Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease.METHODSLevels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays.RESULTSWe found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH.CONCLUSIONAuto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other.

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.

Historical reflections on autoimmune hepatitis

Autoimmune hepatitis(AIH),initially known as chronic active or active chronic hepatitis(and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis(CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier(and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody(ANA),smooth muscle antibody(SMA) and liver-kidney microsomal(LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being(relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.

Immunoglobulin G in non-alcoholic steatohepatitis predicts clinical outcome:A prospective multi-centre cohort study

BACKGROUND Autoimmune markers including plasma cells(PC),anti-smooth-muscle antibody(ASMA),anti-nuclear antibody(ANA),and raised immunoglobulin G(IgG)are commonly observed in non-alcoholic steatohepatitis(NASH),however their clinical significance is unknown.AIM To determine if autoimmune markers in NASH patients are independently associated with poorer clinical outcomes.METHODS Consecutive patients with biopsy proven NASH from Christchurch Hospital,New Zealand and Singapore General Hospital(SGH)were included between 2005 to 2016 in a prospective multi-centre cohort study.Patients with other causes of chronic liver disease were excluded.IgG>14 g/L or globulin fraction>50%,ANA≥1:40,SMA≥1:40 were considered positive.Multivariate analysis was performed to assess which markers were independently associated with mortality and hepatic decompensation.RESULTS Total 261 patients were included of which 201 were from SGH.The median age was 53 and 51.9%were male.Advanced fibrosis was present in 31.4%at diagnosis.PC,ASMA,ANA and raised IgG were observed in 13.1%,4.9%,27.8%and 30.1%of patients respectively.After multivariate analysis,elevated IgG[Hazard Ratio(HR)6.79,95%CI:2.93-17.15]and fibrosis stage(HR 1.37,95%CI:1.03-1.87)were found to be independently associated with increased risk of liver decompensation.Age(HR 1.06,95%CI:1.02-1.10)and elevated IgG(HR 3.79,95%CI:1.90-7.68)were independent factors associated with higher mortality risk.CONCLUSION Elevated IgG,rather than ANA,ASMA or plasma cells,is independently associated with increased risk of hepatic decompensation and mortality in NASH.It could hence be important for prognostication.

Application of autoantibody detection in chronic liver disease

Autoantibody(AAb)detection has become one of the standards of diagnosis for autoimmune liver disease(AILD),and some AAbs have become specific biomarkers of AILD.In addition,AAbs can be detected in patients with non-AILDs,such as viral hepatitis and alcoholic liver disease.However,the distribution characteristics and pathogenic mechanisms of AAbs in patients with non-AILD are unclear.This article summarizes the characteristics of AAbs in several common clinical chronic liver diseases(CLDs)and discusses the value of AAb analysis in CLD.

幽门螺杆菌感染与自身免疫性肝病关系的分析

目的回顾性分析本院首诊、符合纳入标准的AILD患者临床资料,探讨Hp感染对上述AILD患者发生、发展的影响。方法2015年9月—2022年2月期间于聊城市中医医院首诊AILD患者74例,其中男性43例、女性31例,年龄(58.2±12.5)岁。AIH、PBC及PSC符合标准。使用14C-UBT、胃窦组织快速尿速酶试验了解Hp感染情况,根据Hp感染与否状态对本院首诊AILD病例分组,比较不同分组肝功能、自身抗体、淋巴细胞亚群及肝组织病理改变程度。结果74例AILD患者中AIH、PBC及PSC分别为34例(45.9%)、33例(44.6%)及7例(9.5%),依据14C-UBT结果分为Hp阳性、阴性组。前者ANA、AMA、SMA、ANCA、AMA-M2及LKM-1为20例(45.4%)、18例(40.9%)、17例(38.6%)、23例(52.2%)、25例(56.8%)及21例(47.7%),分别显著高于Hp阴性组[6例(20.0%)、4例(13.3%)、4例(13.3%)、5例(16.7%)、2例(6.7%)及2例(6.7%),P<0.05]。Hp阳性组CD3^(+)CD4^(+)T细胞、CD4^(+)/CD8^(+)及CD3-CD19^(+)B细胞为(42.1±6.2)%、(1.9±0.8)及(15.2±3.5)%,分别显著高于Hp阴性组[(37.7±5.5)%、(1.4±0.5)及(11.9±2.5)%,P<0.05];Hp阳性组CD3^(+)CD8^(+)T细胞及CD3-CD16^(+)CD56^(+)NK细胞为(25.4±5.0)%及(11.7±2.8)%,分别显著低于[(29.0±5.1)%及(19.7±3.7)%,P<0.05]。Hp阳性组[30例(68.2%)]≥F3期高于Hp阴性组[13例(43.3%),P<0.05],同时前者[24例(54.6%)]≥G3级也高于后者[8例(26.7%),P<0.05]。结论超半数AILD患者存在Hp感染,与多种自身抗体增加和淋巴细胞亚群紊乱密切相关,可导致肝组织纤维化分期、炎症活动分级增加。

