Clinical Significance of HBV Core Promoter Mutations in HBeAg-Positive Type B Chronic Liver Diseases

Shim, Chan Sup; Lee, Joon Seong; Kim, Yun Soo; Lee, Moon Sung; Cho, Joo Young; Hwang, Seong Gyu; Cho, Young Deok; Lee, Hi Bahl; Hwang, Seung Duk; Hong, Su Jin; Moon, Jong Ho; Kim, Jin Oh; Kim, Sung Il

Abstract

BACKGROUND/AIMS: Transcriptions of precore and pregenomic mRNAs of hepatitis B virus(HBV) are under the control of fee core promoter. Therefore, mutations in this promoter region might change the activity of liver diseases through altered transcriptional level of either mRNA. In chronic HBV carriers, mutations of the promoter are repoited to be frequent in HBV carriers with anti-HBe rather than those with HBeAg. The present study was carried out to identify the .difference in patterns of the mutations according to the severity of the liver diseases, and to investigate whether the presence of the mutant might affect the seroconversion from HBe3g to anti-HBe.
METHODS
DNA sequences of the core promoter region were determined in various chronic HBV carriers with HBeAg, including five cases of asymptomatic carrier(ASC, 21 clones), eight with chronic hepatitis (CH, 50 clones) and two with liver cirrhosis died of liver failure due to spontaneous exacerbation(LC-SE, 13 clones).
RESULTS
Core promoter mutations were found in 3 cases of ASC (11 clones), all of CH(48 clones) and LC-SE(13 clones). 1762(A T) and 1764(G A) mutations were found in all of CH(40 clones) and LC-SE(13 clones), whereas they were not detected in any case of ASC. These mutants were isolated as a dominant strain in the five cases of CH irrespective of natural or interferon-induced seroconversion from HBeAg to anti-HBe. Compared with the patterns of mutations encountered in the cases of CH, similar patterns of mutation were found in the cases of LC-SE.
CONCLUSIONS
1762(A>T) and 1764(G--A) mutation was most frequent in chronic hepatitis and liver cirrhosis. Taken together, it is likely that the presence of the mutants has little effect on the difference of disease severity or seroconversion from HBeAg to anti-HBe in chronic hepatitis and liver cirrhosis.