Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2021; 27(43): 7497-7508
Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7497
Hepatitis B: Who should be treated?-managing patients with chronic hepatitis B during the immune-tolerant and immunoactive phases
Miwa Kawanaka, Ken Nishino, Hirofumi Kawamoto, Ken Haruma
Miwa Kawanaka, Ken Nishino, Hirofumi Kawamoto, Ken Haruma, Department of General Internal Medicine 2, General Medical Center, Kawasaki Medical School, Okayama 700-8505, Japan
Author contributions: Kawanaka M conceived, planned, performed, and supervised the methodology, as well as analyzed the data, interpreted the results, created graphics, wrote, and reviewed the manuscript; Nishino K acquired the funding for the study; Haruma K and Kawamoto H administered the project; all authors provided critical feedback and helped shape the final manuscript.
Conflict-of-interest statement: Authors declare no conflict of interest regarding publication of this manuscript.
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: Miwa Kawanaka, MD, PhD, Associate Professor, Doctor, Department of General Internal Medicine 2, General Medical Center, Kawasaki Medical School, 2-6-1 Nakasange, Kita-ku, Okayama 700-8505, Japan.
Received: April 23, 2021
Peer-review started: April 23, 2021
First decision: June 13, 2021
Revised: July 31, 2021
Accepted: October 31, 2021
Article in press: October 31, 2021
Published online: November 21, 2021

New hepatitis B virus (HBV) infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide; however, the number of HBV infections remains a major cause of liver carcinogenesis. HBV triggers cytotoxic immunity to eliminate HBV-infected cells. Therefore, the HBV pathophysiology changes in persistently infected individuals depending on host immune responses and HBV DNA proliferation state. To prevent liver cirrhosis and carcinogenesis caused by HBV, it is important to treat HBV infection at an early stage. Active treatment is recommended for the immunoactive hepatitis B surface-antigen-positive and -negative phase, but not during the immune-inactive phase or immune-tolerant phase; instead, follow-up is recommended. However, these patients should be monitored through regular blood tests to accurately diagnose the immune-inactive or -tolerant phases. The treatment regimen should be determined based on the age, sex, family history of liver cancer, and liver fibrosis status of patients. Early treatment is often recommended due to various problems during the immune-tolerant phase. This review compares the four major international practice guidelines, including those from the Japanese Society of Hepatology, and discusses strategies for chronic hepatitis B treatment during the immune-tolerant, immune-inactive, and resolved phases. Finally, recommended hepatitis B antiviral therapy and follow-up protocols are discussed.

Keywords: Hepatitis B, Immune tolerance, Immune-inactive, Anti-viral therapy, Hepatocellular carcinoma, Cirrhosis

Core Tip: Hepatitis B virus (HBV) is a global health problem that causes acute and chronic infections and often leads to liver cirrhosis and hepatocellular carcinoma. Treatment of HBV is recommended for patients in the immunoactive hepatitis B surface-antigen-positive and -negative phases. Follow-up is recommended only for patients in the immune-inactive phase and the immune-tolerant phase, but opinion on this recommendation remain divided. This review discusses the major international guidelines for the treatment of chronic hepatitis B and highlights the importance of clinical factors for making decisions regarding the management of patients with HBV infection.