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Background: The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass (SMM). In living-donor liver transplantation (LDLT), liver graft regeneration (GR) represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient. Limited data are available on the correlation between pre-LDLT low SMM and GR. Methods: Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft. The skeletal muscle index (SMI) at L3 level was used for muscle mass measurement, and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. GR was evaluated as rate of volume increase at 1 month post-LT [graft regeneration rate (GRR)]. Results: The median GRR at 1 month post-LT was 91% (IQR, 65-128%) and a significant correlation with graft volume-to-recipient standard liver volume ratio (GV/SLV) (rho -0.467, P＜0.001), graft-to-recipient weight ratio (GRWR) (rho -0.414, P＜0.001), donor age (rho -0.306, P=0.001), 1 month post-LT cholinesterase serum levels (rho 0.397, P=0.002) and pre-LT low muscularity [absent vs. present GRR 97.5% (73.1-130%) vs. 83.5% (45.2-110.9%), P=0.041] was noted. Moreover in male recipients, but not in women, it was shown a direct correlation with pre-LT SMI (rho 0.352, P=0.020) and inverse correlation with 1 month post-LT SMI variation (rho -0.301, P=0.049). A low GRR was identified as an independent prognostic factor for recipient overall survival (HR 6.045, P＜0.001). Conclusions: Additionally to the hemodynamic factors of portal circulation and the quality of the graft, the metabolic status of the recipients has a significant role in the GR process. A pre-LT low SMM is associated with impaired GRR and this negative impact is more evident in male recipients.