HEPATITIS-B VIRUS MUTANTS IN HEPATOCELLULAR-CARCINOMA PATIENTS WITH COEXISTING HBSAG AND ANTI-HBS

We analyzed the sequence of S, precore, and X genes of the hepatitis B virus (HBV) genome in four Korean hepatocellular carcinoma (HCC) pati ents who were seropositive for both HBsAg and anti-HBs. HBV DNA was ex tracted from formalin-fixed, paraffin-embedded liver tissues, and then amplified by nested PCR and sequenced. We found a point mutation in t he S gene of 2 cases, resulting in conversion from Ile-126 or Thr-126 of the wild type virus to Ser-126. Three of four patients had a precor e sequence with a frame TAG stop codon. Interestingly, all patients re vealed nucleotide changes in enhancer II region of the X gene, especia lly the binding region of the nuclear factor CCAAT/enhancer binding pr otein. Three showed a point mutation of T to C at nucleotide position 1753 and one patient showed a 19-base pair deletion resulting in a fra me shift with three novel amino acids followed by the stop codon. No m utation was observed in the HBV genomes isolated from HCC patients wit h HBsAg alone. Although our data are preliminary, these results sugges t that mutations of the X gene and common antigenic domain within 'a' loop of the S gene may be related to the phenomenon in unusual serolog ical findings such as coexistence of HBsAg and anti-HBs. (C) 1997 Else vier Science Ireland Ltd.