Natural History of NAFLD Diagnosed in Childhood: A Single-Center Study

Abstract

Little is known regarding the subsequent course of non-alcoholic fatty liver disease (NAFLD) diagnosed in childhood. The objectives of this single-center study were to gather data on long-term health outcomes and to assess the feasibility of contacting former pediatric patients. In a large pediatric medical center, electronic records were searched to initially identify 162 former patients who had a liver biopsy between 2000 and 2010. Of these, 44 subjects met the criteria for age at follow-up (≥18 year) and biopsy-proven NAFLD, and were recruited via postal and electronic mail. Participants were invited to complete a brief telephone survey on current health status. Supplemental data was also obtained from pediatric medical charts of all subjects. At NAFLD diagnosis, 18% of subjects had diabetes, 91% were obese, 61% had NASH, and 56% had fibrosis on biopsy. At follow-up, 10 subjects (23%) responded to the survey. Based on the survey and chart review, after a mean follow-up of 4.5 years, 5 additional subjects developed diabetes for a period prevalence of 30%, and most subjects (78%) remained obese at last follow-up. Additional prospective studies are needed to fully describe the longitudinal risks associated with pediatric NAFLD, and will require multi-dimensional strategies to successfully recruit former patients.

Youth-Onset Type 2 Diabetes Manifestations in other Specialties: Its Many Disguises

“…These data reflect an earlier study, which also measured liver triglyceride content and showed that children with T2D were twice as likely to have hepatic steatosis compared with weight-matched normoglycemic controls [11]. Data from a third study showed that 18.2% of pediatric patients had T2D when they were diagnosed with NAFLD [30]. These 3 studies indicated that NAFLD is associated with youth-onset T2D.…”

“…Adolescent girls (14-19 years of age) with at least [11,29,30,44] -Mental health/psychiatry [34]: psychosis [36], depression [5,35], autism spectrum disorder [33], binge eating [37,38] 3 delayed menstrual cycles were 6.5 times more likely to develop impaired fasting glucose and T2D when they were young adults (19-24 years of age) than those who never had a delayed cycle [25]. Similarly, the broad symptom of irregular menses was present in 20.5% of girls with T2D, which appeared higher than prevalence rates for healthy populations [26].…”

Development of a Plasma Screening Panel for Pediatric Nonalcoholic Fatty Liver Disease Using Metabolomics

“…The term NAFLD encompasses a range of disease severity from steatosis, defined as fat accumulation in at least 5% of hepatocytes, to nonalcoholic steatohepatitis, defined as steatosis with inflammation and hepatocyte ballooning. There are limited natural history data in children, but studies have shown that childhood NAFLD can result in cirrhosis, severe liver disease, and death . NAFLD is also strongly associated with cardiometabolic disease risk factors, such as prediabetes and type 2 diabetes and atherogenic dyslipidemia .…”

Factors to Consider in Development of Drugs for Pediatric Nonalcoholic Fatty Liver Disease

“…Long-term nationally representative data in US adults having severe hepatic steatosis as well as elevated alanine aminotransferase (ALT), aspartate aminotransferase or gamma-glutamyl transferase were associated with increased liver disease mortality. 23 In adults, type 2 diabetes and cardiovascular disease are also frequent adverse clinical outcomes associated with NAFLD 24 and there are few data suggesting that increased incidence of type 2 diabetes is the most rapid adverse clinical outcome 17,25 in children. One of the most challenging knowledge gaps is the lack of longer term natural history information, which complicates benefit-risk determinations in the development of therapeutics for pediatric NAFLD.…”