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Variability of grade and stage in simultaneous paired liver biopsies in patients with hepatitis C
  1. Silvia Skripenova1,
  2. Thomas D Trainer1,
  3. Edward L Krawitt2,
  4. Hagen Blaszyk1
  1. 1Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont, USA
  2. 2Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA
  1. Correspondence to:
 H Blaszyk
 University of Vermont College of Medicine, Department of Pathology, 89 Beaumont Avenue, Burlington, VT 05405 USA; hagen.blaszyk{at}


Background: Grading and staging of liver biopsies in patients with chronic hepatitis remains an inexact “gold standard” that is influenced by variabilities in scoring systems, sampling, observer agreement and expertise. Spatial disease variability relative to markers of the adequacy of biopsy has not been studied previously.

Methods: Paired liver biopsy specimens were obtained from the right and left hepatic lobes of 60 patients with chronic hepatitis C. Histological grade and disease stage were assessed according to the Ludwig scoring system, and scores were evaluated in relation to differences in size and number of portal tracts in all paired samples.

Results: The relative difference (%) in aggregate biopsy size and number of portal tracts was similar between paired samples with and without a difference in grade. Paired samples with a difference in stage showed a larger relative difference in biopsy size (p = 0.09) and in the number of portal tracts (p = 0.016).

Conclusions: Our study shows a difference of one grade or one stage in 30% of paired liver biopsies, due to a combination of sampling variability and observer variability. Acknowledgment of “built-in” variability in grading and staging chronic hepatitis C by both clinicians and pathologists is essential for managing the individual patient with chronic hepatitis C.

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  • Published Online First 12 May 2006

  • Competing interests: None.

  • Ethical approval: This study was approved by the Institutional Review Board at the University of Vermont.