抗可溶性肝抗原/肝胰抗原抗体在自身免疫性肝炎诊断及分型中的意义

目的探讨抗可溶性肝抗原/肝胰抗原抗体（抗-SLA/LP）在AIH诊断及分型中的意义。方法对6000例采用间接免疫荧光法及免疫印迹法进行自身抗体检测的肝功能异常患者进行回顾性分析。结果6000例肝功异常患者中AIH患者84例,抗-SLA/LP阳性患者18例,占肝功能异常患者的0．3%。在18例抗-SLA/LP阳性患者中17例诊断为AIH,其中2例为AIH重叠原发性胆汁性肝硬化,1例诊断为慢性乙型肝炎。84例中AIH-Ⅰ型65例,AIH-Ⅱ型2例,AIH-Ⅲ型17例。抗-SLA/LP诊断AIH灵敏度为20．2%,特异度为99．7%,诊断AIH的阳性预测值为94．4%。17例AIH-Ⅲ型患者与65例AIH-Ⅰ型患者进行临床资料比较：AIH-Ⅲ型患者ANA滴度低于AIH-Ⅰ组,差异有统计学意义（P＜0．05）;抗-SLA/LP阳性组发病年龄在50岁以上者为58．8% （10/19）,而抗SLA/LP阴性组发病年龄在30～50岁者为52．2%（35/67）。但两组患者在性别构成、发病年龄、肝功能损害程度、凝血酶原活动度、IgG水平、肝硬化发生率及对激素治疗的反应方面的差异均无统计学意义。结论抗-SLA/LP对AIH的诊断有高度特异性。AIH-Ⅲ型患者除发病年龄偏高外,与Ⅰ型患者的临床特点比较,尚未发现差异有统计学意义。     

自身免疫性肝炎的最新概念及其分型

近年来,除ANA、SMA、AMA外又相继发现了一些新的自身抗体:LSP、LMA、LKM-1、ASGPR、LCI、SLA、LP抗体等,随着对自身免疫性肝炎(AIH)的亚型分类、遗传背景与发病、与HCV感染的关系等的阐明,得出了该病的新概念:AIH是一组慢性肝炎综合征,病人呈现肝脏本身的免疫耐受性减低,不能正确识别自身肝组织成分而产生自身免疫反应,引起以门脉周围病变为主的非自限性肝炎。目前将其分为3型:①AIH-Ⅰ型,即经典型,主要为ANA或SMA(或actin抗体)阳性,最近又细分为Ⅰa型(ANA阳性)与Ⅰb型(actin抗体阳性);②AIH-Ⅱ型主要为LKM-1抗体阳性,或同时有LCI抗体,近又细分为Ⅱ     

自身免疫性肝炎患者自身抗体的测定及意义

目的:探讨自身抗体测定对诊断自身免疫性肝炎的临床意义．方法:采用间接免疫荧光法(IIF)检测47例自身免疫性肝炎患者、158例非自身免疫性肝炎患者及40例健康体检者体内抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗中性粒细胞胞质抗体(ANCA)、抗线粒体抗体(AMA)等自身抗体,ELISA法检测抗MPO抗体,并对结果进行回顾性分析．结果:ANA、SMA及ANCA检出率的比较,结果显示AIH中阳性率最高为SMA(66．0％, 31／47),而非AIH中则为6．3％(10／158),两组差异有非常显著性意义(P<0．01)．经X2检验, SMA、AMA和MPO抗体检测在AIH与PBC中,均有非常显著性意义(P<0．01)．AIH各型自身抗体检测结果表明,AIH-Ⅰ与ANA、SMA和ANCA相关,AIH-Ⅱ与LKM相关,而AIH=Ⅲ与SLA和ANCA相关．结论:血清自身抗体的检测对诊断、治疗和阻止自身免疫性肝炎的发展有着十分重要作用,对提高AIH在临床上同其他肝病鉴别诊断和治疗有着非常重要的意义．     

