Clinical Analysis And Preliminary Study Of Association Of HLA Genotypes With Susceptibility To PBC In North Chinese

Primary biliary cirrhosis (PBC) is characterized by an immune mediated, irreversible destruction of the small intrahepatic bile ducts leading to progressive liver cirrhosis and frequently to liver failure. In recent years, more attention has been paid for PBC in our country, and the incidence of detected cases of PBC has been increasing. Because of lacking effective therapeutic measures, so it is necessary to reinforce the study of pathogenesis of PBC.The course of PBC is variable and an early diagnosis is desirable to identify individuals with rapidly progressing disease, to initiate adequate therapeutic measures and to predict the timing of liver transplantation. Clinical data of 80 patients with PBC were reviewed. The clinical features, laboratory tests, pathological finds in all the PBC patients were analysed. Most patients were female in middle-age. The most frequently complained symptoms in the patients were fatigue,anorexia, pruitus. The major physical signs included jaundice, splenomegaly, liver palmor. Serum alkaline phosphatase(ALP)and r glutamyl transpeptidase( r-GT) levels were markedly elevated in most patients and the level of ALP and GGT drop down at the late stage. The level of ALT and AST were only slightly-middly elevated. Forty-three patients had elevated serum total bilirubin level. Seventy-one patients were antimitochondrial antibody (AMA)/ AMA-M; positive. Thirty-two patients underwent pathological examinations, 87.5% in early stage and 12.5% in advanced stage. Conclusions: PBC is mostly found in middle aged and old womem. The main clinical manifestations are fatigue. anorexia. pruitus. The elevated level of ALP. r-GT and positiveAMA/AMA-M2 may be crucial to diagnosis of PBC.As that of many other autoimmune diseases, genetic factors were considered to play an important role in pathogenesis of PBC. Some of MHC class II molecules, especially HLA-DR8, were reported to be associated with susceptibility to PBC, but results from different population are not unanimous and there has been no data about north Chinese people. The HLA-DR and A, B gene of 81 north Chinese patients with PBC and controlled 231 health people, was genotyped by using forward DNA hybridization Microarray technique in this study. The frequency of DRB1 * 08 was 19.8% in PBC patient group, much higher than that (6.93%) in health group (RR=4.22, P=0.000) and that (7.27%) in disease control group (P=0.044); The frequency of HLA-B35 was 19.79% in PBC patient group, much higher than that (9.96%) in health group (P=0.022); The frequency of HLA-B07 was 2.47% in PBC patient group, much lower than that (9.09%) in health group (P=0.049); ; HLA-B35, B07 have not been reported as potential roles in susceptibility to PBC. The results suggested that DR8 and B35 were associated with PBC as a risk factor and B07 was associated with PBC as a pretective factor in north Chinese people. Further study in this respect will be helpful for understanding of etiology and the prediction and diagnosis of this disease.