抗线粒体抗体阴性的原发性胆汁性肝硬化

迄今为止,原发性胆汁性肝硬化(PBC)的诊断依据是组织学检查发现有慢性非化脓性毁坏性胆管炎和抗线粒体抗体(AMA)阳性。这些患者常伴有血清γ-球蛋白、IgM和胆固醇升高。然而约5％病人的肝脏生化学和组织学特征与PBC相符,而AMA检测阴性。但在20％ 经组织学和血清学诊断为自身免疫性慢性肝炎的患者中,AMA可呈阳性,提示AMA并非特异性。 作者等复习了Mayo医院诊断为PBC的597例患者,其中35例(5.8％)均经常规免疫萤光检测AMA阴性,内镜逆行胆管造影正常均为女性。为此,作者回顾性分析了AMA阳性和AMA阴性两组病人的血清AST、ALP、总胆红素、血清γ-球蛋白、免疫球蛋白(IgA、IgM和IgG)和血脂(总胆固醇和甘油三酯)浓度,以及比较了两组间的抗核抗体(ANA)和抗平滑肌抗体(SMA)的阳性率,结果如下。 AMA阳性和阴性组之间在年龄、血清AST、ALP、总胆红素、血清IgA和IgG、胆固醇或甘油三酯上均无差异,但IgM水平在AMA阳性组为584±383mg/dl,而AMA阴性组为368±249 mg/dl(P<0.002);γ-球蛋白在AMA阳性组为1.91±0.55,而AMA阴性组为1.80±0.85(P<0.03)。35例AMA阴性病人中,有29例测定了血清ANA,16例测定了血清SMA;在AMA阳性组测定的91例中有33例(36％)ANA阳性,而29例AMA阴性组中,23例(79％)ANA阳性(P<0.0001)。37例AMA     

抗线粒体抗体阳性和阴性PBC患者临床表现、血清学和免疫学指标及病理特征比较

目的:探讨抗线粒体抗体(AMA)阳性和阴性的原发性胆汁性肝硬化(PBC)患者的临床表现、血清学和免疫学指标及病理特征。方法:选取98例PBC患者,采用间接免疫荧光法测定AMA和AMA-M2,两者均为阳性者即为AMA阳性组,均阴性者为AMA阴性组。观察比较2组患者的临床表现、血清学和免疫学指标、病理特征。结果:98例PBC患者中,AMA阳性组有81例(82.7%),AMA阴性组有17例(17.3%)。2组患者的临床表现、血清学指标、病理特征和分期间的差异均无统计学意义(均P0.05)。AMA阳性组患者IgM水平均明显高于AMA阴性组,AMA阳性组患者ANA、SMA阳性率均明显低于AMA阴性组,差异有统计学意义(P0.05)。结论:AMA阳性与阴性PBC患者的临床表现、血清学指标、病理特征和分期相似,但AMA阳性PBC患者的血清IgM水平升高,ANA、SMA阳性率降低。     

原发性胆汁性肝硬化特异性自身抗体的筛查和分析

目的 调查原发性胆汁性肝硬化(PBC)特异性自身抗体抗线粒体抗体(AMA)M2型、抗gp21t0和抗sp100在普通成人中的流行情况,并初步调查PBC的患病率.方法 以间接免疫荧光法初筛8126名体检者血清抗核抗体(ANA)及AMA,再用酶联免疫吸附法或Western blot检测ANA或AMA阳性血清中AMA-M2、抗sol00和抗gp210,最后结合临床表现和其他检查结果进行诊断.结果 8126名成年人中AMA阳性35例(0.43%,95%可信区间为0.30%～0.58%)、ANA79例(0.97%),两种抗体阳性率均随年龄的增长而增高.PBC特异性自身抗体阳性共22例,其中19例为AMA-M2阳性(0.23%),抗sp100阳性4例(0.05%),抗gp210阳性3例(0.04%).在PBC发病集中的40岁以上妇女中,PBC特异性自身抗体检出率为0.62%.22名PBC特异性自身抗体阳性者中只有1名女性最终被确诊为PBC.结论 PBC特异性自身抗体在普通成人中均较为少见,我国南方地区成人PBC患病率可能并不低于其他地区.     

