Serum bilirubin level is inversely associated with nonalcoholic steatohepatitis in children

Abstract

Objectives: Oxidative stress has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and progression to the more severe form, nonalcoholic steatohepatitis (NASH), in children. We aimed to study the clinical correlation between bilirubin, a potent endogenous antioxidant with cytoprotective properties, and histopathological findings in pediatric patients with NAFLD.

Methods: We included consecutive children with biopsy-proven NAFLD and obtained demographic, clinical, and histopathological data. We performed logistic regression analysis to assess the clinical factors associated with the histological features of NASH or fibrosis.

Results: From a total of 302 biopsies, 67% (203) had evidence of NASH, whereas 64.2% had some degree of fibrosis (stage 1 in 51%, stage 2 in 6.3%, and stage 3 in 6.6%). Mean total bilirubin was significantly lower in the NASH group compared with the non-NASH group (0.65 ± 0.24 vs 0.73 ± 0.22 mg/dL, P = 0.007). Higher total bilirubin levels were negatively correlated with the presence of steatosis and the NAFLD activity score (P < 0.05), whereas a trend in that direction was observed for presence of fibrosis and inflammation (P = 0.051). On multivariable analysis, higher bilirubin levels were significantly associated with a decreased likelihood of a histological diagnosis of NASH on biopsy (odds ratio 0.29, 95% CI 0.10-0.85, P = 0.024).

Conclusions: In children with NAFLD, there is an inverse relation between serum bilirubin levels and the presence of NASH on biopsy. This may be secondary to the antioxidant effect of bilirubin.