Liu J, Zhang P, Hu KZ, Zhao ZH, Xin YN, Bi YZ. Metabolic dysfunction-associated fatty liver and antiviral response in chronic hepatitis B: A systematic review and meta-analysis. World J Gastroenterol 2026; 32(47): 123905 [DOI: 10.3748/wjg.123905]
Corresponding Author of This Article
Yan-Zhen Bi, PhD, Department of Infectious Disease, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), No. 1 Jiaozhou Road, Shibei District, Qingdao 266011, Shandong Province, China. byzh199009@163.com
Research Domain of This Article
Gastroenterology & Hepatology
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research-article
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Liu J, Zhang P, Hu KZ, Zhao ZH, Xin YN, Bi YZ. Metabolic dysfunction-associated fatty liver and antiviral response in chronic hepatitis B: A systematic review and meta-analysis. World J Gastroenterol 2026; 32(47): 123905 [DOI: 10.3748/wjg.123905]
Jia Liu, Yong-Ning Xin, Yan-Zhen Bi, Department of Infectious Disease, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266011, Shandong Province, China
Peng Zhang, Department of Intensive Care Unit, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266011, Shandong Province, China
Ke-Zhen Hu, Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao 266011, Shandong Province, China
Zhi-Hui Zhao, School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China
Co-first authors: Jia Liu and Peng Zhang.
Co-corresponding authors: Yong-Ning Xin and Yan-Zhen Bi.
Author contributions: Liu J and Zhang P prepared material, collected and analyzed date and drafted manuscript as co-first authors; Hu KZ and Zhao ZH collected and analyzed date; Xin YN and Bi YZ designed and revised the original draft, contributed equally to this manuscript as co-corresponding authors; all authors commented on previous versions of the manuscript, contributed to the study conception and design, read and approved the final manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Supported by National Natural Science Foundation of China, No. 82202416; the China Hepatitis Prevention and Control Foundation Mu Xin Chronic Hepatitis B Research Fund, No. MX202409; and the Beijing iGandan Foundation Clinical Research Project, No. iGandanF-1082024-LG002.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Yan-Zhen Bi, PhD, Department of Infectious Disease, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), No. 1 Jiaozhou Road, Shibei District, Qingdao 266011, Shandong Province, China. byzh199009@163.com
Received: June 2, 2026 Revised: August 4, 2026 Accepted: September 22, 2026 Published online: December 21, 2026 Processing time: 148 Days and 21.4 Hours
Abstract
BACKGROUND
Metabolic dysfunction-associated fatty liver disease (MAFLD) frequently coexists with chronic hepatitis B (CHB). However, its association with antiviral treatment responses and long-term clinical outcomes in patients with CHB remains unclear.
AIM
To systematically evaluate the impact of MAFLD on antiviral treatment responses and long-term clinical outcomes in patients with CHB.
METHODS
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, the Cochrane Library, EMBASE, and Web of Science were searched for studies published up to November 30, 2025. Meta-analyses were performed to assess associations between MAFLD and antiviral treatment responses or clinical outcomes. Subgroup analyses were conducted according to antiviral regimen and MAFLD diagnostic approach, and leave-one-out sensitivity analyses were performed to evaluate robustness.
RESULTS
Thirty-two studies were included, of which 20 evaluated antiviral treatment efficacy and 13 assessed clinical outcomes in patients with CHB and concomitant MAFLD (one study reported both treatment responses and clinical outcomes). MAFLD was associated with a higher rate of hepatitis B surface antigen seroclearance at 48 weeks [odds ratio (OR) = 1.41, 95%CI: 1.28-1.55], although this association was attenuated at 96 weeks (OR = 1.44, 95%CI: 0.96-2.16). No significant association was observed between MAFLD and hepatitis B e antigen seroclearance at any time-point. MAFLD was consistently associated with lower rates of alanine aminotransferase normalization and hepatitis B virus DNA clearance throughout the treatment duration. MAFLD was associated with a significantly increased risk of hepatocellular carcinoma (HCC) despite antiviral therapy (OR = 1.50, 95%CI: 1.01-2.24). Subgroup analyses according to the antiviral regimen revealed distinct patterns, partly explaining the heterogeneity in the overall analyses. Subgroup analyses suggested that the antiviral regimen and MAFLD diagnostic approach partly explained the heterogeneity, particularly for hepatitis B virus DNA clearance and HCC.
CONCLUSION
MAFLD was associated with lower virological and biochemical response rates, higher odds of hepatitis B surface antigen seroclearance at week 48, particularly among patients receiving nucleos(t)ide analogue therapy, and higher odds of HCC in patients with CHB, but not with hepatitis B e antigen seroclearance. These findings support metabolic risk assessment in CHB management and highlight the need for standardized MAFLD/metabolic dysfunction-associated steatotic liver disease definitions.
Core Tip: Metabolic dysfunction-associated fatty liver disease (MAFLD) frequently coexists with chronic hepatitis B, but its clinical implications remain unclear. This meta-analysis showed that MAFLD was associated with lower rates of hepatitis B virus DNA clearance and alanine aminotransferase normalization, with no significant difference in hepatitis B e antigen seroclearance, and treatment duration-specific and regimen-specific differences in hepatitis B surface antigen seroclearance. MAFLD was also associated with higher odds of hepatocellular carcinoma, although this finding was influenced by diagnostic approach and showed limited robustness. These results support incorporating metabolic risk assessment into the long-term management of chronic hepatitis B.
