A study of genotypes, mutants and nucleotide sequence of hepatitis B virus in Pakistan

BACKGROUND Hepatitis B virus (HBV) genotypes and mutations are gaining importance in determining the clinical course of chronic liver disease. OBJECTIVES To determine and compare the distribution of HBV genotypes and genomic variations in Pakistan to other parts of the world. PATIENTS AND METHODS We conducted a prospective study at Aga Khan University Hospital from December 2006 to December 2008. HBV genotype was determined in 257 HBV DNA-positive patients. Patients were divided into two groups according to HBeAg positivity. Mutations in the pre-core and core promoter regions of HBV were determined in HBeAg-negative patients by line probe INNOLIPA assay. RESULTS The mean±SD age of patients was 28±5 years; there were 201 (78%) men. HBeAg was positive in 219 (85%) patients and negative in 38 (15%). HBeAg-positive patients were younger than HBeAg-negative patients (95% vs 21% in ≤30 years, p<0.001). HBV genotype D found in 247 (96.2 %) patients followed by a combined infection with HBV genotype B+D in 9 (3.3%) and 1 (0.5%) with genotype A. The mutations identified in 38 HBeAg-negative patients were T1762/A1764 in 21 (55.2%), PC mutant in 7 (18.4%), T1762/A1764/PC mutant in 2 (5%) and T1762/A1764/PC wild mutation in 1 (2%); no mutation identified in 7 (18.4%). Phylogenetic analysis did not show any significant differences between HBV genotype D isolated from Pakistan and those isolated from other parts of the world. CONCLUSIONS HBV genotype D is predominant in Pakistan, irrespective of HBeAg status. PC and BCP mutations were found in significant numbers of patients infected with genotype D. The HBV genotype D isolates from Pakistan are identical to the sequences isolated from other parts of the world.