Value of subtypes of antimitochondrial antibodies in primary biliary cholangitis / 中华风湿病学杂志

Objective:To investigate the distribution and clinical significance of subtypes of antimitochondrial antibodies (AMA)-M2, M4, M9 in primary biliary cholangitis (PBC).Methods:A total of 1 367 patients were detected with AMA-M2, M4, M9 in Peking Union Medical College Hospital (PUMCH) from Jan 2014 to Dec 2019 and the clinical parameters were collected. The distribution patterns of AMA subtypes in different groups were analyzed and the diagnostic sensitivity and specificity of AMA subtypes in PBC were calculated. Chi-square test was used for statistical analysis.Results:In 1 367 patients, 236 of whom were positive for AMA subtypes. The positivity of AMA subtypes in female was significantly higher than in male (20.34% vs 9.41%, χ2=23.792, P<0.01). In addition, the positivity of AMA subtypes was significantly higher in 30-65 years old patients than in patients younger than 30 years old or older than 65 years old [(20.00%(193/965) vs 10.97%(17/155) vs 10.53%(26/247), χ2=17.209, P<0.01]. 110 patients with positive AMA subtypes were diagnosed with PBC. The diagnostic sensitivity and specificity of AMA-M2 were both desirable [94.64%(106/112) and 92.35%(1 159/1 255)]. Although the specificity of AMA-M4 was as high as 99.12%(1 244/1 255), its sensitivity was very low [15.18%(17/122)]. Combined detection of different AMA subtypes could not improve the diagnostic sensitivity and specificity significantly. Diseases other than PBC can be positive for AMA subtypes, predominantly for AMA-M2. Conclusion:Female and 30-65 years old patients were more frequently positive for AMA subtypes. AMA-M2 was the most valuable AMA subtype for diagnosing PBC.

Clinicopathological analysis of anti-mitochondrial antibody negative primary biliary cholangitis-autoimmune hepatitis overlap syndrome / 中华肝脏病杂志

Objective@#To explore the clinicopathological features of anti-mitochondrial antibody (AMA) negative and positive patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome (PBC-AIH OS).@*Methods@#Seventy-four cases diagnosed as PBC-AIH OS from June 2017 to April 2018 were enrolled in this study. Among them, forty cases were AMA negative (negative group) and thirty-four cases were AMA positive (positive group). The clinical manifestations, serum biochemical indexes, immunological indexes and histological data of the negative group were compared with the positive group. Mann-Whitney U test and theχ 2test were used for statistical analysis.@*Results@#There was no significant difference in sex, age, clinical manifestations and major liver function indexes (ALT, AST, ALP, GGT, TB, DB) between the negative group and positive group (P> 0.05). The level of IgM in the negative group (1.68 ± 0.87) was significantly lower than positive group (3.77 ± 2.88)(P< 0.05). The positive rates of antinuclear antibodies (ANA) and gp-210 antibodies was lower than positive group (P< 0.05). There were no significant differences in the stages of inflammation and fibrosis between the two groups (P> 0.05), and the bile duct injury was more significant in the negative than positive group (P< 0.05).@*Conclusion@#The serum IgM level of AMA-negative PBC-AIH OS is low, and immunological antibody is often negative, which makes bile duct injury apparent in liver histology. A liver biopsy should be carried out as soon as possible for early diagnosis and treatment.

Analysis of the relationship between anti-mitochondrial antibody subtypeⅡIgM and anti-centromere antibody IgG in primary biliary cirrhosis patients / 中华风湿病学杂志

