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.