Novel pre-C/C gene mutants of hepatitis B virus in chronic active hepatitis: naturally occurring escape mutants

Area of Science:

• Virology
• Immunology
• Hepatology

Background:

• Chronic active hepatitis (CAH) is a significant global health concern.
• Hepatitis B virus (HBV) infection is a leading cause of CAH.
• Understanding HBV genetic variations is crucial for managing the disease.

Purpose of the Study:

• To analyze mutations in the pre-core/core (C) and pre-S1/S2 open reading frames (ORFs) of HBV.
• To investigate the frequency of these mutations in HBeAg-positive and HBeAg-negative CAH patients.
• To explore the correlation between HBV mutations and immune responses.

Main Methods:

• Serum samples from 18 HBV-infected CAH patients were analyzed.
• Polymerase chain reaction (PCR) was used with specific primers.
• Nucleotide sequence analysis was performed on amplified viral DNA.

Main Results:

• Eleven of 18 patients had a G to A mutation at nucleotide 1896, creating a stop codon.
• One patient exhibited an additional G to A mutation at nucleotide 1899.
• Three HBeAg-negative patients had a 1 bp deletion at nucleotide 1937, leading to pre-termination of the C gene.

Conclusions:

• Mutations in HBV, including stop codons and deletions, are prevalent in CAH.
• Higher mutation frequencies were observed in regions encoding T cell and B cell epitopes.
• These findings suggest that immune responses may drive the selection of specific HBV mutations in CAH.