Antimitochondrial Antibody-Negative Primary Biliary Cholangitis: A Retrospective Diagnosis.

Primary biliary cholangitis (PBC) is an inflammatory cholestatic disease that tends to worsen, leading to hepatic cirrhosis and portal hypertension. We present a case of a middle-aged female who presented with progressively worsening generalized itch; the examination was significant only for urticarial rash and facial swelling. Investigation revealed direct hyperbilirubinemia, mildly elevated transaminase, and significant elevation of alkaline phosphatase. A differential was performed with labs including antimitochondrial antibodies (AMA) for PBC, hepatitis panel, anti-smooth muscle antibodies for autoimmune hepatitis, and tissue transglutaminase IgA for celiac disease, all of which were unremarkable. The patient was empirically treated with ursodeoxycholic acid (UDCA). Given the excellent clinical response at the three-week follow-up to treatment despite negative AMA, further testing with anti-sp100 and anti-gp210 was pursued, which returned positive for anti-sp100, confirming the diagnosis of PBC.

[Is autoimmune cholangitis-anti-mitochondrial antibody-negative primary biliary cholangitis still an independent disease?]

Autoimmune cholangitis (AIC) was first reported in 1987 as a chronic cholestatic disease that occurs predominantly in middle-aged women and has a common clinical manifestations, biochemical abnormalities and pathological changes with primary biliary cholangitis (PBC). However, serum anti-mitochondrial antibodies (AMA) are negative, and ANA and/or smooth muscle antibody positive rates are higher. The treatment response and prognosis with ursodeoxycholic acid and steroids is poor, thus it needs to be treated with immunosuppressive agents. Presently, the exact pathological mechanism of AIC is still unclear, and there is no unified assertion that classifies it as a new autoimmune liver disease or AMA-negative PBC. This article reviews the worldwide published work on AIC and compares them with PBC.

Is autoimmune cholangitis-anti-mitochondrial antibody-negative primary biliary cholangitis still an independent disease? / 中华肝脏病杂志

Autoimmune cholangitis (AIC) was first reported in 1987 as a chronic cholestatic disease that occurs predominantly in middle-aged women and has a common clinical manifestations, biochemical abnormalities and pathological changes with primary biliary cholangitis (PBC). However, serum anti-mitochondrial antibodies (AMA) are negative, and ANA and/or smooth muscle antibody positive rates are higher. The treatment response and prognosis with ursodeoxycholic acid and steroids is poor, thus it needs to be treated with immunosuppressive agents. Presently, the exact pathological mechanism of AIC is still unclear, and there is no unified assertion that classifies it as a new autoimmune liver disease or AMA-negative PBC. This article reviews the worldwide published work on AIC and compares them with PBC.

Autoantibody status and histological variables influence biochemical response to treatment and long-term outcomes in Japanese patients with primary biliary cirrhosis.

AIM: The aim of the present study is to evaluate the factors influencing biochemical response to treatment and the value of biochemical response for predicting long-term outcomes in Japanese patients with primary biliary cirrhosis (PBC). METHODS: Biochemical response to ursodeoxycholic acid (UDCA) or UDCA plus bezafibrate was defined as good (≤upper limit of normal [ULN]), fair (≤1.5 × ULN) or poor (>1.5 × ULN) at 2 years after initiation of UDCA treatment. Associations between various factors (including age, sex, autoantibody status and histological variables at baseline), biochemical response to treatment and long-term outcomes were evaluated in 164 Japanese PBC patients. RESULTS: Anti-gp210 positivity and a higher bile duct loss score were significant risk factors for worse alkaline phosphatase (ALP) response (odds ratios [OR], 2.78 and 1.85, respectively). Age, anti-gp210 positivity and anticentromere positivity were significant risk factors for worse alanine aminotransferase (ALT) response (OR, 1.05, 4.0 and 2.77, respectively). Anti-gp210 positivity and a higher hepatitis score were significant risk factors for worse immunoglobulin (Ig)M response (OR, 2.10 and 2.06, respectively). Worse ALP and IgM response were significant risk factors for progression to late-stage disease without jaundice (OR, 2.27 and 2.32, respectively). Worse ALT response was a significant risk factor for progression to late-stage disease with persistent jaundice (OR, 11.11). CONCLUSION: Biochemical response to treatment at 2 years, which is influenced by autoantibody status and histological variables at baseline, can predict long-term outcomes in Japanese patients with PBC.

Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis.

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Genetic factors are critical in determining susceptibility to PBC. Among human leuocyte antigen (HLA) genes, an association between the DRB1*08 allele and PBC has been reported in many populations, but not in Chinese patients. METHODS: We investigated HLA-A, B, DRB1, and DQB1 alleles and haplotypes in 145 PBC patients and 500 healthy subjects. Patients were also stratified according to autoantibody features, and associations between these and HLA alleles were analyzed. RESULTS: Significant associations existed between HLA-DRB1*08:03 (22.1% vs. 9.0%, Pc < 0.0001, OR = 2.86), DQ2 (41.4% vs. 25.4%, Pc < 0.0001, OR = 2.07) and DQB1*06:01 (31.0% vs. 17.8%, Pc = 0.014, OR = 2.08) alleles and PBC. DRB1*08:03-DQB1*06:01 (22.1% vs. 8.2%, P < 0.0001, OR = 3.17) and DRB1*07:01-DQB1*02:02 haplotypes (28.3% vs. 17.6%, P = 0.005, OR = 1.85) were also associated with PBC susceptibility. In contrast, the DQB1*03:01 allele (21.4% vs. 39.2%, Pc < 0.0001, OR = 0.42) and DRB1*12:02-DQB1*03:01 haplotype (6.9% vs. 14.6%, P = 0.015, OR = 0.43) were significantly decreased in PBC patients compared with controls. DRB1*14:54 and DQ5(1) protected against antinuclear antibody (ANA) (OR = 0.25) and anti-gp210 antibody (OR = 0.39) production, respectively, while HLA-B*44:03 predisposed patients to anti-gp210 antibody (OR = 5.70) production. CONCLUSION: These results suggest that Chinese patients with PBC have a distinct genetic background in eastern Asia, and we confirmed the role of HLA genes in determining PBC susceptibility and autoantibody features in the Chinese population.

Significance of serum anti-gp210 antibody detection in diagnosis of primary biliary cirrhosis / 临床肝胆病杂志

Primary biliary cirrhosis (PBC)is a chronic disease characterized by progressive destruction of intrahepatic small bile ducts, which may progress to liver cirrhosis.Anti-mitochondrial antibodies,especially anti-M2 antibody,have a high diagnostic value for PBC, but they are unrelated to the severity and prognosis of the disease and are negative in some patients.There have been reports from around the world that anti-nuclear antibodies,especially anti-gp210 antibody,are closely associated with PBC.It showed that anti-gp210 antibody has high specificity and sensitivity for the diagnosis of PBC,especially for the patients with negative anti-M2 antibody tests;in addition,it has a high predictive value for the prognosis and development model of the disease.Anti -gp210 antibody has a high diagnostic value for PBC,with great clinical significance,so its detection holds promise for clinical application.

The comparison of two different detection methods for anti-gp210 antibody / 中华风湿病学杂志

Objective To attempt using the synthetic poly-peptides in the carboxyl terminal of gp210 antigen as the substrate for anti-gp210 antibody detection and search for a simple assay method of detecting anti-gp210 antibody. Methods The enzyme linked immunosorbent assay (ELISA) method for anti-gp210 antibody detection was set-up by chessboard test. Anti-gp210 antibody was tested in the serum of both patients with primary biliary cirrhosis (PBC) and the control group by ELISA and immuno-blotting. Results The working concentration of gp210's antigen was 5 μg/ml. The optical density higher than 0.61 (x+3s) was designated as the positive cutoff of anti-gp210 antibody. There was no statistical difference between the two assays (P=0.617). And there was very strongly positive correlation between them (P=0.000, r=0.868). Conclusion The sensitivity and specificity are basically consistent between the assays using synthetic poly-peptides of gp210 antigen and native antigen as the detecting substrates. The former substrate is preferred to be used for the testing of anti-gp210 antibody in clinical laboratories.