自身免疫性肝病基础和临床研究进展

自身免疫性肝病与常见肝病的差异性较大,提高其认知度和诊断水平尤为重要。回顾了有关自身免疫性肝病最近几年的文献资料,总结了自身免疫性肝病的发病机制、自身抗体、诊断及治疗方面取得的进展,指出还须进一步的临床研究及实践加以证实和完善。

183例肝炎病毒血清学标志阴性的肝病病因分析

目的了解肝炎病毒血清学标志阴性的肝病存在情况,探讨其病因。方法选择甲、乙、丙、丁、戊型病毒性肝炎血清学标志阴性血清183例。对临床上诊断为病因不明的肝病血清分别用巢式PCR(nPCR)方法和RT-PCR方法检测HBVDNA和HCVRNA,用间接免疫荧光法检测病因不明的肝病血清自身抗体,用ELISA法检测病因不明的肝病血清抗-EBV/CMVIgM抗体。结果183例肝炎病毒血清学标志阴性的肝病患者中69例是病因不明的肝病。27例是自身免疫性疾病,23例是酒精性肝病,21例是药物性肝病,24例是肝胆外科疾病,4例是非酒精性脂肪肝,2例是传染性单核细胞增多症,13例是其他疾病引起肝功能异常。病因不明的肝病是以成人为主,其血清HBVDNA和HCVRNA均为阴性。在病因不明的69例肝病患者中,7例患者1种以上自身抗体滴度为1∶320。结论在肝炎病毒血清学标志阴性的183例肝病中,病因不明的肝病、自身免疫性肝病、酒精性肝病、药物性肝病、肝胆外科疾病、非酒精性脂肪肝、传染性单核细胞增多症和其他疾病引起肝功能异常分别占37.7%、14.8%、12.6%、11.5%、13.1%、2.2%、1.1%和7.1%。血清学和核酸检测结果提示病因不明的肝病患者未感染已知肝炎病毒如HBV、HCV。对病因不明的肝病有必要检测自身抗体,以排除自身免疫性肝病。

自身抗体检测对肝病患者的鉴别诊断价值

目的探讨自身抗体检测在鉴别诊断自身免疫性肝病(autoimmune liver disease,ALD)与慢性乙型肝炎(chronic hepatitis B,CHB)患者中的价值。方法回顾性分析2011年5月-2014年8月经枣阳市第一人民医院确诊的ALD患者215例,其中自身免疫性肝炎(AIH)患者122例,原发性胆汁性肝硬化(PBC)患者93例,同时选取CHB患者453例,采用间接免疫荧光法和免疫印迹法检测ANA、AMA、SMA、抗SLA/LP、抗LKM-1、抗LC-1及AMA-M2。比较3组患者的ALT、AST、ALP、GGT水平。结果 AIH组、PBC组患者的ALT、AST、ALP、GGT含量高于CHB组,差异有统计学意义(P<0.05);ALD患者ANA总阳性率为83.26%,高于CHB组(15.01%)(P<0.05);AIH组ANA、AMA、SMA、抗SLA/LP、抗LKM-1、抗LC-1及AMA-M2阳性率分别为79.51%、14.75%、45.90%、16.39%、12.30%、6.565%、3.28%;PBC组ANA、AMA、SMA、抗SLA/LP、AMA-M2阳性率分别为88.17%、94.62%、11.83%、3.23%、94.62%;AIH组和PBC组ANA阳性检出率显著高于CHB组(P<0.05)。AIH组和PBC组ANA滴度大于1∶320的比率显著高于CHB组(P<0.05)。结论自身抗体检测是诊断ALD的必要条件,对ALD和CHB的鉴别诊断有重要临床意义。

病毒性肝炎患者抗肝抗原自身抗体的检测与分析

目的分析病毒性肝炎患者中几种抗肝抗原自身抗体的存在状况和临床意义。方法采用酶联免疫吸附试验和免疫印迹法检测941例病毒性肝炎患者和32例自身免疫性肝病患者血清中肝肾微粒抗体Ⅰ型(LKM-1)、肝细胞胞溶质抗原Ⅰ型(LC-1)、可溶性肝抗原(SLA)等自身抗体。结果 941例病毒性肝炎患者中,抗肝抗原自身抗体检测阳性率分别为LKM-1 0.9%(9/941)、LC-1 0.2%(2/941)、SLA 0.0%(0/941),其中153例丙型肝炎患者中,抗肝抗原自身抗体检测阳性率分别为LKM-1 4.5%(7/153)、LC-1 1.3%(2/153)、SLA 0%(0/153);552例乙型肝炎患者中,仅检测出2例(0.4%)LKM-1阳性,在甲型肝炎、戊型肝炎和丁型肝炎中未检测出抗肝抗原自身抗体。在32例自身免疫性肝病患者中,抗肝抗原抗体LKM-1、LC-1和SLA的检出率分别为9.4%、3.1%和9.4%,其中在11例自身免疫性肝炎中,LKM-1、LC-1和SLA阳性率分别为27.3%、9.1%和18.2%。病毒性肝炎患者抗肝抗原自身抗体检出率低,与自身免疫性肝病患者比较,LKM-1和SLA差异有统计学意义(P<0.01)。结论少数丙型病毒性肝炎患者血清中存在多种抗肝抗原自身抗体,对病毒性肝炎患者进行包括抗肝抗原在内的自身抗体检测有助于病毒性肝炎合并自身免疫性肝病的诊断。

自身免疫性肝病抗体在肝病诊断中的临床价值

目的探讨自身免疫性肝病抗体在肝病诊断中的临床价值。方法回顾性分析2145例肝病患者的自身抗体结果,并对自身抗体阳性的结果进行临床分析。结果 2145例患者中共检测出自身抗体阳性359例,阳性率为16.7%。诊断原发性胆汁性肝硬化(PBC)64例,检出率为3.0%,诊断自身免疫性肝炎(AIH)59例,检出率为2.8%。73.4%PBC患者血清抗核抗体(ANA)≥1∶320,且26.6%抗线粒体抗体(AMA)为阳性;49.2%AIH患者血清ANA≥1∶320,且3.3%AMA为阳性。PBC患者核膜型及着丝点型显著多于AIH患者,而均质型及着丝点颗粒型显著少于AIH患者,差异均有统计学意义。ANA阳性≥1∶320乙型肝炎患者谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷酰转肽酶(GGT)及碱性磷酸酶(ALP)水平显著高于ANA阳性≥1∶100及ANA阴性患者,差异有统计学意义。结论自身抗体检测是诊断自身免疫性肝病的必要条件,但需鉴别病毒性肝炎、药物性肝炎和其他疾病。

118例病原学指标阴性的肝病患者病因临床分析

目的了解肝炎病毒血清学标志阴性的肝病患者的病因。方法选择甲、乙、丙、丁、戊型病毒性肝炎血清学标志阴性的患者118例。对临床上诊断为病原学阴性的肝病患者血清,分别进行自身免疫性肝病抗体,ANA全套,FT3、FT4及TSH,血清Cu及铜蓝蛋白的检测。收集临床资料,分析结果。结果118例肝炎病毒血清学标志阴性的肝病患者中47例是病因不明的肝病,在病因不明的47例肝病患者中,14例患者的血清ANA等自身抗体中至少一种抗体为阳性。结论对病因不明的肝病有必要检测自身抗体,以排除自身免疫性肝病。

