Agarwal A K, Sen Sourav, Banerjee Debabrata, Srivastava Rakesh, Praharaj A K
Graded Specialist (Microbiology), INHS Sanjivani, Cochin, India.
Senior Adviser (Microbiology & Pathology) and Trained in AIDS & Virology, Army Hospital (R & R), New Delhi, India.
Med J Armed Forces India. 2015 Jul;71(3):225-32. doi: 10.1016/j.mjafi.2015.04.003. Epub 2015 Jun 9.
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.
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.
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.
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.
慢性乙型肝炎（CHB）感染与包括肝硬化和肝细胞癌在内的肝脏疾病发生风险增加相关。可能增加肝癌发生风险的病毒因素包括乙肝病毒DNA水平、基因型以及自然发生的突变，如乙肝病毒前核心区（PC）（G1896A）和基本核心启动子（BCP）A1762T/G1764A双突变。乙肝病毒基因型和亚基因型可显著影响HBeAg血清学转换率、病毒血症水平、突变模式，这些可能显著影响临床表现的异质性，甚至影响抗病毒治疗的反应。
对94例血清乙肝病毒DNA水平可检测的CHB感染个体进行研究。采用酶联免疫吸附测定法检测HBsAg、HBeAg、抗-HBc IgM抗体。进行乙肝病毒DNA测定。通过巢式PCR确定乙肝病毒基因型，并随机选择10个样本进行DNA测序。通过核心区DNA序列分析确定PC和BCP突变。
在94例血清乙肝病毒DNA水平可检测的研究参与者样本中，75例成功进行了BCP/PC区域的基因分型和测序。30/75（40%）存在PC和BCP突变。BCP在A1762T/G1764A核苷酸位置的双突变和PC在G1896A核苷酸位置的突变分别见于29.3%和21.3%。使用巢式PCR，所有75株分离株均为D亚型。然而，通过测序，2/10为A亚型，8株为D亚型。
我们的研究强化了D型是印度人群中主要基因型这一观点。研究表明，印度慢性乙肝患者中BCP和PC突变的患病率增加，这可能会导致肝癌的发生。