Objective The aim of this study is to analyze the association between IgM anti-mitochon-drial antibody subtypeⅡ(AMA-M2-IgM) and the anti-centromere antibody IgG (ACA-IgG) in primary biliary cirrhosis (PBC) patients, and to investigate the clinical significance of M2-IgM and ACA-IgG in the diagnosis of PBC. Methods We selected 36 cases of PBC patients as research subjects whose AMA-IgG and AMA-M2-IgG were both negative. The M2-IgM positive rate in the ACA-IgG positive group and negative group was compared. We also analyzed the course of disease, pathological changes and the positive conversion rate of M2-IgG between the M2-IgM positive group and negative group. Results There were 9 cases of M2-IgM positive patients (64%) and 5 cases of M2-IgM negative patients (36%) in the ACA-IgG positive group. In the ACA-IgG negative group we found 3 cases of M2-IgM positive patients (14%) and 19 cases of M2-IgM negative patients (86%). So the M2-IgM positive rate in the ACA-IgG positive group was significantly higher than that of the ACA-IgG negative group (P=0.003). According to the tracking detection results, the M2-IgG positive conversion rate in the M2-IgM positive group was 67% (8 patients), which was significantly higher than the M2-IgM negative group 8%, (2 patients) (P=0.001). Conclusion M2-IgM is a specific antibody for PBC in the early stage, which presents earlier than M2-IgG. In the PBC patients whose AMA-IgG and AMA-M2-IgG antibodies are both negative, the M2-IgM positive rate is closely related to the ACA-IgG, so the ACA-IgG detection is very important in the early diagnosis of PBC. Therefore, we speculated that patients with ACA-IgG antibody are more susceptible to PBC.

Clinical features and prognosis of primary biliary cirrhosis in Korea / 대한간학회지

BACKGROUND/AIMS: This study investigated the clinical features and prognosis of primary biliary cirrhosis (PBC) in Korea. METHODS: Clinical data of patients diagnosed as PBC between 1997 and 2008 at eight referral hospitals were analyzed retrospectively. PBC was diagnosed based on liver function tests, presence of serum antimitochondrial antibody (AMA), and histopathological findings. RESULTS: In total, 251 patients (218 females, 33 males; mean age 54 years) were enrolled, and the mean follow-up duration was 33.5 months. At the diagnosis, 61% of the patients were asymptomatic, 12% had decompensated liver cirrhosis, and 98% were positive for AMA. The serum alkaline phosphate (ALP) level was 2.6 times the upper limit of normal, aspartate aminotransferase was 105 U/L, and bilirubin was 2.0 mg/dL. The mean Mayo risk score was 5.5, and the Child-Pugh class was A, B, and C in 79%, 19%, and 2% of the patients, respectively. Ursodeoxycholic acid (UDCA) was used for treatment in 88% of the patients, among which 70% exhibited biochemical responses defined as normalization or a >40% decrease in ALP at 6 months. Eight deaths occurred during the follow-up; the causes were variceal bleeding, hepatic failure, and sepsis. The overall 5-year survival rate was 95%. The poor prognostic factors were being older than 60 years, high bilirubin, low albumin, ascites, high Mayo risk score, Child-Pugh class C, and initial presence of hepatic decompensation. CONCLUSIONS: Most patients diagnosed as PBC were asymptomatic, and these patients had a favorable short-term prognosis. The prognosis of PBC was dependent on the initial severity of liver disease.

Clinical features of 70 patients with primary biliary cirrhosis / 中华消化杂志

Objective Clinical features of primary biliary cirrhosis (PBC) were reviewed in order to improve its diagnosis in our clinical practice. Methods Clinical data of 70 patients with PBC were reviewed including the clinical manifestation, laboratory tests, pathological findings and the response to therapy. Results Sixty-two patients were females (88.6%), eight patients were males (11.4%), and the mean age at diagnosis was (53.1?10.4) years. The most frequently complained symptoms were pruitus (60.0%), fatigue (42.9%), anorexia (41.4%) and jaundice (45.7%). Serum alkaline phosphatase (ALP) and ? glutamyl transpeptidase (GGT) levels were markedly elevated in all patients, while alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were mildly elevated. The serum total bilirubin level increased in sixty-five patients (92.9%). Forty-four patients (62.9%) had elevated serum immunoglobin M (IgM), and 98.6% of patients (69/70) were antimitochondrial antibody (AMA) /AMA-M2 positive. Forty-one patients underwent pathological examinations, 82.9% in early stage (Ⅰ,Ⅱ stage) and 17.1% in advanced stage (Ⅲ,Ⅳ stage).Conclusions PBC most frequently affects middle-aged women and the main clinical manifestations are pruritus, fatigue, anorexia and jaundice. The elevated level of ALP, GGT, IgM and positive AMA/AMA-M2 may be crucial to diagnosis of PBC.

Clinical analysis of 78 patients with primary biliary cirrhosis / 解放军医学杂志

Objective To improve the diagnosis and management of primary biliary cirrhosis (PBC). Methods Clincal data of 78 cases of PBC patients were reviewed. The clinical manifestations,the results of laboratory tests,and response to therapy in all the PBC patients were analysed retrospectively. Results Among 78 patients 68 were female. The mean age was 50.4?9.3years at the time when definite diagnosis was made. The major symptoms in these patients were pruritus,fatigability,and jaundice. The major signs included hepatomegaly,splenomegaly,and ascites. Very high levels of serum alkaline phosphatase (ALP) and serum gamma glutamyl transpeptidase (GGT),hyperbilirubinemia,and hypergammaglobulinemia were also detected in most of the patients. The aminotransferase levels were only slightly elevated,but the AST/ALT ratio was reversed. It took 12 months (ranging from 2 months to 10 years) to confirm the diagnosis after the onset of clinical manifestations. Ursodeoxycholic acid reduced the serum levels of ALP and bilirubin in 80% of patients and improved the symptom of pruritus and fatigability in 73.4% of patients. Conclusion PBC mainly affects middle-aged women with hepatosplenomegaly, jaundice,pruritus and fatigability as presenting features. Liver function tests typically revealed a cholestatic pattern accompanied by hypergammaglobulinemia and a positive antimitochondrial antibody (AMA) including M2 subtype (AMA-M2). Ursodeoxycholic acid could improve the abnormal liver function tests and clinical symptoms in PBC patients.

Polymorphisms of PPARgamma2 gene in patients with type 2 diabetes mellitus and obesity / 대한내과학회지

BACKGROUND: Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulate adipocyte differentiation and modulate intracellular insulin-signaling events. As such, PPARgamma is a candidate gene for several human disorders including obesity and type 2 diabetes mellitus. The objective of our study was to examine the relationship between genetic variation of PPARgamma2 and diabetes and obesity in Korean subjects. METHODS: We studied 99 subjects with type 2 diabetes mellitus, 128 obesity patients and 97 controls. Screening for mutation at codon 12 and 115 of PPARgamma2 were carried out by PCR-RFLP analyses. Statistical significance was evaluated by Chi-square test. RESULTS: The allele frequency of the Pro12Ala PPARgamma2 variant were 0.05 in controls, 0.06 in type 2 diabetes group, and 0.07 in obesity group (p=0.47). Pro115Gln variant were only proline homozygote in all groups. Genotype frequencies were also similar and conformed to expectations of the Hardy-Weinberg rule. The presence of PPARgamma2 gene variant was no associated with concentrations of total cholesterol, triglyceride, HDL-cholesterol, and also with fasting glucose. CONCLUSION: We concluded that the Pro12Ala and Pro115Gln PPARgamma2 missense mutation may not be associated with type 2 diabetes mellitus and obesity in Korean patients.

A case of conventional antimitochondrial antibody test-negative primary biliary cirrhosis / 대한내과학회지

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause that usually affects middle-aged women and eventually leads to cirrhosis and liver failure. It is characterized by the progressive destruction of small intrahepatic bile ducts, portal inflammation, and progressive scarring. The diagnosis is made by these characteristic pathologic findings and the presence of antimitochondrial antibody. Immunofluorescence, the most widely used method for determining antimitochondrial antibody, is less sensitive and specific than ELISA or immunoblotting and influenced by observer interpretation. Therefore, it is important to detect anti-M2 antibody, the most specific antibody of primary biliary cirrhosis, by ELISA or immunoblotting when antimitochondrial antibody is not detected by immunofluorescence method which can lead to the incorrect diagnosis as autoimmune cholangitis. We describe a case of primary biliary cirrhosis with antimitochondrial antibody negative by immunofluorescence, anti-M2 antibody positive by ELISA. We confirmed primary biliary cirrhosis by liver biopsy.