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.     

自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者肝组织病理学特征

目的分析自身免疫性肝炎-原发性胆汁性胆管炎(AIH-PBC)重叠综合征的组织病理学变化,提高对AIHPBC重叠综合征的临床及病理学特征的认识。方法对10例AIH-PBC重叠综合征患者的肝穿刺组织病理资料进行回顾性分析。结果 AIH-PBC重叠综合征患者多发于中年女性(80%),肝组织病理变化兼具界面性肝炎,桥接样坏死及小胆管减少甚至消失。结论自身免疫性肝病在中国人中日趋增多,AIH-PBC重叠综合征并非罕见,其诊断需综合临床表现、生化、免疫指标和组织学变化,重叠综合征兼具AIH和PBC的组织病理学特征,均可见肝小叶界面炎,且多为中重度,可见桥接样坏死及小叶中央融合性坏死,肝细胞炎症活动度从中度到重度不等,纤维化程度从S2到S4,同时均有不同程度的小胆管病变,其中3例有明显胆管数目减少,2例有细小胆管增生。     

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.     

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。     

164例自身免疫性肝病临床分析

目的 分析比较自身免疫性肝炎（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 cholangltis）及其重叠综合征的临床特点、生化特征和治疗反应，提高对自身免疫性肝病的认识。方法对77例AIH患者、46例PBC患者、11例PSC患者和30例PBC-AIH重叠综合征患者的临床及实验室检查资料进行回顾性分析。结果除PSC外，大多数自身免疫性肝病多发于中年女性，从出现症状到明确诊断平均需要2．5年。AIH、PBC-AIH重叠患者具有较高的转氨酶，PBC、PSC具有较明显的GGT、ALP升高。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％。PSC和AIH-PBC具有较高的AIH评分，27％的PSC患者和33％AIH-PBC的评分达到可能的AIH。合理应用UDCA和免疫抑制剂可使90％的PBC和AIH患者症状在六个月内得到缓解、肝功能恢复明显改善。结论 AIH、PBC-AIH的肝功能异常以转氨酶升高为主，PBC、PSC以胆汁淤积为主。应用AIH评分系统诊断可能的AIH时应注意鉴别PSC及其它自身免疫性肝病。UDCA和免疫抑制剂可改善绝大多数患者的症状和肝功能异常。     

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.     

原发性胆汁性肝硬化和自身免疫性肝炎重叠综合征的临床与病理分析

目的 分析原发性胆汁性肝硬化(PBC)和自身免疫性肝炎(AIH)重叠综合征(PBC/AIH重叠综合征)患者的临床表现、肝组织病理学特征。 方法 采用国际自身免疫性肝炎小组新修订的描述性诊断标准和计分系统,从68例PBC患者中筛选出9例PBC/AIH重叠综合征患者,分析比较PBC/AIH重叠综合征和单纯PHC患者的临床表现、肝组织病理学特征。 结果 68例PBC患者中,PBC/AIH重叠综合征9例,单纯PBC 59例,分别占13.2％和86.8％,PBC/AIH重叠综合征血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、γ-球蛋白、免疫球蛋白G,以及抗平滑肌抗体和(或)抗核抗体阳性率明显高于单纯PBC;PBC/AIH重叠综合征合并其他自身免疫性疾病发生率亦明显高于单纯PBC;PBC/AIH重叠综合征兼有PBC和AIH的双重组织学特点,显示界面炎和碎屑样坏死,肝组织免疫荧光检测显示肝细胞膜、汇管区有免疫球蛋白G沉着。 结论 PBC/AIH重叠综合征表现出A·IH和PBC双重特征,不同于单纯的PBC,两者的临床表现、免疫学及肝组织病理学特征上有差异。     

