Mutations of the Pre-S Region in HBV-Associated Liver Cirrhosis and Hepatocellular Carcinoma

Lee, Sang Ook; Lee, Youn Jae; Jang, Yeun Sik; Lee, Sang Hyuk; Seol, Sang Young; Park, Young Hong; Chung, Jung Myung

Abstract

BACKGROUND/AIMS: According to the recent research, mutations in the HBV pre-S region may have an impact on the progression of hepatitis B virus(HBV)-related liver disease. The aim of this study was to clarify the frequency and location of naturally occurring mutations in the pre-S region of HBV, and their possible effects on the clinical course of HBV-associated chronic liver diseases.
METHODS
HBV DNA was extracted from the sera of 15 patients (8 with liver cirrhosis and 7 with hepatocellular carcinoma). The pre-S sequence was amplified via polymerase chain reaction, subcloning and sequenced.
RESULTS
All patients had point mutations in the pre-S region. Nine of 10 mutation sites (90%) in the pre-S1 region, and 4 of 5 mutation sites (80%) in the pre-S2 region were identical in both liver cirrhosis and hepatocellular carcinoma. Deletions were detected in seven patients (4 with liver cirrhosis and 3 with hepatocellular carcinoma). Among the 4 patients with liver cirrhosis, three had deletion in 5'-end of the pre-S2 region and one spanning the 3'-end of the pre-S1 to 5'-end of the pre-S2 region. All 3 patients with hepatocellular carcinoma had deletions in 5'-end of the pre-S1 region, and two patients had simultaneous deletion spanning the 3'-end of the pre-S1 to the 5'-end of the pre-S2.
CONCLUSION
The pre-S mutants were frequently detected in HBV-associated liver cirrhosis or hepatocellular carcinoma and the point mutations or deletions in the pre-S gene were clustered in specific regions.