Post-Transplant HCC Recurrence and Survival: Impact of Bridging Therapy and Tumor Biology in 185 Consecutive Liver...

Background: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT), representing a curative treatment option for selected patients. A remaining clinical challenge is the recurrence of HCC after transplantation, impacting long-term graft and patient survival. The impact of different bridging therapies (BTs) such as transarterial chemoembolization (TACE), local ablation or liver resection on recurrence rates remains unclear. We assessed post-transplant HCC recurrence and survival focusing on the role of pre-transplant bridging therapies. Methods: Adult recipients undergoing LT for HCC at Hannover Medical School from January 2007 to September 2022 were retrospectively analyzed (n = 185). Recurrence was defined as confirmed intra or extrahepatic HCC after LT. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier estimation and log-rank testing; multivariable Cox proportional hazards regression was used to identify independent factors influencing OS. Results: Pre-transplant BT was administered in 85.4% of patients, consisting of only TACE, (n = 20; 10.8%), local ablation, (n = 32; 17.3%), liver resection (n = 27; 14.6%) or a multimodal approach (n = 50; 27%). Post-transplant HCC recurrence rate was 9.2% with a median time to recurrence of 845 days (range 126-3978 days). Patients with post-transplant HCC recurrence had a significantly higher prevalence of viral hepatitis (70.6% vs. 57.1%; p = 0.01), higher pre-transplant AFP peak levels (37.5 vs. 10 ng/mL; p = 0.03), larger tumor sizes (median 3.95 cm vs. 2.6 cm; p = 0.03) and more poorly differentiated tumors (G3; 25.0% vs. 5.3%, p = 0.04). Kaplan-Meier analysis showed significant overall differences in OS and RFS among bridging therapy groups (p = 0.03). In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE (p = 0.035). Last measured pre-transplant AFP < 15 ng/mL was a significant predictor of both improved OS (p = 0.006) and RFS (p = 0.008), whereas peak AFP did not reach significance after correction. Multivariable Cox regression revealed HCC recurrence, high recipient BMI and low LabMELD as independently associated with reduced OS after LT. Median OS after HCC recurrence was 13 months. Conclusions: Our monocentric retrospective data indicate that post-transplant HCC recurrence is uncommon but remains a challenge regarding life expectancy and is influenced by pre-transplant bridging therapy. In the subgroup of early HCC < 3 cm, local ablation was associated with significantly improved OS compared to TACE. Last measured pre-transplant AFP < 15 ng/mL was associated with both improved OS and RFS, suggesting that treatment response may also represent a prognostically relevant factor. Further prospective validation of contemporary locoregional and systemic bridging approaches, especially in the context of tumor biology and treatment response, is warranted.