自身免疫性肝炎的诊断和治疗

自身免疫性肝炎(autoimmune hepatitis,AIH)是一种累及肝脏实质的特发性疾病.临床上,AIH以高血清转氨酶、高γ-球蛋白/Ig、高滴度自身抗体和肝组织学上以界面性肝炎(interface hepatitis)为特点,但需排除其他原因所致慢性肝病的可能.该病一般对糖皮质激素治疗应答良好.基于血清免疫学发现,AIH可分为二型:Ⅰ型AIH是最常见的疾病类型,与抗核抗体(ANA)和/或平滑肌抗体(SMA)、抗肌动蛋白抗体、非典型P-ANCA及抗可溶性肝抗原/肝胰抗体(抗SLA/LP)等有关;Ⅱ型AIH主要发生于儿童,以抗肝/肾微粒抗体1型(抗LKM -1)和抗肝细胞溶质-1抗体(抗LC-1)为主.大约有10％的患者血清自身抗体可呈阴性.按基因型可分为HLADR3( DRBI^0301)、HLA -B8和HLA - DR4CDRBI^0401,0405)等类.在存在相应的组织学改变的基础上,AIH的诊断还需结合临床和生化特点、血清自身抗体和免疫球蛋白水平.     

自身抗体阴性自身免疫性肝炎患者临床病理学特点

目的:分析自身抗体阴性自身免疫性肝炎(AIH)患者临床特点,并总结诊疗经验。方法:对167例AIH患者的临床和病理特点进行分析,将自身抗体阴性AIH患者定义为:符合国际自身免疫性肝炎小组(IAIHG)1999年描述性诊断标准且抗核抗体、抗平滑肌抗体、抗肝肾微粒体1型抗体和抗线粒体抗体均为阴性者。结果:167例中17例自身抗体阴性,占10.2%。自身抗体阳性和自身抗体阴性AIH患者在一般情况(诊断时年龄除外)、生化指标方面均无明显差异(P0.05)。自身抗体阴性组血清IgG水平低于自身抗体阳性组,差异有统计学意义(P=0.004)。两组肝组织学炎症分级无明显差异,而自身抗体阴性组中存在更多纤维化进展期患者(P0.001)。采用1999年诊断积分系统评估时,自身抗体阴性组中11例(64.7%)为可能性诊断,其余6例(35.3%)为确定性诊断;采用简化诊断积分系统重新评估后,仅3例(17.6%)达到可能性诊断,且无1例达到确定性诊断标准。与自身抗体阳性组相比,自身抗体阴性AIH患者接受24个月的免疫抑制治疗后累积完全生化缓解率为86%,两组患者无明显差异(P=0.658)。结论:自身抗体阴性AIH在国人中并非罕见,在应用免疫抑制治疗方面与自身抗体阳性AIH患者类似,能取得满意疗效。     

自身免疫性肝炎(AIH)的分型

根据自身免疫抗体、发病情况、病程经过以及对治疗的反应 ,有学者将其分为三种亚型或四种亚型。一、AIH三种亚型的分类1.Ⅰ型AIH :本型AIH以循环中ANA和SMA阳性为特征。如能检测ASGPR(人唾液酸糖蛋白受体 ) ,常可发现此型有很高的阳性率 ,且随疾病的控制ASGPR抗体滴度也随之下降。出现LSA(抗肝可溶性抗原抗体 )者的 10 %。该型为临床较常见的典型患者。2 .Ⅱ型AIH :Ⅱ型AIH以抗肝肾微粒体抗体 (LKMI)阳性为特征。根据LKM所针对不同的抗原成分 ,将LKM分成三种。LKMI所针对的抗原为细胞色素P450ⅡD6,用于诊断AIH ,LKMI…     

抗去唾液酸糖蛋白受体与自身免疫性肝炎

自身免疫性肝炎(AIH)是一类原因不明的肝实质损害性疾病,诊断AIH的先决条件是免疫学指标阳性,并根据血清中常见的自身抗体分为4型,但这些抗体不具有疾病和器官特异性。人们在探索AIH的发病机制过程中发现了具有疾病和器官特异性的抗去唾液酸糖蛋白受体抗体,该抗体不仅可作为AIH的诊断标志,还可作为判断疾病活动度及其预后的指标。     

