Ann Liver Transplant.  2022 May;2(1):21-27. 10.52604/alt.22.0008.

Very high serum soluble PD-1 is closely associated with hepatocellular carcinoma recurrence after liver transplantation

• Park CS
• Kim YK
• Tak E
• Lee KJ
• Hwang S

• KMID: 2560877
• DOI: http://doi.org/10.52604/alt.22.0008

Abstract

Background
Programmed death protein 1 (PD-1) pathway is one of the most critical mechanisms in tumor biology of hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic influence of very high pretransplant serum soluble PD-1 (sPD-1) in patients undergoing liver transplantation (LT) for treatment of HCC.
Methods
Twelve LT recipients showing very high sPD-1 (>318.9 ng/mL, upper 5 percentiles) were selected. Stored serum samples were used to measure sPD-1 concentrations.
Results
The mean age was 51.8±5.1 years. There were 11 males(91.7%). All patients had hepatitis B virus-associated liver cirrhosis. The mean model for end-stage liver disease score was 13.5±8.8. Six (50.0%) patients met the Milan criteria. The cumulative tumor recurrence rate was 14.7% at 1 year, 75.0% at 3 years, and 75.0% at 5 years. Overall patient survival rate was 83.3% at 1 year, 66.7% at 3 years, 50.0% at 5 years, and 33.3% at 10 years. The median value of sPD-1 concentration was 365.7 ng/mL. Receiver operating characteristic curve analysis of serum sPD-1 concentration for tumor recurrence showed that the area under the curve was 0.556 (p=0.824). The Youden index J was 0.333 at sPD-1 cutoff of 444.8 ng/mL. Application of sPD-1 cutoff of 444.8 ng/mL showed no significant difference in tumor recurrence (p=0.756) or patient survival (p=0.486). Both Milan criteria and ADV score with a cutoff of 5 log showed no prognostic difference (p≥0.377).
Conclusion
Results of the present study revealed that high pretransplant serum sPD-1 over 318.9 ng/mL appeared to be an important risk factor that could surpass the prognostic influences of the Milan criteria and ADV score. Therefore, eligibility of LT should be carefully evaluated for patients showing very high serum sPD-1.

Keyword

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

Figure

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  Figure 1 Posttransplant tumor recurrence curve.

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  Figure 2 Posttransplant overall patient survival curve.

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  Figure 3 Patient survival curve after tumor recurrence.

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  Figure 4 Distribution of pretransplant serum soluble PD-1 concentration. Bars indicate 25–75 percentiles. PD-1, programmed death protein 1.

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  Figure 5 Tumor recurrence (A) and patient survival (B) curves according to pretransplant serum soluble PD-1 concentration. PD-1, programmed death protein 1.

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  Figure 6 Tumor recurrence (A) and patient survival (B) curves according to the Milan criteria.

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  Figure 7 Receiver operating characteristic curve analysis of posttransplant hepatocellular carcinoma recurrence. AUC, area under the curve.

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  Figure 8 Tumor recurrence (A) and patient survival (B) curves according to ADV score. ADV, multiplication of α-fetoprotein, des-γ-carboxyprothrombin and tumor.

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