title: The Prevalence of Nodular Regenerative Hyperplasia in Inflammatory Bowel Disease Patients Treated with Thioguanine Is Not Associated with Clinically Significant Liver Disease.
abstract: Nodular regenerative hyperplasia (NRH) of the liver is associated with inflammatory-mediated diseases and certain drugs. There is conflicting data on the prevalence of NRH and its clinical implications in inflammatory bowel disease (IBD) patients treated with thioguanine.
  
  
  
  A retrospective cohort study involving 7 Dutch centers comprised all IBD patients who were being treated with thioguanine and underwent a liver biopsy as part of the standard toxicity screening. Liver biopsy specimens were reviewed by 2 experienced liver pathologists. Clinical data as well as liver chemistry, blood counts, and abdominal imaging were collected.
  
  
  
  One hundred eleven IBD patients who submitted to liver biopsy were treated with thioguanine in a daily dose of 0.3 mg/kg for a median duration of 20 (4-64) months. NRH was detected in 6% of patients (7; 95% confidence interval, 3-14 patients). Older age (P = 0.02), elevated gamma-glutamyl transferase (P = 0.01) and alkaline phosphatase (P = 0.01) levels, a higher mean corpuscular volume (P = 0.02), and a lower platelet or leukocyte count (P < 0.01 and P = 0.02, respectively) were associated with NRH. Three of the 7 patients with NRH did not have any associated clinical symptoms or signs. The other 4 had minor biochemical abnormalities only. Ultrasonography revealed splenomegaly in 3 of the 78 patients (4%; 95% confidence interval, 0%-9%), only one of whom had NRH. There was no clinically overt portal hypertension.
  
  
  
  The prevalence of NRH was 6% in liver biopsies obtained from IBD patients treated with thioguanine. Histopathological irregularities including NRH were not associated with clinically significant findings over the period of observation.
authors.affiliation: *Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands; †Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands; ‡Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands; §Department of Gastroenterology and Hepatology, Isala Klinieken, Zwolle, the Netherlands; ‖Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, the Netherlands; ¶Department of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, the Netherlands; **Department of Internal Medicine, Gastroenterology and Geriatrics, Atrium-Orbis Medical Center, Heerlen-Sittard-Geleen, the Netherlands; ††Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; Departments of ‡‡Epidemiology and Biostatistics, and §§Pathology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Dirk P
authors.initials: DP
authors.lastname: van Asseldonk
authors.forename: Bindia
authors.initials: B
authors.lastname: Jharap
authors.forename: Joanne
authors.initials: J
authors.lastname: Verheij
authors.forename: Gijsbert
authors.initials: G
authors.lastname: den Hartog
authors.forename: Dik B
authors.initials: DB
authors.lastname: Westerveld
authors.forename: Marco C
authors.initials: MC
authors.lastname: Becx
authors.forename: Maurice G
authors.initials: MG
authors.lastname: Russel
authors.forename: Leopold G
authors.initials: LG
authors.lastname: Engels
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: de Jong
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: Carin M
authors.initials: CM
authors.lastname: van Nieuwkerk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Nanne K H
authors.initials: NK
authors.lastname: de Boer
authors.forename: Ad A
authors.initials: AA
authors.lastname: van Bodegraven
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy*; D008099:Liver / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D012189:Retrospective Studies; D013163:Splenomegaly / Q000000981:diagnostic imaging / Q000453:epidemiology; D013866:Thioguanine / Q000009:adverse effects*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine