Ann Liver Transplant.  2021 May;1(1):29-47. 10.52604/alt.21.0005.

Selection criteria of living donor liver transplantation for hepatocellular carcinoma developed in Korean transplant centers

• Jung DH
• Hwang S
• Song GW

• KMID: 2560851
• DOI: http://doi.org/10.52604/alt.21.0005

Abstract

With accumulated experience on living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC), several major Korean transplant centers presented institutional or multicenter selection criteria of LDLT for HCC based on their own experience. This study intended to review the selection criteria of LDLT for HCC developed in the major Korean LT centers. Extended criteria for primary liver transplantation (LT) were developed in Asan Medical Center (AMC) in 2008, the Catholic University of Korea in 2012, Samsung Medical Center in 2014, National Cancer Center Korea in 2016, the model to predict tumor recurrence after LDLT (MoRAL) in three centers in 2016, A-P 200 criteria in Pusan National University in 2016, patient selection by tumor markers in LT for advanced HCC in eight centers, composite criteria using clinical and PET factors in two centers in 2019, tumor size and number, AFP, PIVKA-II, PET (SNAPP) score in AMC in 2021, and quantitative prognostic prediction using AFP-PIVKA-II-tumor volume (ADV) score in AMC in 2021. The criteria for salvage LT were developed from a multicenter study involving three centers in 2014 and from AMC in 2020. Posttransplant prognostic prediction models for early or non-viable HCC were developed in AMC for super-selection criteria in 2011 and pretransplant treatment-induced complete tumor necrosis in 2017. The importance of tumor biology in HCC treatment has been emphasized more than before. The expression of serum tumor markers is a surrogate biomarker reflecting the tumor biology. Pretransplant radiological assessment of HCC combined with tumor marker expression or PET finding will provide reliable information that will assist the decision to perform LDLT in patients with HCC of various stages.

Keyword

Hepatocellular carcinoma; Tumor marker; Tumor biology; Prognosis; Prediction

Figure

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  Figure 1 Hepatocellular carcinoma recurrence and patient survival curves for 206 surviving patients after application of the Asan Medical Center criteria based on explant pathology. (A) Hepatocellular carcinoma recurrence curves showed 1‐year, 3‐year, and 5‐year recurrence rates of 5.8%, 13%, and 15%, respectively, within the criteria and 43.3%, 73.6%, and 73.6%, respectively, beyond the criteria (p<0.001). (B) The overall patient survival curves showed 1-year, 3‐year, and 5‐year survival rates of 94.3%, 87.5%, and 81.6%, respectively, within the criteria and 71.9%, 37.2%, and 20.7%, respectively, beyond the criteria (p<0.001) [10].

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  Figure 2 Disease-free and overall survival comparison based on the Milan criteria and Catholic Medical Center (CMC) criteria. (A) Disease-free survival. (B) Overall patient survival [11].

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  Figure 3 Disease-free survival curves according to the Samsung Medical Center (SMC) criteria based on (A) radiological and (B) pathological findings [12].

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  Figure 4 Overall and disease-free survival rates according to the National Cancer Center Korea (NCCK) criteria with preoperative imaging findings (A) and explant pathology (B) [13].

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  Figure 5 The cumulative risk of tumor recurrence according to the Milan criteria (MC) and the model to predict tumor recurrence after living donor liver transplantation (MoRAL) score using a cut off of 314.8. The risk of recurrence decreased in the following order: beyond MC/high MoRAL score >within MC/high MoRAL score >beyond MC/low MoRAL >within MC/low MoRAL score (p<0.001). The patients within MC with high MoRAL score experienced higher recurrence than the patients beyond MC with low MoRAL score (hazard ratio=2.56, p=0.035) [15].

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  Figure 6 Overall survival and disease-free survival according to the A-P 200 criteria. (A) The 3-year overall survival rates for patients who were within and patients who exceeded the A-P 200 criteria were 89.2% and 90.3%, respectively (p=0.92). (B) The 3-year disease-free survival rates for the patients who were within and patients who exceeded the A-P 200 criteria were 90.0% and 43.6%, respectively (p<0.001) [16].

