Autoimmune paediatric liver disease

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis（AIH）,autoimmune sclerosing cholangitis（ASC）,and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody（SMA/ANA,type 1） or liver kidney microsomal antibody（LKM1,type 2）.There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity,presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups.The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical,immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters,and decreased inflammatory activity on follow up liver biopsies.However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies,hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH postliver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to t     

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。     

中西医药治疗自身免疫性肝病研究进展

目的 自身免疫性肝病的发病率逐年升高,成为肝脏疾病的研究热点之一。西医治疗有明确的疗效,但中西医结合治疗能让患者有更多的获益,在提高治疗效果的同时,可以减少西药的副作用,提高西药的应答率,更好地改善患者的生存质量,延长生存时间。本文就当前西医、中医和中西医结合治疗进展进行了综述,以为临床提供可参考的中西医结合治疗方案。     

Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plas...     

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.     

Paediatric autoimmune liver diseases: A descriptive study of patients from Saudi Arabia

Background and study aimsAutoimmune liver diseases (ALDs) are a clinico-pathologic spectrum of disorders that share some similarities. They are formally classified as autoimmune hepatitis (AIH), isolated autoimmune sclerosing cholangitis (ASC), and the overlap syndrome of these. We describe the clinical, biochemical, and outcomes data of a cohort of autoimmune ALDs patients in a tertiary care centre.Patients and methodsThis is a cross-sectional study conducted at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Data were collected in 2007–2018. All cases were 18 years old or younger at the time of diagnosis. The data collection comprised clinical, laboratory, imaging, treatment, and longitudinal follow-up data.ResultsTwenty-five patients were identified; 14 (56%) were females. Twenty-one patients (84%) had AIH-1,1 patient (4%) had AIH-2, and 3 patients (12%) had autoimmune sclerosing cholangitis (ASC). An insidious course was found in 21 (84%) cases. Acute hepatitis and fulminant hepatic failure was found to be very rare. Eight cases (32%) had cirrhosis at diagnosis. A total of 20 cases (80%) had complete remission following therapy. The median follow-up period was 45 months. There was no mortality, and only one patient was referred for transplant. Thus, the transplant-free survival was 96%.ConclusionsOur study showed predominance of AIH-1 over AIH-2. Response to treatment in our cohort was found to be similar to the results found in some other key studies. Prognosis and transplant-free survival is better than many published paediatric studies.     

Cirrhosis and autoimmune liver disease:Current understanding

Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells.Persistent liver injury,associated with chronic AILD,leads to un-resolving inflammation,cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts.Liver cirrhosis,and the resultant loss of normal liver function,inevitably ensues.Patients with cirrhosis have higher risks or morbidity and mortality,and that in the decompensated phase,complications of portal hypertension and/or liver dysfunction lead to rapid deterioration.Accurate diagnosis and monitoring of cirrhosis is,therefore of upmost importance.Liver biopsy is currently the gold standard technique,but highly promising non-invasive methodology is under development.Liver transplantation(LT) is an effective therapeutic option for the management of endstage liver disease secondary to AIH,PBC and PSC.LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy;in addition,LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.     

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.     

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.     

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.     

自身免疫性肝病的病理学新进展

自身免疫性肝病是指由于机体免疫系统攻击自体肝组织引起的肝组织损伤和肝功能异常的一组免疫性疾病,包括有自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC).通常情况下这三种肝脏疾病独立存在,约有6％～9％的患者可以在同一时段或病程中出现两种疾病的临床表现、血清学和组织学特征,称为重叠综合征.近年来随着对自身免疫性肝病认识水平的提高以及自身抗体检测方法的不断改进,一些学者在自身免疫性肝病的经典肝组织学病变特点的基础上,提出了一些见解,介绍如下.     

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.     

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.     

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