Clinical Trials Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2020; 12(11): 1076-1088
Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1076
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.
Clinical trial registration statement: The study was registered at http://clinicaltrials.gov with the number NCT02743182.
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
Processing time: 174 Days and 20.9 Hours
Abstract
BACKGROUND

Hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs) rarely achieve hepatitis B surface antigen (HBsAg) loss.

AIM

To evaluate if the addition of pegylated interferon (Peg-IFN) could decrease HBsAg and hepatitis B core-related antigen (HBcrAg) levels and increase HBsAg loss rate in patients under NAs therapy.

METHODS

Prospective, non-randomized, open-label trial evaluating the combination of Peg-IFN 180 µg/week plus NAs during forty-eight weeks vs NAs in monotherapy. Hepatitis B e antigen-negative non-cirrhotic chronic hepatitis B patients of a tertiary hospital, under NAs therapy for at least 2 years and with undetectable viral load, were eligible. Patients with hepatitis C virus, hepatitis D virus or human immunodeficiency virus co-infection and liver transplanted patients were excluded. HBsAg and HBcrAg levels (log10 U/mL) were measured at baseline and during ninety-six weeks. HBsAg loss rate was evaluated in both groups. Adverse events were recorded in both groups. The kinetic of HBsAg for each treatment group was evaluated from baseline to weeks 24 and 48 by the slope of the HBsAg decline (log10 IU/mL/week) using a linear regression model.

RESULTS

Sixty-five patients were enrolled, 61% receiving tenofovir and 33% entecavir. Thirty-six (55%) were included in Peg-IFN-NA group and 29 (44%) in NA group. After matching by age and treatment duration, baseline HBsAg levels were comparable between groups (3.1 vs 3.2) (P = 0.25). HBsAg levels at weeks 24, 48 and 96 declined in Peg-IFN-NA group (-0.26, -0.40 and -0.44) and remained stable in NA group (-0.10, -0.10 and -0.10) (P < 0.05). The slope of HBsAg decline in Peg-IFN-NA group (-0.02) was higher than in NA group (-0.00) (P = 0.015). HBcrAg levels did not change. Eight (22%) patients discontinued Peg-IFN due to adverse events. The HBsAg loss was achieved in 3 (8.3%) patients of the Peg-IFN-NA group and 0 (0%) of the NA group.

CONCLUSION

The addition of Peg-IFN to NAs caused a greater and faster decrease of HBsAg levels compared to NA therapy. Side effects of Peg-IFN can limit its use in clinical practice.

Keywords: Chronic hepatitis B; Hepatitis B e antigen-negative; Hepatitis B surface antigen; Hepatitis B core-related antigen; Pegylated-interferon; Nucleos(t)ids analogues

Core Tip: The functional cure of chronic hepatitis B defined as the loss of the hepatitis B surface antigen is the optimal end-point with the currently available therapies. However, it is rarely achieved in hepatitis B e antigen-negative chronic hepatitis B patients under nucleos(t)ids analogues (NAs). In the present study, we report that the addition of pegylated interferon (Peg-IFN) to NAs during forty-eight weeks caused a greater and faster decrease of hepatitis B surface antigen levels compared to NA monotherapy. No changes in hepatitis B core-related antigen were observed. However, the low applicability and poor tolerance of Peg-IFN make difficult its use in clinical practice.