Background: Miminal information is available regarding the incidence, risk factors and natural history of episodes of severe acute rejection (severe AR) of the intestine allograft.

Methods: We reviewed pathology reports from 38 transplant episodes/ 31 recipients of intestine-inclusive allografts ( isolated intestine[ITx] and liver-inclusive  [LSB] allografts) performed 12/2009 - 12/2016 to identify the incidence and outcomes for severe AR of intestine allograft; defined as complete loss of villous architecture and/or crypts without evidence of other cause. Univariate analysis was performed, categorical variables were evaluated using Chi Square test.

Results: Severe AR of the intestine is frequent and a severe complication of intestine transplantation [n = 9(30%) patients experienced 10 episodes]. Most episodes occurred within the first month (n = 7; mean of 18 days after transplantation) although 3 episodes occurred 15, 45 and 68* months after transplantation. Pediatric recipients were at higher risk for severe AR than adults and there was a trend toward higher rates in ITx compared to LSB recipients. The development of severe AR was associated with decreased patient survival. Re-epithelialization of the intestine allograft with recovery of villi and crypt structures occurred in 6 allografts (5 recipients) and was associated with the type of allograft and strongly correlated with patient survival. Full recovery of absorptive function however is rare (20%) after severe AR even when re-epithelialization occurs. Re-transplantation was performed in 4 patients (2 acutely at 1month and in 2 recipients 9 months after onset of severe AR); 3/4 are alive and well off PN with functional allografts and have not had recurrent severe AR. Explantation of the bowel graft without re-transplantation was performed in 4 additional patients, 2 of whom died of infection early after explant and 1 died 3.5 years later on PN due to advanced liver disease (n = 1); only 1 patient has survived on long-term on PN. (see Table 1)  

Conclusions: Severe acute rejection of the intestine allograft is frequent and has devastating consequences in nearly half of the recipients who develop it. The inability to predict or prevent the occurrence of severe AR limits the applicability of intestine transplantation to patients without severe complications of intestinal failure. A more thorough understanding through larger multicenter studies of the factors that impact the development of severe AR and predict healing (re-epithelialization of the mucosal surface) after the occurrence of severe AR is crucial to making further advances in the field of intestine transplantation.