SPONTANEOUS SEROCONVERSION IN CHRONIC HEPATITIS-B - ROLE OF MUTATIONSIN THE PRECORE CORE GENE/

The mechanism underlying spontaneous clearance of hepatitis B e antige n (HBeAg) and the appearance of antibodies (anti-HBe seroconversion) i n chronic hepatitis B is not known, Previous studies have demonstrated mutations within the precore/core gene before, during, and after sero conversion, suggesting that the;emergence of mutations in the core gen e may abrogate tolerance and that this event may act as a general prin ciple for the initiation of the clearance of HBeAg. To investigate thi s hypothesis, we studied three patients with adult-acquired chronic he patitis B virus (HBV) infection before spontaneous seroconversion by s equential sequencing and single-stranded conformation polymorphism (SS CP) analysis of the entire precore/core genome. In one patient, a new viral strain appeared six months before seroconversion, but no mutatio ns or new viral strains could be detected in the other two patients. S SCP analysis confirmed the sequencing results and revealed no evidence for the emergence of new viral subpopulations before seroconversion, These results suggest that the appearance of nucleotide changes within the precore/core region of the dominant viral strain is not a prerequ isite for the induction of seroconversion in patients with chronic hep atitis B virus infection acquired during adulthood.