Introduction: Myopenia, or low skeletal muscle mass (SMM) is a common clinical condition occurring in children awaiting liver transplantation (Tx). Myopenia is associated with poor outcomes post-LTx. Beyond SMM, muscle fibre size and type may also be affected. In humans, skeletal muscle consist of muscle fibres characterized by slow (Type I)  or fast twitch (Type IIa, IIx) myosin heavy isoforms (MyHC). Muscle fibres are sensitive to atrophy from a variety of physiologic and pathologically induced states. For example, Type II vs. Type I fibres are more vulnerable to atrophy in response to chronic disease and aging. No information is currently available regarding skeletal muscle morphology (muscle fibre type/size) associations with myopenia in children with end-stage liver disease (ESLD) undergoing Tx. The aim of this study was to describe skeletal muscle morphology of children undergoing liver Tx.

Methods: Children were recruited from the Stollery Children’s Hospital Pediatric Liver Tx Clinics. SMM (cm2) was quantified using slices obtained at the L3-vertebrae from abdominal imaging (MR/CT). SMM index (SMMi; cm2)/height (m)2) were determined using Slice-O-Matic® software and values were compared to age-sex matched healthy controls. Myopenia was defined as SMMi z-scores <-2. Rectus abdominus (<1 cm3) biopsies were collected at the LTx incision site. Muscle fibre tissues were demarcated using laminin and dystrophin immunofluorescence stains for quantification of muscle fibre area and fibre types. Fibre types were classified based on proportions of MyHC. 

Results: N=28 children (0.8 – 16.2 years; 13M/15F) have been recruited. N=20 children have been transplanted, with N=17 viable biopsy samples retrieved and analyzed. The most common reason for Tx was biliary atresia (n=10; 36%), Alagille’s syndrome (n=3; 11%), progressive familial intrahepatic cholestasis (n=3; 11%), other (n=12; 43%). Myopenia was present in 35% of children (n=9/25 MRI/CT scans analyzed). Percentage of MyHC fibers type I, I/IIA, IIA, IIA/X, IIX were 63.0 ± 15.6%, 1.4 ± 1.3%, 29.6 ± 14.4%, 5.9 ± 11.1%, 0.03 ± 0.07%, respectively. Children with myopenia were older (9.5 vs. 1.4 yrs; p=0.001) and had lower a percentage of Type I fibres (52% vs. 72%; p=0.005) but no significant differences in other fibre type proportions or size were observed.

Conclusions: Preliminary data shows that children with myopenia were older and had lower proportions of type I muscle fibers.