抗肝抗原自身抗体检测在自身免疫性肝病诊断中的应用

目的:对住院患者的肝抗原自身抗体检测的情况进行分析,了解肝抗原自身抗体在自身免疫性肝脏疾病诊断中的作用。方法:运用间接免疫荧光法检测患者的抗核抗体,运用酶免疫条带技术检测患者的抗肝抗原自身抗体谱,对某医院2016年1月-2017年3月进行了抗肝抗原自身抗体谱检测的55例住院患者的资料进行回顾性分析。结果:在检测的55例患者中,有20例诊断为自身免疫性肝病,其中4例为病毒性慢性乙型肝炎合并自身免疫性肝病。自身免疫性肝病患者中,有2例抗核抗体阴性而抗肝抗原自身抗体谱阳性。在35例非自身免疫性肝病患者中,有6例仅为抗核抗体阳性而抗肝抗原自身抗体谱阴性。结论:抗核抗体结合抗肝抗原自身抗体谱检测对自身免疫性肝病诊断中具有着重要的意义,临床应加强肝抗原自身抗体谱检测。

自身免疫性肝病相关自身抗体的研究进展

自身免疫性肝病(autoimmune liver disease, AILD)是一组由自身免疫反应引起的慢性肝胆系统损伤性疾病,早期诊断及治疗对该疾病发展及预后至关重要。自身抗体的检测对于该组疾病的诊疗具有重要临床价值。医学上对自身抗体检测技术的提高,对于AILD的诊断及鉴别工作都起到了非常大的作用。本文主要探讨自身免疫性肝炎(autoimmune hepatitis,AIH)、原发性胆汁性胆管炎(primary biliary cholangitis, PBC)、原发性硬化性胆管炎(primary sclerosing cholangitis, PSC)三种疾病的相关自身抗体,以期为今后的AILD诊断治疗提供具有建设性的参考意见。

自身抗体检测对自身免疫性肝病诊断的临床意义

目的探讨自身免疫性肝病诊断采用自身抗体检测的临床意义。方法采用免疫印迹法和酶联免疫吸附法检测慢性病毒性肝炎患者和自身免疫性肝病患者中血清的LCI抗体、ANA、gp-210、AMA-M2、SP100、SLA/LP、LKM-1。结果 AIH的SLA/LP和LKM-1的阳性检出率明显高于HBV和HCV,差异显著,有统计学意义,P<0.05;PBC的AMA-M2和gp-210的阳性检出率明显高于HBV和HCV,差异显著,有统计学意义,P<0.05。结论自身抗体检测对自身免疫性肝病诊断和鉴别有重要临床意义。

不同临床类型肝病患者血清中自身抗体的检测及临床应用

目的分析不同临床类型肝病患者血清中各种自身抗体的存在状况,探讨其临床应用价值。方法采用间接免疫荧光法和免疫印迹法,对我院2010年6月至2014年2月3 124例不同类型肝病患者和200例正常健康体检者血清中的抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(ASMA)、抗肝肾微粒体抗体(LKM)和自身免疫肝病谱等9项指标进行检测。结果病毒性肝炎ANA、AMA阳性率分别为11.11%、0.39%,抗肝抗原自身抗体检测阳性率分别为AMA M22.22%,M2-3E 1.86%、Sp100 0.59%、PML 0.42%、gp210 3.81%、LKM-1 0.62%、LC-1 2.28%、SLA-LP 0.26%、Ro52 10.6%。自身免疫性肝病ANA、AMA阳性率分别为90.63%、78.13%,抗肝抗原自身抗体检测阳性率分别依次为71.87%,71.87%、6.25%、6.25%、65.63%、3.13%、0、21.88%、93.75%。与病毒性肝炎比较,自身免疫肝病的9项指标以及ANA、AMA的差异有统计学意义(P<0.01)。与正常对照组比较,丙肝、自身免疫肝病、药物性肝炎的ANA阳性率的差异有显著统计学意义(P<0.01)。甲肝、戊肝、脂肪肝血清中未检测出自身抗体。与病毒性肝炎比较,药物性肝炎的ANA检出率差异有显著统计学意义(P<0.01)。各型肝炎患者ANA的荧光模型存在差异。结论检测自身抗体的类型、滴度以及荧光模型对于不同类型肝病的诊断和治疗具有临床参考价值。

