Hepatitis B Virus DNA Mutation, Pattern of Major Histocompatibility Class-I among Familial Clustered HBV Carriers in Relation to Disease Progression

Jung, Seung Pil; Lee, Hyo Suk; Kim, Chung Yong; Ahn, Yoon Ok

Abstract

OBJECTIVES
Chronic HBsAg carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing serious liver diseases. In Korea, it has been estimated that 65-75% of the HBsAg positives remained as persistent carriers. Additionally, familial clustering of HBV infection has frequently been observed among carriers. Some would become progressive, chronic hepatitis patients, and others would not. The aim of this study was to evaluate the association between various factors, such as the duration of infection, type of virus, mutation of precore/core region in HBV, major histocompatibility class-I, and developing chronic liver diseases among familial HBV carriers.
METHODS
Chronic carrier status was identified by repeated serological tests for HBsAg at intervals of six months or more. A familial chronic carrier was defined when the disease was observed in a family member over two generations. Two families were recruited, among which a total of 20 chronic HBsAg carriers(11 carriers in No.1, and 9 in No.2 family) were identified. Data on the general characteristics and liver disease status were collected. Identification of the HBV-DNA was successful only for 13 subjects among the 20 carriers. Analysis of viral DNA in terms of subtype, pre-core and core region mutations was carried out. The type of major histocompatibility class-I for the 13 subjects was also analysed.
RESULTS
& CONCLUSIONS: Seven of 10 chronic HBV carriers of the 1st generation and one of 10 of the 2nd generation were clinical patients with chronic hepatitis, the others, three of the 1st and nine of the 2nd generation, were asymptomatic carriers. This data indicates that the duration of HBV carriage is one of the major factors for disease severity. The subtype of HBsAg analysed using HBV-DNA identified in 13 carriers were adr, and the pattern of precore nonsense mutation in HBV-DNA was identical among family members, which means that the same virus strains were transmitted between the family members. The association between the precore or core mutations in HBV-DNA and the disease severity was not observed. While it was suggested that a specific type of MHC class-I may be related to disease progression.