自身免疫性肝病的研究进展

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)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)三种疾病,本文就近期此领域的进展进行讨论.在AIH诊断方面,多项研究比较了2008年提出的简化标准及修订标准及各自特点;在PBC方面,对熊去氧胆酸(ursodeoxycholic acid,UDCA)发病机制、应答不良的标准以及新的治疗方案有所扩展;在PSC方面,对UDCA治疗的争议和IgG4相关的PBC成为研究热点.     

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.     

自身免疫性肝病的诊断和治疗

自身免疫性肝病是一组免疫介导的肝脏损伤,根据临床表现、生物化学、影像学和组织病理学特点,可简单地分为以肝炎为主型的自身免疫性肝炎(AIH)和以胆系损害及胆汁淤积为主型的原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎     

自身免疫性肝病的基本概念和诊断思路

自身免疫性肝病指一组以肝脏病理损害和肝脏功能试验异常为主要表现的自身免疫性疾病,通常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)。由于在国内较为少见,所以一般教科书对它们的描述较为简略,多数临床医生对此类疾病的警惕性也不高。随着国     

自身免疫性肝病的实验诊断进展

自身免疫性肝病(autoimmune liver diseases,AILD)是包括原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)、自身免疫性肝炎(AIH)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)的一类疾病,缺乏明显的病因或诱因,血清中常会出现特异性的自身抗体.因此,实验室指标的检测对于AILD特别是PBC和AIH的诊断、辅助诊断和分类具有重要意义. 一、原发性胆汁性肝硬化 PBC患者的血清学特征是抗线粒体抗体(antimitochondrial antibody,AMA)阳性,血清中还存在着多种其他自身抗体,对于PBC的诊断、疗效观察及预后判断具有重要意义. 1.AMA:PBC患者AMA的阳性率可达90％ ～ 95％,在患者出现症状前几年甚至几十年就可以检测到AMA的存在[1].AMA至少有9种抗原亚型(M1-M9),其中AMA-M2、AMA-M4、AMA-M8及AMA-M9与PBC有关,AMA-M2对诊断PBC具有更高的敏感性和特异性,是最重要的AMA亚型,甚至有学者建议将AMA-M2直接作为PBC的一个诊断标准[2].绝大部分患者血清AMA和AMA-M2检测结果是一致的,也有个别患者血清AMA阳性但AMA-M2阴性,反之亦存在.     

近二十年我国自身免疫性肝病领域发展历程的回顾与展望

本文通过大数据回顾了2001年—2020年我国自身免疫性肝病领域获得国家级研究项目和在国内外发表学术论文的情况，结果展现了二十年来的发展变化趋势。介绍了新发布的自身免疫性肝病诊断治疗指南的更新要点，回顾了自身抗体检测技术的发展并分析其进展。     

自身免疫性肝病中的重叠综合征

自身免疫性肝病是一组具有一定自身免疫基础的炎症性肝病,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)等,其共同特点是在肝脏出现病理性炎症损伤的同时、血清中可发     

自身免疫性肝病的组织病理学特点及其临床意义

自身免疫性肝病（AILD）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）。肝活检对于AILD的诊断以及严重程度和预后判断至关重要。AIH-般以界面性肝炎（碎屑样坏死）、淋巴．浆细胞浸润和肝细胞玫瑰样花结为组织病理学特点．而PBC和PSC分别表现为胆管肉芽肿样破坏和胆管周围同心圆样纤维沉积（“洋葱皮样”）。除组织病理学证据外,AILD的诊断还需结合特征性临床、生化改变以及血清自身抗体和球蛋白水平综合判断。     

自身免疫性肝病患者外周血淋巴细胞亚群的频率变化及临床意义

目的调查原发性胆汁性肝硬化(PBC)、自身免疫性肝炎(AIH)及AIH-PBC重叠综合征患者外周血淋巴细胞亚群频率变化及其临床意义。方法本中心2001年6月-2010年12月期间,对41例AIH-PBC、37例AIH和36例PBC患者,以及50例健康人群外周血进行淋巴细胞亚群频率检测。分析患者年龄、性别、肝功能、是否肝硬化及淋巴细胞亚群频率的变化。结果与健康组相比,AIH-PBC重叠综合征组、PBC组和AIH组的CD3+CD4+T细胞频率显著升高,而CD3-CD16+CD56+NK细胞频率显著降低;PBC组和AIH-PBC重叠综合征中CD4+/CD8+比值、CD3-CD19+B细胞频率偏高,CD3+CD8+%T细胞频率降低。在疾病发展的不同阶段,AIH-PBC重叠综合征组和PBC组中,肝硬化组CD3+%T细胞频率、CD3+CD8+%T细胞频率较非肝硬化组偏低。结论通过回顾性分析健康人群和AIH、PBC及AIH-PBC重叠综合征患者淋巴细胞亚群的分布特点及其与疾病进展的关系,为临床科学评价上述自身免疫性肝病人群的免疫状态提供重要的免疫指标。     

自身免疫性肝病与肝移植

终末期自身免疫性肝病是肝移植的最佳适应证,应综合疾病的特点准确把握移植时机。肝移植术后原发病复发率较高。受排异、胆道并发症等因素的干扰,移植后疾病复发的鉴别诊断难度高,临床医师应重视对疾病复发的认识,及早发现,及时处理。     

2010年自身免疫性肝病临床进展回顾

本文的目的在于回顾2010年原发性硬化性胆管炎、原发性胆汁性肝硬化、自身免疫性肝炎及重叠综合征在诊断、治疗及监测等方面的研究进展     

Epidemiology of autoimmune liver disease

Primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) are chronic liver diseases that likely have an autoimmune basis to their pathogenesis. Although significant strides have been made in the clinical management of these conditions, their pathogenesis remains obscure. Understanding of various epidemiological factors may shed light on predisposing or causative factors for these diseases. Most is known about the epidemiology of PBC, with only minimal information on that of PSC and AIH. In this review, the current data on the epidemiology of PBC, AIH and PSC are summarized and suggestions are made for future work in this important area.     