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  Figure 7 Recurrence‐free survival after liver transplantation (LT) in subgroups with far advanced hepatocellular carcinoma. (A) Comparison of tumor markers in only patients with tumor size ≥10 cm. (B) Comparison of tumor markers in only patients with 10 or more tumors. (C) Comparison of tumor markers in only patients with macrovascular invasion. (D) Comparison of macrovascular invasion for all patients with far advanced hepatocellular carcinoma. There were significant differences between the low‐risk (AFP+PIVKA‐II ≤300) and high‐risk (AFP+PIVKA‐II>300) patients in all subgroups. The presence of macrovascular invasion was not as effective as the sum of AFP+PIVKA‐II to predict tumor recurrence in the far advanced group [17].

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  Figure 8 Kaplan-Meier survival curves according to each patient selection criteria. In comparison with other criteria (A–E), the composite criteria exhibited the highest predictive value for recurrence-free survival (RFS) (F) [18].

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  Figure 9 Kaplan‐Meier probability of hepatocellular carcinoma (HCC) recurrence within 5 years for living donor liver transplant recipients in the development and validation groups [19].

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  Figure 10 Tumor recurrence and patient survival according to the pretransplant ADV scores in the treatment-naïve (TN) and pretransplant-treated (PT) groups. (A) Tumor recurrence (left) and overall patient survival (right) curves according to the pretransplant ADV scores in the TN group. (B) Tumor recurrence (left) and overall patient survival (right) curves according to the explant ADV scores in the TN group [20].

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  Figure 11 Tumor recurrence and patient survival curves according to the pretransplant ADV score with a cutoff of 5log. (A) Tumor recurrence. (B) Overall patient survival [20].

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  Figure 12 Prognostic prediction diagrams according to the ADV scores. Diagrams showing the probability of tumor recurrence (A) and overall patient survival (B) at posttransplant 5 years according to the prediction model using pretransplant ADV scores [20].

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  Figure 13 Survival analyses of patients after salvage liver transplantation according to the number of risk factors (tumor recurrence within 8 months after liver resection, serum AFP levels >200 ng/mL at transplantation, beyond the Milan criteria at transplantation). (A) Recurrence‐free survival was significantly decreased with an increasing number of risk factors (p<0.001) except between the subgroups with 1 and 2 risk factors (not significant). (B) The overall survival did not differ between subgroups with 1, 2 or 3 risk factors; however, the survival for all these subgroups was significantly decreased in comparison to the survival of the subgroup with no risk factors (p<0.001) [22].

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  Figure 14 Posttransplant disease-free survival (DFS) curves according to (A) the duration of disease-free survival period after hepatectomy and (B) the interval between hepatectomy and living donor liver transplantation [23].

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  Figure 15 Disease-free survival (DFS) and overall survival (OS) in 125 patients who underwent salvage living donor liver transplantation. The patients were also stratified by 1log intervals of pretransplant ADV scores (A, B) and by pretransplant ADV score cutoffs of 4.0 log and 6.0 log (C, D) [23].

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  Figure 16 Disease-free survival (DFS) in (A, B) 86 patients within the Milan criteria (C, D) and in 39 patients beyond the Milan criteria stratified according to 1log intervals of explant ADV scores (A, C) and by two explant ADV score cutoffs of 4.0 log and 6.0 log (B, D) [23].

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  Figure 17 Cumulative tumor recurrence rates in patients with incidentally diagnosed hepatocellular carcinoma (iHCC) and untreated small pretransplant known hepatocellular carcinoma (pkHCC) ≤2.0 cm in size (p=0.27) [24].

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  Figure 18 Comparison of tumor recurrence and patient survival curves after hepatic resection (HR) and liver transplantation (LT). (A) Comparison of the tumor recurrence curves showed p<0.001 between the HR groups and p=0.019 between the LT groups. (B) Comparison of the patient survival curves showed p<0.001 between the HR groups and p=0.11 between the LT groups [25].

Reference

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