The Prevalence of Nodular Regenerative Hyperplasia in Inflammatory Bowel Disease Patients Treated with Thioguanine Is Not Associated with Clinically Significant Liver Disease

Inflamm Bowel Dis. 2016 Sep;22(9):2112-20. doi: 10.1097/MIB.0000000000000869.

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.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / adverse effects*
  • Chemical and Drug Induced Liver Injury / etiology
  • Female
  • Focal Nodular Hyperplasia / chemically induced
  • Focal Nodular Hyperplasia / epidemiology*
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Liver / pathology*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Niederlande
  • Retrospective Studies
  • Splenomegaly / diagnostic imaging
  • Splenomegaly / epidemiology
  • Thioguanine / adverse effects*
  • Ultrasonography
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Thioguanine