Objective To establish the enzyme-linked immunosorbent assay (ELISA) for the detection of serum alcohol dehydrogenase (ADH) antibody and evaluate its role in its diagnosis of autoimmune hepatitis( AIH ). Methods The reactivity between yeast ADH and human anti-ADH serum antibody was tested by Western blot analysis. ELISA was established using yeast ADH. The method was applied in serums of 67 AIH patients,94 primary biliary cirrhosis(PBC) patients, 199 chronic hepatitis B (CHB) patients, 132 chronic hepatitis(CHC) patients, 24 alcohol hepatitis disease(ALD) patients, 99 connective tissue disease(CTD) patients and 31 healthy individuals. The positive rate of ADH antibody in the patients and healthy individuals was measured. The χ2 test was used to compare the positive rates. Results The ELISA method for detecting human anti-ADH serum antibody was established successfully and the optimum reaction conditions were defined. Western blot showed that yeast ADH has cross reactivity with human anti-ADH antibody. The positive rate of anti-ADH antibody in the AIH group [59. 7% ,40/67 ] was higher than that in the normal control group(0,χ2 = 31. 271 ,P <0. 05), PBC group (6. 4% ,χ2 =54. 492,P <0. 05), CHB group( 14. 1% ,χ2 =54. 848,P <0. 05) ,CHC group(21.2% ,χ2 = 29.269,P<0.05), ALl) group ( 25. 0% ,χ2 =8.512,P <0.05)and CTD group ( 43. 4% ,χ2 =4.229, P <0. 05). Conclusions Compared with the PBC, CHB, CHC, ALD and CTD group, the anti-ADH antibody positive rate in the serums of AIH was significantly increased. The antibody may be helpful to the diagnosis of autoimmune hepatitis.

Drug induced liver injury (DILI) refers to the liver injury caused by chemicals, biological products, traditional Chinese patent medicines and simple preparations and other drugs managed by prescription drugs or non prescription drugs, as well as Chinese medicinal materials, natural drugs, health products, dietary supplements and other products, or their metabolites and even their excipients, pollutants, impurities, etc. DILI is one of the most common Adverse drug reaction. In recent years, the incidence of DILI in China has increased year by year, posing a serious threat to the health of patients. The clinical manifestations of drug-induced liver injury are diverse, and the pathogenesis is complex, making diagnosis and prevention difficult. This article reviews the definition, epidemiology, clinical characteristics, and progress in diagnosis and treatment of DILI.

OBJECTIVETo explore the differential characteristics of the AMA-M2 autoantibody in patients with primary biliary cirrhosis (PBC) and non-PBC patients.

METHODSPatients with abnormal liver function at the Capital Medical University affiliated to Beijing You-an Hospital were enrolled in this study between January 2011 and December 2013. Serum levels of ANA, AMA and AMA-M2 were detected by indirect fluorescence assay and enzyme-linked immunosorbent assay. The patients' clinical data was obtained for retrospective analysis. Statistical analyses were performed using the SPSS 16.0 software. Enumeration data have been presented as numbers and percentages, and were analyzed using the chi-square test and one-way ANOVA test.

RESULTSOf the 5315 patients with abnormal liver function, 15.3% (811/5315) were AMA-M2 positive patients; among those 811 patients, 78.4% (636) had PBC, 4.4% (36) had PBC overlapping with autoimmune hepatitis (AIH), 4.4% (36) had drug-induced liver injury, 6.5% (53) had hepatitis B, 3.3% (27) had hepatitis C, 0.6% (5) had hepatitis E, 0.9% (7) had alcoholic liver disease, 0.5% (4) had non-alcoholic fatty liver, 0.8% (6) had primary hepatic carcinoma, and 0.1% (1) had infectious mononucleosis. Serum AMA-M2 level was significantly higher in the PBC patients (vs. other groups, P less than 0.001) with the exception of the patients with PBC/AIH overlap syndrome. Among the 811 patients with AMA-M2 positivity, 88.5% (718) showed AMA positivity and 91.1% (739) showed ANA positivity. Serum alanine transferase (ALT) and aspartate transferase (AST) levels were significantly higher in the drag-induced liver injury patients (527.74+/-684.65 U/L, 490.60+/-716.89 U/L) and the hepatitis E patients (1015.94 ± 165.55 U/L, 665.4 ± 297.14 U/L) than in the PBC patients (96.02 ± 115.56 U/L, 94.82 ± 83.32 U/L) (ALT: F =8.041, P < 0.001, P < 0.001; AST: F =8.066, P < 0.001, P < 0.001). Serum alkaline phosphatase (ALP; 265.16 ± 179.08 U/L) and glutamyl transferase (GGT; 332.02 ± 279.29 U/L) were significantly higher in the PBC patients than in the hepatitis B patients (135.35 ± 123.17 U/L, 140.27 ± 229.24 U/L) and the hepatitis C patients (85.65 ± 27.77 U/L, 92.70 ± 125.72 U/L) (ALP: F=3.911, P =0.01, P=0.001; GGT: F=4.081, P <0.001, P < 0.001). The serum IgM level was significantly higher in the PBC patients (4.60 ± 2.67 g/L) than in the patients with drug-induced liver injury (1.76 ± 1.15 g/L), hepatitis B (2.02 ± 1.41 g/L), hepatitis C (1.48 ± 0.92 g/L), hepatitis E (1.40 ± 0.68 g/L), alcoholic liver disease (1.57 ± 1.07 g/L), non-alcoholic fatty liver (1.05 ± 0.72 g/L), and primary hepatic carcinoma (2.64 ± 2.26 g/L) (F=16.83, P < 0.001, P < 0.001, Probability value < 0.001, Probability value < 0.05, Probability value < 0.01, Probability value < 0.05 respectively).

