Myosteatosis and muscle loss impact liver transplant outcomes in male patients with hepatocellular carcinoma

Abstract

Background: Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated.

Methods: Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS).

Results: The study comprised 673 males and 83 females. The median follow-up time was 31 months (interquartile range, 19-43 months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5 year OS (P < 0.001) and a 15.0% decrease in 5 year RFS (P = 0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317-1.869; P < 0.001] and RFS (HR, 1.369; 95% CI, 1.182-1.586; P < 0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358-3.849; P = 0.002) and RFS (HR, 2.219; 95% CI, 1.418-3.471; P < 0.001) in non-sarcopenic recipients (N = 209).

Conclusions: Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.

Keywords: Deceased donor liver transplantation; Liver cancer; Muscle mass; Muscle radiodensity.

Figure 1

Flowchart of patient selection procedures. CT, computed tomography; DDLT, deceased donor liver transplantation; HCC, hepatocellular carcinoma; LT, liver transplantation.

Figure 2

Survival curves for recipients with poor muscle status. (A,B) OS and RFS curves in recipients with or without sarcopenia using log‐rank tests. (C,D) OS and RFS curves in recipients with or without myosteatosis using log‐rank tests. CT, computed tomography; OS, overall survival; RFS, recurrence‐free survival.

Figure 3

Survival curves for recipients with myosteatosis in the sarcopenic and non‐sarcopenic populations. (A,B) OS and RFS curves in the sarcopenic group with or without myosteatosis using log‐rank tests. (C,D) OS and RFS curves in the non‐sarcopenic group with or without myosteatosis using log‐rank tests. OS, overall survival; RFS, recurrence‐free survival.

Figure 4

The variation of SMI and survival analyses of muscle loss. (A) The variation of SMI between the pre‐ and post‐LT evaluation using paired samples t‐test (P < 0.001). (B) The correlation between preoperative SMI and muscle loss using Pearson correlation analysis (r = 0.45, P < 0.001). (C,D) OS and RFS curves of non‐sarcopenic patients with muscle loss >14.2% or ≤14.2% using log‐rank tests. LT, liver transplantation; OS, overall survival; RFS, recurrence‐free survival; SMI, skeletal muscle index.

Figure 5

Peri‐transplant muscle assessment: mass, radiodensity, and loss. (A) Peri‐transplant muscle assessments included three aspects: muscle mass, muscle radiodensity and muscle loss. Four populations with diverse patient outcomes were identified based on the above assessment strategy. (B,C) OS and RFS curves for the four populations with different muscle status using log‐rank tests. CT, computed tomography; OS, overall survival; RFS, recurrence‐free survival; SMRA, skeletal muscle radiodensity.