自身免疫性肝病临床及免疫学特征

目的 分析自身免疫性肝病的临床特征和免疫学特点,以提高对该类疾病的认识和诊断水平.方法 对164例自身免疫性肝病患者的临床症状、体征及免疫学检查资料进行回顾性分析.结果 原发性硬化性胆管炎(PSC)多发于青年男性,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)多发于中年女性;临床表现上AIH、PBC、PSC、AIH-PBC黄疸发生率分别为84%、78%、90%和67%,皮肤瘙痒的发生率分别为43%、56%、81%和60%.但AIH、PBC和PBC-AIH患者之间的年龄、性别、黄疸、皮肤瘙痒等症状无显著性差异(P均＞0.05).AIH首诊正确诊断率为8%(6/77),PSC为9%(1/11),PBC为13%(6/46).从发病到确诊PBC平均为38月,AIH为46月,PSC为31月,PBC-AIH重叠综合征确诊最难,平均需51月,常误诊为可能的AIH或单纯PBC.AIH、PBC、PSC和PBC-AIH肝外自身免疫性疾病的发生率分别为47%、11%、27%和24%,各自身免疫性肝病患者均有较高的自身抗体发生率.结论 自身免疫性肝病在临床上并不少见,患者常伴发肝外自身免疫性疾病及较高的自身抗体发生率;诊断需综合临床、生化、自身抗体和病理组织学等指标.     

自身免疫性肝病的临床及影像学分析43例

目的: 分析自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)及原发性硬化性胆管炎(PSC)患者的临床特点及影像学特征.方法: 2003-10/2008-02在烟台毓璜顶医院消化内科住院的自身免疫性肝病患者43例, 排除其他原因引起肝脏损害. 其中AIH 12例, PBC 19例, PSC 12例. 对患者的临床及影像学资料进行回顾性分析, 观察药物治疗的效果.结果: 除PSC外, AIH多发于中年女性, 患者具有较高的转氨酶, PBC、PSC患者具有较明显的GGT、ALP升高. 临床表现上AIH、PBC、PSC黄疸的发生率分别为42%、80%、91%,皮肤瘙痒的发生率分别为38%、68%、79%.合理应用熊去氧胆酸和免疫抑制剂可使68%的PBC和AIH患者症状在6 mo内得到缓解、肝功能明显改善.结论: AIH的肝功能异常以转氨酶升高为主,PBC、PSC以胆汁淤积为主. 熊去氧胆酸和免疫抑制剂可改善绝大多数患者的症状和肝功能.     

自身免疫性肝病重叠综合征的研究现状

自身免疫性肝病主要包括原发性胆汁性胆管炎(PBC)、自身免疫性肝炎(AIH)和原发性硬化性胆管炎(PSC)。同时或相继出现以上任意两种单独自身免疫性肝病特征者称为重叠综合征。其中,以PBC重叠AIH(PBC-AIH)相对最为常见。若不及时接受治疗可迅速进展至肝硬化和肝衰竭。就近年自身免疫性肝病重叠综合征的研究进展进行了总结。     

自身免疫性肝病及其重叠综合征的诊断及治疗

自身免疫性肝病主要包括自身免疫性肝炎( autoimmune hepatitis,AIH)、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)、原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)及其相互重叠的综合征,但就相互重叠关联而言尚没有明确的定义.在重叠综合征中,以AIH - PBC最为多见,在AIH或PBC患者中占10％[1].近年来由于相关临床经验的累积、实验室诊断技术的发展以及肝活检的普及,使得我国自身免疫性肝病检出率明显增高.     

原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征的诊治

自身免疫性肝病(AILD)包括原发性胆汁性胆管炎(PBC)、自身免疫性肝炎(AIH)、原发性硬化性胆管炎(PSC)。患者可在初诊时或随访的过程中出现2种AILD的特征,通常将这种情况称为“重叠综合征”,其中以PBC重叠AIH最为常见。与单纯PBC或AIH相比,PBC-AIH重叠综合征门静脉高压、消化道出血、腹水、死亡及肝移植发生率明显升高,病情进展也更迅速,因此,其早诊早治显得尤为重要。对近年PBC-AIH重叠综合征的诊治进展进行综述。     

