BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seqLDLT) after LR as a strategy for HCC patients with high-risk of recurrence. MethodsWe analyzed data from 27 adult patients who underwent seqLDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS). ResultsAmong 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqLDLT. Five patients (19%) underwent LDLT following LR as a downstaging strategy while the rest received seqLDLT as a preemptive strategy. The median age was 53.5 years with 85% males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0% and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors > 5 cm (19%), and a total tumor diameter > 10 cm (7%). ConclusionsSeqLDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seqLDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.