Editorial: Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Prior to Liver Transplantation—Current Evidence and Future Directions. Authors' reply

We appreciate the authors for their thoughtful editorial and for highlighting key aspects of our study [1, 2]. As acknowledged, our cohort remains relatively small, which limits statistical power and precludes definitive conclusions, particularly for subgroup analyses. Accordingly, our findings should be interpreted as hypothesis-generating rather than practice-changing. We fully agree that factors beyond immune checkpoint inhibitor (ICI) exposure itself merit further investigation, including immunosuppression strategies such as antithymocyte globulin and centre-specific post-transplant immunosuppression protocols [3-7]. These aspects underscore the need for prospective, multicentre studies to better define optimal immunosuppression strategies in this setting. In addition, as illustrated in Figure 1, our exploratory analysis highlights the complex interplay between oncological treatment duration, rejection and hepatocellular carcinoma (HCC) recurrence. While the small sample size limits our conclusions, certain patterns are noteworthy. Patients receiving very short treatment durations (< 30 days) appeared to experience higher recurrence rates compared with those exposed to longer treatment courses. In our cohort, only five patients developed post-transplant HCC recurrence. Of these, two had received less than 30 days of ICI exposure and showed no pathological response on explant; two had received more than 180 days of treatment (one with no pathological response and one with partial response); and one patient received 84 days of treatment with a partial pathological response. Notably, none of the patients showed a complete response and all received two or more locoregional therapies, suggesting that recurrence in this subgroup may reflect more aggressive underlying tumour biology rather than treatment duration alone. Nevertheless, given the very small number of events, these observations should be interpreted with caution. Conversely, prolonged ICI exposure (> 180 days) appeared to be more frequently associated with rejection episodes, underscoring the trade-off between oncologic benefit and immunological risk. Among the nine patients who developed rejection, eight had received more than 180 days of treatment, while the remaining patient had received 63 days of therapy. These findings were also accompanied by shorter washout periods, as detailed in the main results of the study. Thus, these observations support the concept that intensified oncologic strategies may increase immunological vulnerability, underscoring the need for a careful balance between effective cancer control and graft protection. Taken together, these findings emphasise that transplant oncology in the ICI era requires individualised decision-making rather than a uniform approach. Future prospective studies integrating immunological, oncological and treatment-related variables will be essential to define optimal patient selection criteria and personalised immunosuppression pathways that maximise oncologic benefit while minimising rejection risk. L. Aceituno: conceptualization, writing – original draft, visualization, writing – review and editing. A. Vogel: supervision, writing – review and editing, visualization. G. Sapisochin: supervision, visualization, writing – review and editing. The authors have nothing to report. This article is linked to Aceituno et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70528 and https://doi.org/10.1111/apt.70551. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.