AIH-PBC重叠综合征的诊断及治疗

自身免疫性肝病是一组与自身免疫异常有关的肝胆疾病,其包括自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）以及这三种疾病中任两者之间的综合征。AIH-PBC重叠综合征（AIHPBCOS）在PBC患者中的发生率为2％～20％．其定义为一个患者同时具有这二种疾病的主要特征。     

自身免疫性肝病活检组织病理学特征分析109例

目的:分析比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)及其重叠综合征的组织病理学变化,提高对自身免疫性肝病(AILD)的认识.方法:对27例AIH、67例PBC、4例PSC、1例AIH-PSC重叠综合征和10例AIH-PBC重叠综合征患者的肝穿组织病理资料进行回顾性分析.结果:AILD患者多发于中年女性(73.3%),肝组织病理变化以界面性肝炎为主(77.7%),在重度患者则出现重度界面性肝炎、桥样坏死等.PBC患者早期(Ⅰ、Ⅱ)占28.3%,而晚期(Ⅲ、Ⅳ)占71.7%,肝组织病理变化以小胆管减少甚至消失为主(62.6%).AIH-PBC重叠综合征患者并非罕见,他的肝组织病理学具有AIH和PBC的双重特征.结论:AILD是非病毒性肝病的重要组成部分,其诊断需综合临床表现、生化、免疫指标和组织学变化.     

自身免疫性肝病动物模型

自身免疫性肝病主要包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)、原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)及重叠综合征.     

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.     

自身免疫性肝病重叠综合征诊治进展

自身免疫性肝病包括自身免疫性肝炎(AIH)、原发性胆汁性胆管炎(PBC)、原发性硬化性胆管炎(PSC)等。同时存在AIH、PBC或PSC特征者称为重叠综合征,若不及时接受治疗常可迅速进展至肝硬化和肝功能衰竭。早期诊断和治疗可显著改善预后。本文就近年自身免疫性肝病重叠综合征的诊治进展作一阐述。     

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.     

Overlap syndromes

In hepatology, the term overlap syndrome describes variant forms of the major hepatobiliary autoimmune diseases, autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). Patients with overlap syndromes present with both hepatitic and cholestatic biochemical and histological features of AIH, PBC, and/or PSC, and usually show a progressive course toward liver cirrhosis and liver failure without adequate treatment. AIH-PBC overlap syndromes have been reported in almost 10% of adults with AIH or PBC, whereas AIH-PSC overlap syndromes were found in 6 to 8% of children, adolescents, and young adults with AIH or PSC. A minority of patients may also show transition from stable PBC to AIH, AIH to PBC, or AIH to PSC, as documented by single case reports and small case series. Single cases of AIH and autoimmune cholangitis (antimitochondrial antibody-negative PBC) overlap have also been reported. Empiric medical treatment of AIH-PBC and AIH-PSC overlap syndromes includes anticholestatic therapy with ursodeoxycholic acid and immunosuppressive therapy with corticosteroids and azathioprine. In end-stage disease, liver transplantation is the treatment of choice.     

自身免疫性肝病109例的临床与病理特征分析

目的 分析比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)及AIH重叠综合征的临床特点、生化特征和组织学变化,以提高对自身免疫性肝病(AILD)的认识.方法 收集2004年1月-2008年6月肝穿刺病理学检查确诊的AILD患者共109例,其中AIH 27例、PBC 67例、PSC 4例、AIH-PSC重叠综合征1例和AIH-PBC重叠综合征10例,对患者的临床及实验室检查资料进行回顾性分析.结果 AILD患者多发于中年女性(73.3%,80/109),常见症状为黄疸、乏力、纳差和皮肤瘙痒.AIH患者的发病年龄高峰在50岁左右,肝功能检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常值,62.9%的患者(17/27)抗核抗体(ANA)阳性.肝组织病理变化以界面性肝炎为主(77.7%),在重度患者则出现重度界面件肝炎、桥样坏死等.PBC患者主要表现为碱性磷酸酶、γ-谷氨酰转肽酶和胆红素明显升高,伴免疫球蛋白M升高,74.6%的患者(50/67)线粒体抗体(AMA)和(或)AMA-M2亚型阳性.所有PBC患者行肝脏病理学检查,早期(Ⅰ、Ⅱ)占28.3%,晚期(Ⅲ、Ⅳ)占71.7%,肝组织病理变化以小胆管减少甚至消失为主(62.6 0A).AIH-PBC重叠综合征患者的临床表现和肝组织病理学具有AlH和PBC的双重特征,其中有3例患者同时检测到ANA和AMA/AMA-M2阳性.结论 AILD在中国人中并非少见,其诊断需综合临床表现、生化、免疫指标和组织学变化.     

Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes

BACKGROUND: The coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) has been called "overlap syndrome," but diagnosis is challenging and the natural history of this syndrome has not been demonstrated. The importance of the diagnosis of PBC-AIH overlap is due to potential therapeutic options. Patients with PBC should receive ursodeoxycholic acid (UDCA); the role of and response to additional immunosuppressive therapy are unknown when AIH overlaps PBC. METHODS AND RESULTS: We reviewed 135 patients with PBC according to a revised scoring system proposed by the International Autoimmune Hepatitis Group (IAHG). Twenty-six patients had features of PBC-AIH overlap and 109 did not. Mean follow-up was 6.1 yr for overlap syndrome patients and 5.4 yr in PBC patients. There was a higher rate of portal hypertension (P=0.01), esophageal varices (P<0.01), gastrointestinal (GI) bleeding (P=0.02), ascites (P<0.01), and death and/or orthotopic liver transplantation (OLT) (P<0.05) in the overlap group. CONCLUSION: In conclusion, esophageal varices, GI bleeding, ascites, and death and/or OLT were more common in the overlap group. The higher risk of symptomatic portal hypertension and worse outcomes in patients with PBC overlap syndrome may justify the risks of immunosuppressive therapy. Large randomized studies are necessary to establish optimal therapeutic strategies.     

自身免疫性肝炎和原发性胆汁性肝硬化重叠综合征的临床特征及疗效观察

目的观察自身免疫性肝炎和原发性胆汁性肝硬化(AIH-PBC)重叠综合征的临床特征及治疗效果。方法研究1:回顾分析124例PBC、57例AIH、39例AIH-PBC重叠综合征患者的临床特征;研究2:根据不同治疗方案对39例AIH-PBC重叠综合征患者进行分组疗效分析。结果在220例自身免疫性肝病患者中,AIH-PBC重叠综合征占17.73%。3组患者的性别组成差异无统计学意义,但发病年龄AIH组相似文献   

中晚期自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征的临床病理研究

目的探讨中晚期自身免疫性肝炎-原发性胆汁性肝硬化（AIH-PBC）重叠综合征的临床病理特征及治疗直答。方法对具有肝穿刺标本的11例PBC-AIH重叠综合征和13例PBC（Seheuer分期3、4期）患者进行比较，重点分析AIH-PBC重叠综合征的临床、病理特点及治疗应答。结果两组患者的性别、年龄、病程、症状无显著差异；AIH-PBC重叠综合征患者的丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-球蛋白、免疫球蛋白IgG以及抗核抗体或抗平滑肌抗体阳性率明显高于PBC（P〈0．05）。肝组织学见汇管区与肝腺泡内以单个核细胞为主的较多炎细胞浸润，其中易见浆细胞的聚积性浸润。可见不同时期小胆管损伤或毛细胆管反应性增生并侵蚀肝界板；重叠综合征患者经熊去氧胆酸治疗可使肝功能改善，与PBC患者无明显差异。结论中晚期AIH-PBC重叠综合征临床、血清学及组织病理学表现出AIH和PBC双重特征，UDCA治疗有助于血生化指标的改善。     

