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

Abstract

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.

Risk Factors for Hepatocellular Carcinoma in India

“…The influence of GSTM1/T1 null genotypes may contribute in the etiology of HCC in patients with higher levels of AFB1-N7-guanine adducts, who are heavy smokers and those who consume alcohol. 37,38 Genotype D is the most common genotype in HBVassociated HCC as reported from different series. 39 The b-catenin pathway appears not to be significantly involved in HBV-related HCC in India.…”

Genetic Diversity of HBV Genotypes/ Subgenotypes and Their Correlation with Disease Progression

“…19 In a study from New Delhi, HBV/D was the predominant genotype associated with HCC cases seen in India followed by HBV/A. 15 Genotype D was the predominant genotype found in HBV-related liver diseases in North Indian patients. 177 In a study from New Delhi, the most common genotype was D followed by A and C among Indian patients.…”

Avaliação de marcadores de lesão do túbulo proximal renal e incidência de redução da filtração glomerular em pacientes portadores de Hepatite B em uso de tenofovir

“…A predominância do sexo masculino entre os indivíduos com infecção crônica pelo VHB foi previamente descrita em estudos realizados na região de Ribeirão Preto, em diversas regiões do Brasil e do mundo, em proporções semelhantes àquelas encontradas na casuística do presente estudo (Asim et al, 2010, Mota et al, 2009, Chacha et al, 2011, Valente et al, 2005, Pereira et al, 2009. Tal achado, ainda não está totalmente esclarecido, possivelmente possa estar relacionado com as formas de transmissão da infecção, considerando-se as formas de aquisição da infecção que são mais prevalentes entre os indivíduos do sexo masculino, tais como: promiscuidade sexual, uso de drogas injetáveis ilícitas e não ilícitas.…”