Dear Editor,
We thank Dr. Huang and Prof. Nguyen for their thoughtful correspondence in response to our editorial [
1,
2]. We greatly appreciate their important contribution, which provides valuable insights into the long-term impact of metabolic traits in nucleos(t)ide analogue-treated chronic hepatitis B (CHB) [
3].
We concur with their emphasis that diabetes mellitus (DM) is the single most influential metabolic factor associated with adverse outcomes in this population [
3], possibly through a constellation of metabolic and inflammatory mechanisms [
4]. In our large cohort studies on CHB patients, DM consistently emerged as the strongest metabolic predictor of hepatocellular carcinoma (HCC), cirrhosis, and overall mortality. Moreover, both glycemic control, reflected by HbA1c levels, and incident DM diagnosed during follow-up were also independently associated with these adverse outcomes in this special clinical setting [
5-
7]. These findings underscore the need to move beyond a simple count of metabolic abnormalities and toward a more nuanced evaluation to prioritize the type and severity of metabolic dysfunctions. Such a conceptual shift is critical for the development of effective risk stratification strategies and targeted clinical interventions, particularly in resource-limited countries, where optimizing HCC surveillance and antiviral treatment allocation is crucial [
8]. Future hepatitis B virus cure strategies and actions should consider the host metabolic status, integrating systemic approaches to achieve both scientific efficacy and real-world feasibility [
9].
Dr. Huang and Prof. Nguyen should be congratulated for their collegial engagement and valuable perspectives. As metabolic disorders continue to rise globally, the integration of hepatology with metabolic medicine will be indispensable. Continued multidisciplinary collaboration and shared research efforts will be essential to advancing metabolic health and precision care for patients living with CHB.
FOOTNOTES
-
Authors’ contribution
SC Huang: drafting of the manuscript
JH Kao: critical revision for important intellectual content.
-
Acknowledgements
During the preparation of this work, the authors used Grammarly for English proofreading and editing. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
-
Conflicts of Interest
S.-C. H. was on speaker’s bureau for Gilead Sciences.
J.-H. K. has served as a consultant for Abbvie, Abbott, Gilead Sciences, Roche, and Sysmex and on speaker’s bureaus for Abbvie, Bristol-Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, and Sysmex.
Abbreviations
REFERENCES
- 1. Huang R, Nguyen MH. Correspondence to editorial 2 on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”. Clin Mol Hepatol 2026;32:e83-e84.
- 2. Huang SC, Kao JH. Metabolic health in antiviral era of chronic hepatitis B: Editorial on “Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues”. Clin Mol Hepatol 2026;32:423-425.
- 3. Huang R, Jun DW, Toyoda H, Hsu YC, Trinh H, Nozaki A, et al. Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues. Clin Mol Hepatol 2025;31:1003-1017.
- 4. Huang SC, Kao JH. The interplay between chronic hepatitis B and diabetes mellitus: A narrative and concise review. Kaohsiung J Med Sci 2024;40:6-10.
- 5. Huang SC, Su TH, Tseng TC, Chen CL, Hsu SJ, Liao SH, et al. Distinct effects of hepatic steatosis and metabolic dysfunction on the risk of hepatocellular carcinoma in chronic hepatitis B. Hepatol Int 2023;17:1139-1149.
- 6. Huang SC, Su TH, Tseng TC, Liao SH, Hsu SJ, Hong CM, et al. Pre-existing and new-onset metabolic dysfunctions increase cirrhosis and its complication risks in chronic hepatitis B. Am J Gastroenterol 2025;120:401-409.
- 7. Huang SC, Su TH, Tseng TC, Hsu SJ, Hong CM, Lan TY, et al. All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease. J Hepatol 2025;83:43-51.
- 8. WHO. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. WHO web site, <https://www.who.int/publications/i/item/9789240090903>. Accessed 4 May 2025.
- 9. Huang SC, Kao JH. Combining therapeutic agents to target the immune systems of hepatitis B patients: what do we need to consider? Expert Rev Gastroenterol Hepatol 2025;19:371-375.
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