Hepatic Glycogenosis in Children with Nonalcoholic Fatty Liver Disease (NAFLD): A Different Disease Than Glycogenic Hepatopathy
Cynthia D Guy, Elizabeth M Brunt, Cynthia Behling, Michael Torbenson, Matthew M Yeh, Patricia Belt, Brent A Neuschwander-Tetri, Karen F Murray, David E Kleiner. Duke University, Durham, NC; Washington University, Saint Louis, MO; Sharp Hospitals, San Diego, CA; Johns Hopkins School of Medicine, Baltimore, MD; University of Washington, Seattle, WA; Johns Hopkins School of Public Health, Baltimore, MD; Saint Louis University School of Medicine, Saint Louis, MO; Seattle Children's Hospital, Seattle, WA; National Institutes of Health, Bethesda, MD
Background: Diffuse hepatic glycogenosis is the dominant histological finding in glycogenic hepatopathy, a condition sometimes seen with poorly controlled diabetes mellitus type 1 (DM1). A similar histologic feature (glassy, pale cytoplasmic accumulations on H&E stain) has been noted in pediatric NAFLD liver biopsies which lacked the typical clinicopathological pattern of glycogenic hepatopathy. Our aim was to further characterize the clinical and histological correlations of this finding.
Design: Liver biopsies blindly reviewed centrally by the pathology committee of the NASH CRN were scored as having either no, focal (involving <50% of hepatocytes) or diffuse (>50%) glycogenosis. These data were analyzed for associations with other histologic features and clinical characteristics including age, sex, diabetes status, aminotransferases, alkaline phosphatase, fasting glucose, fasting insulin and HOMA-IR.
Results: Biopsies were reviewed in 139 children (≤18 years of age). Mean age was 12.6 years (range 5-18) and 72.7% were male. Glycogenosis was focal in 19 (13.7%) and diffuse in 31 (22.3%). Glycogenosis was associated with low steatosis grade (p=0.016), large droplet macrovesicular steatosis (p=0.014), lower NAFLD Activity Score (NAS) (p = 0.049) and increased non-hepatocellular iron (p=0.038). No associations were identified with ballooning, Mallory-Denk bodies, megamitochondria, lobular inflammation, portal inflammation or fibrosis. The one patient with DM1 had diffuse glycogenosis. There were no associations with aminotransferase levels, fasting glucose, fasting insulin or HOMA-IR.
Conclusions: In pediatric NAFLD, hepatic glycogenosis is found in more than 33% of biopsies. It is associated with lesser degrees of steatosis and a lower NAS. There are no associations with markers of NASH severity, fibrosis or insulin resistance. Hepatic glycogenosis should not be over interpreted as a true glycogenic hepatopathy.
Monday, March 19, 2012 1:30 PM
Platform Session: Section E, Monday Afternoon