Research Papers:

Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBV-infected patients

Ahmed A. Al-Qahtani _, Mashael R. Al-Anazi, Nyla Nazir, Rohit Ghai, Ayman A. Abdo, Faisal M. Sanai, Waleed K. Al-Hamoudi, Khalid A. Alswat, Hamad I. Al-Ashgar, Mohammed Q. Khan, Ali Albenmousa, Damian Dela Cruz, Marie Fe F. Bohol and Mohammed N. Al-Ahdal

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Oncotarget. 2017; 8:105115-105125. https://doi.org/10.18632/oncotarget.22428

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Ahmed A. Al-Qahtani1,2, Mashael R. Al-Anazi1, Nyla Nazir1, Rohit Ghai3, Ayman A. Abdo4,8, Faisal M. Sanai5,8, Waleed K. Al-Hamoudi4,8, Khalid A. Alswat4,8, Hamad I. Al-Ashgar6, Mohammed Q. Khan6, Ali Albenmousa7, Damian Dela Cruz1, Marie Fe F. Bohol1 and Mohammed N. Al-Ahdal1,2

1Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

2Department of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi Arabia

3Institute of Hydrobiology, Department of Aquatic Microbial Ecology, Biology Centre of the Academy of Sciences of the Czech Republic, České Budějovice, Czech Republic

4Section of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia

5Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia

6Gastroenterology Unit, Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

7Department of Gastroenterology, Prince Sultan Medical Military City, Riyadh, Saudi Arabia

8Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia

Correspondence to:

Ahmed A. Al-Qahtani, email: [email protected]

Keywords: HCC; hepatitis; cirrhosis; HBx; mutations

Received: August 03, 2017     Accepted: October 17, 2017     Published: November 06, 2017


Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combinational mutations in HBx gene on the pathogenesis of HCC during progressive stages of liver disease. The patients were categorized into inactive HBV carriers, active carriers, cirrhosis and HCC groups based on disease severity. Male sex, age > 50 years, and high serum alanine aminotransferase level were associated with risk of progressive liver disease. I127T, V131I, and F132Y/I/R mutations showed a significant increasing trend associated with the disease progression to HCC. H94Y and K130M mutations were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed, with significant rising prevalence through progressive clinical phases of liver disease to HCC. Several single and combinational mutations in HBx correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating the progression to HCC. These specific patterns of HBx mutations can be useful in predicting the clinical outcome of HBV-infected patients and may serve as early markers of high risk of developing HCC.

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