熊去氧胆酸治疗无重叠和有重叠特征原发性胆汁性肝硬化的疗效及生存分析

目的观察熊去氧胆酸（ursodeoxyeholicacid,UDCA）对具有自身免疫性肝炎（autoimmunehepatitis,AIH）重叠特征的原发性胆汁性肝硬化（Drimarybiliarycirrhosis．PBC）和单纯PBC患者的疗效以及对生存期的影响。方法回顾性分析20例因PBC死亡的患者,以患者死亡为研究终点,采用简化评分标准进行分组。其中12例诊断可能为AIH,将此12例具重叠特征和8例无重叠特征的PBC患者分别进行研究,分析2组在UDCA初治及研究终点时的临床特征、UDCA治疗的生化学应答及生存期情况。结果2组在UDCA治疗基线的PLT、ALP、GGT、ALT、AST、ALB、TBIL、TBA、CRE、PT、INR水平及梅奥风险评分差异均无统计学意义,而抗核抗体或抗平滑肌抗体≥1：80的阳性率、血清球蛋白或IgG／〉1．1倍正常值上限的百分比及AIH治疗前的简化评分差异均有统计学意义。UDCA治疗后有重叠特征组的生存时间为（24．4＋16．5）个月,中位生存时间为22．0个月;无重叠特征组生存时间为（60．6＋43-3）个月,中位生存时间为50．5个月。采用Kaplan-Meier生存分析显示,重叠特征组经过UDCA治疗后预后较差,Log-rank检验结果显示2组生存时间差异有统计学意义。在导致死亡的原因中,2组发病率差异均无统计学意义,但数据显示上消化道出血仍为主要死亡原因。结论对于巴黎标准不能确诊而简化评分标准可确诊的AIH—PBC患者,单纯UDCA治疗预后差,生存时间较无重叠特征的PBC患者短。     

107例自身免疫性肝炎及其重叠综合征患者的临床分析

目的 分析自身免疫性肝炎(AIH)77例及其重叠综合征患者30例的临床表现、免疫学及生物化学特点及其治疗方案.方法 164例自身免疫性肝病患者中,AIH患者77例和AIH胆汁性肝硬化(PBC)重叠综合征患者30例,分析患者的临床特点、生物化学及组织学变化和治疗应答反应等. 结果 AIH患者的发病年龄高峰在50岁左右,肝功能生物化学检查结果显示为肝炎样异常,丙种球蛋白和免疫球蛋白G均明显高于正常.74%的患者抗核抗体阳性,32%的患者抗平滑肌抗体阳性,52%的患者伴发了肝外自身免疫性疾病.肝组织病理变化以界面性肝炎为主(65%),在中、重度患者则出现小叶性肝炎、玫瑰花结样改变、桥接样坏死等.AIH-PBC重叠综合征患者血清ALT、AST、γ谷氨酰转移酶、碱性磷酸酶和抗核抗体、抗线粒体抗体(AMA)/AMA-M2阳性率较高,组织学检查往往还伴有胆管的病变.60例AIH患者接受免疫抑制剂强的松龙联合硫唑嘌呤治疗第1年时,AIH治疗患者达完全缓解者42例(70%),其中26例持续缓解,16例复发(激素减量至≤10 mg/d或停药后),10例部分缓解,8例无应答.持续缓解者的AST、ALT、免疫球蛋白G、丙种球蛋白及血总胆红素水平均显著低于非持续缓解者(34例,JD值均＜0.05),此类患者撤除了硫唑嘌呤,单用激素的剂量均可维持在5～10 mg/d.AIH-PBC重叠综合征组经联合熊去氧胆酸治疗后除碱性磷酸酶和γ谷氨酰转移酶外,其余肝功能指标(ALT、AST、总胆红素)亦明显改善(P值均＜0.01).结论 AIH及AIH-PBC重叠综合征在临床上并不少见,诊断需综合临床、生物化学、免疫学和病理学等检测结果.AIH患者联合应用糖皮质激素、硫唑嘌呤达持续缓解者,可改为单用小剂量激素治疗.AIH-PBC患者加用熊去氧胆酸治疗,亦可获得较好的疗效.     

Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis

Primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome is a clinical entity characterized by the occurrence of both conditions at the same time in the same patient. In addition to PBC-AIH overlap syndrome, transitions from one autoimmune disease to another have been reported, but no systematic series have been published. We report a series of 12 patients with consecutive occurrence of PBC and AIH (i.e., PBC followed by AIH). Among 282 PBC patients, 39 were identified who fulfilled criteria for probable or definitive AIH. AIH developed in 12 patients (4.3%). The baseline characteristics of the patients were similar to those of patients with classical PBC. Time elapsed between the diagnosis of PBC and the diagnosis of AIH varied from 6 months to 13 years. Patients with multiple flares of hepatitis at the time of diagnosis of AIH had cirrhosis on liver biopsy. Ten patients were given prednisone +/- azathioprine; short-term as well as sustained remissions were obtained in 8 of these, while two had multiple relapses and eventually died 8 and 7 years after diagnosis of AIH. In conclusion, the development of superimposed AIH could not be predicted from baseline characteristics and initial response to UDCA therapy. If not detected early, superimposed AIH can result in rapid progression toward cirrhosis and liver failure in PBC patients.