Clinical And Pathological Characteristics Of Primary Biliary Cholangitis With Negative And Positive Anti-Mitochondrial Antibodies

Objectives: Anti-mitochondrial antibody(AMA)is an important serological marker for the diagnosis of primary biliary cholangitis(PBC).Due to the high specificity of AMA and the high detection rate,AMA-negative patients are easily missed the diagnosis and delay treatment.Therefore,comparing the clinical and pathological features of AMA-negative and AMApositive PBC patients,it can provide a reference for the diagnosis and treatment of PBC.This article clarifies characteristics of AMA-negative and AMA-positive PBC from the following aspects: 1.To explore the similarities and differences of clinical manifestations between AMApositive and AMA-negative PBC patients;2.To study the similarities and differences of pathological characteristics between AMA-positive and AMA-negative PBC patients;3.To understand the similarities and differences of the treatment response between AMA-positive and AMA-negative PBC patients.Methods: 1.To explore the similarities and differences of clinical manifestations between AMA postivite and negeative PBC patients: Restropectively collected primary biliary cholangitis patients with liver biopsy from January 2016 to September 2018 in the outpatients and inpatients from the Nanjing Second Hospital.The diagnostic criteria were based on the consensus of the Society of Hepatology of Chinese Medical Association in 2015.Age,sex,course of disease,complications,combined diseases and so on were collected.Blood routine,liver function,blood lipid,immunoglobulin,autoimmune antibody,coagulation function indexes.According to the expressions of AMA antibody,AMA-negative and AMA-positive PBC groups were divided into two groups.The differences of clinical indicators between the two groups was statistically analyzed.2.To study the similarities and differences of pathological characteristics between AMA antibody expression and pathology of PBC patients: HE staining,CD38,CK7 immunohistochemical sections were collected,and the pathological characteristics of PBC patients were assessed by semi-quantitative scoring scale.The number of portal areas,lymphocyte aggregation,granuloma,bile duct injury,grade of bile duct loss,plasma cells,CK7 positive hepatocytes,fibrosis and pathological stages were evaluated.Data were evaluated and the differences of pathological indexes between AMA-negative PBC patients and AMA-positive PBC patients groups were analyzed.3.To understand the similarities and differences of the treatment response between AMApositive and AMA-negative PBC patients: The indexes of liver function and immunoglobulin of the patients in the outpatient follow-up or telephone follow-up from 1,3 and 6 months after the liver puncture were collected,and the decrease of the indexes in the two groups was statistically analyzed.4.Statistical analysis: After collecting the above data,SPSS 20.0 was used for analysis.The counting data and grade data are described by examples and percentages,and analyzed by chi-square test and rank sum test;the measurement data of normal distribution are described by(mean ±standard deviation)and analyzed by t-test;the measurement data of non-normal distribution are described by median and extreme value,and rank sum test;P < 0.05 means statistical significance.Result: 1.A total of 85 patients with primary biliary cholangitis were enrolled.The age distribution of the patients was(52.2 ± 9.2)years old.There were 15 males and 70 females.Among them,50 were AMA positive and 35 were AMA negative.2.In the comparison of clinical data between AMA negative group and AMA positive PBC group,AMA negative group had lower appetite loss ratio,lower levels of TG and TC in blood lipids,lower levels of Ig M in immunoglobulin,higher positive rate of ANA in autoimmune antibody,lower positive rate of anti-gp210 antibody and lower proportion of light spot increase in B-mode ultrasonography than AMA positive group.Gender,age,course of disease,symptoms(except loss of appetite),signs,complications,blood routine(WBC,RBC,PLT,HB),liver function(total bilirubin TB,direct bilirubin DB,ALT,glutathione AST,albumin Alb,glutamyl transpeptidase GGT,alkaline phosphatase ALP),thrombin function(prothrombin activity P)There were no significant differences in TA,INR,PT,Ig A,Ig G,anti-sp100,ASMA,B-mode ultrasound,Fibroscan,CT and MRI.3.There were no significant differences in the number of intact portal areas,typical and atypical lymphoid follicles,typical and atypical granulomas,bile duct injury(no-obvious injury)distribution,fine bile duct reaction,plasma cells,fibrosis and pathological stages between AMA negative group and AMA positive PBC group.There were no significant differences in the number of intact portal areas and intact portal areas in AMA negative group.The distribution of bile duct absence in incomplete portal areas was low,and the proportion of bile duct absence and the distribution of CK7 positive expression in hepatocytes were significantly different.4.There was no significant difference in ALP and Ig M levels between AMA-negative and AMA-positive PBC patients in the first,third and sixth months of follow-up.Conclusion: 1.The basic characteristics and treatment responses of AMA-negative and AMA-positive PBCs were similar.2.The clinical manifestation of AMA-negative PBC was lighter than that of AMA-positive PBC.The increase of TG,TC and Ig M in AMA negative group was lower than that in AMA positive group,and the positive rate of anti-gp210 was lower than that in positive group.3.Biliary duct injury in AMA-negative PBC was lighter than that in positive PBC.The main pathological patterns of AMA-negative PBC were lymphocyte aggregation + bile duct injury,lymphocyte aggregation + granuloma + bile duct injury.4.The positive rate of AMA-negative PBC was higher than that of positive PBC-ANA,and the positive rate of anti-gp210 was lower.There was no difference between anti-sp100 and ASMA.The above-mentioned antibodies could be used for assistant diagnosis of AMAnegative PBC.