抗Ro52抗体与Ⅰ型自身免疫性肝炎患者病情的相关性研究

[目的]探究抗Ro52抗体与I型自身免疫性肝炎患者病情的相关性。[方法]选取68例于2014年8月之2016年5月入我院诊治的Ⅰ型自身免疫性肝炎(autoimmune hepatitis,AIH)患者,运用免疫印迹法检测患者血清抗Ro52抗体,依据检测结果,将所有患者分为抗Ro52抗体阳性组(26例)和抗Ro52抗体阴性组(42例),收集2组患者的抗核抗体(ANA)滴度、抗可溶性肝原(抗SLA/LP)抗体、抗Ro60抗体、肝病相关并发症、肝外自身免疫性疾病、免疫球蛋白等资料,并进行对比。[结果]2组AIH患者的ANA抗体滴度主要分布于1:320~1:1 000之间;在抗Ro52抗体阳性组中,有7例合并有抗SLA/LP抗体阳性、有16例合并有抗Ro60抗体阳性;在肝病相关并发症方面,抗Ro52抗体阳性组发生率要高于阴性组,但差异无统计学意义(χ~2=0.11,P=0.75);在肝外自身免疫性疾病方面,抗Ro52抗体阳性组发生率显著高于阴性组,差异具有统计学意义(χ~2=5.13,P=0.02);在免疫球蛋白水平方面,抗Ro52抗体阳性组IgG水平显著高于阴性组,差异具有统计学意义(t=3.67,P0.01)。[结论]抗Ro52抗体阳性的Ⅰ型AIH患者合并有肝病相关并发症和肝外自身免疫性疾病的可能性较高,Ⅰ型AIH的发病可能与抗Ro52抗体和IgG共同作用有关。     

原发性胆汁性肝硬化患者的免疫学特点分析

目的 分析原发性胆汁性肝硬化(PBC)出现的自身抗体等免疫学指标及其临床意义。 方法对3000例肝功能异常患者采用间接免疫荧光法检测抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)和抗肝肾微粒体抗体(抗-LKM)等,并对ANA和AMA亚型及抗可溶性肝抗原/肝胰抗原(抗-SLA/LP)、LKM-1和抗肝特异性胞浆抗原型1抗体(抗-LC-1)等肝脏疾病相关的自身抗体进行了检测。结果 3000例肝病患者中,PBC 52例占1.7％。PBC患者的AMA和AMA-M2抗体均为阳性,52例PBC中,94.0％呈AMA高滴度(≥1:320)阳性,79.0％M2>200 RU/L,78.0％ANA阳性。ANA的主要荧光模式为细胞核膜型、细胞核点型和着丝点型。少见的荧光模式有抗干燥综合征A/B(SS-A/SS-B)、细胞核均质型、核仁型及颗粒型等。PBC患者免疫球蛋白M、碱性磷酸酶和γ-谷氨酰转肽酶高于乙型肝炎肝硬化患者;其白细胞介素(IL)-6、IL-10、肿瘤坏死因子α和干扰素γ水平高于正常人。5例表现为自身免疫性肝病重叠综合征,其中2例抗-SLA/LP阳性,提示PBC与自身免疫性肝炎(AIH)3型的重叠;1例抗-LKM-1阳性,提示PBC与AIH 2型的重叠;2例ANA阳性,且肝活体组织检查证实存在AIH和PBC的病理改变,提示为PBC与AIH 1型的重叠综合征。 结论 PBC在我国肝病患者中约占1％~2％。临床已出现典型症状者一     

