Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review of the Literature
Ioannis A. Ziogas1,2, Christos D. Kakos2, Charikleia D. Demiri2,3, Stepan M. Esagian2, Konstantinos P. Economopoulos2,4, Dimitrios Moris4, Sophoclis P. Alexopoulos1.
1Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN, United States; 2Surgery Working Group, Society of Junior Doctors, Athens, Greece; 32nd Department of Pediatric Surgery, “Papageorgiou” General Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece; 4Department of Surgery, Duke University Medical Center, Durham, NC, United States
Introduction: Pediatric hepatocellular carcinoma (HCC) is an aggressive chemo-resistant tumor which usually presents at an advanced stage. Liver resection with negative margins is often not possible, so liver transplantation (LT) has been employed as a therapeutic option for children with unresectable HCC. We aimed to systematically review the clinical characteristics and outcomes of children undergoing LT for HCC.
Methods: We performed a systematic review of the MEDLINE, Scopus, Cochrane Library, and Web of Science databases according to the PRISMA statement. Our outcomes were overall survival (OS) and disease-free survival (DFS). We evaluated the effect of gender, chemotherapy, histology, Milan criteria, and graft type on outcomes using the Kaplan Meier method and log-rank test.
Results: A total of 67 studies reporting on 245 children undergoing LT for HCC were included
Most patients underwent deceased donor LT (59.1%), and the most common underlying liver disease was tyrosinemia (34.1%). The majority of patients (57.9%) had HCC beyond the Milan criteria and recurrence of cancer was reported in 16.2%. DFS data were available for 150 patients and the 1-, 3-, and 5-year DFS rates were 92.3%, 89.1%, and 84.5%, respectively. Sixty of the 238 patients (25.2%) died over a mean follow up of 46.8 ± 47.4 months. OS data were available for 222 patients and the 1-, 3-, and 5-year OS rates were 87.9%, 78.8%, and 74.3%, respectively. No statistically significant differences were observed in OS when patients were stratified by gender (P = 0.40), receipt of neoadjuvant (P = 0.76) or adjuvant chemotherapy (P = 0.33), histology type (non-fibrolamellar vs. fibrolamellar) (P = 0.16), and within Milan vs. beyond Milan criteria (P = 0.15). However, inferior OS was observed in children who received deceased donor whole graft compared with children who received living donor graft (P = 0.01), while no difference was observed between children who received deceased donor whole vs. partial/split graft (P = 0.40).
Conclusion: LT can yield favorable long-term outcomes for children with HCC even beyond the Milan criteria. A living graft may yield superior survival outcomes and may thus be the preferred option when available.