A systematic survey evaluating 6-thioguanine-related hepatotoxicity in patients with inflammatory bowel disease.
OBJECTIVE
Drug-induced liver injury was recently reported as a major complication leading to hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD) and 6-thioguanine (6-TG) therapy. The aim of the study was to evaluate the prevalence of 6-TG-related hepatotoxicity in a large multi-centered IBD population by means of a systematic online survey.


METHODS
Clinical and laboratory data, imaging techniques (sonography, CT, MRI) and histology of liver biopsies were surveyed in IBD patients treated with 6-TG. The decision on whether liver imaging and/or liver biopsy were performed was exclusively at the discretion of the investigator.


RESULTS
6-TG use was fully documented in 296 patients (median treatment duration 56 weeks, range < 1-207). Laboratory signs of drug-induced liver injury were found in 43 patients (14.5%). Liver imaging revealed pathologic results in 68/176 patients (38.6%). Liver biopsy was performed in a subset of 60 patients; using silver-reticulin staining (n = 59), NRH was considered in 16 patients (27.1%). Age was the only independent, albeit weak, risk factor for development of NRH.


CONCLUSIONS
This large online survey confirms the strong association between 6-TG treatment and the significant risk of development of NRH in patients with IBD. The definitive diagnosis of NRH depends solely upon liver biopsy.
Teml
Alexander
A
Medical University of Vienna, Austria.
Schwab
Matthias
M
Hommes
Daan W
DW
Almer
Sven
S
Lukas
Milan
M
Feichtenschlager
Thomas
T
Florin
Timothy
T
Seiderer
Julia
J
Petritsch
Wolfgang
W
Bokemeyer
Bernd
B
Kreisel
Wolfgang
W
Herrlinger
Klaus R
KR
Knoflach
Peter
P
Bonaz
Bruno
B
Klugmann
Thomas
T
Herfarth
Hans
H
Pedarnig
Nikolaus
N
Reinisch
Walter
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D003625:Data Collection; D003627:Data Interpretation, Statistical; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced* / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D020407:Internet; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking; D011795:Surveys and Questionnaires; D013866:Thioguanine / Q000009:adverse effects*; D016896:Treatment Outcome; D014463:Ultrasonography
D013866:Thioguanine