Cross-Match as an Immuno-Oncological Risk Factor for Hepatocellular Carcinoma Recurrence and Inferior Survival After Living Donor Liver Transplantation: A Call for Further Investigation

Abstract

Background: The success of immunotherapy for patients with hepatocellular carcinoma (HCC) suggests that immune dysregulation occurs in HCC patients. This warrants an immuno-oncological risk assessment in the platform of liver transplantation. Methods: This retrospective single-center study analyzed risk factors for—particularly cross-matching performed through conventional complement-dependent cytotoxicity cross-match tests—and the outcomes of HCC recurrence following living donor liver transplant. Results: A total of 71 patients were included. The median follow-up period was 29.1 months; 17 (23.9%) patients had posttransplant HCC recurrence, and their 1-, 3-, and 5-year-survival rates were 70.6%, 25.7%, and 17.1%, respectively, which were inferior to those of patients without HCC recurrence (87.0%, 80.7%, and 77.2%, respectively; P < .001). In addition to microvascular invasion, positive cross-match results for B cells at 37°C (B- 37°C) or T cells at 4°C (T- 4°C) were associated with inferior overall survival in multivariable analysis after adjustment for tumor status beyond Milan criteria and elevated alpha-fetoprotein levels. Rejection alone cannot be the mechanism underlying the effects of positive cross-match results on patient outcomes. Adjusted survival curves suggested that positive cross-match B- 37°C or T- 4°C was associated with inferior recurrence-free and patient survival, but the robustness of the finding was limited by insufficient power. Conclusions: Additional large-scale studies are required to validate positive cross-match as an immuno-oncological factor associated with HCC recurrence and inferior patient survival.

Editorial: Transplant Oncology of Liver Malignancies

“…Novel risk factors and biomarkers of malignancies that specific and unique to patients in the transplant setting, such as cross-match ( 3 ) and graft size ( Kim et al ), can be evaluated under this theme. Kim et al suggested that positive graft weight change during organ solution perfusion indicates poor prognosis in live donor liver transplantation (LDLT) for HCC.…”