Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 7, 2023; 29(25): 3964-3983
Published online Jul 7, 2023. doi: 10.3748/wjg.v29.i25.3964
Past, present, and future of long-term treatment for hepatitis B virus
Teresa Broquetas, José A Carrión
Teresa Broquetas, José A Carrión, Liver Section, Gastroenterology Department, Hospital del Mar, Barcelona 08003, Spain
Teresa Broquetas, José A Carrión, Institut Hospital del Mar D’Investigacions Mèdiques, PSMAR, Barcelona 08003, Spain
José A Carrión, Universitat Pompeu Fabra, Facultat de Ciències de la Salut i de la Vida, Barcelona 08003, Spain
Author contributions: Broquetas T contributed to the acquisition of data, interpretation, drafting, critical revision, and final approval; Carrión JA contributed to conception and design, acquisition of data, interpretation, drafting, critical revision, and final approval.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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:
Corresponding author: José A Carrión, Doctor, MD, PhD, Assistant Professor, Liver Section, Gastroenterology Department, Hospital del Mar, 25-29 Passeig Marítim, Barcelona 08003, Spain.
Received: March 27, 2023
Peer-review started: March 27, 2023
First decision: May 12, 2023
Revised: May 22, 2023
Accepted: June 6, 2023
Article in press: June 6, 2023
Published online: July 7, 2023

The estimated world prevalence of hepatitis B virus (HBV) infection is 316 million. HBV infection was identified in 1963 and nowadays is a major cause of cirrhosis and hepatocellular carcinoma (HCC) despite universal vaccination programs, and effective antiviral therapy. Long-term administration of nucleos(t)ide analogues (NA) has been the treatment of choice for chronic hepatitis B during the last decades. The NA has shown a good safety profile and high efficacy in controlling viral replication, improving histology, and decreasing the HCC incidence, decompensation, and mortality. However, the low probability of HBV surface antigen seroclearance made necessary an indefinite treatment. The knowledge, in recent years, about the different phases of the viral cycle, and the new insights into the role of the immune system have yielded an increase in new therapeutic approaches. Consequently, several clinical trials evaluating combinations of new drugs with different mechanisms of action are ongoing with promising results. This integrative literature review aims to assess the knowledge and major advances from the past of hepatitis B, the present of NA treatment and withdrawal, and the future perspectives with combined molecules to achieve a functional cure.

Keywords: Hepatitis B, Therapy, Antigen, Functional cure, Antiviral agents, Drug development

Core Tip: Treatment for chronic hepatitis B has been used for decades, showing a good safety profile and high virological and clinical efficacy, decreasing hepatocellular carcinoma, clinical decompensation, and mortality. However, the low probability of hepatitis B virus surface antigen seroclearance with therapy made necessary indefinite treatment in a majority of patients. With the new insights about the immune system role in hepatitis B virus infection and the knowledge of the viral cycle phases, there has been in recent years increased activity in new therapeutic approaches. This review focuses on the past, present, and future of chronic hepatitis B therapy.