Abstract
BackgroundHepatitis B virus (HBV) genotypes have distinct geographic distribution. Moreover, much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. The local prevalence of HBV genotypes and mutations has not been well studied. The aim of the present study is to determine the prevalence of HBV genotypes and mutations in the PC and BCP region in HBV strains in Karachi.MethodsA total of 109 chronic hepatitis B patients with detectable HBV DNA by a PCR assay were enrolled in the study. Sera were tested for HBeAg, anti-HBe antibody and liver profile. HBV genotypes and mutations in the PC and BCP regions were detected by INNO-LiPA line-probe assays.ResultsOf the 109 patients investigated, 38 (35%) were HBeAg positive while 71 (65%) were HBeAg negative. Genotype D was present in 100% of the patients. Two patients had co-infection with genotype A. There was no significant difference in the baseline characteristics, mean ALT levels, and presence of clinical cirrhosis in patients with HBeAg positive or negative strains with or without PC and BCP mutations. Of the 38 HBeAg positive patients, 9 (24%) had PC and BCP mutations. In the HBeAg negative patient group, mutations were detected in 44 (62%) of the strains investigated. More than one mutation was common, seen in 26 (37%) patients with HBeAg negative disease and 6 (16%) patients with HBeAg positive disease. Twelve (17%) HBeAg negative patients had dual T1762 and A1764 mutations. None of the HBeAg positive patients had T1762 mutation. Mutations were undetectable in 27 (38%) of patients with HBeAg negative disease.ConclusionOur study shows that type D is the main HBV genotype in Karachi, Pakistan. Significant numbers of patients infected with this genotype have PC and BCP variants. Mutations at more than one site are common. Patients harboring these mutants do not differ significantly in their clinical presentation from patients having wild type infection.
Highlights
Hepatitis B virus (HBV) genotypes have distinct geographic distribution
HBV has been classified into eight genotypes (A-H) according to the criterion of = 8% differences in the complete nucleotide sequence of the viral genome [2,3,4,5]
In the natural course of chronic HBV infection, the loss of HBeAg expression and the appearance of antibodies directed against it (Anti-HBe) are usually accompanied by cessation of viral replication
Summary
Hepatitis B virus (HBV) genotypes have distinct geographic distribution. much genetic variability has been described in the precore (PC) and basal core promoter (BCP) regions of the HBV genome. HBV has been classified into eight genotypes (A-H) according to the criterion of = 8% differences in the complete nucleotide sequence of the viral genome [2,3,4,5] These genotypes show variation in their geographic distribution [4,6,7,8]. In the natural course of chronic HBV infection, the loss of HBeAg expression and the appearance of antibodies directed against it (Anti-HBe) are usually accompanied by cessation of viral replication Such a serology profile may be seen in individuals who harbor precore (PC) and basal core promoter (BCP) mutants where replicative infection continues. PC variants are more common among patients with genotype D (65 to 75 percent) than genotype A (9 to 18 percent) [10,11]
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