Subgenotype and Genetic Variability in the Precore/Core Regions of Hepatitis B Virus in Korean Patients with Chronic Liver Disease

Abstract

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) subgenotypes, the spectrum of mutations in the precore/core region through phylogenetic analysis, and the relevance of viral characteristics in disease progression in Korean patients. Methods: 133 patients with chronic HBV infection were enrolled. The precore and core region of HBV was amplified and sequenced. Phylogenetic analysis was performed for subgenotyping and the changes of nucleotides and amino acid were compared in liver disease stages. Results: HBV/C2 subgenotype was predominant in chronic HBV carriers (98.5%), followed by HBV/A2 (0.75%) and HBV/C7 (0.75%). The mutations of the precore region were not different between liver disease stages. However, amino acid changes in the cytotoxic T lymphocyte epitope (p < 0.020), CD4+ T cell epitope (p < 0.027), or B cell epitope (p < 0.029) were significantly higher in liver cirrhosis patients than in chronic hepatitis patients, but not in hepatocellular carcinoma patients. Conclusion: HBV/C2 is the most prevalent subgenotype in Korea, and HBV/C7 subgenotype found in the Philippines was first identified in the Korean population. Mutations in immune epitopes within the core gene were significantly associated with disease progression.

CD8 + T-Cell Response-Associated Evolution of Hepatitis B Virus Core Protein and Disease Progress

“…Immune escape mutations within HLA class I-associated epitopes are associated with viral adaption to the host CD8 ϩ T-cell response in CHB. Previous studies showed that HBV preferably accumulates escape mutations within the highly expressed core proteins to reduce the number of epitopes (8,9), and mutations in immune epitopes within the core gene were significantly correlated with higher stages of liver fibrosis and disease progression of CHB (6,10,12,18). These studies support the notion that the HBc epitope repertoire elicits a key role against HBV infection, which is involved in viral immune escape and adaption mechanisms.…”

“…Mutations in HBc are associated with HLA class I alleles in response to CD8 ϩ T-cell selection pressure (10). Furthermore, increased mutations in T-cell epitopes of the core protein are significantly associated with the development of CHB, transition from the immunotolerant to immunoactive phase, and disease progression (11)(12)(13). HBV mutations under immune selection are not equally distributed inside or in the flanking region of HLA class I-and class II-restricted epitopes from viral antigens.…”

Hepatitis B virus genotypes: epidemiological and clinical relevance in Asia

“…1 HBsAg endemicity in 1990-2013 and geographic distribution of HBV genotypes in Asia. The prevalence data are retrieved from a systematic review [1]; this map is prepared according to the literature [1,6,15,[17][18][19][20][21][22][23][24][25][26][27][28][29][30] HBV genotypes and response to antiviral therapy in Asia HBV genotypes and response to interferon (IFN)-based therapies HBV genotypes are significantly associated with sustained response to IFN-based therapies. In general, for HBeAgpositive patients, the probability of sustained response is in a descending order from genotype A-D [50].…”