慢性乙型肝炎患者血清中肝特异性自身抗体的检测

目的：阐明慢性乙型肝炎中是否也存在肝特异性自身抗体及其在病情转归中的作用。方法：以猴肝组织切片和可溶性肝抗原为抗原基质，用间接免疫荧光和蛋白质印迹法检测３３７例慢性乙型肝炎和肝硬化患者血清中的自身抗体。结果：免疫荧光法显示乙型肝炎后肝硬化自身抗体总的阳性率（２４．０７％）高于慢性乙型肝炎组（１４．２９％），且两组均显著高于正常对照组。蛋白质印迹的阳性率各为４３．４２％和４２．５９％，两者无显著差异。两组病例靶抗原相对分子质量多集中在３．０万～５．５万之间，但肝硬化患者在相对分子质量２．５万和９．０万左右处的阳性条带均多于慢性肝炎患者。结论：慢性肝炎、肝硬化患者血清中存在抗肝组织自身抗体，其相对应的靶抗原有多种。进一步分离、鉴定有意义的靶抗原，并对其进行抗原表位、细胞表面表达等分析，将有助于探讨自身免疫在慢性肝炎发病及转归中的作用。

慢性肝炎与肝癌患者血清中肝特异性自身抗体的差异分析

目的 阐明慢性肝炎与肝癌患者血清中肝特异性自身抗体的差异。方法 以肝组织切片和可溶性肝抗原为抗原基质 ,用间接免疫荧光法和蛋白印迹检测 40 0例慢性肝炎、肝硬化和 12 1例原发性肝癌患者血清中的肝特异性自身抗体。结果 免疫荧光法显示肝癌患者血清中肝特异性自身抗体的阳性率 (2 9.7% )显著高于慢性肝炎 (18.75 % )。蛋白印迹法测得两组病例自身抗体的阳性率相近 ,且靶抗原相对分子质量多分布在2 0× 10 3 ～ 5 5× 10 3 之间 ,有 19.83%肝癌和 1.75 %的慢性肝病患者的血清在 2 0× 10 3 左右处有 1～ 2条明显的阳性带。结论 慢性肝病和肝癌患者体内不仅存在相似的自身免疫紊乱 ,且随着病情的变化部分肝癌患者体内的自身靶抗原发生了改变。进一步纯化、鉴定这些有意义的靶抗原分子将有助于探讨自身免疫在慢性肝病的转归和恶性变中的作用。

丙型肝炎患者HCV-RNA感染与血清自身抗体的相关性分析

目的研究丙型肝炎患者HCV-RNA感染与血清自身抗体产生的相关性,进一步探讨丙型肝炎的发病机理。方法对本院消化科220例丙型肝炎抗体IgG（＋）患者进行HCV-RNA检测及抗肝抗原自身抗体谱检测。结果220例患者中,有122例HCV-RNA阳性,阳性率为55.4%,98例患者HCV-RNA阴性,阴性率为44.6%。将其分为两组,丙型肝炎抗体IgG（＋）,HCV-RNA阳性组,测得抗线粒体抗体M2（AMA-M2）阳性9例（7.3%）,抗可溶性肝抗原抗体（SLA）14例（11.47%）,肝抗肾微粒体抗体（LKM-1）阳性26例（21.3%）,抗肝细胞溶质抗原1型（LC-1）阳性7例（5.7%）;丙型肝炎抗体IgG（＋）,HCV-RNA阴性组,测得AMA-M2阳性3例（2.46%）,SLA阳性4例（3.28%）,LKM-1阳性13例（10.65%）,LC-1阳性3例（2.46%）。两组肝抗原抗体谱阳性率差异有统计学意义（χ-2=93.4,P〈0.05）。结论丙肝患者抗肝抗原自身抗体谱检测阳性率与丙肝患者HCV-RNA阳性呈正相关。

血清抗肝抗原自身抗体检测对自身免疫性肝病的诊断价值(附49例分析)

