Letter on “Efficacy and Safety of Tenofovir Alafenamide (TAF) and Tenofovir Disoproxil Fumarate (TDF) Followed by TAF in Chronic Hepatitis B Patients of East Asian Ethnicity Following 5 Years of Treatment”

We read with great interest the article by Wong et al. [1]. This post hoc analysis of East Asian patients from two pivotal Phase 3 trials provides valuable long-term data on antiviral efficacy, biochemical response and safety profiles in a population disproportionately affected by chronic hepatitis B (CHB). The authors' focus on this demographic, which constitutes a significant portion of the global HBV burden, is commendable and contributes meaningfully to evidence-based management of CHB in Asian cohorts.

While the study demonstrates robust virologic suppression (89%–94% at Year 5) and ALT normalisation rates (78%–90% by central lab criteria) across groups, one methodological consideration is the impact of the protocol amendment on treatment switching. The variation in implementation led to uneven subgroups (TAF continuous, TDF → TAF at 2 or 3 years), precluding formal statistical comparisons between arms. This introduces potential selection bias, as site-specific factors may have influenced rollover timing. Future analyses could benefit from sensitivity testing or propensity score matching to mitigate such biases and enhance comparability.

Another point pertains to the generalizability of renal and bone safety improvements post-switch from TDF to TAF. The observed reversals in eGFR declines and BMD reductions are promising, particularly given the higher osteoporosis risk in East Asian populations with lower BMI. However, the study population had relatively preserved baseline renal function (median eGFR_CG > 98 mL/min) and low osteoporosis prevalence (2%–14% by T-score). It would be insightful to explore subgroup analyses in patients with preexisting comorbidities, such as those with eGFR < 60 mL/min or established osteoporosis, to better inform switching decisions in higher-risk individuals. Additionally, the handling of missing data via missing failure analysis is appropriate, but reporting imputation methods for bone/renal markers could further strengthen robustness.

The low rates of HBsAg loss (< 1%) align with prior literature on nucleos(t)ide analogues in genotypes B/C predominant cohorts [2], yet this underscores an opportunity for deeper exploration. Quantitative HBsAg declines were modest (−0.24 to −0.37 log₁₀ IU/mL at Year 5), and incorporating predictive factors like baseline HBsAg levels or HBV genotype subgroups might refine prognostic insights [3]. Clinically, this could guide expectations in East Asian patients, where sustained off-therapy responses remain elusive.

These findings advocate for broader real-world studies incorporating diverse East Asian subgroups, including migrants or those with coinfections (e.g., HIV/HBV), to validate long-term outcomes outside controlled trials. From a public health perspective, integrating pharmacoeconomic analyses could support policy recommendations for TAF preferential use in regions with high HBV prevalence and ageing populations, potentially reducing healthcare burdens from renal/bone complications. Collaborative registries across Asia could facilitate such extensions, emphasising patient-centred outcomes like quality of life.

In summary, Wong, Gane, Pan, Fung, Ma, Izumi, Shalimar, Lim, Chuang, Mehta [1] have advanced our understanding of TAF's role in East Asian CHB management, highlighting its favourable profile over extended periods. Our suggestions aim to build upon this solid foundation, fostering more nuanced applications in clinical practice.