Mutations of Hepatitis B Virus Enhancer II in Chronic Hepatitis B Virus Infection - Comparison with Basic Core Promoter and Precore Mutation -

Kim, Yun Soo; Lee, Jin Woo; Kim, Young Seok; Moon, Jong Ho; Cho, Young Deok; Lee, Moon Sung; Shim, Chan Sup

Abstract

BACKGROUND/AIMS: Transcriptional activity of the basic core promoter (BCP) in hepatitis B virus (HBV) is influenced by several regulatory sequences including enhancer II (EN II), and mutation in the EN II (T1653) was reported to be frequent in fulminant hepatitis B. This study was carried out to identify the frequency of mutations in the EN II, BCP and preC regions according to activity of liver disease and HBeAg status in chronic HBV infection.
METHODS
Forty-two chronic HBV carriers were included in this study. We assigned ten HBeAg-positive asymptomatic HBV carriers to group I, eighteen HBeAg-positive patients with chronic liver disease to group II, and fourteen HBeAg- negative patients with chronic liver disease to group III. The mutations in EN II, BCP and preC regions were analysed from serum DNA by the PCR and direct sequencing method.
RESULTS
In group I, there was no mutation in EN II (T1653) or PreC (A1896), but mutations in BCP (T762 and A1764) were observed in one case (10%). In group II, 8 (44%) cases had mutation in EN II (T1653), 17 (94%) cases had mutations in BCP (T1762 and A1764), and 4 (22%) cases had mutation in PreC (A1896). In group III, 9 (64%) cases had mutation in EN II (T1653), 12 (86%) cases had mutations in BCP (T1762 and A1764), and 11 (79%) had mutation of PreC (A1896) (p<0.05). Most of the patients who showed mutation of EN II (T1653) in group II had liver cirrhosis.
CONCLUSION
In view of the HBeAg status, mutation in EN II as well as mutations in BCP might decrease the transcription of preC mRNA. Additionally, it seems that mutations in EN II and PreC follow mutations in BCP as HBeAg-suppressive mutations during the course of chronic HBV infection.