Distribution of hepatitis B virus genotype and cancer predicting precore and basal core promoter mutations.
BACKGROUND
Chronic hepatitis B (CHB) infection which is associated with an increased risk of developing liver disease including cirrhosis and hepatocellular carcinoma. Viral factors that may increase the risk for HCC development include HBV DNA level, genotypes, and naturally occurring mutations such as hepatitis B virus precore (PC) (G1896A) and basal core promoter (BCP) A1762T/G1764A double mutations. HBV genotypes and subgenotypes can significantly influence HBeAg seroconversion rates, viremia levels, mutational patterns that could significantly influence the heterogeneity in clinical manifestations and even response to antiviral therapy.


METHODS
94 CHB infected individuals with detectable serum HBV DNA levels were studied. HBsAg, HBeAg, anti-HBc IgM antibody estimations were done by ELISA. HBV DNA estimation was done. The HBV genotypes were determined by TSP-PCR and 10 samples randomly selected for DNA sequencing. PC and BCP mutations were determined by DNA sequence analysis of core region.


RESULTS
Of 94 study participant samples with detectable serum HBV DNA levels, 75 were successfully genotyped and sequenced for BCP/PC region. 30/75 (40%) harbored PC and BCP mutations. The total Double mutations of BCP at A1762T/G1764A nucleotide positions, and PC mutation at G1896A nucleotide position were seen in 29.3% and 21.3%, respectively. All 75 isolates were subtype D using TSP-PCR. However, by sequencing 2/10 were subtype A, while 8 were subtype D.


CONCLUSIONS
Our study reinforces that D is the predominant genotype in Indian population. It reveals that Indian CHB subjects have increased prevalence of BCP & PC mutations, which possibly may lead to development of HCC.
Graded Specialist (Microbiology), INHS Sanjivani, Cochin, India.
A K
AK
Agarwal
Senior Adviser (Microbiology & Pathology) and Trained in AIDS & Virology, Army Hospital (R & R), New Delhi, India.
Sourav
S
Sen
Senior Adviser (Medicine & Gastroenterology), Command Hospital (Northern Command), C/O 56 APO, India.
Debabrata
D
Banerjee
Assistant Professor (Microbiology), R D Gardi Medical College, Ujjain, India.
Rakesh
R
Srivastava
Professor and Head (Microbiology), All India Institute of Medical Science, Bhubaneswar, India.
A K
AK
Praharaj
Basal core promoter mutations; Chronic hepatitis B; Genotype; Pre core mutations