The rate of muscle wasting in liver transplant recipients on waiting list: post-transplant outcomes and associated serum metabolite patterns

Abstract

Background: Sarcopenia at the time of liver transplantation (LT) is an established risk factor for mortality following LT. However, most studies in this context have defined sarcopenia by one-time, static measurements. The aims of this study were (I) to determine the impact of the rate of muscle loss in waitlisted LT recipients on post-LT outcomes and (II) to identify patterns of serum metabolites associated with patients with more progressive sarcopenia.

Methods: Patients undergoing liver transplant from 2008 to 2018 who received more than one computed tomography (CT) scans within 12 months prior to liver transplant were included (n=61). The psoas muscle index (PMI) was calculated using Slice-O-Matic software and corrected for patient height (m²). Patients were classified into two groups based the rate of reduction in PMI-high wasting [HW; change in PMI (ΔPMI) ≤-1%/month] and low wasting (LW; ΔPMI >-1%/month). Pre-transplant serum metabolic profiles were collected using nuclear magnetic resonance (NMR) spectroscopy. Living kidney donor sera was used as healthy controls.

Results: Median ΔPMI was -2.0%/month in HW and -0.15%/month in LW patients (P<0.001). Post-transplant 1-year mortality was significantly higher in HW patients. There were no significant differences in metabolite concentrations between HW and LW patients. However, perturbations in taurine, sarcosine, betaine and the aromatic amino acids (AAAs), were observed in patients with liver disease as compared to healthy controls. Liver disease was also associated with a decrease in lipoprotein profiles, especially high-density lipoprotein (HDL) particles.

Conclusions: In patients undergoing LT, the rate of progression of sarcopenia is a strong prognostic indicator of post-LT death. Serum metabolite profiles were not characteristically unique to HW patients, and most closely resemble derangements associated with chronic liver disease.

Keywords: Liver transplantation (LT); metabolome; psoas muscle index (PMI); sarcopenia.

Figure 1

One-year patient and graft survival curves, comparing VHW and LW cohorts. LW, low wasting; VHW, very high wasting.

Figure 2

Volcano plot of metabolomics data comparing HW_med (red) and LW_med (blue) vs. LKD. The plot shows the metabolites which have −log₁₀P value >1.3, which is equal to an unadjusted P value of <0.05. Dashed lines connect the 14 metabolites that were significantly altered in both groups. For clarity, only the blue dots are labeled. LKD, living-related kidney donor; HW, high wasting; LW, low wasting; Tyr, tyrosine; Taur, taurine; Phe, phenylalanine; Trp, tryptophan; Citr, citrate; Bet, betaine; bHIB, b-hydroxyisobutyrate; Asp, aspartate; Sarc, sarcosine; Val, valine; HW_med, median HW; LW_med, median LW.

Figure 3

Volcano plot of lipidomics data comparing HW_med (red) and LW_med (blue) vs. LKD. The plot shows the metabolites which have −log₁₀P value >1.3, which is equal to an unadjusted P value of <0.05. Dashed lines connect the lipoprotein measurements that were altered in both the HW and LW groups. For clarity, only the HW_med (red) dots were labeled. LKD, living-related kidney donor; S.cHDLP, small cHDLP; cHDLP, calibrated high-density lipoprotein particle; VL.TRLP, very large triglyceride-rich lipoprotein; ApoA1, apolipoprotein A1; NTG, triglyceride; H3P, high-density lipoprotein 3; H4P, high-density lipoprotein 4; M.cHDLP, medium cHDLP; H1P, high-density lipoprotein 1; HW_med, median HW; HW, high wasting; LW_med, median LW; LW, low wasting.