Hepatitis B virus mutants in hepatocellular carcinoma patients with coexisting HBsAg and anti-HBs

Abstract

We analyzed the sequence of S, precore, and X genes of the hepatitis B virus (HBV) genome in four Korean hepatocellular carcinoma (HCC) patients who were seropositive for both HBsAg and anti-HBs. HBV DNA was extracted from formalin-fixed, paraffin-embedded liver tissues, and then amplified by nested PCR and sequenced. We found a point mutation in the 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 precore sequence with a frame TAG stop codon. Interestingly, all patients revealed nucleotide changes in enhancer II region of the X gene, especially the binding region of the nuclear factor CCAAT/enhancer binding protein. 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 frame shift with three novel amino acids followed by the stop codon. No mutation was observed in the HBV genomes isolated from HCC patients with HBsAg alone. Although our data are preliminary, these results suggest 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 serological findings such as coexistence of HBsAg and anti-HBs.