Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease

Abstract

Objective: To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD).

Study design: Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis.

Results: Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03).

Conclusion: Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity.

Figure 1

A CONSORT diagram of subject enrollment into the study.

Figure 2

A, NAFLD inflammation grade was similar between subjects with and without OSA/hypoxemia. B, Subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis than those without OSA/hypoxemia.

Figure 3

Correlations between key polysomnographic paraemteres and AST, ALT, and liver histology in subjects with NAFLD. A, Lower oxygen saturation nadir correlated with higher AST. B, Lower oxygen saturation nadir trended to correlate with higher ALT. C, Greater time with SaO₂ <90% correlated with higher AST. D, Greater time with SaO₂ <90% correlated with higher ALT. E, Lower oxygen saturation nadir correlated with higher fibrosis stage. F, Greater time with SaO₂ <90% correlated with higher inflammation grade. G, Greater time with SaO₂ <90% correlated with higher degree of steatosis. H, Greater time with SaO₂ <90% correlated with a more severe NAFLD Activity Score. Regression lines were calculated by arcsine-root transformation.