Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial ...Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.展开更多
AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (...AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.展开更多
AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to Se...AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.展开更多
AIM:To determine the association between seroprevalence of Helicobacter pylori(H pylori)infection and primary biliary cirrhosis(PBC). METHODS:In this case-control study,149 consecutive patients(10 males,139 females,me...AIM:To determine the association between seroprevalence of Helicobacter pylori(H pylori)infection and primary biliary cirrhosis(PBC). METHODS:In this case-control study,149 consecutive patients(10 males,139 females,mean age 58.2±11 years, range 26-82 years)suffering from PBC and 619 consecutive healthy volunteer blood donors(523 males,96 females, mean age 47±5.3 years,range 18-65 years)attending the Hospital Blood Bank and residing in the same area were recruited.A commercial enzyme linked immunosorbent assay was used to detect anti-H pylori(IgG)antibodies in serum. RESULTS:AnUbodies to Hpyloriwere present in 78(52.3%) out of 149 PBC-patients and in 291(47%)out of 619 volunteers(P=0.24,OR 1.24,95% CI 0.85-1.80).In the subjects less than 60 years old,the prevalence of H pylori infection among PBC-patients(40/79)was slightly higher than in controls(50.6% vs 46.2%)P=0.46,OR=1.19,95% CI:0.72-1.95).In those over 60 years,the prevalence of Hpylori infection was similar between PBC-patients and controls(54.2% vs57.8%,P=0.7,OR 0.86,95% CI 0.36- 2.07). CONCLUSION:There is no association between seroprevalence of H pylori in fection and primary biliary cirrhosis.展开更多
目的探讨抗着丝点抗体(ACA)在原发性胆汁性肝硬化(PBC)中的临床意义。方法收集67例抗线粒体抗体(AMA)和AMA-M2阳性PBC患者的临床资料,检测其抗核抗体(ANA)和ACA、生化、凝血酶原活动度(PT)及免疫指标等。结果 ACA阳性组27例,ACA和ANA均...目的探讨抗着丝点抗体(ACA)在原发性胆汁性肝硬化(PBC)中的临床意义。方法收集67例抗线粒体抗体(AMA)和AMA-M2阳性PBC患者的临床资料,检测其抗核抗体(ANA)和ACA、生化、凝血酶原活动度(PT)及免疫指标等。结果 ACA阳性组27例,ACA和ANA均阴性组40例。ACA阳性组脾肿大的发生率高于ACA和ANA阴性组(77.8% vs. 40.0%,P=0.002)。ACA阳性组黄疸的发生率、血清总胆红素(TBIL)水平、IgG水平和IgG异常升高率明显低于ACA和ANA阴性组[25.9% vs. 55.0%,P=0.018;(41.62±45.96)μmol/L vs. (88.49±99.13)μmol/L,P=0.012;(13.90±2.75)g/L vs. (18.32±6.34)g/L,P=0.002;29.4% vs. 60.0%,P=0.044]。两组在其他临床表现、肝功能及其他免疫指标的差异无统计学意义。结论单一ACA阳性PBC患者疾病的进展比ACA和ANA阴性患者更加隐匿。ACA阳性PBC患者是PBC的一个特殊类型。展开更多
文摘Primary biliary cirrhosis(PBC)is a chronic progressive cholestatic liver disease characterized by immunemediated destruction of the small-and medium-sized intrahepatic bile ducts and the presence of antimitochondrial antibodies(AMA)in the serum.AMA are detected in over 90%of patients with PBC,whereas their prevalence in the general population is extremely low,varying from 0.16%to 1%.Previous studies have shown that the unique characteristics of biliary epithelial cells undergoing apoptosis may result in a highly direct and very specific immune response to mitochondrial autoantigens.Moreover,recent studies have demonstrated that serum from AMA-positive PBC patients is reactive with a number of xenobiotic modified E2 subunits of the pyruvate dehydrogenase complex,which is not observed in the serum of normal individuals.These findings indicate that chemicals originating from the environment may be associated with a breakdown in the tolerance to mitochondrial autoantigens.While it is currently generally accepted that AMA are the most specific serological markers of PBC,more than 60 au-toantibodies have been investigated in patients with PBC,and some have previously been considered specific to other autoimmune diseases.This review covers the recent progress in research on the pathogenetic and clinical significance of important autoantibodies in PBC.Determining the pathogenic role of those autoantibodies in PBC remains a priority of basic and clinical research.
