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

• Published in: Journal of hepatology 2004-03, Vol.40 (3), p.507-514
• Main Authors: Jardi, Rosendo, Rodriguez, Francisco, Buti, Maria, Costa, Xose, Valdes, Auristela, Allende, Helena, Schaper, Melanie, Galimany, Roman, Esteban, Rafael, Guardia, Jaime
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alanine Transaminase - blood; Base Sequence; Biological and medical sciences; DNA, Viral - analysis; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Genetic Variation; Genotype; HBV genotypes; HBV-basic core promoter; HBV-DNA; HBV-precore region; Hepatitis B e Antigens - blood; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis B virus - physiology; Heterozygote; Human viral diseases; Humans; Infectious diseases; Liver cirrhosis; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Mutation; Mutations; Other diseases. Semiology; Promoter Regions, Genetic - genetics; Protein Structure, Tertiary - genetics; Spain; Viral Core Proteins - genetics; Viral diseases; Viral hepatitis; Virus Replication
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2003.11.015

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.