Specialist in Nephrology
Chronic Hepatitis B (CHB) remains a substantial public health burden in Hong Kong, with recent data indicating approximately 5.6% of the local population living with the infection, affecting over 410,000 individuals1. While antiviral therapies have significantly improved liver-related outcomes, the clinical landscape is transforming as the CHB population ages2. With the median age of CHB patients in Hong Kong now exceeding 50 years, this demographic shift has led to increased prevalence of comorbidities such as diabetes mellitus (DM) and chronic kidney disease (CKD)3. This creates a complex clinical challenge of achieving sustained viral suppression while also preserving renal function in an increasingly vulnerable population4. In a recent interview, Prof. Desmond Y. H. Yap, a specialist in nephrology, shared his expert perspective on optimising treatment strategies in this complex patient population.
Prof. Yap explained that the clinical management of ageing CHB patients requires expanding focus beyond liver-specific complications to include antiviral-related nephrotoxicity. "We are managing a dual challenge: controlling viral replication while protecting renal function in patients who are already at risk," he noted. He emphasised that many patients now present with age-related conditions like diabetes and hypertension, which substantially increase their vulnerability to renal impairment.
This demographic challenge is underscored by data showing that CKD prevalence in CHB patients doubled with age: from 5.3% in patients aged 30-39 to 11.3% in those aged 50-595. This trend, which aligns with Hong Kong's current patient profile, signals a growing burden on the healthcare system1,5. Real-world evidence indicates that CHB patients with concurrent comorbidities such as diabetes and hypertension have a substantially greater likelihood of developing kidney disease. The confluence of ageing chronic viral infection and these comorbidities has a synergistic effect leading to a cumulative probability of kidney disease that surpasses the additive risk from the individual factors alone6.
This evolving patient profile necessitates a critical re-evaluation of antiviral selection. Tenofovir disoproxil fumarate (TDF), while highly effective, has been associated with dose-dependent renal toxicity and reduced bone mineral density during long-term therapy7,8. This safety profile presents significant limitations for patients with existing renal risk factors.
Prof. Yap emphasised that renal safety considerations should fundamentally guide antiviral selection in patients with comorbidities. The treatment goal is not only to suppress the virus but also to protect the patient's organs long-term, requiring careful monitoring of serum creatinine, estimated glomerular filtration rate (eGFR), proteinuria, and phosphate levels.
Crucially, emerging evidence suggests that renal impairment in this context is not necessarily irreversible. Recent studies demonstrate that timely intervention with renally safe antiviral regimens can lead to meaningful improvements in eGFR and a reduction in proteinuria9.
In response to this clinical imperative, long-term data provide strong support for Tenofovir Alafenamide (TAF). The final 8-year analysis from two global phase 3 trials, which included a majority of Asian patients, offers robust evidence for renal protection10. TAF's improved safety profile stems from its more targeted delivery, resulting in lower systemic tenofovir levels. This analysis demonstrated that patients receiving TAF maintained remarkable renal stability over the entire study period, with only small decline in eGFR from baseline of approximately 5 mL/min (median, ranging from 4.9 to 5.4 mL/min) after 8 years of continuous TAF treatment10. This minimal decrease is consistent with the expected rate of decline from normal ageing10. Furthermore, hip and spine bone mineral density also remained stable over the 8-year period (Figure 1)10. This sustained safety profile supports the concept of early renal protection and aligns perfectly with the goal of optimising lifelong management for the ageing CHB population in Hong Kong10.
Figure 1: Pooled changes in renal and bone safety parameters over 8 years. (A) Pooled median change in eGFRCG (mL/min) from baseline by year. (B) Pooled mean percent change in hip BMD and (C) spine BMD from baseline by year10. BMD, bone mineral density; eGFRCG, estimated glomerular filtration rate by Cockcroft-Gault; Q, quartile; SD, standard deviation; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Prof. Yap highlighted the practical advantages of this approach in routine clinical practice. "The simplified dosing of TAF across various stages of renal impairment streamlines management for most CKD patients," he stated, noting this represents a significant advantage over agents requiring complex dose adjustments and aligns with the goal of protecting renal function from the very start of therapy.