基金Supported by The Research Committee of the University of Thessaly, No. 2466
文摘AIM:To determine the prevalence and significance of primary biliary cirrhosis (PBC)-specific autoantibodies in firstdegree relatives (FDRs) of Greek PBC patients. METHODS:The presence of antimitochondrial antibodies (AMA) and PBCspecific antinuclear antibodies (ANA) were determined using indirect immunofluores-cence assays, dot-blot assays, and molecularly based enzyme-linked immunosorbent assays in 101 asymp-tomatic for liver-related symptoms FDRs of 44 PBCpatients. In order to specify our results, the same investigation was performed in 40 healthy controls and in a disease control group consisting of 40 asymptomatic for liver-related symptoms FDRs of patients with other autoimmune liver diseases namely, autoimmune hepati-tis-1 or primary sclerosing cholangitis (AIH-1/PSC). RESULTS: AMA positivity was observed in 19 (only 4 with abnormal liver function tests) FDRs of PBC patients and none of the healthy controls. The preva-lence of AMA was significantly higher in FDRs of PBC patients than in AIH-1/PSC FDRs and healthy controls [18.8%, 95% confidence interval (CI):12%-28.1% vs 2.5%, 95% CI:0.1%-14.7%, P = 0.01; 18.8%, 95% CI:12%-28.1% vs 0%, 95% CI: 0%-10.9%, P = 0.003, respectively]. PBC-specific ANA positivity was observed in only one FDR from a PSC patient. Multivariate analysis showed that having a proband with PBC independently associated with AMA positivity (odds ratio: 11.24, 95% CI:1.27-25.34, P = 0.03) whereas among the investigated comorbidities and risk factors, a positive past history for urinary tract infections (UTI) was also independently associated with AMA detection in FDRs of PBC patients (odds ratio:3.92, 95% CI:1.25-12.35,P = 0.02). CONCLUSION:In FDRs of Greek PBC patients, AMA prevalence is significantly increased and independently associated with past UTI. PBC-specific ANA were not detected in anyone of PBC FDRs.
基金Supported by the Research Committee of the University of Thessaly in part(Code No.2466)
文摘AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC.
文摘AIM:To determine the association between seroprevalence of Helicobacter pylori(H pylori)infection and primary biliary cirrhosis(PBC). METHODS:In this case-control study,149 consecutive patients(10 males,139 females,mean age 58.2±11 years, range 26-82 years)suffering from PBC and 619 consecutive healthy volunteer blood donors(523 males,96 females, mean age 47±5.3 years,range 18-65 years)attending the Hospital Blood Bank and residing in the same area were recruited.A commercial enzyme linked immunosorbent assay was used to detect anti-H pylori(IgG)antibodies in serum. RESULTS:AnUbodies to Hpyloriwere present in 78(52.3%) out of 149 PBC-patients and in 291(47%)out of 619 volunteers(P=0.24,OR 1.24,95% CI 0.85-1.80).In the subjects less than 60 years old,the prevalence of H pylori infection among PBC-patients(40/79)was slightly higher than in controls(50.6% vs 46.2%)P=0.46,OR=1.19,95% CI:0.72-1.95).In those over 60 years,the prevalence of Hpylori infection was similar between PBC-patients and controls(54.2% vs57.8%,P=0.7,OR 0.86,95% CI 0.36- 2.07). CONCLUSION:There is no association between seroprevalence of H pylori in fection and primary biliary cirrhosis.
文摘目的探讨抗着丝点抗体(ACA)在原发性胆汁性肝硬化(PBC)中的临床意义。方法收集67例抗线粒体抗体(AMA)和AMA-M2阳性PBC患者的临床资料,检测其抗核抗体(ANA)和ACA、生化、凝血酶原活动度(PT)及免疫指标等。结果 ACA阳性组27例,ACA和ANA均阴性组40例。ACA阳性组脾肿大的发生率高于ACA和ANA阴性组(77.8% vs. 40.0%,P=0.002)。ACA阳性组黄疸的发生率、血清总胆红素(TBIL)水平、IgG水平和IgG异常升高率明显低于ACA和ANA阴性组[25.9% vs. 55.0%,P=0.018;(41.62±45.96)μmol/L vs. (88.49±99.13)μmol/L,P=0.012;(13.90±2.75)g/L vs. (18.32±6.34)g/L,P=0.002;29.4% vs. 60.0%,P=0.044]。两组在其他临床表现、肝功能及其他免疫指标的差异无统计学意义。结论单一ACA阳性PBC患者疾病的进展比ACA和ANA阴性患者更加隐匿。ACA阳性PBC患者是PBC的一个特殊类型。