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation

Background/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end‐stage autoimmune liver disease (ESALD), (ii) the correlation among auto‐antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics. Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non‐autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6–12 and ≥24 months post‐transplantation. Results were correlated with the HLA type of the recipient. Results: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non‐autoimmune) of the patients (five‐fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA‐DQ2 or HLA‐DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post‐transplantation. Post‐transplantation, of the five patients with symptoms of ‘classical’ CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically ‘silent’ CD. Conclusions: Patients with ESALD, especially those who are HLA‐DQ2 or HLA‐DQ8 positive had a high prevalence of CD‐associated antibodies. Both tTGAs and EMAs decreased post‐transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.     

New insights into autoimmune liver diseases.

Autoinflammatory liver disease represents an important aspect of global hepatological practice. The three principal disease divisions recognized are autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis. Largely, but not exclusively, these diseases are considered to be autoimmune in origin. Increased recognition of outlier and overlap syndromes, changes in presentation and natural history, as well as the increased awareness of IgG4-associated sclerosing cholangitis, all highlight the limitations of the classic terminology. New insights continue to improve the care given to patients, and have arisen from carefully conducted clinical studies, therapeutic trials, as well as genetic and laboratory investigations. The challenges remain to treat patients before liver injury becomes permanent and to prevent the development of organ failure.     

儿童自身免疫性肝病

儿童自身免疫性肝病是一种由自身免疫反应介导的慢性进行性肝脏疾病,包括自身免疫性肝炎、自身免疫性硬化性胆管炎、肝移植后新发自身免疫性肝炎。近年来儿童自身免疫性肝病的发病率逐渐上升,但临床表现缺乏特异性,有不同于成人的临床特点,现有的IAIHG积分系统并不适合儿童患者,故临床上容易误诊或漏诊。及时应用免疫抑制剂治疗至关重要,可明显改善预后。本文主要对该病的诊治研究进展进行综述。     

Overlap syndromes with autoimmune hepatitis in chronic cholestatic liver diseases

Conditions exhibiting features of two different autoimmune liver diseases are commonly designated overlap syndromes, although there is no current agreement on what constitutes an overlap syndrome or specific diagnostic criteria. As in the classic autoimmune liver diseases, such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), the etiology is unknown but presumed to be related to alterations of immune regulation. Distinction of these clinical entities is important for management as outcomes may differ from outcomes of patients with diagnosis of classic autoimmune liver diseases. Due to their presumed rarity, no large therapeutic trials are available and treatment of overlap conditions is empirical and based upon extrapolation of data from the primary autoimmune liver diseases. PBC–AIH overlap is the most frequently described overlap syndrome and may be associated with a poor prognosis. This may represent an important and unrecognized cause of resistance to ursodeoxycholic acid in patients with PBC. PSC–AIH overlap is less commonly reported. Prognosis may be better than in patients with PSC alone; however, worse than in patients with AIH alone. Further studies are needed for determining diagnosis, natural history and optimal therapeutic strategies of overlap syndromes of autoimmune liver disease.     

Pathology of autoimmune liver diseases in children

Liver disorders are more diverse in children than in adults, and autoimmune liver diseases also develop in childhood, although rarely. The autoimmune diseases in children comprise autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The pathology of AIH and PSC is described. Although AIH in children is rare, it occurs in early childhood, and some elementary school students have been reported to develop cirrhosis. The histology of AIH in children is essentially the same as that in adults. We analyzed eight patients with childhood AIH. Four of these patients had a high AIH score, with typical histological features of AIH, that is, interface hepatitis with infiltration of lymphocytes and plasma cells, a severe necroinflammatory reaction and rosette formation of hepatocytes. Multinucleated hepatocytes were observed in three patients. This finding seems characteristic of childhood AIH, although rarely observed in adult AIH. Clinically, the distinction between AIH and PSC is often difficult in childhood, and the overlapping of both has also been reported. PSC-like histological features may be observed in some pediatric patients with AIH. In patients with acute onset of AIH, they show a pronounced necroinflammatory reaction in zone 3 (central area). Because an autoimmune phenomenon may occur in the early stage of childhood PSC, it is difficult to differentiate it from AIH in some patients. Some patients are diagnosed with AIH in the early stage, but with PSC during long-term follow up. The histopathological findings of childhood PSC are the same as those of adult PSC, and are characterized by biliary-type portal fibrosis and onion-like periductal fibrosis in medium-sized portal tracts.     

自身免疫性肝病诊断与治疗进展

自身免疫性肝病是一组由自身免疫介导的慢性肝胆系统损伤性疾病,主要包括自身免疫性肝炎、原发性胆汁性肝硬化及原发性硬化性胆管炎.本文就自身免疫性肝病的诊断与治疗进展进行综述.