Authors’ Reply to the Letter “Reevaluating the Role of Demographic and Etiological Factors in Immune Checkpoint Inhibitor Therapy for Advanced Hepatocellular Carcinoma”

We appreciate the comments of Chen et al. [1] regarding the complexity of treating the advanced hepatocellular carcinoma (HCC), and their questions about our methodology.In our paper, [2] we selected studies for our meta-analysis using bibliographic databases such as PubMED and Embase, along with the abstracts of two recent major conferences: the annual meeting of the American Society of Clinical Oncology (2024) and the congress of the European Society for Medical Oncology (2023).Although the online published abstracts lacked detailed information, the onsite presentations themselves provided all necessary data for our subgroup metaanalysis.Attending these meetings in person was essential to accessing that up-to-date information.We seized an opportunity to gather all required data, which is now available in our Github repository and shared with the original study. [3]We hope this clarifies our approach and supports the validity of our conclusions.Analyzing the overall treatment effect, assessing the risk of bias, and taking into account the diversity of the studies is the essence of systematic reviews and meta-analyses. [4]Our study summarizes current knowledge and provides conclusive evidence that advanced HCC can be more effectively treated using combinational immunotherapies rather than treatments with a multikinase inhibitor across all included subgroups.Individual studies may produce varying conclusions, but when combined within the given inclusion criteria, the overall average effect can be determined.The authors cite a study by Pfister et al. as an example of such a deviation, [5] but that study published in 2021 did not include recently conducted clinical trials.Some studies published more recently have been more in line with our conclusions. [6,7]s our study illustrates, treatment of advanced HCCs with combinational immunotherapy is highly effective regardless of ethiology and demographics.Chen et al. highlight the necessity to stratify patient cohorts further, specifically, patients within a non-viral HCC group.It is possible, for example, to subdivide it into subgroups based on HCCs associated with nonalcoholic steatohepatitis (NASH), non-NASH, and others.While we agree with the authors, this information generally was not available in the selected studies, so we were unable to assess the efficacy of immunotherapy in more detailed subgroups of non-viral HCC. Conflict of interest:The authors have no conflicts of interest to declare.