Letter: Comparison of the Efficacy of Adjuvant PD-1 Inhibitor After Curative Resection for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Related HCC Versus Other Aetiologies

We read with substantial interest the study by Uluk et al. [1], which assessed the impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) on long-term outcomes subsequent to curative surgery for hepatocellular carcinoma (HCC). Their retrospective investigation examines the novel MASLD and MetALD classifications among HCC patients who underwent curative surgery, further corroborated by body composition analysis. They discovered that patients with MASLD-related HCC exhibited shorter overall survival compared to patients with HCC of other aetiologies. Indeed, one previous study comparing patients with MASLD-related HCC to those with HCC of other aetiologies has also identified shorter overall survival in the MASLD-related HCC group [2]. However, some other findings indicate that patients suffering from HCC associated with MASLD may potentially experience extended recurrence-free and overall survival in comparison to those with HCC of alternative aetiologies [3, 4]. These discordant results emphasise the necessity for further investigations into the prognosis of MASLD-related HCC patients following curative resection.

Immunotherapy is one of the main treatments for HCC in recent years. One study found that patients with MASLD-related advanced HCC receiving immune checkpoint inhibitors have a comparable prognosis to those with other aetiologies [5], while another study has indicated that patients with non-alcoholic steatohepatitis-related HCC may not obtain optimal benefits from immunotherapy [6]. Nowadays, no studies have reported whether MASLD affects the efficacy of adjuvant immunotherapy in patients with HCC after curative resection.

A retrospective analysis was conducted on the medical data of patients who underwent adjuvant PD-1 therapy after curative resection within 10 medical centers of the GUIDANCE collaboration in China, spanning from January 16, 2019, to January 24, 2024. The patients were classified into the MASLD group and the non-MASLD group in accordance with the guideline [7]. The survival curves were estimated using the Kaplan–Meier method and compared by means of the log-rank test. A total of 409 patients were enrolled (most patients were enrolled after 2022), including 72 with MASLD-related HCC and 337 with HCC from other aetiologies. After a median follow-up period of 30.0 months (interquartile range: 21.4–44.1 months), no significant differences were found in the recurrence-free survival (hazard ratio 1.04, 95% confidence interval: 0.74–1.50; Figure 1A) and overall survival (hazard ratio 0.95, 95% confidence interval: 0.53–1.70; Figure 1B) between patients with MASLD-related HCC and those with HCC of other aetiologies.

FIGURE 1

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Kaplan–Meier curves of recurrence-free (A) and overall survival (B). CI, confidence interval; MASLD, metabolic dysfunction-associated steatotic liver disease.

At present, the official guidelines do not have a standardised adjuvant therapy regimen for HCC [8]. However, several studies have revealed that adjuvant programmed death-1 (PD-1) inhibitor therapy significantly enhances the recurrence-free survival in HCC patients at high risk of recurrence [9, 10]. Our retrospective analysis is the first to report whether MASLD affects the efficacy of adjuvant immunotherapy for patients with HCC after curative resection, which provides a basis for the exploration of the best benefit population from adjuvant immunotherapy.