Incidence of nodular regenerative hyperplasia in inflammatory bowel disease patients treated with azathioprine

Nodular regenerative hyperplasia (NRH) is a rare hepatic disorder that may lead to severe portal hypertension. Cases of NRH have been reported in patients receiving thiopurines for inflammatory bowel disease (IBD). Since azathioprine (AZA) is used more and more frequently as a maintenance treatment in IBD, the risk of NRH must be known. The objective of this study was to evaluate the prevalence of NRH and its predictive factors in IBD patients treated with AZA.

From the same tertiary referral center, 1888 consecutive IBD patients treated with AZA were studied. Clinical diagnosis of NRH was proven by liver biopsy in all cases except one. The cumulative risk of NRH was estimated with the Kaplan-Meier method. Factors associated with NRH were tested independently with the log-rank method and multivariate proportional hazards model with time-dependent covariates.

Fifteen patients developed NRH in a median treatment duration of 52.4 months (SE 1.6). The cumulative incidence of NRH was 1.28±0.45% at 10 years. Only two variables were independently associated with NRH occurrence: male gender (P=0.0001, hazard ratio [HR] 8.5, 95% confidence interval [CI] 1.9-37.9) and small bowel resection≥50 cm (P<0.0001, HR 6.6, 95% CI 2.2-20.0), either prior to or after AZA initiation.

The risk of developing NRH during AZA treatment is low. This study suggests that male patients with small bowel resection≥50 cm constitute the group with the higher risk of developing NRH while treated with AZA.