Response to the Letter on “Role of ALBI Grade as a Predictive Factor for Long‐Term Mortality in Patients With Hepatocellular Carcinoma (HCC) Undergoing Transarterial Chemoembolization (TACE)”

We thank the authors for their interest in our study and for their constructive comments regarding the prognostic role of albumin–bilirubin (ALBI) grade in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) [1]. We appreciate the opportunity to further clarify the rationale of our study design and would like to discuss several related issues in detail. First, we agree that liver function after TACE may change over time. However, our study was retrospective, and serial ALBI measurements at fixed intervals or after each TACE session were not feasible because follow-up schedules and laboratory testing varied substantially among patients. This limitation is inherent to retrospective analyses based on real-world data. Importantly, the primary aim of our study was not to evaluate dynamic changes in liver function, but to assess the prognostic value of baseline ALBI grade, which reflects hepatic reserve at the time of the initial treatment decision for TACE. Although recent studies have explored post-TACE changes or ALBI trajectories, such analyses generally require prospectively predefined follow-up intervals with standardized assessment [2]. Therefore, the use of baseline ALBI grade remains clinically relevant for addressing the primary objective of our study. Second, regarding the homogeneous nature of our cohort, our study was retrospective, and the decision to perform TACE was based on individual physician judgment. In this setting, a single-center design may reduce variability in treatment indication, TACE technique, and follow-up strategy, which may enhance internal validity despite a relatively smaller sample size. The predominance of hepatitis B virus–related HCC reflects the epidemiologic characteristics of HCC in East Asia. ALBI grade is derived solely from serum albumin and bilirubin and was originally developed as an objective measure of hepatic reserve independent of disease etiology [3]. Thus, the prognostic relevance of baseline ALBI grade is unlikely to be substantially affected by etiologic distribution. Furthermore, TACE is a locoregional therapy generally indicated for patients with preserved liver function, and Child–Pugh class A remains the standard population for whom TACE is recommended [4]. In patients with Child–Pugh class B or C, prognosis is already largely driven by impaired hepatic reserve, limiting the additional prognostic value of ALBI grade. Our focus on Child–Pugh class A patients allowed us to assess whether ALBI grade could further discriminate prognosis within a population considered suitable for TACE. Third, we acknowledge that the neutrophil-to-lymphocyte ratio (NLR) has been investigated as a prognostic marker in patients undergoing TACE. NLR is generally regarded as a marker of systemic inflammation and tumor-related immune status, reflecting the tumor microenvironment rather than hepatic reserve [5]. In the TACE setting, its prognostic value has been reported with considerable variability, with substantial heterogeneity in cut-off values, timing of measurement, and clinical context across studies [6]. In contrast, our study specifically focused on liver function–based risk stratification using ALBI grade, which directly reflects hepatic reserve relevant to treatment tolerance after TACE. Accordingly, the omission of NLR, a marker reflecting a different clinical aspect, does not undermine the validity or clinical relevance of our findings. Finally, we acknowledge that treatment strategies for HCC have evolved, and recent studies have reported improved outcomes with combination approaches involving TACE, tyrosine kinase inhibitors, and immune checkpoint inhibitors [7]. However, our cohort was intentionally designed to evaluate the long-term prognostic impact of baseline hepatic reserve, with extended follow-up over a decade, which remains clinically meaningful. In addition, the adoption of such combination therapies varies across regions and health-care systems, and in some countries, including South Korea, their routine use is limited by reimbursement policies. Consequently, TACE alone continues to be widely used in routine clinical practice. Therefore, assessing the prognostic value of ALBI grade in patients treated with TACE remains relevant. In summary, our study evaluated the long-term prognostic value of baseline ALBI grade in patients with preserved liver function undergoing TACE. Despite the limitations of its retrospective design, our findings highlight the clinical relevance of hepatic reserve in long-term outcomes after TACE. We agree that future prospective, multicenter studies incorporating newer treatment strategies will be valuable. The authors declare no conflicts of interest.