6-thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension.
BACKGROUND
Recent studies suggest an association between 6-thioguanine (6-TG) therapy and hepatic nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease (IBD). An influence of 6-TG on portal pressure remains to be determined. The aim of the study was to examine the functional relevance of long-term 6-TG treatment on hepatic hemodynamics in IBD patients and its association with NRH.


METHODS
Patients treated with 6-TG for IBD underwent measurement of the hepatic venous pressure gradient (HVPG) and liver biopsy. 6-TG therapy was stopped when NRH was diagnosed. If elevated, HVPG measurement was repeated after 1 yr.


RESULTS
Twenty-six patients (15 women, 11 men; median age 41 yr, range 23-76) treated with 6-TG for 38 months (median; range 12-45) were included. Among 24 patients with sufficient liver biopsy, 6 patients (25%) were diagnosed with NRH. In these 6 patients, the HVPG was higher (median HVPG 7 mmHg, range 3-14) than in the 18 patients without NRH (median 3 mmHg, range 2-5; P < 0.001). In the patients with NRH, two had clinically significant portal hypertension (CSPH) (13 and 14 mmHg, respectively); in one patient the HVPG was slightly elevated (7 mmHg). No overt clinical signs of portal hypertension were observed. One year after stopping 6-TG therapy, HVPG decreased in all 3 patients with initially elevated HVPG levels.


CONCLUSIONS
We demonstrate that IBD patients under long-term 6-TG therapy are at a substantial risk for developing NRH. NRH results in elevation of HVPG and may cause CSPH. Discontinuation of 6-TG therapy extenuates portal hypertension and may thus reduce the risk of complications.
Ferlitsch
Arnulf
A
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
Teml
Alexander
A
Reinisch
Walter
W
Ulbrich
Gregor
G
Wrba
Fritz
F
Homoncik
Monika
M
Gangl
Alfred
A
Peck-Radosavljevic
Markus
M
Vogelsang
Harald
H
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D001706:Biopsy; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000139:chemically induced*; D006801:Humans; D006975:Hypertension, Portal / Q000139:chemically induced*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013866:Thioguanine / Q000009:adverse effects*
D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine