The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease
Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (pre...
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Frontiers Media S.A.
2018-10-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2018.00355/full |
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English |
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DOAJ |
author |
Ahmed A. Al-Qahtani Ahmed A. Al-Qahtani Mashael R. Al-Anazi Nyla Nazir Ayman A. Abdo Ayman A. Abdo Faisal M. Sanai Faisal M. Sanai Waleed K. Al-Hamoudi Waleed K. Al-Hamoudi Khalid A. Alswat Khalid A. Alswat Hamad I. Al-Ashgar Mohammed Q. Khan Ali Albenmousa Ahmed El-Shamy Salah K. Alanazi Damian Dela Cruz Marie Fe F. Bohol Mohammed N. Al-Ahdal Mohammed N. Al-Ahdal |
spellingShingle |
Ahmed A. Al-Qahtani Ahmed A. Al-Qahtani Mashael R. Al-Anazi Nyla Nazir Ayman A. Abdo Ayman A. Abdo Faisal M. Sanai Faisal M. Sanai Waleed K. Al-Hamoudi Waleed K. Al-Hamoudi Khalid A. Alswat Khalid A. Alswat Hamad I. Al-Ashgar Mohammed Q. Khan Ali Albenmousa Ahmed El-Shamy Salah K. Alanazi Damian Dela Cruz Marie Fe F. Bohol Mohammed N. Al-Ahdal Mohammed N. Al-Ahdal The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease Frontiers in Cellular and Infection Microbiology HCC hepatitis cirrhosis core gene mutations HBV |
author_facet |
Ahmed A. Al-Qahtani Ahmed A. Al-Qahtani Mashael R. Al-Anazi Nyla Nazir Ayman A. Abdo Ayman A. Abdo Faisal M. Sanai Faisal M. Sanai Waleed K. Al-Hamoudi Waleed K. Al-Hamoudi Khalid A. Alswat Khalid A. Alswat Hamad I. Al-Ashgar Mohammed Q. Khan Ali Albenmousa Ahmed El-Shamy Salah K. Alanazi Damian Dela Cruz Marie Fe F. Bohol Mohammed N. Al-Ahdal Mohammed N. Al-Ahdal |
author_sort |
Ahmed A. Al-Qahtani |
title |
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease |
title_short |
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease |
title_full |
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease |
title_fullStr |
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease |
title_full_unstemmed |
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease |
title_sort |
correlation between hepatitis b virus precore/core mutations and the progression of severe liver disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2018-10-01 |
description |
Viral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC. |
topic |
HCC hepatitis cirrhosis core gene mutations HBV |
url |
https://www.frontiersin.org/article/10.3389/fcimb.2018.00355/full |
work_keys_str_mv |
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doaj-a82823c7c6d64790950b6d0eef9555942020-11-24T23:43:17ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-10-01810.3389/fcimb.2018.00355388595The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver DiseaseAhmed A. Al-Qahtani0Ahmed A. Al-Qahtani1Mashael R. Al-Anazi2Nyla Nazir3Ayman A. Abdo4Ayman A. Abdo5Faisal M. Sanai6Faisal M. Sanai7Waleed K. Al-Hamoudi8Waleed K. Al-Hamoudi9Khalid A. Alswat10Khalid A. Alswat11Hamad I. Al-Ashgar12Mohammed Q. Khan13Ali Albenmousa14Ahmed El-Shamy15Salah K. Alanazi16Damian Dela Cruz17Marie Fe F. Bohol18Mohammed N. Al-Ahdal19Mohammed N. Al-Ahdal20Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaSection of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi ArabiaLiver Disease Research Center, King Saud University, Riyadh, Saudi ArabiaLiver Disease Research Center, King Saud University, Riyadh, Saudi ArabiaGastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi ArabiaSection of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi ArabiaLiver Disease Research Center, King Saud University, Riyadh, Saudi ArabiaSection of Gastroenterology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi ArabiaLiver Disease Research Center, King Saud University, Riyadh, Saudi ArabiaGastroenterology Unit, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaGastroenterology Unit, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi ArabiaDepartment of Pharmaceutical and Biomedical Sciences, California Northstate University, Elk Grove, CA, United StatesDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Infection and Immunity, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaDepartment of Microbiology and Immunology, Alfaisal University School of Medicine, Riyadh, Saudi ArabiaViral mutations acquired during the course of chronic hepatitis B virus (HBV) infection are known to be associated with the progression and severity of HBV-related liver disease. This study of HBV-infected Saudi Arabian patients aimed to identify amino acid substitutions within the precore/core (preC/C) region of HBV, and investigate their impact on disease progression toward hepatocellular carcinoma (HCC). Patients were categorized according to the severity of their disease, and were divided into the following groups: inactive HBV carriers, active HBV carriers, liver cirrhosis patients, and HCC patients. Two precore mutations, W28* and G29D, and six core mutations, F24Y, E64D, E77Q, A80I/T/V, L116I, and E180A were significantly associated with the development of cirrhosis and HCC. Six of the seven significant core mutations that were identified in this study were located within immuno-active epitopes; E77Q, A80I/T/V, and L116I were located within B-cell epitopes, and F24Y, E64D, and V91S/T were located within T-cell epitopes. Multivariate risk analysis confirmed that the core mutations A80V and L116I were both independent predictors of HBV-associated liver disease progression. In conclusion, our data show that mutations within the preC/C region, particularly within the immuno-active epitopes, may contribute to the severity of liver disease in patients with chronic hepatitis. Furthermore, we have identified several distinct preC/C mutations within the study population that affect the clinical manifestation and progression of HBV-related disease. The specific identity of HBV mutations that are associated with severe disease varies between different ethnic populations, and so the specific preC/C mutations identified here will be useful for predicting clinical outcomes and identifying the HBV-infected patients within the Saudi population that are at high risk of developing HCC.https://www.frontiersin.org/article/10.3389/fcimb.2018.00355/fullHCChepatitiscirrhosiscore genemutationsHBV |