title: Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients.
abstract: BACKGROUND
  The use of 6-thioguanine has been proposed as a rescue drug for inflammatory bowel disease patients. Initial data on short-term efficacy and toxicity of 6-thioguanine were promising; however, these have been challenged by reports concerning its potential hepatotoxic effect (nodular regenerative hyperplasia). We proposed that these histological liver abnormalities may well be dose- or level-dependent.
  
  
  OBJECTIVE
  We performed a prospective multi-centre study on the hepatotoxic potential of long-term and (as compared with prior studies) low-dose 6-thioguanine use.
  
  
  METHODS
  Inflammatory bowel disease patients using 6-thioguanine for at least 30 consecutive months and consenting to undergo a liver biopsy were enrolled.
  
  
  METHODS
  Liver biopsy specimens were scored by two pathologists, unaware of clinical data. Laboratory parameters, determined prior to initiation of 6-thioguanine therapy and prior to biopsy, were reviewed.
  
  
  RESULTS
  Twenty-eight biopsies were analysed. The majority of patients (89%) were azathioprine and/or 6-mercaptopurine intolerant inflammatory bowel disease patients. In 26 patients (93%) no signs of nodular regenerative hyperplasia were detected; in two additional patients nodular regenerative hyperplasia could not be excluded due to inconclusive pathological findings. The mean 6-thioguanine dosage, 6-thioguaninenucleotides level, duration of use and cumulative dosage were 19.5mg, 564 pmol/8 x 10(8) RBC, 38 months and 22491 mg, respectively.
  
  
  CONCLUSIONS
  We have demonstrated that low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients is not likely to be associated with induction of nodular regenerative hyperplasia. The induction of nodular regenerative hyperplasia appears to be 6-thioguanine dose or 6-thioguaninenucleotides level dependent.
authors: Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. KHN.deBoer@vumc.nl <KHN.deBoer@vumc.nl>
authors: N K H
authors: NK
authors: de Boer
authors: P E
authors: PE
authors: Zondervan
authors: L P L
authors: LP
authors: Gilissen
authors: G
authors: G
authors: den Hartog
authors: B D
authors: BD
authors: Westerveld
authors: L J J
authors: LJ
authors: Derijks
authors: E
authors: E
authors: Bloemena
authors: L G J B
authors: LG
authors: Engels
authors: A A
authors: AA
authors: van Bodegraven
authors: C J J
authors: CJ
authors: Mulder
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine