6-thioguanine can cause serious liver injury in inflammatory bowel disease patients.
OBJECTIVE
Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammatory bowel disease (IBD). Short-term safety and efficacy data were favorable. Experience with 6-TG in patients with acute lymphoblastic leukemia raised long-term safety concerns when implicated in nodular regenerative hyperplasia (NRH) of the liver and portal hypertension. The aim of this study was to describe the association between 6-TG and NRH in IBD.


METHODS
Liver chemistries and complete blood counts were monitored, and patients were encouraged to undergo liver biopsy. Clinical data were collected by chart review, and associations were tested by univariate and multivariable analyses. Patients were classified based on the presence (group 1) or absence (group 2) of laboratory abnormalities.


RESULTS
Laboratory abnormalities occurred in 29 of 111 patients (26%). Elevations of liver enzymes and a decrease in platelet counts (<200,000) were most commonly observed. Male gender (odds ratio, 2.9; 95% CI, 1.1-7.3; P < 0.03) and preferential 6-methylmercaptopurine production on 6-mercaptopurine/azathioprine (odds ratio, 3.0; 95% CI, 1.2-7.4; P < 0.04) were independently associated with laboratory abnormalities. No association was seen with duration of 6-TG treatment, cumulative dose, or 6-TG nucleotide levels. The median increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels was 39, 30, and 75 U/L, respectively, in group 1, and the median decrease in platelet count was 115,000 in group 1 versus 7000 in group 2 (P < 0.001). NRH occurred in 76% of patients undergoing biopsy in group 1 and 33% in group 2.


CONCLUSIONS
NRH is a common finding in 6-TG-treated patients with IBD. The progression or reversibility of NRH remains unknown. Our findings suggest that 6-TG should not be considered as therapy for patients with IBD.
Dubinsky
Marla C
MC
Pediatric Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, 8635 West Third Street, Suite 1165W, Los Angeles, California 90048, USA. dubinskym@csmc.edu
Vasiliauskas
Eric A
EA
Singh
Hardeep
H
Abreu
Maria T
MT
Papadakis
Kostas A
KA
Tran
Tram
T
Martin
Paul
P
Vierling
John M
JM
Geller
Stephen A
SA
Targan
Stephan R
SR
Poordad
Fred F
FF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; 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; D013866:Thioguanine / Q000009:adverse effects*
D013866:Thioguanine