Surgery, whether liver resection or liver transplantation, is the predominant curative-intent therapy for HCC beyond 2 cm [
16••]. Thanks to advances in patient selection, both modalities achieve 5-year patient survival rates of approximately 70–80% [
5•,
20]. For patients with limited tumor burden determined by morphometric tumor characteristics, well-maintained liver function, and lack of clinically significant portal hypertension, the AASLD favors resection over other treatment options [
16••]. Such patients should have compensated cirrhosis without evidence of portal hypertension, such as ascites, varices, splenomegaly, low platelet count (< 100 k per µL), or a hepatic venous pressure gradient over 10 mmHg, as well as a sufficient future liver remnant to minimize the risk of post-hepatectomy liver failure [
21,
22]. The main drawback of liver resection is the high 5-year recurrence rate of 50–70%, as compared to 11–18% after liver transplantation [
23‐
25]. However, the benefit of reduced recurrence rates must be viewed in the context of liver transplant wait times due to a shortage of grafts, as well as the risk of waitlist dropout due to tumor progression while awaiting LT. Indeed, depending on donor availability, on an intention-to-treat basis, overall survival may favor surgical resection due to waitlist drop-out [
26].
In the event of a recurrence following surgical resection, patients can be considered for a salvage liver transplant. Factors associated with unsalvageable recurrences include pre-operative disease beyond Milan criteria, the presence of microsatellite lesions, and microvascular invasion [
27]. While some studies have shown no differences in 5-year overall survival between salvage and primary LT for HCC, a recent meta-analysis by Guerrini et al., indicated that salvage LT has slightly poorer 5-year disease-free and overall survival rates compared to primary LT [
28].