High Prevalence and Mapping of Pre-S Deletion in Hepatitis B Virus Carriers With Progressive Liver Diseases

Background & Aims: The interactions among pre-S deletion, precore (PC) mutation, and basal core promoter (BCP) mutation in various stages of chronic hepatitis B virus (HBV) infection remain unclear and were thus investigated in this study. Methods: The sequences of the pre-S region and the BCP (A₁₇₆₂T, G₁₇₆₄A) and PC (G₁₈₉₆A) mutations were determined in 46 HBV chronic carriers (CC) and 106 age-matched carriers with different stages of liver diseases, including 38 chronic hepatitis (CH), 18 cirrhosis (LC), and 50 hepatocellular carcinoma (HCC). Results: A higher prevalence of pre-S deletion and BCP and PC mutations was found in carriers with progressive liver diseases compared with the CC group. By logistic regression analysis, patients with pre-S deletion and BCP mutation were significantly associated with the development of progressive liver diseases than those without. Combination of mutations rather than single mutation was associated with the development of progressive liver diseases, especially in combination with pre-S deletion. Sequencing analysis showed that the deleted regions were more often in the 3′ terminus of pre-S1 and the 5′ terminus of pre-S2. Further mapping of these pre-S deletion sequences found that all the deletion regions encompassed T- and B-cell epitopes, and most of them lost 1 or more functional sites. Conclusions: Our data indicate that patients with progressive liver diseases have a higher frequency of pre-S deletion.

Abbreviations used in this paper:  aa, amino acid , BCP, basal core promoter , CC, chronic carrier , CH, chronic hepatitis , HBV, hepatitis B virus , HBV/B, HBV genotype B , HBV/C, HBV genotype C , HCC, hepatocellular carcinoma , LC, cirrhosis , nt, nucleotide , PC, precore , pHSA, polymerized human serum albumin