Dear Editor,
We appreciate the insightful editorial by Dr. Huang and Dr. Kao on our recent study regarding the impact of components of metabolic syndrome on long-term outcomes of patients with chronic hepatitis B (CHB) who received nucleos(t)ide analogue (NA) treatment [
1,
2]. The editorial succinctly outlines the role of metabolic dysfunction as a prognostic “game-changer” in NA-treated CHB, steatotic liver disease (SLD) as paradox worth understanding in CHB, and a call towards integrated and individualized CHB care [
2].
First, while we agree with Dr. Huang and Dr. Kao on the prognostic role of metabolic dysfunction in general, we would like to point out that the major impact on adverse outcomes we observed in our study cohort was mainly with diabetes and not other metabolic diseases regardless of their numerical numbers. Consequently, given the considerable residual risk of adverse outcomes among NA-treated CHB patients and their association with diabetes, diabetes should be incorporated as a prognostic factor for closer disease monitoring including hepatocellular carcinoma (HCC) surveillance as proposed by the REAL-B HCC risk score in which diabetes is one of the components [
3]. We would also advocate for inclusion of diabetes as a selection criterion for antiviral treatment initiation as recently proposed by the 2024 World Health Organization management guideline for CHB [
4].
Second, we also find the interaction between SLD, diabetes and CHB intriguing with the inverse association between SLD and adverse outcomes among CHB patients and agree that additional research is needed to elucidate the mechanisms of these observations. We also would like to note here that the association between diabetes and adverse outcomes observed in our study cohort is independent of the presence of SLD, further highlighting the important impact of diabetes in the natural history of CHB.
Lastly, we cannot agree more with the editorial on the importance of integrated and individualized care. Given the high prevalence of metabolic disease in the CHB population (54.6% in our study cohort) and its important impact on the natural history of CHB, metabolic disease and specifically diabetes should be screened, diagnosed and its treatment optimized. As a result, CHB management would require collaboration between primary care providers and liver and metabolic specialists. Active engagement of primary care providers and metabolic specialist care providers in the management of CHB has become even more important in recent years with the availability of highly effective antidiabetic and weight loss medications such as glucagon-like peptide 1 receptor agonists [
5-
8].
FOOTNOTES
-
Authors’ contribution
Manuscript drafting: RH. Review and revision: RH and MHN.
-
Conflicts of Interest
Mindie H. Nguyen: Research grants via Stanford University: Pfizer, Enanta, Astra Zeneca, GSK, Delfi, Innogen, Exact Science, CurveBio, Gilead, Vir Biotech, Helio Health, National Institute of Health, Glycotest, Roche and personal fees from consulting/advisory board: Exelixis, Gilead, GSK. Rui Huang: none to disclose.
Abbreviations
REFERENCES
- 1. 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.
- 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. Yang HI, Yeh ML, Wong GL, Peng CY, Chen CH, Trinh HN, et al. Real-world effectiveness from the Asia Pacific Rim Liver Consortium for HBV risk score for the prediction of hepatocellular carcinoma in chronic hepatitis B patients treated with oral antiviral therapy. J Infect Dis 2020;221:389-399.
- 4. World Health Organization (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 14 Apr 2024.
- 5. Brown E, Heerspink HJL, Cuthbertson DJ, Wilding JPH. SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet 2021;398:262-276.
- 6. Andersen A, Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol 2018;14:390-403.
- 7. Wang L, Berger NA, Kaelber DC, Xu R. Association of GLP-1 receptor agonists and hepatocellular carcinoma incidence and hepatic decompensation in patients with type 2 diabetes. Gastroenterology 2024;167:689-703.
- 8. Engström A, Wintzell V, Melbye M, Svanström H, Eliasson B, Gudbjörnsdottir S, et al. Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study. Hepatology 2024;79:1401-1411.
Citations
Citations to this article as recorded by
- Advancing metabolic risk profiling in chronic hepatitis B: Reply to correspondence on “Metabolic health in antiviral era of chronic hepatitis B”
Shang-Chin Huang, Jia-Horng Kao
Clinical and Molecular Hepatology.2026; 32(1): e117. CrossRef
