Expression Patterns of Tumor Markers in Liver Transplant Recipients Showing Complete Pathological Response of Hepatocellular Carcinoma

Abstract

Complete pathological response (CPR) is achieved with various pretransplant locoregional treatments for hepatocellular carcinoma (HCC). This study aimed to investigate pretransplant expression of HCC tumor markers in liver transplantation (LT) recipients showing CPR. For the CPR group, 166 patients were selected from a single-institution LT database. Two control groups of 332 patients without HCC and 184 patients with partial pathological response (PPR) were also selected. The model for end-stage liver disease score in the CPR group was 11.5 ± 7.7. The number of transcatheter arterial chemoembolization sessions before LT was one in 68 patients (14.0%), two in 38 patients (22.9%), and three or more in 60 patients (36.1%). A solitary non-viable tumor was identified in 120 (86.4%) of the explant livers and the largest tumor size was 2.4 ± 1.3 cm. Living-donor and deceased-donor LTs were performed in 152 (91.6%) and 14 (8.4%) patients, respectively. The median levels of α-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) measured within two weeks before LT were 4.2 ng/mL and 20 mAU/mL, respectively. These tumor marker levels were comparable to those in the no-HCC control group, but much lower than those in the PPR group (p < 0.001). Receiver operating characteristic curve analysis of AFP and PIVKA-II showed no definite cutoff values for CPR in the cohort of CPR and no-HCC patients, but significant cutoffs of 6.5 ng/mL for AFP and 29 mAU/mL for PIVKA-II were obtained in the cohort of CPR and PPR patients. The 1-, 3- and 5-year HCC recurrence and overall patient survival rates of the CPR group were 5.1% and 93.3%, 7.6% and 89.6%, and 7.6% and 89.6%, respectively. These tumor recurrence rates were much lower than those in the PPR group (p < 0.001). In conclusion, the present study results suggest that normalizing AFP and PIVKA-II after locoregional treatment is indicative of CPR. However, some CPR patients showed high expression of tumor markers; thus, pretransplant values of HCC tumor markers should be interpreted with caution.

Research progress of protein induced by vitamin K absence or antagonist II in liver transplantation for hepatocellular carcinoma

“…Due to the loss of live HCC cells led by CPR, it is considered a reliable indicator of a favorable prognosis after LT [ 34 ]. Follow-up data from Kim MJ et al [ 33 ] also confirmed significantly lower HCC recurrence rates at 1, 3, and 5 years in CPR patients compared to pre-LT partial pathological response (PPR) patients (5.1%, 7.6%, and 7.6% vs. 15.3%, 20.9%, and 25.4%, p < 0.001). Importantly, preoperative PIVKA-II levels were significantly lower than those of patients in the PPR group (mean ± SD: 46.7 ± 126.2 vs. 77.4 ± 164.4, p < 0.001), and receiver operating characteristic curve analysis showed that the critical value of PIVKA-II between the two groups was 29 mAu/mL.…”

“…Complete pathological response (CPR) is an essential concept after LRT: ≥99% of the total HCC volume is extensively necrotic, with no live tumor cells in any node [ 33 ]. Due to the loss of live HCC cells led by CPR, it is considered a reliable indicator of a favorable prognosis after LT [ 34 ].…”

“…Importantly, preoperative PIVKA-II levels were significantly lower than those of patients in the PPR group (mean ± SD: 46.7 ± 126.2 vs. 77.4 ± 164.4, p < 0.001), and receiver operating characteristic curve analysis showed that the critical value of PIVKA-II between the two groups was 29 mAu/mL. Furthermore, the return to normalization of PIVKA-II and AFP after LRT was a marker for CPR [ 33 ].…”