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Research Article: Pretransplant plasma soluble PD-1 and recurrence after liver transplantation in ICI-treated hepatocellular carcinoma: an exploratory biomarker study

Date Published: 2026-10-15

Abstract:
Immune checkpoint inhibitors (ICIs) are increasingly used as bridging or downstaging therapy before liver transplantation (LT) for hepatocellular carcinoma (HCC), but biomarkers of posttransplant recurrence in this setting are lacking. We evaluated the association between pretransplant plasma soluble programmed death-1 (sPD-1) and posttransplant outcomes after pretransplant ICI therapy. We enrolled 105 HCC patients undergoing LT, including 51 receiving ICIs and 54 without prior ICI exposure. Pretransplant plasma sPD-1 and sPD-L1 were measured by ELISA. The primary endpoint was 2-year recurrence-free survival (RFS). Associations were evaluated using Kaplan–Meier analysis and Cox regression. Pretransplant sPD-1 was higher in the ICI group than in the non-ICI group (P < 0.0001). Within the ICI-treated cohort, patients who experienced recurrence had higher sPD-1 than those who did not (P = 0.0002), whereas sPD-L1 did not differ. At an internally derived exploratory cutoff of 2073 pg/mL, high sPD-1 was associated with lower 2-year RFS (7.7% vs. 76.3%; log-rank P < 0.0001; HR, 4.42; 95% CI, 1.75–11.17). As a continuous variable, each doubling of pretransplant sPD-1 was associated with an increased risk of recurrence in the unadjusted analysis (HR = 1.51, 95% CI 1.25–1.82; P < 0.001). The association remained significant after adjustment for AFP, tumor number, and maximum tumor diameter (adjusted HR = 1.51, 95% CI 1.20–1.89; P < 0.001). Elevated pretransplant sPD-1 is independently associated with increased posttransplant recurrence risk in HCC patients receiving ICIs before LT. This association remained after adjustment for AFP and pretransplant tumor burden, and appeared distinct from MVI status, ACR occurrence, and the timing of blood sampling. sPD-1 may serve as a complementary biomarker for risk stratification, but external validation is required.

Introduction:
Immune checkpoint inhibitors (ICIs) are increasingly used as bridging or downstaging therapy before liver transplantation (LT) for hepatocellular carcinoma (HCC), but biomarkers of posttransplant recurrence in this setting are lacking. We evaluated the association between pretransplant plasma soluble programmed death-1 (sPD-1) and posttransplant outcomes after pretransplant ICI therapy.

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