title: Hepatic stellate cells and fibrosis progression in patients with nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Many patients with nonalcoholic fatty liver disease (NAFLD) have a benign clinical course, but a subgroup of patients progress to advanced fibrosis and cirrhosis. However, there are no available clinical tools to predict fibrosis progression in this population. Activated hepatic stellate cells (HSCs) are the source of collagen deposition in the liver. We aimed at determining whether an HSC activation score predicts fibrosis progression in NAFLD patients.
  
  
  METHODS
  The cohort consisted of 39 untreated patients with NAFLD with paired liver biopsies performed 5-59 months apart (mean, 22 months). Patients were divided into 2 groups on the basis of whether fibrosis progression was noted on their second liver biopsy. Liver tissue was immunostained for alpha-smooth muscle actin, and the HSC score was determined independently by 2 pathologists in the NAFLD population and in control subjects without liver disease.
  
  
  RESULTS
  The HSC activation score was significantly increased in patients with fibrosis progression versus patients in whom no fibrosis progression was observed (4.8 +/- 0.5 vs 1.8 +/- 0.6, respectively; P < .001). The HSC score was accurate in predicting fibrosis progression, with a positive predictive value of 90%, specificity of 94%, and an area under the receiver operating characteristic curve of 0.82. However, the negative predictive value and sensitivity were 56% and 41%, respectively. The inter-pathologist agreement for the HSC score was excellent (kappa coefficient, 0.95).
  
  
  CONCLUSIONS
  These findings suggest that the HSC activation score is a suitable clinical tool to determine the risk of fibrosis progression in patients with NAFLD.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.forename: Bettina G
authors.initials: BG
authors.lastname: Papouchado
authors.forename: Paul
authors.initials: P
authors.lastname: Angulo
authors.forename: Schyler
authors.initials: S
authors.lastname: Sanderson
authors.forename: Leon
authors.initials: L
authors.lastname: Adams
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Gores
mesh_terms: D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D015331:Cohort Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric