The Prevalence and Clinical Significance of Precore and Core Promoter Mutations in Korean Patients with Chronic Hepatitis B Virus Infection

Korean J Hepatol > Volume 8(2); 2002 > Article

The Korean Journal of Hepatology 2002;8(2): 149-156.

원저 : 한국인 만성 B 형 간염 바이러스 감염에서 Precore 및 Core promoter 변이의 발현빈도 및 임상적 의의 ( Original Articles : The Prevalence and Clinical Significance of Precore and Core Promoter Mutations in Korean Patients with Chronic Hepatitis B Virus

The Prevalence and Clinical Significance of Precore and Core Promoter Mutations in Korean Patients with Chronic Hepatitis B Virus Infection

Hyung Joon Kim,Byung Chul Yoo

Department of Gastroenterology, College of Medicine, Chung Ang University, Seoul, Korea

ABSTRACT

Background/Aims
Precore and core promoter mutations of hepatitis B virus (HBV) have been reported in Korea but their prevalence and clinical significance have not been determined. The aims of this study were to determine the prevalence of precore and core promoter mutations and their relationships to hepatitis B e antigen(HBeAg) status, viral replication level, and severity of liver disease in Korea. Methods: Among the patients who visited the Liver Diseases Clinics (Chung Ang University Hospital) between December 1998 and August 1999, 150 patients were randomly selected: 50 HBeAg-positive HBV-DNA positive patients by a branched DNA (bDNA) assay, 50 HBeAg-negative bDNA-positive patients, and 50 HBeAg-negative bDNA-negative patients. Serum HBV-DNA was amplified by a polymerase chain reaction (PCR) in these patients and the core promoter/precore HBV sequence was determined in 135 of the patients whose sera were positive for HBV-DNA by PCR. Results: All of the 135 determined HBV-DNA sequences had HBV genotype with T at nucleotide 1858. Precore mutation (A1896) was detected in 95.7% of HBeAg-negative bDNA-positive patients and 94.9% of HBeAg-negative bDNA-negative patients. In HBeAg-positive patients 88% had wild type and 12% had mixture of wild type and A1896 mutant. Core promoter TA mutation (T1762/A1764) was detected in 93.5% of HBeAg-negative bDNA-positive patients, 94.9% of HBeAg-negative bDNA-negative patients and 74% of HBeAg-positive patients. No correlation was found between the presence of precore/core promoter mutations and liver disease severity or HBV-DNA levels. Conclusion: Precore stop codon mutation occurred almost invariably, along with HBeAg seroconversion, irrespective of subsequent viral replication levels or disease severity. Core promoter TA mutation was frequent both in the HBeAg-positive patients and HBeAg-negative patients irrespective of viral replication levels or disease severity.(Korean J Hepatol 2002;8:149-156)

KeyWords: Hepatitis B virus, Precore mutation, Core promoter TA mutation