自身免疫性肝炎

195 0年Walddnstr m第一次报道一名年青妇女患自身免疫性肝炎 (autoimmunehepatitis,AIH ) ,此后不久 ,美国也报道了这种综合征。由于自身免疫性肝炎常伴有抗核抗体 (ANA)阳性 ,故Mackay建议将其命名为“狼疮性肝炎”。近来国际自身免疫性肝炎组织(IAIHG)确定了自身免疫性肝炎的诊断标准。在诊断时该病通常已持续 6个月或更长时间 ,病人表现为血清转氨酶水平升高 ,组织学检查可以发现门脉周围和 /或界板周围性肝炎 (碎屑样坏死 ) ,近一步发展为桥架样坏死、全小叶性和多小叶性坏死 ,以及活动性肝硬化。如果得不到治疗 ,AIH的病死率很高 ,超过 5 0 %的严重AIH病人大约 5年左右死亡 ,自行缓解比例很低。AIH的诊断主要根据典型AIH的临床表现并除外慢性肝炎的其他病因。需要除外的情况主要包括肝炎病毒感染和有临床意义的酒精摄入量。AIH的临床特征包括女性 (女 /男 =4 / 1)、高丙种球蛋白血症、循环自身抗体、对免疫抑制剂治疗的良好反应、肝外自身免疫的临床表现和HLADR3或DR4的过度表达。AIH可以根据自身抗体分为 3种亚型 ,Ⅰ型AIH以抗核和 /或抗平...     

Hepatitis autoinmune en niños: evolución de 20 casos del norte de México

BackgroundAutoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver with nonspecific clinical manifestations that causes greater liver damage in children than in adults.AimsTo analyze the clinical progression, biochemical profiles, histopathologic changes, and treatment response in 20 children with AIH.Material and methodsA retrospective study was carried out on the variables associated with clinical progression, diagnosis, and treatment response in children seen at the the Unidad Médica de Alta Especialidad (UMAE) No. 71 IMSS in Torreón, Coahuila, Mexico, from 1992 to 2012.ResultsTwenty patients were analyzed, 75% with type 1 AIH (AIH-1) and 25% with type 2 AIH (AIH-2). Girls predominated with a 3:1 ratio of girls to boys. The mean age was 10.07 ± 6.53 years for the AIH-1 cases and 6.75 ± 3.77 years for the AIH-2 cases. There was an association with immunologic diseases in 40% of the patients.The patients in the AIH-2 group had greater biochemical profile alterations and IgA deficiency. Anti-nuclear antibody and anti-smooth muscle antibody were positive in 100% of the patients with AIH-1, and anti-liver kidney microsomal type 1 antibody was positive in 100% of the AIH-2 patients. Liver biopsy revealed interface hepatitis in both groups. The AIH-2 group responded more quickly to treatment, but had a higher recurrence rate.ConclusionsAutoimmune hepatitis in the pediatric patient should be suspected in order to make an early diagnosis and thereby establish opportune treatment. Determining the type of AIH is necessary for making adequate diagnosis and for achieving a better outcome in relation to recurrence and complication rates.     

Autoimmune liver serology：Current diagnostic and clinical challenges

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases（AiLD）,namely autoimmune hepatitis types 1 and 2（AIH-1 and 2）,primary biliary cirrhosis（PBC）,and the sclerosing cholangitis variants in adults and children.AIH-1 is specified by anti-nuclear antibody（ANA） and smooth muscle antibody（SMA）.AIH-2 is specified by antibody to liver kidney microsomal antigen type-1（anti-LKM1） and anti-liver cytosol type 1（anti-LC1）.SMA,ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation.PBC is specified by antimitochondrial antibodies（AMA） reacting with enzymes of the 2-oxo-acid dehydrogenase complexes（chiefly pyruvate dehydrogenase complex E2 subunit） and disease-specific ANA mainly react-ing with nuclear pore gp210 and nuclear body sp100.Sclerosing cholangitis presents as at least two variants,first the classical primary sclerosing cholangitis（PSC） mostly affecting adult men wherein the only（and non-specific） reactivity is an atypical perinuclear antineutro-phil cytoplasmic antibody（p-ANCA）,also termed perinuclear anti-neutrophil nuclear antibodies（p-ANNA） and second the childhood disease called autoimmune sclerosing cholangitis（ASC） with serological features resembling those of type 1 AIH.Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens,and automatedtechnologies such as ELISAs and bead assays,become available to complement（or even compete with） traditional immunofluorescence procedures.We survey for the first time global trends in quality assurance impacting as it does on（1） manufacturers/purveyors of kits and reagents,（2） diagnostic service laboratories that fulfill clinicians＇ requirements,and（3） the end-user,the physician providing patient care,who must properly interpret test results in the overall clinical context.     

