Mutations in the basal core promoter and precore/core gene of hepatitis B virus in patients with chronic active but not acute hepatitis B

Around 5-10% of adults infected with hepatitis B virus (HBV) develop a chro nic liver disease such as chronic active hepatitis (CAH), and it is unclear whether the clinical outcome depends solely on the immune response or whet her viral factors also play a role. In this study, a search was therefore m ade for nucleotide mutations in the basic core promoter (BCP) and amino-aci d substitutions in the precore/core region of HBV infecting patients with C AH or with acute hepatitis. The nucleotide sequences of the BCP and of the precore/core region were determined in virus from ten patients with CAH and ten with acute hepatitis. The precore/core sequences were also analysed in 14 additional patients (6 with CAH, 8 with acute hepatitis). In seven of t he ten patients with CAH, five types of mutations were found in the BCP. De letions in the precore/core region were observed in six patients. In all si x patients where only the precore/core region was studied, amino-acid subst itutions were present. In contrast, in the ten patients with acute hepatiti s studied for BCP, a mutation was found in the BCP of one patient only. Of the 18 patients in whom the precore/core was studied, three had an amino-ac id substitution in this region. The results show a clear link between CAH a nd both HBV BCP and precore/core region mutations, suggesting these mutatio ns may play a role in the persistence of HBV infection.