Absence of nodular regenerative hyperplasia after low-dose 6-thioguanine maintenance therapy in inflammatory bowel disease patients.
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.
de Boer
N K H
NK
Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands. KHN.deBoer@vumc.nl <KHN.deBoer@vumc.nl>
Zondervan
P E
PE
Gilissen
L P L
LP
den Hartog
G
G
Westerveld
B D
BD
Derijks
L J J
LJ
Bloemena
E
E
Engels
L G J B
LG
van Bodegraven
A A
AA
Mulder
C J J
CJ
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
D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine