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Variations of hepatitis B virus core gene sequence in Western patients with chronic hepatitis B virus infection
A H Gray1, J W Fang, G L Davis
1Department of Medicine, College of Medicine, University of Florida, Gainesville 32610, USA.
Insights
Hepatitis B virus (HBV) core gene heterogeneity was studied in Western patients. Unlike in Japan, HBV core gene variations were not significantly linked to active liver disease in this population.
Area of Science:
- Hepatology
- Virology
- Genetics
Background:
- Chronic hepatitis B virus (HBV) infection is a global health concern.
- Previous studies in Japanese patients suggested a link between HBV core gene heterogeneity and active liver disease.
- The significance of HBV core gene heterogeneity in Western populations remained unclear.
Purpose of the Study:
- To investigate the association between hepatitis B virus (HBV) core gene heterogeneity and active liver disease in Western patients.
- To compare HBV core gene variation patterns between patients with inactive versus active chronic HBV infection.
- To explore correlations between HBV core gene variations and clinical parameters, treatment response, and antigen expression.
Main Methods:
- Polymerase chain reaction (PCR) amplification of the hepatitis B virus (HBV) precore/core gene from patient serum.
- Gel electrophoresis to detect large deletions.
- Cloning and sequencing of PCR amplicons from a subset of patients.
- Enzyme immunoassay (EIA) for hepatitis B surface antigen (HBsAg) serotyping.
- Immunohistochemistry to assess hepatic HBV antigen expression.
Main Results:
- HBV core gene was successfully amplified from all 45 patients.
- Three patients with mixed precore mutant and wild-type HBV infection all had active liver disease.
- No large deletions in the HBV core gene were observed.
- Sequence variations were more frequent in the midcore region, with no significant difference in substitutions between inactive and active disease groups.
- No correlation was found between nucleotide/amino acid substitutions and clinical parameters, interferon-alpha therapy response, or hepatic HBV antigen expression.
Conclusions:
- Hepatitis B virus (HBV) core gene variation is not preferentially associated with active liver disease in Western patients with chronic HBV infection.
- The observed pattern of HBV core gene variation aligns with the virus's genomic organization.
- Further research may be needed to understand the specific factors driving HBV pathogenesis in diverse populations.
Abstract:
Heterogeneity of the hepatitis B virus (HBV) core gene has been reported to be associated with the presence of active liver disease in Japanese patients with chronic HBV infection. This study evaluated the significance of HBV core gene heterogeneity in Western patients with chronic HBV infection. The hepatitis B virus precore/core gene from 45 patients (inactive:active liver disease ratio 16:29) was amplified from serum by polymerase chain reaction (PCR). Gel electrophoresis was employed to detect large deletions. The PCR amplicons from 13 patients (all HBV serotype adw but with a different spectrum of liver disease) were cloned and sequenced. Hepatitis B surface antigen (HBsAg) serotypes were tested by enzyme immunoassay (EIA) and hepatic expression of HBV antigens was assessed by immunohistochemistry. The HBV core gene was amplified from the serum of all 45 patients. Three patients had mixed infection with both precore mutant and wild-type HBV and all three had active liver disease. No patient had a large deletion of the HBV core gene. Hepatitis B virus core gene sequence variations were more common in the midcore region and there was no difference in the number of silent and missense substitutions between those with inactive and active liver disease. There was no correlation between the nucleotide or encoded amino acid substitutions and the clinical and biochemical parameters, including the subsequent response to interferon-alpha therapy (n = 37) or hepatic HBV antigen expression. Variation of the HBV core gene was not found to be preferentially associated with active liver disease in Western patients with chronic HBV infection. The pattern of hepatitis B core gene variation is in accord with the genomic organization of HBV.