Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2021; 27(19): 2312-2324
Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2312
Risk of hepatitis B virus reactivation in patients with autoimmune diseases undergoing non-tumor necrosis factor-targeted biologics
Shintaro Akiyama, Thomas G Cotter, Atsushi Sakuraba
Shintaro Akiyama, Thomas G Cotter, Atsushi Sakuraba, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL 60637, United States
Author contributions: Akiyama S performed the literature search, figures, tables, and data collection; all authors conducted study design, data interpretation, and drafting of manuscripts.
Conflict-of-interest statement: The authors have nothing to disclose.
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: Shintaro Akiyama, MD, MSc, PhD, Academic Fellow, Doctor, Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, 5841 S. Maryland Ave. MC 4076, Chicago, IL 60637, United States.
Received: January 24, 2021
Peer-review started: January 24, 2021
First decision: February 23, 2021
Revised: February 27, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 21, 2021

Hepatitis B virus reactivation (HBVr) can occur in patients treated with immunosuppressive medications. Risk stratification for HBVr based on hepatitis B virus (HBV) serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use. Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies. Tumor necrosis factor (TNF)-α inhibitors have been widely used for patients with inflammatory bowel disease, psoriasis, and rheumatic diseases. Further, the clinical benefits of interleukin (IL)-12/23, IL-17, or Janus kinases inhibitors have been demonstrated in these patients. It is well known that TNF-α inhibitor use can lead to HBVr, however, the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood. In this review, we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics, and immunological mechanisms of these medications causing HBVr.

Keywords: Hepatitis B virus, Autoimmune diseases, Biological therapy, Interleukin-23, Interleukin-17, Janus kinases

Core Tip: Although the risk of hepatitis B virus reactivation (HBVr) in patients undergoing non-tumor necrosis factor (TNF)-targeted biologics have not been fully understood, some previous studies showed that the risk of HBVr in patients with non-TNF-targeted biologics might be higher than that in patients with TNF-α inhibitors. While patients with chronic hepatitis B virus (HBV) should receive antiviral prophylaxis when they start non-TNF-targeted biologics, antiviral prophylaxis may be a favorable strategy rather than the pre-emptive strategy in patients with resolved HBV. Large-scale studies are needed to ascertain the differential risk of HBVr between patients with TNF-α inhibitors and non-TNF-targeted biologics.