Non-Transplantable Recurrence After Initial Liver Resection of Hepatocellular Carcinoma: A Narrative Review

Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying liver disease, yet its application is limited by organ scarcity, waitlist dropout, and eligibility criteria. Hence, LR remains widely used due to greater accessibility but is associated with high recurrence rates. Salvage LT is a treatment option for patients with HCC recurrence post-LR, but up to 40% of patients develop non-transplantable recurrence (NTR), defined as recurrence beyond transplant criteria, which precludes LT and is associated in poor outcomes. Methods: The present review aims to summarize the current state of evidence on the comparison of LT and LR, the management of recurrent HCC, and the risk factors associated with NTR. Results: Clinical and histopathologic factors consistently associated with NTR across studies include larger tumor size, multiple tumors, elevated alpha-fetoprotein levels, underlying liver fibrosis or cirrhosis, microvascular invasion, and satellite nodules-features that reflect aggressive tumor biology and impaired hepatic reserve. Conclusions: Improved preoperative risk stratification and identification of patients at high risk for NTR is essential to inform optimal treatment selection.