Juvenile autoimmune hepatitis: Spectrum of the disease

Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.     

Autoimmune hepatitis: diagnostic and management challenges

Abstract   There are two main types of autoimmune hepatitis (AIH): AIH type 1, characterized by anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies; and AIH type 2, positive for anti-liver kidney microsomal antibody type 1 (LKM1). AIH type 1 affects equally adults and children, while AIH type 2 affects mainly children. There is a female preponderance for both; AIH type 1 is associated with the HLA haplotype DR3, while AIH type 2 is associated with DR7. In young patients, both types of AIH frequently present with features of acute hepatitis. The diagnosis must be suspected and the appropriate tests sought promptly, because treatment should be started as soon as possible to avoid rapid progression to cirrhosis and liver failure. Though new drugs have been used for the treatment of AIH, including ciclosporin A, the standard treatment with prednisolone, to which azathioprine may be added as a steroid sparing agent, remains the best, with excellent short and long term results. Treatment, however, has to be finely tuned, to avoid severe steroid side effects.     

Autoantibodies and defined target autoantigens in autoimmune hepatitis: an overview

Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by hypergammaglobulinaemia, non-organ and liver-related autoantibodies, association with HLA-DR3 or DR4 and a favourable response to immunosuppression. The current classification of AIH and the several autoantibodies/target autoantigens found in this disease are reported. The importance of these markers in the differential diagnosis and the study of pathogenesis of AIH is also given. AIH is subdivided into two major types: AIH type 1 (AIH-1) and AIH type 2 (AIH-2). AIH-1 is characterised by the detection of smooth muscle autoantibodies (SMA) and/or antinuclear antibodies (ANA). Antineutrophil cytoplasmic autoantibodies (ANCA), in most cases of perinuclear pattern (p-ANCA), by the indirect immunofluorescence assay, antibodies against the asialoglycoprotein receptor (anti-ASGP-R) and antibodies to soluble liver antigens or liver-pancreas (anti-SLA/LP) may be useful for the identification of individuals who are seronegative for ANA/SMA. AIH-2 is characterised by the presence of specific autoantibodies against liver and kidney microsomal antigens (anti-LKM type 1 or infrequently anti-LKM type 3) and/or autoantibodies against liver cytosol 1 antigen (anti-LC1). Anti-LKM-1 and anti-LKM-3 autoantibodies are also detected in some patients with chronic hepatitis C (HCV) and chronic hepatitis D (HDV). For these reasons, the distinction between AIH and chronic viral hepatitis is of particular importance. Cytochrome P450 2D6 (CYP2D6) is the major target autoantigen of anti-LKM-1 autoantibodies in both conditions (AIH-2 and HCV infection). Recent data have demonstrated the expression of CYP2D6 on the surface of hepatocytes, suggesting a pathogenetic role of anti-LKM-1 autoantibodies in liver injury. Family 1 of UDP-glycuronosyltransferases has been identified as the target autoantigen of anti-LKM-3. The molecular target of anti-SLA/LP autoantibodies has been identified recently as a 50 kDa protein with unknown structure and function. A liver-specific enzyme, the formiminotransferase cyclodeaminase, was identified as the target autoantigen of anti-LC1 autoantibodies. Anti-ASGP-R and anti-LC1 autoantibodies appear to correlate better with the severity of AIH and the response to treatment. The latter may suggest a pathogenic role of these autoantibodies in the hepatocellular damage in AIH. In general, however, autoantibodies should not be used to monitor treatment or to predict AIH activity or outcome. Finally, current knowledge concerning a specific form of AIH that may develop in some patients with a rare genetic syndrome, the autoimmune polyglandular syndrome type-1 (APS-1), is also discussed. Autoantibodies against liver microsomes (anti-LM) are the specific autoantibodies found in AIH as a disease component of APS-1. However, anti-LM autoantibodies have also been described in cases of dihydralazine-induced hepatitis. Cytochrome P450 1A2 has been identified as the target autoantigen of anti-LM autoantibodies in both disease entities.     

