Zhang RL, Zhang HY, Jia YY, Wang ZY, Liu F, Chen HS, Rao HY. Risk factors for low-level viremia in tenofovir disoproxil fumarate-treated chronic hepatitis B patients with advanced hepatic fibrosis/compensated cirrhosis. World J Gastroenterol 2026; 32(31): 119706 [DOI: 10.3748/wjg.119706]
Corresponding Author of This Article
Hui-Ying Rao, MD, Professor, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on Nonalcoholic Fatty Liver Diagnosis, Infectious Disease and Hepatology Center, Peking University Hepatology Institute, Peking University People’s Hospital, No. 133 Fuchengmennei Street, Xicheng District, Beijing 100044, China. rao.huiying@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
research-article
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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 Gastroenterol. Aug 21, 2026; 32(31): 119706 Published online Aug 21, 2026. doi: 10.3748/wjg.119706
Risk factors for low-level viremia in tenofovir disoproxil fumarate-treated chronic hepatitis B patients with advanced hepatic fibrosis/compensated cirrhosis
Run-Ling Zhang, Hai-Ying Zhang, Yu-Yuan Jia, Zhen-Yu Wang, Feng Liu, Hong-Song Chen, Hui-Ying Rao, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on Nonalcoholic Fatty Liver Diagnosis, Infectious Disease and Hepatology Center, Peking University Hepatology Institute, Peking University People’s Hospital, Beijing 100044, China
Hong-Song Chen, Peking University Third Hospital, Beijing 100191, China
Co-first authors: Run-Ling Zhang and Hai-Ying Zhang.
Author contributions: Zhang RL and Zhang HY designed the experiments and completed the manuscript writing and they contribute equally to this study as co-first authors; Jia YY and Wang ZY were responsible for patient enrollment and data collection; Zhang HY and Zhang RL conducted the collation and statistical analysis; Liu F, Chen HS and Rao HY made critical revisions to important knowledge content; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethical Review Committee of Peking University People's Hospital (Approval No. 2025PHB523-001).
Informed consent statement: This study does not require the signing of an informed consent form, as it employs de-identified data for analysis and adheres to the principles of the Declaration of Helsinki and the ethics committee of the institution agreed to waive informed consent.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Hui-Ying Rao, MD, Professor, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on Nonalcoholic Fatty Liver Diagnosis, Infectious Disease and Hepatology Center, Peking University Hepatology Institute, Peking University People’s Hospital, No. 133 Fuchengmennei Street, Xicheng District, Beijing 100044, China. rao.huiying@163.com
Received: February 6, 2026 Revised: March 16, 2026 Accepted: April 15, 2026 Published online: August 21, 2026 Processing time: 179 Days and 21.7 Hours
Abstract
BACKGROUND
Patients diagnosed with chronic hepatitis B (CHB) complicated by advanced hepatic fibrosis/compensated cirrhosis face a significant risk of disease progression. Despite first-line nucleos(t)ide analog therapy, some patients continues to exhibit low-level viremia (LLV). Furthermore, LLV is closely associated with accelerated liver fibrosis progression and a higher likelihood of hepatocellular carcinoma. Clinical studies on accurate prognostic indicators for LLV in this patient group are still comparatively rare.
AIM
To identify the high-risk factors linked to the occurrence of LLV among CHB patients with advanced hepatic fibrosis/compensated cirrhosis.
METHODS
This retrospective study enrolled 141 CHB patients with advanced hepatic fibrosis/compensated cirrhosis who received tenofovir disoproxil fumarate (TDF). Patients were allocated into two groups according to their virological response at week 48 after treatment initiation: LLV, defined as hepatitis B virus (HBV) DNA levels of 20-2000 IU/mL, and complete virological response (CVR), defined as HBV DNA levels below 20 IU/mL. Univariate and multivariate logistic regression analysis were carried out to determine risk factors for LLV development.
RESULTS
A total of 141 patients were included in this study, among whom 17.0% (24/141) developed LLV. Significant differences were identified between the LLV and CVR groups regarding baseline HBV DNA, HBV RNA, hepatitis B e antigen positivity, HBV DNA ≥ 5.0 Log10 IU/mL, 6.0 Log10 IU/mL, 7.0 Log10 IU/mL, HBV RNA ≥ 5.0 Log10 copies/mL, and baseline alpha-fetoprotein. Multivariate logistic regression confirmed that that HBV DNA ≥ 7.0 Log10 IU/mL (OR = 18.824, 95%CI: 1.608-220.404, P = 0.019) at baseline was associated with the occurrence of LLV.
CONCLUSION
In TDF-treated CHB with advanced hepatic fibrosis/compensated liver cirrhosis, HBV DNA ≥ 7.0 Log10 IU/mL is a high-risk factor associated with LLV.
Core Tip: Our retrospective study enrolled 141 chronic hepatitis B (CHB) patients with advanced hepatic fibrosis/compensated cirrhosis undergoing tenofovir disoproxil fumarate therapy, with the incidence of low-level viremia (LLV) reaching 17.0% at 48 weeks of treatment. Multivariate logistic regression analysis confirmed that baseline hepatitis B virus DNA ≥ 7.0 Log10 IU/mL was an independent high-risk factor for LLV development. This finding provides comprehensive clinical evidence for early risk stratification and individualized intervention of LLV in this specific high-risk CHB population.
