Ann Surg Treat Res.  2022 Jan;102(1):46-54. 10.4174/astr.2022.102.1.46.

Prognostic impact of serum soluble PD-1 and ADV score for living donor liver transplantation in patients with previously untreated hepatocellular carcinoma

• Hwang S
• Lee KJ
• Moon DB
• Song GW
• Jung DH
• Kim YK
• Yang H
• An DE
• Lee S
• Lee SG

• KMID: 2523769
• DOI: http://doi.org/10.4174/astr.2022.102.1.46

Abstract

Purpose
The programmed death protein 1 (PD-1) pathway is the critical mechanism in development of hepatocellular carcinoma (HCC). The present study analyzed the prognostic impact of pretransplant serum soluble PD-1 (sPD-1) concentration and α-FP–des-γ- –tumor volume (ADV) score in patients with previously untreated HCC undergone liver transplantation (LT).
Methods
This retrospective single-center study enrolled 100 patients with HCC who underwent living donor LT from 2010 to 2016. Concentrations of sPD-1 were measured in stored serum samples.
Results
Receiver operating characteristic curve analysis of 2-year tumor recurrence resulted in an sPD-1 cutoff of 177.1 µg/mL, which was associated with higher rates of tumor recurrence (P = 0.022), but not with overall patient survival (P = 0.460). The derived cutoff for pretransplant ADV score was 5.4log, which was associated with higher tumor recurrence rate (P < 0.001) and lower overall patient survival rate (P < 0.001). Both sPD-1 of >177.1 µg/mL (hazard ratio [HR], 2.26; P = 0.020) and pretransplant ADV score of >5.4log (HR, 3.56; P < 0.001) were independent risk factors for posttransplant HCC recurrence. The combination of these 2 factors enabled the stratification of patients into 3 groups, with groups having 0, 1, and 2 risk factors differing significantly in the prognosis of tumor recurrence (P < 0.001) and overall patient survival (P = 0.006).
Conclusion
Both sPD-1 concentration and ADV score have prognostic impacts in patients who underwent LT for untreated HCCs. These factors, both individually and combined, can help in predicting posttransplant prognosis.

Keyword

Hepatocellular carcinoma; Immune checkpoint; Prognosis; Recurrence; Tumor biology

Figure

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  Fig. 1 Expression of pretransplant serum soluble programmed death protein 1 (sPD-1) relative to tumor recurrence status at 2 years. The long horizontal bar indicates the median sPD-1 concentration.

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  Fig. 2 Receiver operating characteristic curve analysis of the effects of soluble programmed death protein 1 (sPD-1) concentration and α-FP–des-γ-carboxyprothrombin–tumor volume (ADV) score on hepatocellular carcinoma recurrence at 2 years.

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  Fig. 3 Kaplan-Meier analysis of (A) tumor recurrence and (B) and overall patient survival rates in patients with pretransplant serum soluble programmed death protein 1 (sPD-1) concentrations of ≤177.1 µg/mL and >177.1 µg/mL.

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  Fig. 4 Kaplan-Meier analysis of (A) tumor recurrence and (B) overall patient survival rates in patients with pretransplant α-FP–des-γ-carboxyprothrombin–tumor volume (ADV) scores of ≤5.4log and >5.4log.

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  Fig. 5 Kaplan-Meier analysis of (A) tumor recurrence and (B) overall patient survival rates in patients with explant α-FP–des-γ-carboxyprothrombin–tumor volume (ADV) scores of ≤5.9log and >5.9log.

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  Fig. 6 Kaplan-Meier analysis of (A) tumor recurrence and (B) overall patient survival rates in patients with 0, 1, and 2 risk factors for hepatocellular carcinoma recurrence based on a pretransplant serum soluble programmed death protein 1 (sPD-1) concentration cutoff of 177.1 µg/mL and a pretransplant α-FP–des-γ-carboxyprothrombin–tumor volume (ADV) score cutoff of 5.4log.

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