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Abstract Details
Glycogenosis is Common in Nonalcoholic Fatty Liver Disease and is Independently Associated with Ballooning, but Lower Steatosis and Lower Fibrosis
Liver Int. 2020 Dec 22. doi: 10.1111/liv.14773. Online ahead of print.
Daniela S Allende1, Samer Gawrieh2, Oscar W Cummings3, Patricia Belt4, Laura Wilson4, Mark Van Natta4, Cynthia A Behling5, Danielle Carpenter6, Ryan M Gill7, David E Kleiner8, Mathew M Yeh9, Naga Chalasani2, Cynthia D Guy10, NASH Clinical Research Network
Author information
1Department of Pathology, Cleveland Clinic, Cleveland, OH, USA.
2Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
3Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA.
4Center for Clinical Trials, The Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
5Department of Pathology, Pacific Rim Pathology, San Diego, CA, USA.
6Department of Pathology, Saint Louis University, St Louis, MI, USA.
7Department of Pathology, University of California San Francisco, San Francisco, CA, USA.
8Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
9Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA.
10Department of Pathology, Duke University, Durham, NC, USA.
Abstract
Background/aims: Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFLD).
Methods: Glycogenosis in NAFLD liver biopsies was graded as "none", "focal" (in < 50% of hepatocytes), or "diffuse" (in ≥ 50% of hepatocytes). Clinical and pathological variables associated with glycogenosis were assessed. 2047 liver biopsies were prospectively analyzed.
Results: In adults and children, any glycogenosis was present in 54% of cases; diffuse glycogenosis was noted in approximately 1/3 of cases. On multiple logistic regression analysis, adults with glycogenosis tended to be older (p=0.003), female (p=0.04), have higher serum glucose (p=0.01), and use insulin (p=0.02). Adults tended to have lower steatosis scores (p=0.006) and lower fibrosis stages (p=0.005); however, unexpectedly, they also tended to have more hepatocyte injury including ballooning (p=0.003). On multiple logistic regression analysis, pediatric patients with glycogenosis were more likely to be Hispanic (p=0.03), have lower body weight (p=0.002), elevated triglycerides (p=0.001), and a higher fasting glucose (p=0.007). Pediatric patients with glycogenosis also had less steatosis (p<0.001) than those without.
Conclusions: Glycogenosis is common in adult and pediatric NAFLD, and is associated with clinical features of insulin resistance. Glycogenosis is important to recognize histologically because it may be misinterpreted as ballooning, and when diffuse, confusion with glycogen storage disorders or glycogenic hepatopathy must be avoided. The newly observed dichotomous relationship between glycogenosis and increased liver cell injury but decreased steatosis and fibrosis requires further study.