存的特征。ＡＩＨ显示门静脉区炎症、淋巴细胞、单核细胞、浆细胞浸润、坏死、纤维化。结论ＰＢＣ和ＡＩＨ是自身免疫性肝病临床上两个常见类型,其中ＡＩＨ以Ⅰ型为主;而血中ＡＭＡ－Ｍ２是ＰＢＣ特征抗体,强的松龙治疗效果ＡＩＨ优于ＰＢＣ。     

自身免疫性肝病的诊断和治疗现状

自身免疫性肝病(autoimmune liver diseases,AILD)是一组由异常自身免疫介导的肝、胆损伤,根据其临床表现、生化、免疫学、影像学和组织病理学特点,可简单分为以肝炎为主型,即自身免疫性肝     

Spectrum of autoimmune liver diseases in western India

BACKGROUND AND AIM: The prevalence and spectrum of autoimmune liver diseases (AILDs) in India are rarely reported in comparison to the West. METHOD: During a study period of 7 years, all patients with chronic liver diseases (CLDs) were evaluated for the presence of AILDs on the basis of clinical, biochemical, imaging, serological, and histological characteristics. RESULTS: Of a total of 1760 CLD patients (38.1% females), 102 patients (5.7%) had an AILD. A total of 75 (11.2%) female patients had an AILD. Among males, 27 (2.4%) had an AILD. The prevalence of AILDs in women increased from 11.2% to 45.7% and in men from 2.4% to 10.3%, after excluding alcohol, hepatitis B virus, and hepatitis C virus as a cause of CLD. Of the AILDs, autoimmune hepatitis (AIH) was present in 79 patients (77.4%), followed in descending order by primary biliary cirrhosis (PBC) in 10 patients (9.8%), PBC/AIH true overlap syndrome in six patients (5.8%), primary sclerosing cholangitis (PSC) in five patients (4.9%), and PBC/AIH switchover syndrome in two patients (1.9%). None had PSC/AIH or PBC/PSC overlap syndrome. Associated known autoimmune diseases were found in 40 (39.2%) patients. CONCLUSIONS: AILDs are not uncommon in India. They should be suspected in all cases of CLDs, especially in middle-aged women who do not have problems with alcoholism and who are without viral etiology, as well as in all patients with known autoimmune diseases.     

自身免疫性肝病在住院患者中的分布特征

目的研究自身免疫性肝病住院疾病谱的分布特征及变化趋势。方法回顾性分析2002年1月至2011年12月住院的4 014例自身免疫性肝病患者的疾病构成情况。结果自身免疫性肝病在住院肝病患者中的构成总体呈上升趋势,其构成比由2002年的1.76%升至2011年的3.66%;原发性胆汁性肝硬化和自身免疫性肝炎是自身免疫性肝病疾病谱中的重要组成部分,其构成比分别为51.82%和38.39%;自身免疫性肝病疾病谱中,各组患者年龄及女性构成比均差异有统计学意义（χ^2=332.51、57.36,均P〈0.01）。各组患者的治愈好转率及肝功能衰竭的发生率均差异有统计学意义（χ^2=31.52、31.63,均P〈0.01）。但各组患者出现肝功能衰竭的性别构成比之间差异无统计学意义（χ^2=5.72,P=0.126）。结论目前自身免疫性肝病已成为肝病的重要组成部分,应引起临床医师的高度重视。     

2014年自身免疫性肝病诊疗进展

<正>自身免疫性肝病(Autoimmune liver diseases,AILD)是因免疫系统过度激活从而出现肝功能异常及相应临床综合征的一组疾病,可简单分为以肝炎为主型,即自身免疫性肝炎(Autoimmune hepatitis,AIH)及以胆管损害和胆汁淤积为主型,即原发性胆汁性肝硬化(Primary biliary cirrhosis,PBC)和原发性硬化性胆管炎(Primary sclerosing cholangitis,PSC)。此外,部分     

