In 1988, a report was published on the nucleotide sequence of the genome of a strain of HBV cloned from the serum of a naturally infected chimpanzee. A surprising feature was a point mutation in the penultimate codon of the precore region to a termination codon. This mutation was found subsequently in some patients with anti-HBe who were positive for HBV DNA in serum by hybridisation. In most cases there was an additional mutation in the preceding codon. Precore variants have been described in many patients with severe chronic liver disease and some failed to respond to treatment with interferon. It has been suggested that the mutants are more pathogenic than the wild-type virus. A precore variant which produces hepatitis B e antigen has also been described.
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