Growth hormone resistance in children with chronic cholestatic liver disease and reduced skeletal muscle mass.

Objectives: To investigate potential mechanisms of muscle wasting in children with chronic cholestatic liver disease (CCLD).

Methods: This is a cross-sectional study comparing estimated skeletal muscle mass (eSMM) z-score, assessed by whole body dual energy X-ray absorptiometry (DXA), in children with CCLD versus healthy controls. Relationships between eSMM z-score and serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), myostatin, and ammonia were analyzed by Spearman correlation and multiple linear regression. Myopenia was defined as eSMM z-score ≤ -2.

Results: DXA was obtained in 15 children with CCLD (eight biliary atresia, four Alagille syndrome, one alpha-1-antitrypsin deficiency, one bile salt export protein deficiency, one idiopathic cirrhosis; mean age 12.1 ± 3.9 years) and 19 controls (mean age 11.5 ± 3.9 years). Although growth and muscle mass (eSMM z-score) were similar between CCLD and controls, children with CCLD had significantly higher GH levels (2.7 ± 4.0 ng/mL vs. 0.5 ± 0.6 ng/mL, p = 0.04) and lower IGF-1 z-score (-0.9 ± 0.8 vs. 0.0 ± 0.5, p < 0.01), indicating GH resistance in CCLD. Children with CCLD and myopenia had significantly higher GH levels than those without myopenia (median 7.9 [0.5-13.0] ng/mL vs. 0.3 [0.0-4.6] ng/mL, p = 0.04), with a trend toward a moderate inverse correlation between GH and eSMM z-score in CCLD (rho = -0.48, p = 0.07).

Conclusions: GH resistance is prevalent in CCLD, even in older children with relatively mild liver disease severity and preserved growth. The relationship between eSMM z-score and GH indicates a potential role for GH resistance in the development of myopenia in CCLD.