Sarcopenia Is Associated with Osteopenia and Impaired Quality of Life in Children with Genetic Intrahepatic Cholestatic Liver Disease

Authors

Julia M Boster
Nathan P Goodrich
Cathie Spino
Kathleen M Loomes
Estella M Alonso
Binita M Kamath
Ronald J Sokol
Saul Karpen
Alexander Miethke
Benjamin L Shneider
Jean P Molleston
Rohit Kohli
Simon P Horslen
Philip Rosenthal
Pamela L Valentino
Jeffrey H Teckman
Thomas N Hangartner
Shikha S Sundaram

Publication Date

11-1-2023

Journal

Hepatology Communications

DOI

10.1097/HC9.0000000000000293

PMID

37902507

PMCID

PMC10617863

PubMedCentral® Posted Date

10-31-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Child, Quality of Life, Sarcopenia, Cholestasis, Bone Diseases, Metabolic, Cholestasis, Intrahepatic

Abstract

BACKGROUND: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

METHODS: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Relationships between eSMM, liver disease, and transplant-free survival were assessed.

RESULTS: eSMM was calculated in 127 participants (5-18 y): 12 BASD, 41 a1ATd, 33 CIC, and 41 ALGS. eSMM z-score was lower in CIC (-1.6 ± 1.3) and ALGS (-2.1 ± 1.0) than BASD (-0.1 ± 1.1) and a1ATd (-0.5 ± 0.8, p < 0.001). Sarcopenia (defined as eSMM z-score ≤- 2) was present in 33.3% of CIC and 41.5% of ALGS participants. eSMM correlated with bone mineral density in the 4 disease groups (r=0.52-0.55, p < 0.001-0.07), but not serum bile acids, bilirubin, aspartate aminotransferase/platelet ratio index, or clinically evident portal hypertension. Of the 2 patients who died (1 with sarcopenia) and 18 who underwent liver transplant (LT, 4 with sarcopenia), eSMM z-score did not predict transplant-free survival. eSMM z-score correlated with the Physical Pediatric Quality of Life Inventory score (r=0.38-0.53, p = 0.007-0.04) in CIC and a1ATd.

CONCLUSION: Severe sarcopenia occurs in some children with ALGS and CIC. The lack of correlation between eSMM and biochemical cholestasis suggests mechanisms beyond cholestasis contribute to sarcopenia. While sarcopenia did not predict transplant-free survival, LT and death were infrequent events. Future studies may define mechanisms of sarcopenia in genetic intrahepatic cholestasis.