Editorial: Advancing HCC Surveillance in Hepatitis B With Biomarker‐Based Strategy—Authors' Reply

We thank Dr. Wong for highlighting the promise of biomarker-based strategies in hepatocellular carcinoma (HCC) surveillance among patients with chronic hepatitis B (CHB) [1]. The accompanying study by Saeoui et al. provides timely and robust economic evidence from Thailand, demonstrating that biomarker-based surveillance, particularly semiannual ASAP testing, is the most cost-effective strategy for HCC detection compared with ultrasound plus alpha-fetoprotein (AFP) [2]. We agree that biomarker-based algorithms such as GALAD, GAAD, and ASAP offer greater diagnostic sensitivity for early HCC detection and reduce the operator dependency inherent to ultrasound [3, 4]. This is particularly relevant in resource-limited settings, where shortages of trained radiologists and access to high-quality imaging constrain programmatic implementation. Importantly, ASAP comprising only four parameters (age, sex, AFP, and Protein Induced by Vitamin K Absence-II [PIVKA-II]) is simple, reproducible, and cost-efficient, aligning well with Thailand's current willingness-to-pay thresholds [2]. Unlike imaging, biomarker assays can be standardised, enabling more equitable access and potentially improving uptake among patients unable to access regular ultrasound surveillance [5]. While economic modelling strongly favours biomarker-based surveillance, further considerations remain. First, the heterogeneity of HCC risk among CHB patients highlights the potential of precision surveillance approaches that integrate validated risk scores, cirrhosis stage, sex, aetiology of liver disease, Child–Pugh class, and body mass index [6]. Transitioning from universal to precision surveillance may increase efficiency but could complicate clinical workflows and physician adoption. Second, healthcare providers' acceptance and patient adherence are crucial but underexplored. In principle, biomarker-based surveillance has several advantages—easy access, rapid turnaround, cost savings, operator independence, and potential for universal implementation—which may improve adherence [5]. However, physician acceptance has not yet been studied. Third, prospective validation remains essential. To date, no randomised trial has directly compared biomarker-based surveillance with ultrasound combined with AFP. The ongoing TRACER trial in the United States is addressing this gap, randomising 5500 participants to GALAD versus ultrasound-based surveillance, with reduction in late-stage HCC as the primary endpoint [7]. Until then, local cost-effectiveness analyses such as Saeoui et al. provide essential policy guidance. In particular, subgroup analyses from the Thai study demonstrated that ASAP remained cost-effective across age, sex, and cirrhosis strata (Table 1) [2]. Thailand and many Asian countries face the dual challenges of high CHB prevalence and limited healthcare resources [8]. Biomarker-based strategies could be incorporated into national surveillance guidelines to reduce inequities and operator dependence. Pragmatic trials comparing biomarker-based strategies with ultrasound, particularly in community and rural settings, will be essential to confirm real-world performance. Moreover, evaluations should extend to non-viral populations, such as MASLD or alcohol-related cirrhosis, which are becoming prominent drivers of HCC burden in the region [9, 10]. In Conclusion, the convergence of diagnostic performance, cost-effectiveness, and feasibility positions biomarker-based surveillance particularly ASAP as a compelling alternative to ultrasound. Local cohort validation, precision risk stratification, and real-world implementation studies will further refine these strategies. As treatment paradigms evolve, ongoing economic reassessment will be necessary. Nevertheless, the present findings provide a strong basis for policymakers in low- and middle-income countries to consider biomarker-based surveillance as an important step forward in reducing the burden of HCC. Tanat Saeoui: writing – review and editing. Chayanis Kositamongkol: writing – review and editing. Pochamana Phisalprapa: writing – review and editing, supervision. Apichat Kaewdech: conceptualization, writing – original draft, writing – review and editing, visualization, supervision. This article is linked to Saeoui et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70386 and https://doi.org/10.1111/apt.70394. The data that support the findings of this study are available from the corresponding author upon reasonable request.