Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers

Background/Aims: To determine the prevalence and significance of hepatitis B virus (HBV) basic core promoter (BCP) mutations and to establish their relationship with precore (preC) mutations, HBV genotypes and HBV-DNA levels. Methods: BCP and preC mutations and genotypes were determined by sequencing. Results: Genomic analysis was performed in 129 (71%) of 182 patients. BCP mutations were detected in 83% of 18 HBeAg-negative (e−) chronic hepatitis B (CHB) patients with fluctuating ALT levels, and in 76% of 58 e− CHB with elevated ALT. The prevalence was lower and similar, 55% in 30 HBeAg-positive CHB (e+ CHB) with elevated ALT and in 23 e− inactive carriers. Frequency of preC mutations was higher in e− CHB (80%) than in e− inactive carriers (65%). Among e− CHB, patients with elevated ALT and preC mutations at nt 1896 showed highest HBV-DNA, regardless of BCP mutations. BCP mutations were similar in genotypes A and D, while preC mutations were most common in genotype D (82 vs. 40%). Simultaneous presence of the main BCP (1762, 1764) and preC (1896, 1899) mutations was associated with the degree of histological injury. Conclusions: Combined BCP and preC mutational and genotype analysis provides clinically relevant information in the study of HBV infection.