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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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Autores principales: Al-Qahtani, Ahmed A., Al-Anazi, Mashael R., Nazir, Nyla, Abdo, Ayman A., Sanai, Faisal M., Al-Hamoudi, Waleed K., Alswat, Khalid A., Al-Ashgar, Hamad I., Khan, Mohammed Q., Albenmousa, Ali, El-Shamy, Ahmed, Alanazi, Salah K., Dela Cruz, Damian, Bohol, Marie Fe F., Al-Ahdal, Mohammed N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204459/
https://www.ncbi.nlm.nih.gov/pubmed/30406036
http://dx.doi.org/10.3389/fcimb.2018.00355
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author Al-Qahtani, Ahmed A.
Al-Anazi, Mashael R.
Nazir, Nyla
Abdo, Ayman A.
Sanai, Faisal M.
Al-Hamoudi, Waleed K.
Alswat, Khalid A.
Al-Ashgar, Hamad I.
Khan, Mohammed Q.
Albenmousa, Ali
El-Shamy, Ahmed
Alanazi, Salah K.
Dela Cruz, Damian
Bohol, Marie Fe F.
Al-Ahdal, Mohammed N.
author_facet Al-Qahtani, Ahmed A.
Al-Anazi, Mashael R.
Nazir, Nyla
Abdo, Ayman A.
Sanai, Faisal M.
Al-Hamoudi, Waleed K.
Alswat, Khalid A.
Al-Ashgar, Hamad I.
Khan, Mohammed Q.
Albenmousa, Ali
El-Shamy, Ahmed
Alanazi, Salah K.
Dela Cruz, Damian
Bohol, Marie Fe F.
Al-Ahdal, Mohammed N.
author_sort Al-Qahtani, Ahmed A.
collection PubMed
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.
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spelling pubmed-62044592018-11-07 The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease Al-Qahtani, Ahmed A. Al-Anazi, Mashael R. Nazir, Nyla Abdo, Ayman A. Sanai, Faisal M. Al-Hamoudi, Waleed K. Alswat, Khalid A. Al-Ashgar, Hamad I. Khan, Mohammed Q. Albenmousa, Ali El-Shamy, Ahmed Alanazi, Salah K. Dela Cruz, Damian Bohol, Marie Fe F. Al-Ahdal, Mohammed N. Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2018-10-22 /pmc/articles/PMC6204459/ /pubmed/30406036 http://dx.doi.org/10.3389/fcimb.2018.00355 Text en Copyright © 2018 Al-Qahtani, Al-Anazi, Nazir, Abdo, Sanai, Al-Hamoudi, Alswat, Al-Ashgar, Khan, Albenmousa, El-Shamy, Alanazi, Dela Cruz, Bohol and Al-Ahdal. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Al-Qahtani, Ahmed A.
Al-Anazi, Mashael R.
Nazir, Nyla
Abdo, Ayman A.
Sanai, Faisal M.
Al-Hamoudi, Waleed K.
Alswat, Khalid A.
Al-Ashgar, Hamad I.
Khan, Mohammed Q.
Albenmousa, Ali
El-Shamy, Ahmed
Alanazi, Salah K.
Dela Cruz, Damian
Bohol, Marie Fe F.
Al-Ahdal, Mohammed N.
The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease
title 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_short 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
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204459/
https://www.ncbi.nlm.nih.gov/pubmed/30406036
http://dx.doi.org/10.3389/fcimb.2018.00355
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