自身免疫性肝炎患儿临床特点与预后

目的了解自身免疫性肝炎(AIH)患儿临床特点与预后。方法回顾性分析2016年8月至2019年8月于湖北省襄阳市中心医院收治的138例AIH患儿的临床资料,分析临床特征及治疗、预后。结果138例患儿中AIH-1型96例(69.57%),AIH-2型42例(30.43%)。发热6例(4.35%),恶心、乏力12例(8.70%),转氨酶异常39例(28.26%),黄疸81例(58.70%)。AIH-1型患儿合并炎症性肠病、原发性硬化性胆管炎、系统性红斑狼疮、原发性胆汁性胆管炎分别为6例(4.35%)、9例(6.52%)、3例(2.17%)、3例(2.17%)。入院时所有患儿均有肝功能异常,AIH-1型者γ球蛋白、免疫球蛋白G显著高于AIH-2型者(P<0.05)。117例行肝活组织检查,提示界面性肝炎108例(92.31%),玫瑰花结9例(7.69%),浆细胞或淋巴细胞浸润69例(58.97%);肝脏炎症分级G≥3级66例(56.41%),纤维化分期S≥3级78例(66.67%)。120例行糖皮质激素规范治疗,完全缓解87例(72.50%),部分缓解30例(25.00%),无应答3例(2.50%)。完全缓解后激素减量期45例(51.72%)复发。结论儿童AIH多见于AIH-1型,临床表现复杂,发病时多数患儿肝脏炎症及纤维化已明显进展,激素单用或联合硫唑嘌呤治疗后可改善患儿生化指标及病理,但易复发。     

Update on Autoimmune Hepatitis

Autoimmune hepatitis (AIH), a liver disorder affecting both children and adults, is characterized by inflammatory liver histology, elevated transaminase levels, circulating nonorganspecific autoantibodies, and increased levels of immunoglobulin G, in the absence of a known etiology. Two types of AIH are recognized according to seropositivity: smooth muscle antibody and/or antinuclear antibody define AIH type 1 and antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is mainly a paediatric disease, though it does occasionally affects young adults. AIH should be considered during the diagnostic workup of any patient with increased liver enzyme levels. AIH is exquisitely responsive to immunosuppressive treatment with prednisolone with or without azathioprine, with symptom free long-term survival for the majority of patients. For those who do not respond to standard treatment, or who are difficult-to-treat, mycophenolate mofetil and, in the absence of a response, calcineurin inhibitors should be tried in addition to steroids. The pathogenesis of AIH is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4 T-cells, although recent studies support the involvement of diverse populations, including Th17 cells. A deeper understanding of the pathogenesis of AIH is likely to contribute to the development of novel treatments, such as the adoptive transfer of autologous expanded antigenspecific regulatory T-cells, which ultimately aim at restoring tolerance to liver-derived antigens.     

