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Mutations of hepatitis B virus liver disease
1First Department of Medicine, Chiba University School of Medicine, Japan.
Insights
Mutations in the hepatitis B virus (HBV) core antigen gene were found in patients with advanced chronic liver disease. These specific mutations may drive progressive liver disease, unlike in healthy carriers.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B virus (HBV) infection presents as asymptomatic carriers or chronic liver disease.
- Hepatitis B core antigen (HBcAg) is a potential target for cytotoxic T lymphocytes (CTLs).
Purpose of the Study:
- To investigate potential CTL pressure sites within the HBV core region.
- To correlate HBV core gene mutations with disease progression in chronic hepatitis B.
Main Methods:
- Sequencing of the entire HBV core DNA region in 30 subjects (10 healthy carriers, 20 with chronic liver disease).
- Analysis of nucleotide and amino acid sequences for mutations.
- Correlation of identified mutations with liver disease severity.
Main Results:
- No significant sequence changes were observed in 10 healthy carriers.
- A cluster of 18 amino acid mutations (codons 84-101) was identified in 15 of 20 chronic liver disease patients.
- These mutations were exclusively found in patients with advanced liver disease (chronic active hepatitis, cirrhosis), not in those with mild disease (chronic persistent hepatitis).
Conclusions:
- A specific region within the HBV core gene (codons 84-101) is frequently mutated in patients with progressive chronic liver disease.
- These mutations likely play a role in the pathogenesis of HBV-related liver disease and are associated with disease advancement.
Abstract:
Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the core antigen (HBcAg) could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in small segment of 18 amino acids (codon 84 to 101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the 5 patients without mutation. These data suggest that this region with clustering mutations may play an important role in the pathogenesis of B viral liver disease, and the mutations in the region may be related to progressive liver disease.