title: Sampling variability of liver biopsy in nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH.
  
  
  METHODS
  Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test.
  
  
  RESULTS
  No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error.
  
  
  CONCLUSIONS
  Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.
authors.affiliation: Service d'Hépatogastroentérologie, Groupe Hospitalier Pitié Salpêtrière, Paris, France. vratziu@teaser.fr
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Frédéric
authors.initials: F
authors.lastname: Charlotte
authors.forename: Agnès
authors.initials: A
authors.lastname: Heurtier
authors.forename: Sophie
authors.initials: S
authors.lastname: Gombert
authors.forename: Philippe
authors.initials: P
authors.lastname: Giral
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.forename: André
authors.initials: A
authors.lastname: Grimaldi
authors.forename: Frédérique
authors.initials: F
authors.lastname: Capron
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy / Q000592:standards; D003951:Diagnostic Errors; D005234:Fatty Liver / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006505:Hepatitis / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013048:Specimen Handling