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Serum Bilirubin Level Is Inversely Associated With Nonalcoholic Steatohepatitis in Children

Puri, Kanika*; Nobili, Valerio§; Melville, Katherine; Corte, Claudia D.§; Sartorelli, Maria R.§; Lopez, Rocio; Feldstein, Ariel E.||; Alkhouri, Naim

Journal of Pediatric Gastroenterology and Nutrition: July 2013 - Volume 57 - Issue 1 - p 114–118
doi: 10.1097/MPG.0b013e318291fefe
Original Articles: Hepatology and Nutrition

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.

*Department of Pediatrics, SUNY Downstate, Brooklyn, NY

Department of Pediatric Gastroenterology

Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH

§Liver Unit, “Bambino Gesù” Children's Hospital and Research Institute, Rome, Italy

||Department of Pediatric Gastroenterology, Rady Children's Hospital, University of California, San Diego.

Address correspondence and reprint requests to Naim Alkhouri, MD, Department of Pediatric Gastroenterology, A-31, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 (e-mail:

Received 12 December, 2012

Accepted 7 March, 2013

The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,