Hepatitis B virus BCP, precore/core, X gene mutations/genotypes and the risk of hepatocellular carcinoma in India

• Published in: Journal of medical virology 2010-07, Vol.82 (7), p.1115-1125
• Main Authors: Asim, Mohammad, Malik, Abdul, Sarma, Manash P, Polipalli, Sunil K, Begum, Nargis, Ahmad, Istaq, Khan, Luqman A, Husain, S.A, Akhtar, Naseem, Husain, Sajid, Thayumanavan, L, Singla, Rajiv, Kar, P
• Format: Article
• Language: English
• Subjects: Age Factors; and precore/core gene; basal core promoter (BCP); Carcinoma, Hepatocellular - epidemiology; Carcinoma, Hepatocellular - etiology; Female; Hepatitis B Core Antigens - genetics; Hepatitis B virus - genetics; Hepatitis B, Chronic - complications; hepatocellular carcinoma; Humans; India - epidemiology; Liver Neoplasms - epidemiology; Liver Neoplasms - etiology; Male; Middle Aged; Mutation; Promoter Regions, Genetic; Risk Factors; Sex Factors; Trans-Activators - genetics; Viral Load; X gene
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.21774

The study aims to characterize mutations of the HBV genome involving BCP, Precore/core and X regions and also defines HBV genotypes in patients of hepatocellular carcinoma (HCC). The study involved 150 HBV-related HCC cases and 136 HBV-related chronic liver disease patients without HCC as controls. HBV DNA was subjected to mutational analysis using SSCP technique, genotyping by RFLP, and direct nucleotide sequencing. HBV DNA was found in 58.7% (88/150) of the HCC cases and 74.3% (101/136) of controls. HBV mutants were observed in 44.3% of HCC cases and 43.2% of controls. HBV/D was prevalent amongst the patients and controls, followed by HBV/A. The prevalence of the TT1504 mutation in the X gene, the V1753 and T1762/A1764 mutations in the BCP region, and G1914 mutation in the core gene were significantly higher in the HCC group than in the non-HCC group. Multivariate analyses showed that the TT1504, V1753, A1762T/G1764A, and the G1914 mutations and the patient's age, sex, and HBeAg status increased the risk of HCC development significantly. Also, patients with HCC had lower levels of serum albumin, viral load, and platelet counts but higher values of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, and Alpha feto-protein than those of controls (P < 0.001 for all comparisons). HBV/D was the predominant genotype associated with HCC cases seen in India. The presence of different types of HBV mutations, age, sex, HBeAg status, and viral load was found to increase significantly the risk of HCC development in India. J. Med. Virol. 82: 1115-1125, 2010.