AMA-M2抗体、gp210抗体和sp100抗体对原发性胆汁性胆管炎的诊断的价值探讨

[目的]探讨AMA-M2抗体、抗gp210和sp100抗体的检测对原发性胆汁性胆管炎(PBC)的诊断价值和意义。[方法]采取免疫印迹法检测62例PBC患者以及64例非PBC患者的抗线粒体抗体M2亚型(AMA-M2)、抗gp210及sp100抗体,分别计算这3种抗体的阳性率以及对PBC诊断的敏感性、特异性、阳性预测值、阴性预测值。[结果]62例PBC患者中,AMA-M2、抗gp210、sp100抗体的阳性率分别为75.8%、41.9%和19.4%,与非PBC组的阳性率比较差异有统计学意义;AMA-M2、抗gp210、sp100抗体诊断PBC的敏感性分别为:75.8%、41.9%和19.4%,特异性分别为:89.1%、95.3%和95.3%。AMA-M2阴性的PBC患者共15例,其中10例(66.7%)gp210抗体阳性,7例(46.7%)sp100抗体阳性。[结论]AMA-M2、抗gp210以及sp100抗体对PBC有高度的特异性。抗gp210以及sp100抗体对PBC的诊断尤其是AMA-M2阴性患者具有重要意义。     

原发性胆汁性肝硬化患者特异性自身抗体的实验研究

目的探讨原发性胆汁性肝硬化(PBC)患者自身抗体相关性及临床意义。方法采用免疫印迹法及间接免疫荧光法检测48例PBC、182例非PBC患者及50例健康对照抗线粒体抗体M2亚型(AMA-M2)、抗核包膜蛋白抗体(GP210)、抗核多点抗体(SP100)、抗核抗体(ANA)、抗双链DNA抗体(ds-DNA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)及抗细胞质抗体(ACYA)等自身抗体并观察其临床评估指标,对其结果进行回顾性分析。结果48例PBC患者ANA、AMA、SMA、ACYA及ds-DNA抗体阳性率分别为41.7%、93.8%、12.5%、79.2%和2.1%;ANA、AMA、SMA和ACYA与对照组比较,P均<0.01;AMA和ACYA与非PBC组比较,P均<0.01。48例PBC患者AMA-M2、GP210及SP100抗体阳性率分别为68.8%、41.7%和16.7%;与非PBC组和对照组比较,P均<0.01。结论检测AMA-M2、GP210、SP100和AMA等自身抗体对PBC的诊断、鉴别诊断、治疗及预后具有重要的作用,可提高PBC诊疗水平。     

抗gp210抗sp100抗体与原发性胆汁性肝硬化活动性的相关性

目的 评估原发性胆汁性肝硬化(PBC)患者血清中抗gp210和抗sp100抗体与PBC活动性的关系.方法 采集72例PBC患者的静脉血,以酶联免疫吸附试验(ELISA)检测抗gp210、抗sp100的水平,分析患者的临床资料.结果 抗gp210阳性患者白蛋白水平较阴性组降低,Mayo危险评分较后者升高,差异均有统计学意义(分别为P＜0.01和P＜0.05).随着疾病好转,抗gp210抗体多呈下降趋势.抗sp100阳性组与阴性组在血清生化指标、Mayo危险评分方面差异均无统计学意义.结论 抗gp210阳性患者病情较重,需加强随访,积极治疗.     

23例原发性胆汁性肝硬化患者临床特征分析

目的分析原发性胆汁性肝硬化（PBC）患者临床资料,总结其临床特征,以提高对该病的诊断水平。方法回顾性分析23例PBC患者的临床资料,观察预后。结果 23例患者确诊时平均年龄为53.5±12.7岁;17例为女性;ALP均明显升高（380.6±375.3U/L）,20例GGT升高（360.8±633.2U/L）,15例血清总胆红素升高（72.8±97.2μmol/L）,血清IgM、IgG、IgA浓度超过正常值的比率分别为78.3%、69.3%和17.4%;19例（82.6%）血清AMA及其M2亚型阳性,14例（60.9%）ANA阳性,10例（43.5%）抗gp210抗体阳性;影像学检查均未发现胆管阻塞或扩张。结论 PBC好发于中年女性,血清ALP、GGT、IgM明显升高、AMA及其M2亚型阳性有助于诊断。抗gp210抗体阳性者可能预后较差。     

多抗原组合筛查试剂筛查自身免疫性肝病的临术意义

目的：探讨自身免疫性肝病多抗原组合筛查试剂的临床意义。方法选择2011年9月至2012年9月在首都医科大学附属北京佑安医院就诊的肝病患者140例,健康献血员30例,PBC患者家属8例。分别应用筛查试剂（ELISA）法（以AMA-M2、sp100、gp210、LKM-1、SLA/LP为混合靶抗原）、常规检测项目包括间接免疫荧光法（IFA）、免疫印迹法（IBT）、AMA-M2 ELISA 法检测178例血清样本。组间比较采用χ^2检验。结果178例样本,应用筛查试剂检测阳性70例（50％）,强阳性49例。70例阳性样本采用常规试剂进一步检测自身抗体,IFA检测抗核抗体（ANA）阳性61例,AMA阳性63例。其中61例ANA阳性样本中21例荧光核型为核膜型,但IBT检测抗gp210抗体16例为阳性,5例为阴性。63例AMA阳性样本,应用AMA-M2 ELISA法检测AMA-M260例为阳性,3例为阴性。49例强阳性样本应用常规检测,其中抗gp210抗体单独阳性2例、抗sp100抗体单独阳性5例、AMA-M2单独阳性20例、抗gp210抗体和AMA-M2同时阳性12例、抗sp100抗体和AMA-M2同时阳性10例。178例样本中,65例PBC患者采用常规检测均可检出PBC相关抗体,而采用筛查试剂检测则63例PBC患者阳性,2例为阴性,符合率为96．9％（63/65）,常规试剂检出例数高于筛查试剂检出例数,但二者差异无统计学意义（χ^2＝0．016,P＞0．05）。4例样本采用筛查试剂检测为阳性而常规试剂检测各单一自身抗体均为阴性。结论自身免疫性肝病多抗原组合筛查试剂筛查自身免疫性肝病有较高的敏感性、特异性,具有操作简便、快速、低成本的特点。可应用于自身免疫性肝病的初步筛查。     

表达gp210抗体的原发性胆汁性肝硬化患者临床特点分析

目的总结表达gp210抗体的原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者临床特点,为临床诊治提供循证医学依据。方法回顾性分析155例PBC患者,分为抗gp210阳性组63例、抗gp210阴性组92例,比较其症状、生化指标、免疫学指标、Mayo评分与Child评分、合并其他免疫性疾病情况及病理分期的特点差异。结果抗gp210阳性组和抗gp210阴性组在年龄、性别、临床表现、其他相关抗体阳性率、Mayo评分与Child评分及病理分期上的差异均无统计学意义(P0.05)。抗gp210阳性PBC患者Ig M、ALP均高于抗gp210阴性组(P0.05),而甲减发生率明显低于抗gp210阴性组(P0.05)。结论 gp210抗体对PBC的诊断有一定价值,可做抗线粒体抗体(anti-mitochondrial antibody,AMA)的有益补充,gp210与甲减是否有关有待进一步研究。     

原发性胆汁性肝硬化的实验室指标分析

目的分析原发性胆汁性肝硬化(PBC)实验室指标,为临床诊治提供依据。方法选取2016年解放军第三〇二医院诊断为PBC的患者593例,对其自身抗体指标抗线粒体抗体(AMA)、抗核抗体(ANA)、抗平滑肌抗体(SMA)、抗线粒体抗体-M2(AMA-M2)、抗可溶性肝抗原/肝胰抗原抗体(SLP)、抗核孔复合物糖蛋白210抗体(gp210)、核点型靶抗原蛋白(Sp100)、早幼粒白血病蛋白(PML)以及生化免疫学指标谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、免疫球蛋白A(IgA)、免疫球蛋白M(IgM)、免疫球蛋白G(IgG)进行检测并分析结果。结果PBC患者血清内ANA、AMA、SMA、AMA-M2、SLP/LP、gp210、Sp100的检出率显著高于慢性乙型肝炎组,差异均有统计学意义(P0.05)。ANA的主要核型是核膜型(225例,52.33%)以及核点型(90例,20.93%),滴度以中高滴度为主(≥1∶320),复合核型也有相当比例(113例,26.28%)。AMA以高滴度(≥1∶1 000)为主(470例,84.79%)。AMA-M2的滴度以高滴度(≥"3+")为主(358例,88.18%)。PBC组患者的GGT、ALP、IgM、IgG与慢性乙型肝炎组患者比较均显著升高,差异有统计学意义(P0.05),IgA差异无统计学意义(P0.05)。结论各型自身抗体对于PBC具有诊断意义,ALP、GGT、IgM不明原因升高也是PBC特殊指征,临床应该重视各种实验室指标,对于PBC患者早诊断早治疗,积极改善PBC患者的生存质量。     

Are Antibodies to Carbonic Anhydrase II Specific for Anti-Mitochondrial Antibody-Negative Primary Biliary Cirrhosis?

