Characterization of HBV viral mutations associated with the development of hepatocellular carcinoma (HCC) in patients with HBV infection

• Grant number: 12/14149-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2013
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: João Renato Rebello Pinho
• Grantee: Livia de Souza Botelho Lima
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of death by cancer worldwide. It is an important cause of death in patients with chronic hepatitis B virus (HBV) infection and accounts for about one million of deaths by year. About 70% to 80% of HCC cases occur in patients with chronic HBV infection in regions where this virus is endemic. HBV causes chronic injury of hepatocytes with inflammation and necro-repair activity, leading to inflammation of hepatocytes. Consequently, the accumulation of potentially critical viral mutations in the hepatocytes, with subsequent malignant transformation and clonal expansion, leads to HCC development. In addition, HBV is an oncogenic virus by the expression of X protein that presents transactivation activity and by its ability to integrate the viral DNA into the host genome increasing the expression of pro-cellular oncogenes. No studies have been conducted to characterize HBV genotypes in patients with HCC in São Paulo or in Brazil. Any study did not identify specific mutations present in the HBV genome that may be associated with HCC progression in our country. The aim of the present study is to characterize HBV genotypes and mutations in the viral genome that are associated with progression to HCC in a population of 60 patients infected with HBV with HCC the and compare to a control group with the same number of patients without HCC with chronic hepatitis B and liver cirrhosis. Liver cirrhosis is defined according to the pattern obtained by ultrasound and liver elastography (FibroScan). Case and control groups are paired by sex, age, alcohol consumption and Asian origin. Liver function and serological markers of HBV markers will also be assessed. The cohort of the studied patients are followed at the Department of Gastroenterology, Clinics Hospital, School of Medicine, University of São Paulo. Through sequence analysis, we will characterize HBV genotypes circulating in the HCC population and the mutations in HBV genomes associated with this pathology. Finally, we will determine the differences in the profile of mutations among different viral genotypes in this population as well as the relation of these mutations with clinical and demographic variables for each patient. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LIMA, Livia de Souza Botelho. Virological evaluation factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.