Perspectives on Sarcopenia as a Predictor for Outcomes in Pediatric Patients with Chronic Liver Disease

Abstract

Sarcopenia, a pathologic deficiency of muscle mass and function, has emerged as an important secondary feature of many chronic disease states. For adults with end stage liver disease, there are multiple mechanisms which contribute to sarcopenia and its presence has proven to be an important predictor of morbidity and mortality. In children, there are only a limited number of reports which investigate the role of sarcopenia in liver disease. These studies, which are discussed and summarized in this review, report small, single-center analyses with dissimilar study cohorts and varying clinical definitions. Still, children meeting the study entry criteria have sarcopenia with a reported prevalence of 24–70%. When assessed, sarcopenia appears to be associated with more severe disease but is independent of the Pediatric End-Stage Liver Disease (PELD) score and does not correlate with age, gender, or traditional anthropometric measures such as weight, height, weight-for-height, or body mass index (BMI). While individual studies may identify sarcopenia as a statistically significant risk factor for certain post-transplant outcomes such as longer ICU stay, longer duration of intubation, repeat operation, development of serious infection, longer hospital stay, death, or long-term growth failure, such associations are not consistently replicated across studies. Finally, although various methods of muscle mass quantification are utilized, the most reported is the total psoas muscle surface area (tPMSA) on computed tomography. This method, along with others such as skeletal muscle area and skeletal muscle index, have had normative values recently defined and these collective efforts should enable researchers a common basis of comparison when delineating sarcopenia, and its impact, across various study populations in future investigations – including in children with liver disease.

Optimizing the pediatric transplant candidate

“…Sarcopenia, a pathologic deficiency of muscle mass and function, has also emerged as an important secondary feature of many chronic disease states in pediatrics [19]. In adults, the assessment of muscle function, either by strength or physical performance, is used as the primary parameter to determine sarcopenia [20,21].…”

Pediatric sarcopenia: An imperfect science in evolution

“…Chen et al recently published a review of studies assessing muscle mass and frailty specific to pediatric liver disease, which nicely highlights the heterogeneity in modalities and definitions used to study sarcopenia. [7] In the current study, because normative data for TMSI do not exist, the authors had to select a cutoff value below which they categorized muscle mass as low and above which was defined as high or normal muscle mass. They chose to divide patients into 2 groups according to the median TSMI in the second quintile of subjects, an approach described in a prior study assessing muscle mass in children with congenital heart disease undergoing Fontan procedure.…”

“…), pediatric sarcopenia research has been plagued by heterogeneity both in terms of how muscle is measured (which modality and which muscle groups) as well as how it is defined between studies. [7] Data in this space must be interpreted with caution, given the risk that each individual study may be employing imperfect measurements and/or definitions of sarcopenia in childhood. The field of pediatric sarcopenia would benefit from establishing a better understanding of what a clinically significant reduction in muscle mass is for children across the age span, including those in the <1-year-old category, who are among the most vulnerable of patients.…”

“…While the cross-sectional measurement of muscle on abdominal CT, standardized to height, is generally considered to be a gold standard in adult sarcopenia research, 6 the lack of predictive cutoff values in children leads to problematic heterogeneity in pediatric sarcopenia studies. Chen et al recently published a review of studies assessing muscle mass and frailty specific to pediatric liver disease, which nicely highlights the heterogeneity in modalities and definitions used to study sarcopenia 7 …”

“…Without a reliable understanding as to what truly constitutes a clinically significant “low TMSI” in children (or “low PMSA,” “low SMM,” etc. ), pediatric sarcopenia research has been plagued by heterogeneity both in terms of how muscle is measured (which modality and which muscle groups) as well as how it is defined between studies 7 . Data in this space must be interpreted with caution, given the risk that each individual study may be employing imperfect measurements and/or definitions of sarcopenia in childhood.…”