CHRONIC ACTIVE HEPATITIS WITH HEPATITIS-B VIRUS-DNA AND ANTIBODY AGAINST E-ANTIGEN IN THE SERUM - DISTURBED SYNTHESIS AND SECRETION OF E-ANTIGEN FROM HEPATOCYTES DUE TO A POINT MUTATION IN THE PRECORE REGION

Some patients with type B chronic active hepatitis have a high titer of hepatitis B virus DNA despite antibody against e antigen in the serum. Clones of hepatitis B virus were propagated from the sera of seven patients with this disease, and the precore region was sequenced. Essentially all clones ( 128 131 or 98%) showed a point mutation from guanine to adenine at nucleotide 83, converting codon 28 for tryptophan (TGG) to a stop codon (TAG); the second guanine-to-adenine point mutation at nucleotide 86 was identified in only 29 clones from two patients. In patients followed up since they had hepatitis B e antigen, a shift from guanine to adenine was observed at nucleotide 83 along with the seroconversion to the antibody to e antigen. The precore-region product is required for the synthesis and secretion of e antigen from hepatocytes. A point mutation from guanine to adenine at nucleotide 83 observed in the seven patients, therefore, would be responsible for disturbed secretion of e antigen. © 1990.