自身免疫性肝炎和原发性胆汁性肝硬化患者自身免疫性甲状腺疾病流行率调查*

目的 调查自身免疫性肝病(AILD)患者自身免疫性甲状腺疾病(AITD)发病率情况。 方法 2018年6月～2020年12月我院诊治的自身免疫性肝炎(AIH)41例和原发性胆汁性肝硬化(PBC)患者45例,采用间接免疫荧光法或免疫印迹法检测血清抗核抗体(ANA)、抗线粒体抗体(AMA)或AMA-M2)、抗平滑肌抗体(ASMA)、抗双链DNA抗体(抗dsDNA)和抗着丝点抗体(ACA);采用ELISA法检测血清免疫球蛋白,包括IgG、IgM和γ-球蛋白。结果 在本组41例AIH患者中,合并HT患者12例,合并GD患者6例,在45例PBC患者中,合并HT患者8例,合并GD患者7例;AIH患者血清IgG水平为17.5(14.8,19.8)g/L,显著低于AIH合并HT组【21.6(17.5,29.0)g/L,P<0.05】或AIH合并GD组【22.4(20.2,26.4)g/L,P<0.05】,血清γ-球蛋白为22.2(19.3,25.6)%,显著低于合并HT组【26.5(22.2,32.2)%,P<0.05】或合并GD组【27.1(24.3,32.0)%,P<0.05】;PBC患者年龄为(55.2±1.1)岁,显著小于合并HT组【(62.4±1.6)岁,P<0.05】或合并GD组【(62.2±1.5)岁,P<0.05】,血清IgG水平为15.4(12.2,18.0)g/L,显著低于合并HT组【20.3(16.8,24.7)g/L,P<0.05】或合并GD组【21.3(16.8,25.6)g/L,P<0.05】,血清γ-球蛋白水平为21.2(17.8,25.6)%,显著低于合并HT组【26.7(21.7,30.4)%,P<0.05】或合并GD组【25.4(22.2,29.4)%,P<0.05】。结论 AILD合并AITD的发病率较高,合并AITD患者血清IgG和γ-球蛋白水平较高,其原因还有待于进一步研究。     

Clinical analysis of liver transplantation in autoimmune liver diseases

Background: Autoimmune liver diseases(ALDs) consist of autoimmune hepatitis(AIH), primary biliary cirrhosis(PBC), primary sclerosing cholangitis(PSC), Ig G4-associated cholangitis and overlap syndromes.Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation.Methods: The clinical data of 80 patients with ALD(24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIHPBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan–Meier method. Recurrence and other complications were also analyzed.Results: Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease(MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3-and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed(3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients(12.5%). The new onset of tumor was observed in 1 patient(1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively.Conclusion: Liver transplantation is an effective and safe treatment for end-stage ALD.     

Overlap syndromes among autoimmune liver diseases

The three major immune disorders of the liver are autoimmune hepatitis（AIH）,primary biliary cirrhosis（PBC） and primary sclerosing cholangitis（PSC）.Variant forms of these diseases are generally called overlap syndromes,although there has been no standardised definition.Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC.The AIH-PBC overlap syndrome is the most common form,affecting almost 10% of adults with AIH or PBC.Single cases of AIH and autoimmune cholangitis（AMA-negative PBC） overlap syndrome have also been reported.The AIH-PSC overlap syndrome is predominantly found in children,adolescents and young adults with AIH or PSC.Interestingly,transitions from one autoimmune to another have also been reported in a minority of patients,especially transitions from PBC to AIH-PBC overlap syndrome.Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment.Therapy for overlap syndromes is empiric,since controlled trials are not available in these rare disorders.Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes.In end-stage disease,liver transplantation is the treatment of choice.     

Clinical significance of autoantibodies to p53 protein in patients with autoimmune liver diseases

BACKGROUND:Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies.OBJECTIVE:To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH/PBC overlap syndrome (AIH/PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases.METHODS:Forty patients with AIH, 41 patients with PBC, eight patients with AIH/PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53.RESULTS:Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH/PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH/PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH/PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213).CONCLUSION:The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH/PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH/PBC OS.