title: Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Liver biopsies from patients with nonalcoholic fatty liver disease (NAFLD) sometimes exhibit non-zonal aggregates of hepatocytes with microvesicular steatosis, but its prevalence and significance are unclear. In this study, we have evaluated the frequency of microvesicular steatosis and assessed its association with histological markers of disease severity in a large sample of NAFLD liver biopsies.
  
  
  METHODS
  Liver biopsies from a large cohort of adults who participated in two studies conducted by the NASH Clinical Research Network (NASH CRN) were included in this cross-sectional study. Liver histology was assessed centrally and various histological features scored in a systematic fashion. The relationship between microvesicular steatosis and various histological features that characterize NAFLD was tested by multiple logistic regression, after controlling for age, gender, race, body mass index, and diabetes.
  
  
  RESULTS
  Among 1022 liver biopsies included, 102 (10%) had microvesicular steatosis. No demographic differences were noted between patients with or without microvesicular steatosis. The presence of microvesicular steatosis was associated with higher grades of steatosis (p<0.001), ballooning cell injury (p<0.001), presence of Mallory-Denk bodies (p<0.007), presence of megamitochondria (p<0.0001), higher NAS scores (p<0.0001), more advanced fibrosis (p<0.0001), and diagnosis of borderline or definite NASH (p<0.0001).
  
  
  CONCLUSIONS
  Microvesicular steatosis correlates with more advanced histology of NAFLD. Longitudinal studies are needed to address the role of microvesicular steatosis in mediating cellular injury and disease progression in NAFLD.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Tandra
authors.affiliation: University of Washington School of Medicine, Department of Pathology, Seattle, WA, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: Washington University School of Medicine, Department of Pathology and Immunology, St. Louis, MO, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Vuppalanchi
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Oscar W
authors.initials: OW
authors.lastname: Cummings
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Aynur
authors.initials: A
authors.lastname: Ünalp-Arida
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wilson
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: nchalasa@iupui.edu.
authors.forename: Naga
authors.initials: N
authors.lastname: Chalasani
mesh_terms: D000328:Adult; D001706:Biopsy; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D059609:Mallory Bodies / Q000473:pathology; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease; D012720:Severity of Illness Index