Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria : A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy

Simple Summary This research delves into better treatment options for patients with liver cancer (HCC) who fall outside the eligibility criteria of traditional Milan guidelines for liver transplants. By reviewing patient data from Jena University spanning from 2007 to 2023, the study explores whether new patient classification systems and the use of living donor liver transplantation (LDLT) could extend life-saving options to those previously considered unsuitable. Findings indicate that patients not meeting the Milan criteria still benefit significantly from transplantation, showcasing similar survival rates between those undergoing standard transplants and LDLT. Key factors such as tumour grade and vascular invasion emerged as predictors for cancer recurrence, highlighting the importance of pre-transplant treatments in enhancing survival outcomes. The study underscores LDLT as a feasible alternative, particularly for patients undergoing successful bridging therapies, thereby broadening the scope of liver transplantation for liver cancer and offering new therapeutic approaches for advanced liver tumours. Abstract Purpose: This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). Methods: The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. The Results: Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). Conclusions: Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.