Necrotic foci, elevated chemokines and infiltrating neutrophils in the liver of glycogen storage disease type Ia

J Hepatol. 2008 Mar;48(3):479-85. doi: 10.1016/j.jhep.2007.11.014. Epub 2007 Dec 28.


Background/aims: Glycogen storage disease type Ia (GSD-Ia) patients manifest the long-term complication of hepatocellular adenoma (HCA) of unknown etiology. We showed previously that GSD-Ia mice exhibit neutrophilia and elevated serum cytokine levels. This study was conducted to evaluate whether human GSD-Ia patients exhibit analogous increases and whether in GSD-Ia mice a correlation exists between immune abnormalities and, biochemical and histological alterations in the liver.

Methods: Differential leukocyte counts and cytokine levels were investigated in GSD-Ia patients. Hepatic chemokine production, neutrophil infiltration, and histological abnormalities were investigated in GSD-Ia mice.

Results: We show that GSD-Ia patients exhibit increased peripheral neutrophil counts and serum interleukin-8 (IL-8). Compared to normal subjects, HCA-bearing GSD-Ia patients have a 2.8-fold higher serum IL-8 concentration, while GSD-Ia patients without HCA have a 1.4-fold higher concentration. Hepatic injury in GSD-Ia mice is evidenced by necrotic foci, markedly elevated infiltrating neutrophils, and increased hepatic production of chemokines.

Conclusions: Peripheral neutrophilia and elevated serum chemokines are characteristic of GSD-Ia with HCA-bearing GSD-Ia patients having the highest serum IL-8. In GSD-Ia mice these elevations correlate with elevated hepatic chemokine levels, neutrophil infiltration, and necrosis. Taken together, peripheral neutrophilia and increased serum chemokines may indicate hepatic injuries in GSD-Ia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Count
  • Chemokine CXCL2 / metabolism*
  • Child
  • Child, Preschool
  • Disease Models, Animal
  • Glycogen Storage Disease Type I / metabolism*
  • Glycogen Storage Disease Type I / pathology*
  • Humans
  • Interleukin-8 / metabolism*
  • Liver / metabolism*
  • Liver / pathology*
  • Mice
  • Mice, Mutant Strains
  • Necrosis / metabolism
  • Necrosis / pathology
  • Neutrophils / pathology*


  • Biomarkers
  • Chemokine CXCL2
  • Interleukin-8