自身免疫性肝炎与原发性胆汁性胆管炎重叠综合征患者的临床病理学特征分析

目的对自身免疫性肝炎(AIH)-原发性胆汁性胆管炎(PBC)重叠综合征患者的血清学指标、自身抗体及肝脏组织病理学表现进行记录,并分析这些患者的临床病理学特征。方法选取2016年6月至2019年6月我科临床确诊的自身免疫性肝病(AILD)患者78例,其中AIH患者32例(AIH组),PBC患者24例(PBC组),AIH-PBC重叠综合征患者22例(AIH-PBC组)。对于计量资料以(■±s)表示,组间比较采用t检验分析;计数资料以百分比表示,组间比较采用卡方检验。结果 AIH-PBC组[(412.4±226.4)U/L]患者ALP明显高于AIH组[(108.2±68.1)U/L],(P0.05);AIHPBC组[(430.5±152.8)U/L]患者GGT明显高于AIH组[(118.7±65.2)U/L](P0.05);AIH-PBC组[(5.2±1.7)g/L]患者IgM明显高于AIH组[(2.5±0.8)g/L](P0.05);AIH-PBC组[(182.6±68.1)U/L]中患者ALT明显高于PBC组[(98.7±45.7)U/L](P0.05);AIH-PBC组[(174.9±70.2)U/L]中患者AST明显高于PBC组[(104.6±52.4)U/L](P0.05);AIH-PBC组[(19.5±6.6)g/L]中患者IgG明显高于PBC组[(15.2±1.9)g/L](P0.05)。AIHPBC组中患者(72.7%)AMA表达明显高于AIH组(0%)(P0.05);AIH-PBC组中患者(100%)AMA M2表达明显高于AIH组(0%)(P0.05);AIH-PBC组中患者(72.7%)SMA表达明显高于PBC组(16.7%)(P0.05);AIH-PBC组中患者(90.9%)ANA表达明显高于PBC组(12.5%)(P0.05)。结论 AIH-PBC组患者血清学指标、自身抗体及肝组织穿刺病理学表现兼具AIH及PBC疾病的特点,而血清生化指标、自身抗体检测水平的差异可以作为鉴别AIH-PBC重叠综合征的依据。     

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.     

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.     

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.     

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease

OBJECTIVES: To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. METHODS: Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). RESULTS: From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. CONCLUSION: Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.     

慢性肝病中抗肝抗原自身抗体的检测

目的　探讨中国人不同病因所致慢性肝病患者中抗肝抗原自身抗体的存在状况及自身免疫性肝病的自身抗体特征。方法　 166例肝功能异常患者分为 6组 :自身免疫性肝炎 (AIH ) 12例、原发性胆汁性肝硬化 (PBC) 2 0例、原发性硬化性胆管炎 (PSC)13例、HBV组 66例、HCV组 2 2例、肝豆状核变性 (HDL) 3 9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I型抗体 (anti LKM1)、抗线粒体抗体 (AMA)和抗中性粒细胞胞浆抗体 (ANCA) ,免疫印迹法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　 166例中ANA、AMA、M_2、pANCA阳性率在 7组中有显著差异 (P <0 .0 1)。PBC中AMA、M 2阳性检出率均为 10 0 % ,PSC中pANCA阳性检出率为 5 3 8% ,Fisher精确检验在a =0 .0 0 2水准与其他各组比较有显著差异。AIH与PBC的ANA阳性率分别为10 0 %和 60 % ,Fisher精确检验在a =0 .0 0 2水准二者无显著差异。与其他各组比较有显著差异。在AIH组SMA阳性率为 2 5 % ,LKM 1、LC 1、SLA/LP阳性率均为 8.3 % ,统计学处理与其他组无显著差异 (P >0 0 5 ) ,可能与病例少有关。PBC中分别有 1     

Autoimmune hepatitis and overlap syndromes

Autoimmune hepatitis (AIH) is an immune-mediated, autodestructive liver disease with hepatocytes as target cells, mostly affecting young women. Primary biliary cirrhosis (PBC) is also regarded as an autoimmune liver disease with bile duct epithelia as the target cells, resulting in a continuous loss of bile ducts. Both diseases may occur simultaneously in their full manifestations in about 10% to 20% of cases, thus constituting an overlap syndrome with PBC directing the course of the disease. AIH may also occur simultaneously with primary sclerosing cholangitis (PSC), with a frequency of between 2% and 8% of patients with PSC. In most cases, AIH precedes manifestation of PSC. In children, the overlap syndrome of AIH and PSC seems to make up an entity of its own: autoimmune sclerosing cholangitis.     

自身免疫性肝病重叠综合征的诊断和治疗

自身免疫性肝病（AILD）是一组以肝脏病理损害和肝功能异常为主要表现的自身免疫性疾病,可分为自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC）,重叠综合征指同时具有其中两种疾病的临床和病理表现。重叠综合征相对少见,主要包括AIH—PBC和AIH—PSC。由于重叠综合征在临床表现、血清学和组织学方面综合了两种AILD的特点,其诊断和治疗有一定难度并存在争议。对其临床表现以及诊断和治疗方案进行深入研究有助于对该病的认识和防治。     

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.