Clinicopathologic Significance of HBV X, Core promoter, Precore Mutants in Patients with Chronic HBV Infection

Lee, Youn Jae; Yang, Young Il; Jang, Won Hee; Yea, Sung Su; Paik, Kye Hyung

Abstract

BACKGROUND/AIMS: There have been much debates on the effects of HBV mutants on the clinical course of HBV-associated chronic liver diseases. The purpose of this study was to define the relationship among HBV mutants, severity of hepatitis and expression patterns of HBcAg
METHODS
HBV DNA was extracted from the liver tissue of 31 patients who had been HBsAg positive for more than 6 months. The amplification of X was performed as well as core promoter/precore region of HBV DNA by polymerase chain reaction and then direct sequencing of them. Pathologic severity was classified utilizing Scheuer's scoring system and immunohistochemical staing for HBcAg in hepatocytes was performed. The expression patterns of HBcAg were divided into four types according to expression location of HBcAg: Type I as a nuclear predominant expression of HBcAg; Type II as mixed patterns, combined expression of cytoplasmic and nuclear localization of HBcAg; Type III as a diffuse cytoplasmic expression of HBcAg; and Type II as an inclusive body-like expression in cytoplasm.
RESULTS
In investigating the relationship between HBV mutants and clinical findings, ALT, HBV DNA and hepatitis activity index (HAI) in hepatitis with wild HBV were normal to high but those in hepatitis with core promoter or precore mutants were high . There were no statistically significant differences (p=0.062). In terms of the relationship between HBV mutants and the expression pattern of HBcAg, type I, II, IV were noticed in hepatitis with wild HBV but in almost all mutants cases type III, II were noticed (p<0.01). The score of HAI increased as the number of the expression pattern of HBcAg increased from type I to type III or IV(p<0.05). No relationships among the mutation in X region, the mutations in other regions and clinicopathological severity could be found.
CONCLUSION
The mutation in X, core promoter and precore region had little association with the severity of hepatitis. And the relationship did not exist between precore mutants and X mutants. The expression pattern of HBcAg could be a useful indicator in determining what stage of chronic hepatitis B is in and whether mutant strains exist.