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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Hepatitis B surface antigen and hepatitis B core-related antigen kinetics after adding pegylated-interferon to nucleos(t)ids analogues in hepatitis B e antigen-negative patients
Teresa Broquetas, Montserrat Garcia-Retortillo, Miquel Micó, Lidia Canillas, Marc Puigvehí, Nuria Cañete, Susana Coll, Ana Viu, Juan Jose Hernandez, Xavier Bessa, José A Carrión
Teresa Broquetas, Montserrat Garcia-Retortillo, Lidia Canillas, Marc Puigvehí, Nuria Cañete, Susana Coll, Ana Viu, Xavier Bessa, José A Carrión, Department of Gastroenterology, Liver Section, Hospital del Mar Medical Research Institute, Barcelona 08003, Spain
Teresa Broquetas, Montserrat Garcia-Retortillo, Marc Puigvehí, Nuria Cañete, Susana Coll, Xavier Bessa, José A Carrión, Departament of de Medicina, Universitat Autònoma de Barcelona, Barcelona 08003, Spain
Miquel Micó, Juan Jose Hernandez, Laboratori de Referencia de Catalunya, El Prat de Llobregat, Barcelona 08820, Spain
Author contributions: Broquetas T completed statistical analysis and drafting of the manuscript; Broquetas T and Carrión JA analyzed and interpreted the data; Micó M and Hernandez JJ analyzed samples; Carrión JA completed concept, design and supervision of the study; all authors performed the acquisition of data, critical revision of the manuscript.
Supported by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad No. PI14/00540; Fondo Europeo de Desarrollo Regional; Unión Europea; Una manera de hacer Europa.
Institutional review board statement: The study protocol was reviewed and approved by the Ethical Committee of our Institution “Comitè Ètic d’Investigació Clínica - Parc de Salut Mar”, study reference 2014/5787/I, in accordance with the ethical guidelines of the 1975 Declaration of Helsinki.
Informed consent statement: Study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Authors declare no conflict-of-interest.
Data sharing statement: No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: José A Carrión, MD, PhD, Doctor, Department of Gastroenterology, Liver Section, Hospital del Mar Medical Research Institute, Parc de Salut Mar, Passeig Marítim 25-29, Barcelona 08003, Spain. 95565@parcdesalutmar.cat
Received: June 2, 2020
Peer-review started: June 2, 2020
First decision: June 15, 2020
Revised: June 23, 2020
Accepted: September 4, 2020
Article in press: September 4, 2020
Published online: November 27, 2020
ARTICLE HIGHLIGHTS
Research background
Functional cure of chronic hepatitis B (CHB), defined as the loss of hepatitis B surface antigen (HBsAg), is very unusual with current antiviral treatments in hepatitis B e antigen (HBeAg)-negative patients. HBsAg levels decline very slow in patients receiving nucleos(t)ids analogues (NAs). Therefore, they need long-term antiviral treatment.
Research motivation
The hypothesis that we wanted to answer with our study was that the addition of pegylated-interferon (Peg-IFN) could accelerate the decline of HBsAg levels in patients that were receiving NAs and that this therapeutic strategy could increase the HBsAg loss rate.
Research objectives
In our study we wanted to evaluate in patients under NAs therapy if the addition of Peg-IFN could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels, and increase HBsAg loss rate. If HBeAg-negative patients could achieve low levels of HBsAg it could be a good strategy to shorten the antiviral treatment.
Research methods
We have performed a prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/wk plus NAs during forty-eight weeks vs NAs in monotherapy, in HBeAg-negative non-cirrhotic CHB patients after a minimum of two years of NA therapy and with virological response.
Research results
We have shown that the addition of Peg-IFN 180 µg/wk during forty-eight weeks to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy alone, especially in those patients with interleukin 28B polymorphism CC. However, the HBcrAg levels remained stable after adding Peg-IFN to NAs. We have also shown that, the low acceptance by the patients of this therapeutic strategy and the side effects of Peg-IFN can limit its use in clinical practice.
Research conclusions
This study shows that the addition of Peg-IFN to NA therapy accelerates the decline of HBsAg, especially in patients with interleukin 28B polymorphism CC. Therefore, even Peg-IFN has several side effects, this treatment strategy could be offered to some selected patients in order to achieve the functional cure of CHB. On the other hand, our study shows that HBcrAg levels do not seem useful to monitor this kind of treatment, neither as a predictor of HBsAg loss.
Research perspectives
It is well known that patients with HBeAg-negative CHB usually need a long-term therapy with NAs, even lifelong, to achieve HBsAg loss. However, it has been suggested that low levels of HBsAg are related to higher rates of HBsAg loss after NA discontinuation, being advisable to achieve low levels of HBsAg before stopping NA therapy.
