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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment
Ana Isabel Gil-García, Antonio Madejón, Irene Francisco-Recuero, Ana López-López, Emiliana Villafranca, Miriam Romero, Araceli García, Antonio Olveira, Rocío Mena, Juan Ramón Larrubia, Javier García-Samaniego
Ana Isabel Gil-García, Antonio Madejón, Irene Francisco-Recuero, Emiliana Villafranca, Miriam Romero, Araceli García, Antonio Olveira, Javier García-Samaniego, Hepatology Unit, Hospital Universitario La Paz, Madrid 28046, Spain
Ana Isabel Gil-García, Antonio Madejón, Irene Francisco-Recuero, Miriam Romero, Antonio Olveira, Javier García-Samaniego, Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Madrid 28029, Spain
Irene Francisco-Recuero, Javier García-Samaniego, Instituto de Investigación del Hospital Universitario la Paz, Madrid 28046, Spain
Ana López-López, Biochemistry Department, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid 28029, Spain
Rocío Mena, Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid 28046, Spain
Juan Ramón Larrubia, Translational Hepatology Unit, Hospital General Universitario de Guadalajara, Guadalajara 19002, Castilla-La Mancha, Spain
Author contributions: Gil-García AI, Madejón A and García-Samaniego J studied concept, designed and drafted the manuscript; Gil-García AI and Madejón A interpreted the data and revised the manuscript; Ana I Gil-García AI and Madejón A analysed data; Francisco-Recuero I, López-López A, Villafranca E, Romero M and García A got and interpreted data; Mena R sequenced analysis of samples; Olveira A and Larrubia JR reviewed the manuscript; García-Samaniego J revised the manuscript key intellectual contribution, funded provision and studied supervision. All the authors reviewed and approved the final version of the manuscript.
Supported by Análisis genético y epigenético del VHB en pacientes portadores asintomáticos. Implicaciones en la decisión terapéutica funded in the 1st Edition of the Gilead Fellowship Program, No. GLD13/00046 and Modificaciones de los niveles de expresión génica mediada por mutantes naturales de la región PreS del virus de la hepatitis B, y asociación con genes implicados en el desarrollo de hepatocarcinoma Efecto del tratamiento antiviral.
Institutional review board statement: The study was approved by the Ethical Committee of the Hospital Carlos III in Madrid, conforms to the ethical guidelines of the 1975 Declaration of Helsinki.
Informed consent statement: All the participants received and signed written consent for its participation.
Conflict-of-interest statement: All the authors have nothing to disclose.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Javier García-Samaniego, MD, PhD, Chief Doctor, Hepatology Unit, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain. Centro de Investigación Biomédica en Red. Instituto de Investigación del Hospital Universitario la Paz, Paseo de la Castellana 261, Madrid 28046, Spain. javiersamaniego@telefonica.net
Telephone: +34-91-7277204
Received: June 3, 2019
Peer-review started: June 3, 2019
First decision: July 21, 2019
Revised: August 8, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: October 14, 2019
ARTICLE HIGHLIGHTS
Research background
The indication of treatment in patients with chronic hepatitis B in the grey zone is not clear, and it is necessary to balance the risks and benefits for health outcomes, including the evaluation of the risk of hepatocellular carcinoma development.
Research motivation
To optimize the management of patients in the grey zone of treatment in order to identify suitable subpopulations for antiviral treatment.
Research objectives
To analyze the prevalence, and persistence over time, of hepatitis B virus (HBV) mutants that predispose to the development of hepatocellular carcinoma in patients in the grey zone of treatment.
Research methods
We analyzed the presence of basal core promoter/precore/core and preS deletion mutants related with hepatocellular carcinoma development in 106 samples from 31 patient in the grey zone of treatment.
Research results
A significant number of the patients analyzed in this work shows hepatocellular carcinoma related mutations. All these hepatocellular carcinoma related mutants are major viral strains and persist over time. Some patients have hepatocellular carcinoma related mutants in basal core promoter/precore/core and preS regions simultaneously. The presence of preS deletions is associated with sub-Saharan subpopulations infected with HBV-A and HBV-E genotypes.
Research conclusions
The presence of preS mutations should be assessed in patients with sub-Saharan origin, especially if they are infected with HBV-E and HBV-A genotype, in order to identify subpopulations of patients in whom the antiviral treatment could be indicated to minimize the risk of hepatocellular carcinoma due to accumulation of high-risk HBV genetic variants.
Research perspectives
The analysis of preS deletions could be indicated in the management of sub-Saharan patients in grey zone of treatment. Analysis of higher sample size populations during long-time longitudinal follow-up should be further performed in these patient subpopulation.
