A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6-thioguanine.
OBJECTIVE
Although 6-thioguanine (6-TG) has been suggested as an effective treatment option for patients with inflammatory bowel disease (IBD), the recent description of its hepatotoxicity has led to the recommendation not to consider this drug. We initiated a multicenter safety study in IBD-patients treated with 6-TG to investigate hepatic changes by liver biopsy and magnetic resonance imaging (MRI).


METHODS
Forty-five patients from three European centers treated with 6-TG (40-80 mg/d) at least for 8 weeks were enrolled. In all patients liver biopsy and MRI were performed. Slides and MR images were independently read by two pathologists and radiologists, respectively, and interpreted according to predefined criteria by consent.


RESULTS
In 8 patients nodular regenerative hyperplasia (NRH) was diagnosed by liver biopsy, in 8 additional patients NRH could not be excluded due to equivocal pathological findings. MRI demonstrated a sensitivity of 77% and a specificity of 72% in the detection of pathohistological findings consistent with and/or possibly related to NRH.


CONCLUSIONS
Our study suggests that 6-TG therapy in IBD patients is associated with NRH of the liver. Based on a special MRI protocol, non-invasive diagnosis of NRH with promising sensitivity and specificity was demonstrated.
Seiderer
Julia
J
Department of Internal Medicine II, University Hospital Munich-Grosshadern, Munich, Germany.
Zech
Christoph J
CJ
Reinisch
Walter
W
Lukas
Milan
M
Diebold
Joachim
J
Wrba
Friedrich
F
Teml
Alexander
A
Chalupna
Petra
P
Stritesky
Jan
J
Schoenberg
Stefan O
SO
Schima
Wolfgang
W
Göke
Burkhard
B
Ochsenkühn
Thomas
T
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000209:etiology / Q000473:pathology*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012449:Safety; D013866:Thioguanine / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine