Fish and long-chain omega-3 fatty acids in pediatric liver disease

Abstract

Pediatric nonalcoholic fatty liver disease (NAFLD) and parenteral nutrition-associated liver disease (PNALD) are difficult to manage conditions that have been rising with increasing rates of childhood obesity and survival of infants with intestinal failure, respectively. This dissertation is comprised of five research studies, which examine: a) the burden of pediatric NAFLD in Hawaiʻi, b) the effect of dietary fish and long-chain omega-3 fatty acid intake (LCω3) on pediatric NAFLD, and c) the use of fish oil-based lipid emulsions (FOLEs) in infants with PNALD. In a cross-sectional analysis of 195 patients referred to a pediatric endocrinologist at Kapi'olani Medical Center for Women and Children (KMCWC) with metabolic syndrome, approximately two-thirds had elevated serum alanine aminotransferase (ALT) concentrations indicative of NAFLD, which makes it one of the most common obesity-related comorbidities in this population. Examination of 81 pediatric NAFLD patients referred to two pediatric gastroenterologists at KMCWC showed that these children were typically overweight (98%) and suffered from obesity-related comorbidities, particularly dyslipidemia, and often exhibited histological features of steatohepatitis. There was a significant reduction in serum ALT concentration in these patients over time; however, body weight tended to increase and was not associated with changes in serum ALT concentrations. In a prospective cohort of 200 Asian and White female adolescents recruited among members of Kaiser Permanente Oahu, greater fish consumption appeared to reduce two-year changes in waist circumference (n=103), a risk factor for NAFLD, although relatively few girls, mostly of Asian ethnicity, consumed the recommended eight ounces of fish per week (12.4%). Children who were attending one of the eight clinical centers of the Nonalcoholic Steatohepatitis Clinical Research Network (n=223) reported similarly low rates of eating eight or more ounces of fish per week (9.9%). In this study, greater fish and long-chain omega-3 fatty acid intake were associated with less severe of portal and lobular inflammation on liver biopsy. Among ten infants diagnosed with PNALD at KMCWC who were treated with FOLE, earlier initiation of FOLE treatment was associated with reduced length of hospital stay. In summary, the findings of this dissertation demonstrated that a) pediatric NAFLD is a common consequence of obesity in Hawaiʻi that is associated with serious disease sequelae, b) fish and Lcω3s consumption is low in adolescents, which may increase risk for and severity of hepatic inflammation in NAFLD, and c) early initiation of FOLE treatment in infants with PNALD may reduce length of hospital stay. Strategies to improve fish and LCω3 intake in children and infants at risk of NAFLD and PNALD, respectively, are needed to reduce the burden of pediatric liver disease.