自身抗体及肝功能检测在自身免疫性肝病与病毒性肝炎鉴别诊断中的价值

目的分析自身抗体及肝功能检测在自身免疫性肝病与病毒性肝炎鉴别诊断中的价值。方法本次研究对象为医院在2018年6月至2019年6月收治的48例自身免疫性肝病患者为A组及48例病毒性肝炎患者为B组,对比两组患者的自身抗体[可溶性酸性磷酸化核蛋白SP100抗体(SP100)、抗可溶性肝抗原抗体(SLA)、抗肝肾微粒体抗体1型(LKM-1)、血清抗核胞膜糖蛋白210抗体(GP210)、抗肝细胞溶质抗原1型抗体(LC-1)、抗线粒体抗体M2型(AMA-M2)]、抗核抗体(ANA)、肝功能指标以及ANA荧光核型占比。结果A、B组的LKM-1与LC-1的检查率对比,差异无统计学意义(P>0.05);A组患者的SP100、GP210、AMA-M2、SLA、ANA、肝功能水平均比B组高(P<0.05);A、B组荧光核型中均质型、颗粒型占比对比,差异有统计学意义(P>0.05);A组ANA荧光核型主要以均质型、核仁型为主,B组则以颗粒型为主。结论自身抗体及肝功能检测在自身免疫性肝病及病毒性肝炎的鉴别及诊断中均具有重要意义。

血清自身抗体检测对诊断自身免疫性肝病的应用研究

目的研究血清自身抗体检测在自身免疫性肝病中的应用价值。方法选择2016年3月—2017年12月本院接诊的自身免疫性肝病患者57例为A组、病毒性肝炎患者40例为B组。两组均实行血清自身抗体检测,并对其检测结果做出分析比较。结果 A组的血清自身抗体总阳性率高于B组,差异具有统计学意义(P<0.05)。AIH组的LC-1抗体阳性率为13.33%、ASMA抗体阳性率为93.33%、LKM1抗体阳性率为23.33%,明显比B组的3.7%、3.7%、0.0%高,差异具有统计学意义(P<0.05)。A组的Gp210、AMA-2与Sp100抗体阳性率比B组低,差异具有统计学意义(P<0.05)。结论积极检测血清自身抗体有助于鉴别诊断自身免疫性肝病。

ANA、LKM-1、AMA M2、LC-1及SLA/LP联合检测在乙肝病毒感染分型中的应用研究

目的探讨ANA、LKM-1、AMA M2、LC-1及SLA/LP联合检测在乙肝病毒感染分型中的应用研究。方法选取2015年1月~2019年5月我院传染科35例乙肝合并自身免疫性肝病患者作为观察组,同时选取65例乙肝病毒感染患者作为对照组。观察两组血清抗核抗体(ANA)、抗肝肾微粒体Ⅰ型抗体(LKM-1)、抗线粒体抗体(AMA M2)、抗肝胞浆Ⅰ型抗体(LC-1)、抗可溶性肝抗原/肝胰抗原抗体(SLA/LP)阳性率,对结果进行分析。结果观察组中ANA的阳性率(35.00%)高于对照组(21.86%),观察组中LKM-1、AMA M2、LC-1及SLA/LP的阳性率均显著高于对照组(P<0.05),差异均有统计学意义(P<0.05)。对照组ANA阳性主要为核颗粒型,主要在1:100的血清稀释度中检出,观察组ANA阳性主要为核均质性,主要在1:1000的血清稀释度中检出,两种核型稀释度组间差异有统计学意义(P<0.05)。结论多项自身抗体联合检测对乙肝及自身免疫性肝病的抗体检测全面,ANA检测是初筛试验,LKM-1、AMA M2、LC-1及SLA/LP等是确证试验,有助于临床诊断及指导用药。

自身抗体及肝功能检测在自身免疫性肝病与病毒性肝炎鉴别诊断中的价值

目的观察自身抗体及肝功能检测在自身免疫性肝病与病毒性肝炎鉴别诊断中的价值。方法选择2016-2018年我院接收的自身免疫性肝病患者60例作为观察组,病毒性肝炎患者60例作为对照组。两组患者应用间接免疫荧光法、免疫印迹法分别进行自身抗体测定、肝功能检测。比较分析两组的检测结果。结果观察组ANA、AMA-M2、SLA/LP、gp210、sp100阳性率高于对照组(P<0.05)。观察组AST、ALT、ALP、GGT、IgG水平均高于对照组(P<0.05)。两组ANA荧光核型中均质型、颗粒型占比比较,差异显著(P<0.05);观察组ANA荧光核型以均质型、核仁型为主,而对照组以颗粒型为主。结论利用自身抗体及肝功能检测能对自身免疫性肝病、病毒性肝炎进行良好的鉴别诊断,值得临床应用推广。