HEPATITIS-B VIRUS CORE PROTEIN MUTATIONS ARE CONCENTRATED IN B-CELL EPITOPES IN PROGRESSIVE DISEASE AND IN T-HELPER CELL EPITOPES DURING CLINICAL REMISSION

The distribution and temporal and clinical features of amino acid subs titutions of the core protein of hepatitis B (HB) virus were analyzed, using at least 2 sequential samples from 27 patients. Six patients se roconverted from HBe antigen (HBeAg)-positive to anti-HBe-positive (3 went into remission), and 21 were continuously anti-HBe positive with progressive hepatitis. Precore mutations, which terminate HBeAg transl ation, all appeared by the second sample. Most core mutations occurred between the first and second samples; significantly fewer occurred af ter the second, In seroconverters who went into remission, mutations o ccurred in the T helper epitope from aa 50 to 69 (P = .00045); for ant i-HBe-positive patients with ongoing disease, mutations occurred in B cell epitopes (P = .0007 for aa 74-83). An ineffective anti-HBc B cell response accounts for ongoing disease and selection of mutations afte r seroconversion, In those who remit, mutations in the major T helper epitope allow immune escape, thus minimizing immune-mediated hepatitis .