Significance of pre-S region–defective hepatitis B virus that emerged during exacerbation of chronic type B hepatitis

✍ Scribed by Masahito Minami; Takeshi Okanoue; Etsuro Nakajima; Koichiro Yasui; Keizo Kagawa; Kei Kashima

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 640 KB
• Volume: 17
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840170406

✦ Synopsis

A defective form of the hepatitis B virus has been found in a patient with chronic type B hepatitis. Sequence analysis of the viral DNA after polymerase chain reaction amplification revealed a 117-base pair deletion (nucleotides 3129-53, subtype adr). This deletion includes the initiation codon of the pre-S2 region and a newly created in-frame stop codon in the pre-S1 region (nucleotide 3055) located 230 base pairs downstream from the pre-Sl initiation codon. This virus coexisted with the wild-type virus during the exacerbation period, as evidenced by an elevation of serum transaminase levels. It was not detected in the stable period, and the blood chemistry results were normal. We assayed antibodies against the mutationrelated region by enzyme immunoassay in serial serum samples to clarify the mechanism of the emergence of this variant virus. Antibodies against the pre-S2 region were negative; however, the antibody response against the pre-Sl epitopes coincided with the appearance of the variant virus. These findings suggest that an activated T-cell and B-cell response had developed against the pre-S1 region during hepatic inflammation in this patient and that, consequently, selection occurred for a pre-S antigen-defective mutant strain of the virus that might be resistant to such an immune response. (HEPATOLOGY 1993;17:558-563.) The HBV, a double-stranded DNA virus, causes acute and chronic liver disease. This virus has a higher intrinsic mutation rate than other DNA viruses, probably because its replication requires an intermediate RNA molecule and reverse transcriptase (1-3). In fact, recent reports have described the emergence of novel HBV variants that can influence their behavior and thus alter the clinical course of their hosts. For example, a seroconversion from the HBeAg-positive state to the HBe antibody (anti-HBe)-positive state usually accompanies a point mutation in the viral