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B형 만성 간질환 환자에서 HBV core promoter 변이에 대한 고찰
김호철,이연재,장윤식,이상혁,설상영,박영흥,정정명 인제대학교 2000 仁濟醫學 Vol.21 No.1
Objectives: Chronic hepatitis B virus(HBV) infection may cause various kinds of liver disease. The pathophysiologic mechanisms of such clinical manifestations are still not clearly understood. According to the recent reports, mutations in the HBV core promoter may have an impact on the progression of HBV-related liver disease. The aim of this study was to clarify the frequency and location of naturally occurring mutations in the core promoter region of HBV, and their possible effects on the clinical course of HBV -associated chronic liver diseases. Methods: and Materials: HBV DNA was extracted from the sera of 31 patients who had been HBsAg positive for more than 6 months. The core promoter/precore sequence was amplified via polymerase chain reaction, and direct sequenced. And in this study. 31 patients were divided into 3 groups according to the histopathological severity of liver disease i.e. Group 1 as minimal change and chronic persistent hepatitis, Group 2 as chronic active and lobular hepatitis, Group 3 as liver cirrhosis and hepatocellular carcinoma, respectively. Results: 1.Frequent mutated nucleotides(nt) were 1764(77.4%), 1762(58.1%) and 1753 (25.8%). 2.A double-nucleotide mutation at nt1762 and nt1764 (M1) was observed in 18 cases of 31 patients(58.1%), a single-nucleotide mutation at nt1764(M2) in 5 cases. But a single-nucleotide mutation at nt1753 or nt1762 were not observed at all. 3.M1 had nothing to do with the severity of hepatitis. In case of M2. there was association with severity of hepatitis only in comparisons among Group 2 vs. Group 3(p<0.05) 4.The frequency of mutation in core promoter region had little association with the status of HBeAg/Anti-HBe. 5.The frequency of mutation at nt1896(G→A) in precore region was related with status of HBeAg/Anti-HBe(p<0.01) rather than the severity of disease. Conclusion: We could not find the definite relationship between core promoter mutation and the histopathologic severity of HBV associated liver disease. Further investigations are needed with larger number of patients.