Anti-mitochondrial antibody positive autoimmune hepatitis triggered by EBV infection in a young girl

Autoimmune hepatitis (AIH) is rare in children. Two types of childhood autoimmune hepatitis are recognized: AIH type 1 which is characterized by the presence of smooth muscle (SMA) and/or antinuclear (ANA) antibodies; and AIH type 2 which is positive for anti-liver kidney microsomal type 1 (anti-LKM-1) antibody. Anti-mitochondrial antibody (AMA) is considered the hallmark for primary biliary cirrhosis (PBC) that occurs primarily in adult women and is characterized by destruction of the intralobular bile ducts and progression to cirrhosis and liver failure. Antimitochondrial-antibody-positive AIH is extremely rare in children. We report a 13 year old Saudi girl with type-1 AIH who had a strongly positive anti-mitochondrial antibody and no evidence of small bile duct disease in the liver biopsy.     

Features and outcome of autoimmune hepatitis type 2 presenting with isolated positivity for anti-liver cytosol antibody.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) type 2 is identified by the presence in the serum of anti-liver/kidney microsome type 1 autoantibody. Anti-liver cytosol autoantibody has been reported in children with autoimmune liver disorders mostly in association with anti-liver/kidney microsome reactivity. However, its role as a sole marker of AIH type 2 is debated. We describe here a series of 18 children and adolescents (15 girls, 3 boys) with AIH with serum anti-liver cytosol type 1 (aLC1) as the only autoimmune marker. METHODS: A retrospective review was conducted from 3 pediatric hepatology units of all children with an autoimmune liver disease associated with aLC1 as found by immunofluorescence and/or immunodiffusion or immunoblotting. RESULTS: Age at first symptoms ranged from 11 months to 14 years; 12 children presented with acute hepatitis, 1 with progressive jaundice, and 5 were asymptomatic. Anti-liver/kidney microsome, antimitochondria, and anti-actin autoantibodies were not detected. Signs of cirrhosis were present in 11 children. Immunosuppressive treatment was effective in all except 2 children who had subfulminant hepatic failure and who required liver transplantation. Sixteen patients (14 with their native liver) currently are alive; 14 patients still are on immunosuppressive therapy after 1 to 22 years. According to the international scoring system for the diagnosis of AIH, 16 patients corresponded to a definite diagnosis and 2 corresponded to a probable diagnosis. CONCLUSIONS: The presence of aLC1 in children with acute or chronic liver disease of unknown origin strongly supports a diagnosis of AIH and is an indication for early immunosuppressive therapy.     

Anti-liver cytosolic antigen type 1 (LC1) antibodies in childhood autoimmune liver disease

Antibodies to liver cytosol antigen type 1 (anti-LC1), which recognize a 60-kd peptide contained in the liver cytosolic fraction, have been reported to define a subset of autoimmune hepatitis (AIH) either negative for other autoantibodies or positive for anti-liver kidney microsomal antibody type 1 (LKM-1) and to be best detected in immunodiffusion. To analyze the prevalence of antiLC1 in childhood liver disease, we have tested the sera of 95 patients using immunoblot, indirect immunofluorescence, and immunodiffusion. Fifteen children had smooth muscle antibody (SMA) and/or anti-nuclear antibody (ANA)-positive AIH, 13 had anti-LKM-1-positive AIH, 14 had autoimmune sclerosing cholangitis (ASC) (all SMA and/or ANA positive), and 53 had non-autoimmune liver disease (10 had al-anti-trypsin deficiency [α1-ATD], 11 had Wilson's disease [wd], 14 had Alagille's syndrome, and 18 had chronic hepatitis B virus [HBV] infection). Twenty healthy children were studied as controls. Anti-LC1 positivity in immunodiffusion and strong reactivity in immunoblot were found in 4 LKM-1- and 2 SMA/ANA-positive patients with AIH and in 1 patient with ASC, but in none of the patients with other liver diseases nor in controls. A weak 60-kd band was detected by immunoblot in 6 more patients with AIH (2 were LKM-1- and 4 were SMA/ANA-positive) and 6 patients with ASC, all anti-LC1-negative by immunofluorescence and immunodiffusion. No distinct clinical features characterized the anti-LC1-positive patients. Our data show that, in pediatric age, LC1 reactivity, although associated with autoimmune liver disease, does not identify a distinct disease subset and that immunoblot is the most sensitive technique to detect anti-LC1.