Missense Mutationsof Hepatitis B Virus Core Gene in Chronic Hepatitis B Virus Carriers

Kim, Yun Soo; Kim, Young Seok; Cho, Young Deok; Kim, Jin Oh; Cho, Joo Young; Kim, Hong Soo; Lee, Joon Seong; Lee, Moon Sung; Hwang, Seong Gyu; Shim, Chan Sup

Abstract

BACKGROUND/AIMS: Missense mutations of HBV (hepatitis B virus) core gene have been reported to occur frequently in the immune clearance phase of chronic HBV infection. The present study was carried out to identify whether the number of missense mutation might be related to the disease progression, presence of HBeAg or precore stop codon and to determine the locations where the missense mutations are concentrated.
METHODS
This study involved 41 patients with HBeAg and 10 HBeAg-negative patients whose serum ALT (alanine aminotransferase) were elevated. The 41 patients with HBeAg were consisted of 15 patients with asyptomatic HBV carriers (ASC), 14 patients with chronic hepatitis (CH) and 12 patients with liver cirrhosis (LC). The core gene sequences from al 51 patients were analysed by PCR-direct sequencing method.
RESULTS
Mean numbers(M +/-SD) of amino acid changes/patient were as follows; 0.2 +/-0.4 in ASC, 2.0 +/-1.4 in CH, 2.2 +/-1.6 in LC and 4.5 +/-2.3 in HBeAg-negative patients. In the cases with chronic liver diseases, mean numbers of amino acid changes/patient were 4.0 +/-2.5 in the cases with precore stop codon and 2.0 +/-1.1 in the cases without it (p=0.002). Missense mutations were most frequently found in codon 80-100 and 130-135 where 34 and 26 amino acid changes were observed, respectively.
CONCLUSIONS
It is likely that the number of missense mutation in the core gene is more closely related to the presence of HBeAg oprecore stop codon than the progression of liver diseases.