The management of CHB in kidney transplant recipients requires an antiviral strategy that meets several specific criteria for optimal patient outcomes. Prof. Yap outlines that an ideal prescription must provide effective hepatitis B virus (HBV) suppression, demonstrate low resistance rates, prevent both short- and long-term hepatic complications, and exhibit a lack of nephrotoxicity. These considerations are particularly crucial given the concurrent use of nephrotoxic immunosuppressants and the paramount importance of preserving allograft function.
Recent clinical evidence confirms the renal safety profile of TAF in this vulnerable population. A 2025 retrospective cohort study demonstrated stable serum phosphate levels over 2-year TAF treatment, with mean values remaining at 1.1 mmol/L at baseline through 12 months and showing only minimal decline to 1.0 mmol/L at 24 and 36 months. Similarly, renal allograft function remained stable, with mean eGFR maintained at 43.6 mL/min before treatment and 47.4 mL/min after 2-year TAF treatment, demonstrating no significant deterioration in renal function. Overall, this study showed that TAF provides favourable efficacy, renal safety, and tolerability in kidney transplant recipients (Figure 2)11.
Figure 2: Longitudinal changes in (A) HBV DNA (B) ALT levels and (C) renal allograft function in treatment-naïve (Group I) or treatment-experienced (Group II) HBsAg-positive kidney transplant recipients11. ALT, alanine transferase; DNA, deoxyribonucleic acid; eGFR, estimated glomerular filtration rate; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.
The European Association for the Study of the Liver (EASL) clinical practice guidelines have accordingly positioned TAF as a first-line treatment option, recognising its favourable safety profile12. Prof. Yap affirmed that TAF is fundamental to their management strategy, as it delivers potent antiviral control while supporting the maintenance of renal allograft function. This combination of efficacy and renal safety is critical for protecting both the liver and the transplanted organ. Furthermore, TAF may offer additional advantages for long-term management, such as a high genetic barrier to resistance that minimises concern over viral resistance, and it does not require dose adjustment based on eGFR levels11.
For an ageing CHB population like Hong Kong's, the treatment paradigm must expand beyond viral suppression to proactively preserve renal function from the outset4. As Prof. Yap emphasised, "Our therapeutic strategy should simultaneously target viral suppression and organ preservation." Utilising antiviral agents such as TAF, which has demonstrated long-term renal safety profile supported by 8-year data showing minimal impact on kidney function, is fundamental to this approach10. This dual-protection strategy is essential for ensuring long-term patient well-being10,11.
References
1. Centre for Health Protection, Department of Health, Hong Kong SAR. Hepatitis B prevalence in Hong Kong. Available from: https://www.hepatitis.gov.hk/english/health_professionals/files/iCE_HBV_prevalence.pdf 2. Rodríguez & Martinez, International Journal of Hepatology Research, 2024 3. ePulse – June 2025, Hong Kong Adventist Hospital 4. Chen et al., BMC Gastroenterology, 2025 5. Ning l. apasl 2016. Poster P-0497 Abstract. 6. Ito et al., BMC Nephrology, 2025 7. Liu, Z., Zhao, Z., Ma, X. et al. Renal and bone side effects of long-term use of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide fumarate in patients with Hepatitis B: a network meta-analysis. BMC Gastroenterol. 2023;23:384. Available from: https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-023-03027-4 8. Casado JL, Bañón S, Andrés R, et al. Renal and bone toxicity with the use of tenofovir: understanding at the end. AIDS Rev. 2016;18(2):59–68. Available from: https://www.researchgate.net/publication/303787479 9. Ogawa E, Kohjima M, Koyanagi T, et al. Five-Year Effectiveness and Renal Safety Following Switching to Tenofovir Alafenamide in Chronic Hepatitis B Patients With Renal Impairment. J Gastroenterol Hepatol. 2025;40(10):2560-2567.Available from: https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31793 10. Buti M, et al. Aliment Pharmacol Ther. 2024;60(11-12):1573-1586. 11. Desmond Y.H. YAP, et al, Biomedical Journal. 2025;100833. https://doi.org/10.1016/j.bj.2025.100833. 12. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025;83(2):502-583. Available from: https://www.hepb.org/assets/Uploads/EASL-guidelines-May-2025.pdf
