Detection of mutations in the enhancer 2/core promoter region of hepatitisB virus in patients with chronic hepatitis B virus infection: Comparison with mutations in precore and core regions in relation to clinical status

To investigate the meaning of the mutations in the enhancer 2/core promoter (Enh2/CP) region of hepatitis B virus (HBV) during the chronic HBV infecti on, mutations were examined in the Enh2/CP region (carboxyl half of X regio n) and their correlation with mutations in the precore and core regions in relation to the presence of chronic liver disease. The entire nucleotide se quences of the Enh2/CP region were determined by direct sequencing of the a mplified products derived from 30 cases with chronic HBV infection. The res ults were compared to the mutations in the precore and core regions. In the Enh2/CP region, 91 generally scattered nucleotide substitutions were detec ted. There were 11 substitutions in the 10 asymptomatic healthy carriers (m ean, 1.1/case) and 80 in the 20 chronic liver disease patients (4.0/case). The most frequent substitutions from A to T at nucleotide 1764 and from G t o A at nucleotide 1766 were seen in none of the 10 asymptomatic carriers an d in 14 (70%) of the 20 chronic liver disease patients. Comparisons of muta tions in the precore and core regions revealed that 14 of 16 patients with mutations in the core region had the mutations in the Enh2/CP region and/or a precore stop codon mutation. These data suggest that mutations in the En h2/CP and precore regions may affect the expression of the core and HBeAg p eptides and might be involved in the pathogenesis of chronic liver disease. (C) 1999 Wiley-Liss, Inc.