目的探讨抗肝抗原自身抗体检测对自身免疫性肝病诊断的意义。方法采用免疫印迹法测定49例自身免疫性肝病、166例非自身免疫性肝病及25例健康体检者血清抗线粒体2型抗体(AMA-M2)、抗肝肾微粒体1型抗体(LKM-1)、抗肝细胞溶质抗原1型(LC-1)及抗可溶性肝抗原/肝胰抗原抗体(SLA/LP)水平。结果自身免疫性肝病中,自身免疫性肝炎(AIH)组LKM-1阳性率13.16%,LC-1阳性率7.89%,SLA/LP阳性率26.32%;原发性胆汁性肝硬化(PBC)组AMA-M2阳性率为100%。非自身免疫性肝病组仅检出LKM-1阳性率1.20%。健康体检者未检出。自身免疫性肝病组的阳性检出率明显高于非自身免疫性肝病组,差异有统计学意义(χ2=34.46,P<0.05)。结论血清抗肝抗原自身抗体检测对自身免疫性肝病诊断、分型有一定参考价值。

自身免疫性肝病诊断中的抗肝抗原自身抗体检测分析

自身免疫性肝病是一种特殊的慢性肝疾病,主要损伤肝胆,自身免疫性肝炎、原发性硬化性胆汁性肝硬化、原发性硬化性胆管炎等是其主要病症[1]。现阶段,临床仍然缺乏特异性的指标诊断自身免疫性肝病。在自身免疫性肝病的诊断与分型中,血清抗肝抗原自身抗体检测具有极为重要的临床意义[2]。本研究分析了自身免疫性肝病诊断中的抗肝抗原自身抗体检测。现报告如下。

肝病患者抗肝抗原自身抗体及抗核抗体的研究

目的：观察我国不同类型肝病患者中几种抗肝抗原自身抗体的存在状况；结合抗核抗体（ANA）探讨非甲-非戊型肝炎中存在自身免疫性肝病的可能性。方法：200例肝功能异常患者分为5组：（1）自身免疫性疾病组24例；自身免疫性肝炎5例，原发性胆汁性肝硬化6例，原发性硬化性胆管炎2例，干燥综合征4例，SLE1例和6例自身免疫性肝病未分型者；（2）HAV组23例；（3）HBV组67例；（4）HCV组26例；（5）非甲-非戊型肝炎组60例，免疫荧光，Western blot，免疫印迹和EISA法分别检测ANA，AMA，SMA，LKM-1，LC-1，SLA/LP和AMA中M2，M4和M9亚型，以及SS-A，SS-B，dsDNA等ANA的多种抗原成分抗体。结果：200例血清LKM-1和LC-1全部阴性，2/200例SLA/LP阳性，NonA-E组4例AMA和M2阳性，3例SMA高滴度阳性，4例出现SS-A，SS-B或dsDNA等自身抗体，ANA在HBV组22例，HCV组10例滴度超过1：320，HAV组1例出现SS-A，SS-B或dsDNA等自身抗体，ANA在HBV组22例，HCV组10例滴度超过1：320。HAV组1例SMA达1：1000，结论：三种肝抗原抗体（LKM-1，LC-1和SLA/LP）是自身免疫性肝病特异性抗体；非甲-非戊型肝炎中存在自身免疫性疾病；病毒标志阳性患者是否合并自身免疫性疾病值得进一步探讨。

肝抗原自身抗体检测对自身免疫性肝病的诊断价值探讨

目的探讨肝抗原自身抗体检测对自身免疫性肝病(ALD)的诊断价值。方法分别采用间接免疫荧光法和免疫印迹法检测51例ALD患者、85例各类病毒性肝炎和其他肝病患者血清中的抗核抗体(ANA)和肝抗原自身抗体。结果 51例ALD患者中,自身免疫性肝炎(AIH)组患者血清中检出的ANA、抗LKM-1抗体、抗SLA抗体阳性率分别为87.4%、27.8%和29.4%;原发性胆汁性肝硬化(PBC)组中ANA、抗线粒体抗体(AMA-M2)、抗Sp100抗体和抗gp210抗体阳性率分别为85.2%、92.6%、33.3%和25.9%;原发性硬化性胆管炎(PSC)组中ANA阳性率为18.6%,其他各项检测指标均为阴性;对照组ANA阳性率为11.6%,其他检测指标均为阴性。结论肝抗原自身抗体检测对ALD的明确诊断和分类有重要的临床意义。

肝抗原自身抗体检测对自身免疫性肝病的诊断价值

目的分析自身免疫性肝病患者实施肝抗原自身抗体检测的结果。方法：以55例自身免疫性肝病患者作为试验组，同期体检健康人员55例作为对照组，抽取血液样本进行肝抗原检测和ANA检测。观察检测结果，平行比较阳性检出率。结果：AIH患者抗LKM-1抗体、抗SLA抗体存在阳性结果，PBC患者AMA—M2、抗gp210抗体、抗Spl00抗体存在阳性结果，Os患者AMA-M2、抗LKM-1抗体、抗SLA抗体存在阳性结果。和对照组、PSC组差异明显，具有统计学意义（P〈0．05）；试验组／LNA检测阳性率均高于对照组，P〈0．05，差异有统计学意义。结论：针对自身免疫性肝病患者，肝抗原自身抗体检测有利于临床诊断和病情分类，具有较高的应用价值。

肝抗原自身抗体检测对自身免疫性肝病的诊断意义分析

目的:研究肝抗原自身抗体检测对自身免疫性肝脏疾病的诊断有何影响。方法:对某院2005年～2010年5年间收治的50例自身免疫性肝病患者和非自身免疫性肝病患者进行系统的检测,将50例患者分为2组,分别为自身免疫性肝病和非自身免疫性肝病,运用酶免疫条带技术和间接免疫荧光法,检测患者的自身抗体。结果:50例患者中,采用肝抗原自身抗体检测出的自身免疫性肝病组的抗核抗体[1](ANA)、抗LKM-1抗体、抗SLA抗体、抗线粒体抗体M2亚型(AMA-M2)均明显高于非自身免疫性血液中的抗体数量。结论:肝抗原自身抗体对自身免疫性肝病的诊断与治疗有着重要的临床意义。

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。

不同肝病患者抗肝抗原自身抗体的研究

目的 观察我国不同类型肝病患者中几种抗肝抗原自身抗体的存在状况 ;探讨自身免疫性肝脏疾病的自身抗体特征。方法 由 14 12例标本中选择 2 30例肝功能异常患者分为 5组 :①自身免疫性肝病组 4 2例 :自身免疫性肝炎 (AIH) 18例、原发性胆汁性肝硬化 (PBC) 2 1例、原发性硬化性胆管炎 (PSC) 3例。②HAV组 2 3例 ;③HBV组 70例 ;④HCV组 35例 ;⑤非甲～戊型肝炎组 6 0例。用间接免疫荧光、Westernblot、酶免疫条带技术等分别检测抗核抗体 (ANA)、抗线粒体抗体(AMA)、平滑肌抗体 (SMA)、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) 肝胰抗原 (LP)和AMA M2亚型 ,以及SS A、SS B、dsDNA等多种抗体。结果 14 12例中诊断AIH、PBC和PSC者分别为送检标本的 1.2 7% ,1.4 9%和 0 .2 1%。 2 30例血清中 2例LKM 1阳性和 2例SLA LP阳性 ,分别见于AIH和HCV感染者。PBC患者AMA和M2全部阳性 ;其ANA以核膜型为主 (7 14 ) ;AIH患者ANA抗体未见特定的荧光类型 ,而抗 Actin仅见于AIH者。非甲～戊组 4例AMA和M2阳性 ,3例SMA高滴度阳性 ,4例出现SS A、SS B或dsDNA等抗体。结论 肝抗原抗体和ANA及AMA分型的检测有助于自身免疫性肝病和重叠多种免疫性肝病的诊断 ;非甲～戊型肝炎诊断时应?

HBV感染孕妇肝特异性自身抗体的存在情况及其自身意义

目的：分析HBV感染孕妇肝特异性自身抗体的存在情况及其自身意义。方法：选取该科2011年6月~2014年6月HBV感染孕妇共80例作为研究对象,同时选取80例健康孕妇作为对照组。对比两组孕妇的自身抗体水平,同时对比感染HBV孕妇组中自身抗体阳性/阴性者肝功能、免疫球蛋白水平和HBV DNA阳性率。结果：感染HBV孕妇组的血清中自身抗体总阳性率为27.50%,显著高于正常孕妇组（3.75%）,χ2=22.818 8,P〈0.01。自身抗体阳性组患者的丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、IgG、IgM和IgA水平均显著高于自身抗体阴性组,P〈0.05。自身抗体阳性患者的HBV DNA阳性率显著高于自身抗体阴性患者,χ2=4.702 2,P〈0.05。结论：HBV感染可能是引起孕妇自身免疫功能损害的机制之一,同时自身抗体阳性和肝功能受损及病毒活跃复制相关。

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.

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.

Inhibition of p38 mitogen-activated protein kinase attenuates experimental autoimmune hepatitis: Involvement of nuclear factor kappa B

To investigate the role of p38 mitogen-activated protein kinase （p38MAPK） in murine experimental autoimmune hepatitis （EAH）.METHODS： To induce EAH, the syngeneic S-100 antigen emulsified in complete Freud＇s adjuvant was injected intraperitoneally into adult male C57BI/6 mice. Liver injury was assessed by serum ALT and liver histology. The expression and activity of p38 MAPK were measured by Western blot and kinase activity assays. In addition, DNA binding activities of nuclear factor kappa B （NF-KB） were analyzed by electrophoretic mobility shift assay. The effects of SB203580, a specific p38 MAPK inhibitor, on liver injuries and expression of proinflammatory cytokines （interferon-y, IL-12, IL-1β and TNF-α） were observed.RESULTS： The activity of p38 MAPK and NF-~：B was increased and reached its peak 14 or 21 d after the first syngeneic S-100 administration. Inhibition of p38 MAPK activation by SB203580 decreased the activation of NF-~：B and the expression of proinflammatory cytokines. Moreover, hepatic injuries were improved significantly after SB203580 administration.

Acute hepatitis B or exacerbation of chronic hepatitis B-that is the question

Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. Starting from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currently available assays that may help distinguishing between the different conditions and lead to the optimal management of each patient.

Role of autoimmunity in primary biliary cirrhosis

Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.

Autoantibodies and hepatitis C virus genotypes in chronic hepatitis C patients in Estonia

AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes. METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region. RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%), TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases, sera were positive for two autoantibodies (ANA and SMA). AMA, PCA and LKMAI were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%) patients. CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1:10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.

肝抗原自身抗体检测在自身免疫性肝病诊断中的意义

目的:研究肝抗原自身抗体检测在自身免疫性肝病诊断中的意义。方法:从2012年8月—2014年8月,来我院被查出患有肝病的患者中随机抽取符合研究要求的病患80名,以数字法随机分成观察组和对照组各40例,观察组为自身免疫学肝病患者,对照组为非自身免疫性肝病患者,对两组肝病患者均进行肝抗原自身抗体检测。对比分析两组患者的检查结果。结果:观察组ANA的检测率为82.50%(33/40),SMA检测率为75.00%(30/40),均显著高于对照组的42.50%(17/40),37.50%(15/40)。差异均有统计学意义(P<0.05)。观察组自身免疫抗体AMA-M2的检测率为32.50%(13/40),LKM-1的检测率为50.00%(20/40),均显著高于对照组的2.50%(1/40),15.00%(6/40)。差异均有统计学意义(P<0.05)。结论:肝抗原自身抗体的检测对判断和诊治自身免疫性肝病有着重要的指导意义,其更科学更直接地为自身免疫性肝病的诊断提供强有力的实验室依据。