Dirk P van Asseldonk1, Bindia Jharap, Joanne Verheij, Gijsbert den Hartog, Dik B Westerveld, Marco C Becx, Maurice G Russel, Leopold G Engels, Dirk J de Jong, Birgit I Witte, Chris J Mulder, Carin M van Nieuwkerk, Elisabeth Bloemena, Nanne K H de Boer, Ad A van Bodegraven. 1. *Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, the Netherlands; †Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands; ‡Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands; §Department of Gastroenterology and Hepatology, Isala Klinieken, Zwolle, the Netherlands; ‖Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, the Netherlands; ¶Department of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, the Netherlands; **Department of Internal Medicine, Gastroenterology and Geriatrics, Atrium-Orbis Medical Center, Heerlen-Sittard-Geleen, the Netherlands; ††Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands; Departments of ‡‡Epidemiology and Biostatistics, and §§Pathology, VU University Medical Center, Amsterdam, the Netherlands.
Abstract
BACKGROUND: Nodular regenerative hyperplasia (NRH) of the liver is associated with inflammatory-mediated diseases and certain drugs. There is conflicting data on the prevalence of NRH and its clinical implications in inflammatory bowel disease (IBD) patients treated with thioguanine. METHODS: A retrospective cohort study involving 7 Dutch centers comprised all IBD patients who were being treated with thioguanine and underwent a liver biopsy as part of the standard toxicity screening. Liver biopsy specimens were reviewed by 2 experienced liver pathologists. Clinical data as well as liver chemistry, blood counts, and abdominal imaging were collected. RESULTS: One hundred eleven IBD patients who submitted to liver biopsy were treated with thioguanine in a daily dose of 0.3 mg/kg for a median duration of 20 (4-64) months. NRH was detected in 6% of patients (7; 95% confidence interval, 3-14 patients). Older age (P = 0.02), elevated gamma-glutamyl transferase (P = 0.01) and alkaline phosphatase (P = 0.01) levels, a higher mean corpuscular volume (P = 0.02), and a lower platelet or leukocyte count (P < 0.01 and P = 0.02, respectively) were associated with NRH. Three of the 7 patients with NRH did not have any associated clinical symptoms or signs. The other 4 had minor biochemical abnormalities only. Ultrasonography revealed splenomegaly in 3 of the 78 patients (4%; 95% confidence interval, 0%-9%), only one of whom had NRH. There was no clinically overt portal hypertension. CONCLUSIONS: The prevalence of NRH was 6% in liver biopsies obtained from IBD patients treated with thioguanine. Histopathological irregularities including NRH were not associated with clinically significant findings over the period of observation.
BACKGROUND:Nodular regenerative hyperplasia (NRH) of the liver is associated with inflammatory-mediated diseases and certain drugs. There is conflicting data on the prevalence of NRH and its clinical implications in inflammatory bowel disease (IBD) patients treated with thioguanine. METHODS: A retrospective cohort study involving 7 Dutch centers comprised all IBDpatients who were being treated with thioguanine and underwent a liver biopsy as part of the standard toxicity screening. Liver biopsy specimens were reviewed by 2 experienced liver pathologists. Clinical data as well as liver chemistry, blood counts, and abdominal imaging were collected. RESULTS: One hundred eleven IBDpatients who submitted to liver biopsy were treated with thioguanine in a daily dose of 0.3 mg/kg for a median duration of 20 (4-64) months. NRH was detected in 6% of patients (7; 95% confidence interval, 3-14 patients). Older age (P = 0.02), elevated gamma-glutamyl transferase (P = 0.01) and alkaline phosphatase (P = 0.01) levels, a higher mean corpuscular volume (P = 0.02), and a lower platelet or leukocyte count (P < 0.01 and P = 0.02, respectively) were associated with NRH. Three of the 7 patients with NRH did not have any associated clinical symptoms or signs. The other 4 had minor biochemical abnormalities only. Ultrasonography revealed splenomegaly in 3 of the 78 patients (4%; 95% confidence interval, 0%-9%), only one of whom had NRH. There was no clinically overt portal hypertension. CONCLUSIONS: The prevalence of NRH was 6% in liver biopsies obtained from IBDpatients treated with thioguanine. Histopathological irregularities including NRH were not associated with clinically significant findings over the period of observation.
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