Antibodies to carbonic anhydrase II (CAII) have been reported to be specific to anti-mitochondrial antibody (AMA) -negative primary biliary cirrhosis (PBC). We examined whether antibodies to CAII are specific for AMA-negative PBC or a nonspecific response in autoimmune liver disease. Antibody assays to CAII, by western immunoblot (dilution 1:200), were performed on sera from 16 AMA-negative PBC patients, 21 AMA-positive PBC patients, 21 autoimmune hepatitis type 1 (AIH) patients, and 18 alcoholic liver disease (ALD) patients. CAII antibody activity was found in 8 of 16 (50%) of the AMA-negative PBC patients, 9 of 21 (43%) of the AMA-positive PBC group, 10 of 21 (48%) of the AIH group, and in 3 of 18 (17%) of the ALD control group. There was no difference in the prevalence of CAII antibody reactivity between the AMA-negative PBC, AMA-positive PBC, and AIH groups. In conclusion, we determined that CAII antibodies are detected with equal frequency in AMA-positive PBC and AIH. Given that CAII antibodies have been reported in other nonhepatic autoimmune diseases, we conclude that CAII antibodies are likely a nonspecific marker of autoimmunity rather than specific for AMA-negative PBC.     

Autoimmune cholangitis

Autoimmune cholangitis is the term that has been used to describe patients who have the clinical, biochemical, and histologic characteristics of primary biliary cirrhosis (PBC), but who are antinuclear antibody positive rather than anti-mitochondrial antibody (AMA) positive in their sera. The course of their disease is similar to AMA positive cases, and the associated nonhepatic autoimmune diseases are the same in both AMA-positive and AMA-negative PBC. Serial testing for AMA using highly sensitive and specific techniques over time suggests that in subjects with autoimmune cholangitis, their AMA negative status remains negative. The beneficial response to treatment with ursodeoxycholic acid is the same as for AMA-positive PBC. It may be preferable to use the term autoimmune cholangitis, further stratified by AMA status, instead of the somewhat innapropriate term primary biliary cirrhosis.     

Changes in titers of antimitochondrial and antinuclear antibodies during the course of primary biliary cirrhosis

A case of primary biliary cirrhosis (PBC) in whom a complete biochemical (serum bilirubin, transaminases and alkaline phosphatase) remission was noted after combination treatment with ursodeoxycholic acid (UDCA) and corticosteroid is reported. The antimitochondrial antibody (AMA) detected by indirect immunofluorescence was initially positive, and the antinuclear antibody (ANA) was negative, but these two antibodies subsequently fluctuated independently (AMA-positive/ANA-negative, AMA-negative/ANA-negative, AMA-negative/ANA-positive, AMA-positive/ANA-positive, and again AMA-negative/ANA-positive) in spite of a lack of histopathological improvement in the liver after treatment. The clinical presentation in our case suggests that in some cases the diagnosis of PBC or so-called autoimmune cholangitis (AIC) might depend on the 'phase' of the same disease. Our results also suggest that detailed immunoreactive profiles against 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by using immunoblotting, together with a serial histological examination, should provide more precise information for a diagnosis of PBC.     

Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis.

BACKGROUND/AIMS: An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls. METHODS: Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRbeta1 and DQbeta1. RESULTS: Higher allele frequencies of HLA-DRbeta1*08 and DQbeta1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR)=3.3, global P=0.03 and 14.4% vs. 6.5%, OR=2.6, global P=0.002). All patients positive for DRbeta1*0801 were positive for the DQbeta1*0402 allele, delta score=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRbeta1*08 and DQbeta1*04 was 0%, significantly different from the AMA-positive patients (P=0.05, P=0.05). CONCLUSIONS: AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6.     

Primary biliary cirrhosis--presentation and diagnosis

Primary biliary cirrhosis is predominantly seen in middle-aged women. Typical symptoms are fatigue, pruritus, and abdominal pain. Jaundice develops in the endstage disease. At presentation, about 40% of the patients are asymptomatic, but 30% to 50% already have hepatomegaly, and 15% present with splenomegaly. Even patients with fully developed liver cirrhosis may be free of symptoms. Abnormal physical signs and advanced histological stage are more frequent in symptomatic than in asymptomatic patients. Fatigue, pruritus, and Sj?gren's syndrome are more common in women than men, but other signs and symptoms do not differ in the two sexes. PBC is associated with a large variety of other diseases, like arthropathy, CREST syndrome, autoimmune thyroiditis, and so on, which in addition will or will not produce symptoms. Hepatocellular carcinoma is a rare complication in women, but more frequent in men. Diagnosis can be established by the triad antimitochondrial antibodies (AMA), cholestatic indices, and liver histology, diagnostic or compatible with PBC. When AMA are not detected, then antinuclear antibodies (autoantibodies against gp.210 and others) can be detected in 50% of AMA-negative patients. AMA titers do not correlate with the course of the disease nor histological progression. After liver transplantation, AMA recur in nearly 100%. The liver enzyme pattern in PBC patients is cholestatic: alkaline phosphatase and gammaglutamyltransferase increase to 10 or more times the upper limit of normal. The amount of enzymes does not correlate with disease progression or stage of the disease. The only prognostic factor in PBC is serum bilirubin. AMA-negative patients account for about 10% to 15%. Routine biochemical tests are not different from AMA-positive patients, but usually higher ANA, SMA, and IgG concentrations are detected. Histologically, it is PBC. The overlap-syndrome, autoimmune hepatitis-PBC presents with the histological features of autoimmune hepatitis and PBC, with AMA, ANA, or SMA. Imaging procedures are not helpful for the diagnosis of PBC, except for liver histology. Histologically, four different stages can be assessed, ranging from florid bile duct lesions, ductular proliferation, and fibrosis to liver cirrhosis. Liver histology is of interest for the assessment of the diagnosis and for staging of the disease.     

A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis

The antimitochondrial response in primary biliary cirrhosis (PBC) is the most highly directed and specific self-reacting antibody in human immunopathology. Originally, antimitochondrial antibodies (AMAs) were detected by indirect immunofluorescence (IIF) and found in approximately 90% of well-documented patients with PBC. The introduction of recombinant autoantigens and the use of immunoblotting have increased the sensitivity and specificity of AMAs, and they are now considered positive in approximately 95% of patients with PBC. Clearly, accurate autoantibody detection represents one of the fundamental requirements for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative patients with PBC, we have generated and validated a bead assay for the detection of AMA. We enrolled 120 patients with PBC, including a non-random group of 30 rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2, and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients remained positive with this assay but, interestingly, 20% of the rigorously defined AMA-negative patient group had antibodies to one or more of the mitochondrial autoantigens. Furthermore, 100% of these newly detected AMA-positive patients were anti-nuclear antibody (ANA) positive. CONCLUSION: The development of this assay reflects the potential for automated detection with rapid and reliable assaying and further highlights the diminished number of truly AMA-negative PBC patients.     

原发性胆汁性肝硬化自身抗体特征及其对药物治疗的反应

目的研究原发性胆汁性肝硬化（primary biliary cirrhosis,PBC）患者抗线粒体抗体（antimitochondrial antibody,AMA）、抗线粒体抗体M2亚型（AMA-M2）、抗GP210抗体和抗SP100抗体的临床相关性及对药物治疗的反应。方法82例初诊未治疗的PBC患者随机分为熊去氧胆酸（ursodeoxycholic acid,UDCA）（U组,28例）、UDCA联合泼尼松龙（UP组,27例）、UDCA联合硫唑嘌呤（azathioprine,AZP）（UA组,27例）3组,治疗前观察各组患者的AMA、AMA-M2、抗GP210抗体和抗SP100抗体,治疗后3、6个月复查AMA、AMA-M2。治疗前24例患者行肝穿刺检查获得标本,按组织学特点对其进行分期。结果PBC患者AMA滴度、AMA-M2水平与其临床症状、肝生化指标、肝脏病理改变无关,AMA与IgM呈正相关（P=0.046）。三种治疗方案对AMA、AMA-M2水平无影响。抗GP210抗体阳性患者比阴性患者病情重,治疗6个月时的肝脏生化指标缓解率低（P=0.012）。抗SP100抗体阳性与阴性PBC患者的临床症状、肝脏生化指标、IgM无差异。结论AMA、AMA-M2及抗SP100抗体对PBC患者有诊断意义,但其水平与病情无关,不受药物治疗影响,也不影响药物疗效。抗GP210抗体阳性PBC患者病情重,肝脏生化指标缓解率低。     

扶正化瘀胶囊联合熊去氧胆酸胶囊治疗原发性胆汁性肝硬化临床研究

目的观察扶正化瘀胶囊联合熊去氧胆酸胶囊对原发性胆汁性肝硬化(PBC)患者症状、血清细胞因子、免疫相关指标的影响。方法选择PBC患者60例,随机分为实验组及对照组各30例。实验组给予扶正化瘀胶囊联合熊去氧胆酸胶囊口服,对照组单用熊去氧胆酸胶囊口服,疗程均为24周。记录并分析治疗12、24周患者中医临床症状、抗线粒体抗体(AMA)、抗线粒体抗体-M2亚型(AMA-M2)、免疫球蛋白G(IgG)、免疫球蛋白M(IgM)、免疫球蛋白A(IgA)、免疫球蛋白B(IgB)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、ALT、AST、TBil及总胆固醇(CH)、甘油三酯(TG)等各项指标的变化。结果两组患者在治疗12、24周ALT、AST、TBil、ALP、GGT、TG、CH、AMA、AMA-M2、IgM与治疗前组内比较均改善显著,差异均有统计学意义(P均0.05);而IgA、IgB、IgG与治疗前组内比较均无明显改善,差异均无统计学意义(P均0.05)。实验组治疗12、24周中医临床症状较前明显改善,而对照组治疗12周中医临床症状无改善,治疗24周中医临床症状略有改善,但治疗前后差异无统计学意义(P0.05)。实验组治疗12、24周中医临床症状、ALP、GGT、ALT、AST、TG、AMA-M2均较对照组明显改善,差异均有统计学意义(P均0.05),而实验组治疗12周AMA、IgM及TBil与治疗前比较略有下降,但与对照组比较差异无统计学意义(P均0.05)。实验组治疗24周中医临床症状、ALP、GGT、ALT、AST、TG、AMA-M2较对照组均有显著下降,差异有统计学意义(P0.05)。结论熊去氧胆酸胶囊联合扶正化瘀胶囊治疗PBC,在改善中医临床症状、转氨酶及线粒体抗体方面较单纯使用熊去氧胆酸胶囊有明显疗效,但对降低CH、lgA、IgB、IgG无显著作用。     

抗线粒体抗体阴性原发性胆汁性肝硬化患者的临床及病理学特点

目的 分析抗线粒体抗体(AMA)阴性的原发性胆汁性肝硬化(PBC)患者临床及病理学特点.方法 对208例PBC患者的临床及病理学资料进行分析,并将AMA阴性PBC患者与典型PBC和自身免疫性肝炎(AIH)患者进行比较.非正态连续变量的比较使用Mann Whitney U检验,分类资料构成比的比较使用Chi-Square检验.结果 208例PBC患者中,AMA阴性者30例,占14.4%.AMA/AMA-M2阳性PBC和AMA阴性PBC患者在一般情况,临床表现、体征、肝功能(ALT、AST,碱性磷酸酶、γ-谷氨酰转移酶和总胆红素)和肝组织学表现上的差异均无统计学意义(P值均>0.05).AMA/AMA-M2阳性PBC组患者γ-球蛋白、IgG、IgM和IgA明显升高,中位数(P25,P75)分别为8.6(6.6,10.9)g/L,16.8(13.7,19.4)g/L、3.6(2.7,5.4)g/L和2.9(2.2,3.8)g/L,与AMA阴性组[分别为7.1(5.6,7.9)g/L、14.1(11.3,17.6)g/L、2.7(1.9,4.5)g/L和2.1(1.5,3.4)g/L]相比,差异有统计学意义(Z值分别为-2.088、-2.177、-2.372和-2.764,P值均<0.05);两组间总胆固醇差异无统计学意义(P>0.05).AMA阴性PBC患者中,29例(96.7%)呈抗核抗体(ANA)阳性,其中胞质颗粒型14例(48.3%)、核膜型8例(27.6%)、着丝点型6例(20.7%)、均质型1例(3.4%).与AIH患者比较,AMA阴性PBC患者以胆汁淤积表现为主,碱性磷酸酶、γ-谷氨酰转移酶、IgM和胆固醇水平均较AIH组明显升高(P值均<0.05),而血清AST,IgG和IgA水平低于AIH患者(P值均<0.05).结论 在以胆汁淤积表现为主,IgM和胆固醇水平升高、ANA为非均质型为主要表现的患者中,AMA虽阴性仍需考虑PBC的可能.

Abstract：

Objective To explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA). Methods Two hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases. Results 30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P> 0.05). The γ -globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively). Conclusion In cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemcial and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.