Wang L, Liang H, Wang C, Liang MY, Zeng QL, Zhu PF, Lv J. Functional cure in an occult hepatitis B virus infection patient on sequential therapy: A case report. World J Hepatol 2025; 17(9): 109340 [DOI: 10.4254/wjh.v17.i9.109340]
Corresponding Author of This Article
Jun Lv, Associate Chief Physician, Associate Professor, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fcclvj@zzu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Hepatol. Sep 27, 2025; 17(9): 109340 Published online Sep 27, 2025. doi: 10.4254/wjh.v17.i9.109340
Functional cure in an occult hepatitis B virus infection patient on sequential therapy: A case report
Lin Wang, Han Liang, Chen Wang, Meng-Yu Liang, Qing-Lei Zeng, Peng-Fei Zhu, Jun Lv
Lin Wang, Han Liang, Chen Wang, Meng-Yu Liang, Qing-Lei Zeng, Jun Lv, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Peng-Fei Zhu, Department of Clinical Laboratory and Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Wang L reviewed the literature and contributed to the drafting of the manuscript; Wang L, Liang H, Wang C, Liang MY, Zeng QL, Zhu PF, and Lv J contributed to the final version of the article; Lv J provided case information and reviewed and revised the article; and all authors thoroughly reviewed and endorsed the final manuscript.
Informed consent statement: Informed verbal consent was obtained from the patient for publication of this case report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jun Lv, Associate Chief Physician, Associate Professor, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. fcclvj@zzu.edu.cn
Received: May 8, 2025 Revised: June 21, 2025 Accepted: September 2, 2025 Published online: September 27, 2025 Processing time: 140 Days and 19.4 Hours
Abstract
BACKGROUND
Occult hepatitis B virus infection (OBI) is defined by the detection of replication-competent hepatitis B virus (HBV) DNA in the liver and/or blood despite the absence of detectable hepatitis B surface antigen (HBsAg) using conventional serological assays. Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy, reports of its occurrence during sequential antiviral treatment remain scarce. This report describes a case of chronic hepatitis B (CHB) transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure. This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance.
CASE SUMMARY
A 33-year-old Chinese male was diagnosed with HBV infection in 2001. The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy, which failed to achieve a virological response. Antiviral therapy was subsequently switched to entecavir monotherapy. By August 2019, the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA (< 25 IU/mL). At this point, combination therapy with entecavir and pegylated interferon α (PEG-IFN α) was initiated. Remarkably, while HBsAg declined to 0.42 IU/mL by April 2020, a paradoxical HBV DNA rebound to 173 IU/mL was observed. The regimen was consequently modified to tenofovir alafenamide and PEG-IFN α. By October 2020, the patient achieved HBsAg seroconversion (HBsAg 0.01 IU/mL, hepatitis B surface antibody 52.18 mIU/mL) for the first time, while maintaining low-level viremia (37 IU/mL), consistent with transition to OBI. The patient was then switched to PEG-IFN α monotherapy. In November 2021, he discontinued PEG-IFN α therapy, and one month later, both HBV DNA (< 10 IU/mL) and HBsAg (< 0.05 IU/mL) were negative. This response has been sustained through follow-up.
CONCLUSION
This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients, including those with a prolonged infection history. It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy. While the patient ultimately achieved functional cure, the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring. This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.
Core Tip: This case illustrates the emergence of occult hepatitis B infection (OBI) as a distinct transitional phase during sequential combination therapy for chronic hepatitis B. Unlike previously reported cases where OBI develops in individuals with resolved infection, this case suggests that antiviral therapy itself may induce an OBI-like state before achieving functional cure. As OBI has been associated with potential reactivation risks. Understanding the mechanisms behind treatment-induced OBI will be crucial in refining therapeutic strategies and improving long-term hepatitis B virus management.
