title: Diagnosing Nodular Regenerative Hyperplasia of the Liver Is Thwarted by Low Interobserver Agreement.
abstract: OBJECTIVE
  Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH.
  
  
  METHODS
  Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index.
  
  
  RESULTS
  After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45).
  
  
  CONCLUSIONS
  The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone.
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Bindia
authors.initials: B
authors.lastname: Jharap
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: van Asseldonk
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Nanne K H
authors.initials: NK
authors.lastname: de Boer
authors.affiliation: Department of Pathology, Beaujon Hospital, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.affiliation: Department of Pathology, Cantonal Hospital, Lucerne, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
authors.affiliation: Department of Pathology, Refaja Hospital, Stadskanaal, the Netherlands.
authors.forename: A Mieke
authors.initials: AM
authors.lastname: Jonker
authors.affiliation: Department of Pathology, CHRU Lille, Lille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Pathology, Saint-Antoine Hospital, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Wendum
authors.affiliation: Department of Pathology, University Medical Center Vienna, Vienna, Austria.
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.affiliation: Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Zondervan
authors.affiliation: Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Chris J J
authors.initials: CJ
authors.lastname: Mulder
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.affiliation: Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands; Department of Internal Medicine, Gastroenterology and Geriatrics, ORBIS Medical Center, Sittard-Geleen, the Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Bodegraven
mesh_terms: D001706:Biopsy; D006801:Humans; D006965:Hyperplasia; D006975:Hypertension, Portal / Q000473:pathology; D008099:Liver / Q000473:pathology* / Q000503:physiopathology*; D008107:Liver Diseases / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D015588:Observer Variation; D012038:Regeneration