CONCLUSIONAlthough detection of serum AMA-M2 is an important feature of PBC diagnostic testing,there is a high ratio of serum AMA-M2 detected in patients with drug-induced liver injury, hepatitis B, C and E, alcoholic liver disease, non-alcoholic fatty liver,and primary hepatic carcinoma. The AMA-M2 positive non-PBC patients still require close observation to watch for future development of PBC.

Autoantibodies ; Beijing ; Carcinoma, Hepatocellular ; Chemical and Drug Induced Liver Injury ; Enzyme-Linked Immunosorbent Assay ; Hepatitis B ; Hepatitis C ; Hepatitis, Autoimmune ; Humans ; Liver Cirrhosis, Biliary ; Liver Diseases, Alcoholic ; Liver Function Tests ; Liver Neoplasms ; Retrospective Studies

Objective: To understand the characteristics and clinical significance of anti-soluble liver antigen antibody (anti-SLA) in patients with liver diseases. Methods: Serum samples from seventy-seven patients with anti-SLA were collected from Beijing You'An Hospital during the period between January 2010 and December 2018. Anti-SLA, anti-liver cytosol type 1 antibody (anti-LC1), anti-glycoprotein 210 antibody(anti-gp210) and anti-nuclear body protein sp100 antibody(anti-sp100) were detected by immunoblotting; indirect immunofluorescence assay used for detecting anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), and anti-liver kidney microsome antibody (anti-LKM). One-way analysis of variance was used to compare the ages of different anti-SLA groups. The non-parametric rank sum test was used to compare the liver function indexes and immunoglobulins in different intensity groups of anti-SLA. P<0.05 was considered statistically significant. Further comparisons were made between the two groups, the correction level α′=0.008 3, P<0.008 3 was considered statistically significant. Results: The average age of 77 anti-SLA positive patients was (52.50±1.25) years old, 70 females (90.9%) and 7 males (9.1%). 80.5% of anti-SLA-positive patients (62/77 cases) were strongly positive at the time of initial diagnosis (+++ to ++++).The Alanine aminotransferase (ALT) level in the SLA++ group was higher than that in the SLA++++ group (232.7 U/L vs 65.6 U/L,χ²=7.751,P=0.005) and the immunoglobulin M(IgM) level in the SLA+++ group was lower than that in the SLA++++ group (1 270 mg/L vs 2 270 mg/L,χ²=8.337,P=0.004).There was no significant difference in age, other liver function and immunological indicators among the different groups.Seventy cases (90.9%) were both anti-SLA and ANA positive, 13 cases (16.9%) were positive with SMA, and none positive with anti-LKM and anti-LC1. Among anti-SLA positive patients, 58 cases were diagnosed with autoimmune hepatitis (AIH), 12 were AIH/primary biliary cholangitis (PBC) overlap syndrome (OS), 2 were drug-induced liver injury, 2 were chronic hepatitis B, and 3 were hepatitis A, hepatitis E and acquired immune deficiency syndrome (AIDS) with liver injury, respectively.Cases of AIH and AIH/PBC OS accounted for 90.9% (70/77 cases) of anti-SLA-positive patients, and 5 of 7 patients diagnosed with non-AIH (and OS) had elevated IgG, showing AIH feature.92.3% (12/13 cases) of anti-SLA with high titers of AMA were diagnosed as AIH/PBC overlap syndrome. Of the 77 anti-SLA-positive patients, 28 (36.4%) had advanced or end-stage liver disease, including decompensated cirrhosis (22 cases), chronic acute liver failure (4 cases), and liver transplantation (1 case) and death from liver failure (1 case). Conclusions Anti-SLA has high diagnostic specificity for AIH;anti-SLA positive in patients with PBC should be an important biomarker for the diagnosis of AIH/PBC overlap syndrome.