Hepatic macrosteatosis in the US pediatric deceased liver donor population

Abstract

Introduction:The pediatric obesity epidemic is associated with early development of hepatic macrosteatosis, a hallmark of non-alcoholic fatty LI disease, which is thought to be more rapidly progressive in children than adults. Macrosteatosis in adult allografts is associated with allograft loss, but this has not been examined in pediatric donors. Methods:We studied all pediatric potential whole LI donors (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) who had a LI biopsy in the SRTR (n = 862) and whose LI was transplanted (n = 862). Macrosteatosis was abstracted from biopsy reports and compared to values in the SRTR standard analytic file. Recipients of macrosteatotic pediatric allografts were matched 1:1 to recipients of non-macrosteatotic pediatric allografts by propensity score matching on donor/recipient variables. All-cause allograft loss was estimated via Kaplan-Meier analysis and Cox proportional hazards model. Results:From 2005 to 2018, the proportion of pediatric donors (age ≥2 years) with obesity increased (14.8% to 21.7%; p < .001), as did the proportion of pediatric deceased whole LI-only donor allografts with macrosteatosis (n = 10 648; 1.8% to 3.9%; p < .001). The median degree of macrosteatosis among macrosteatotic donors was 10% (IQR 5-30). There were no significant differences in all-cause allograft loss between recipients of pediatric LI allografts with and without macrosteatosis at 90 days (p = .11) or 1 year (p = .14) post-transplant in Kaplan-Meier analysis or a Cox proportional hazards model (p > .05).

Abnormal Liver Biopsies of Donor Grafts in Pediatric Liver Transplantation: How Do They Fare?

“…When comparing outcomes of AL by each abnormal variable, we further found that AL with >5% macrosteatosis were no different in terms of overall graft survival compared to NL. Our results correspond with the evolving paradigm that livers with increased levels of macrosteatosis may still be suitable for pediatric transplants [10][11][12][13][14]. In our cohort, the presence of inflammation in donor liver biopsies led to a lower overall graft survival and was found in 90% of graft loss events.…”

“…Historically, in pediatric liver transplantation, healthier grafts with lower levels of macrosteatosis are preferred. Recent studies have shown that obese donors or liver grafts with >5% macrosteatosis do not adversely impact the outcomes of pediatric transplant recipients, thus we chose 5% macrosteatosis as a threshold for our study [12,13]. Irie et al demonstrated that pediatric patients who received a living donor liver transplant with moderate-to-severe macrosteatosis also had no difference in patient survival and that the degree of macrosteatosis decreased over time [14].…”

NO–IL-6/10–IL-1β axis: a new pathway in steatotic and non-steatotic liver grafts from brain-dead donor rats

“…Considering previous publications that reported a regulatory role of IL-6 and IL-10 on IL-1 ( 11 , 12 , 14 , 15 ), IL-1 was investigated as a possible mediator involved in signaling mechanism underpinning IL-6 and IL-10 beneficial effects. For this, hepatic levels of IL-1α and IL-1β in LT and BD surgical settings were first determined.…”

“…In consideration of the previous data that suggest that the effects resulting from NO could involve signaling mechanisms requiring interleukins ( 12 , 16 , 17 , 19 – 21 ), we evaluated whether endogenous NO affects IL-6, IL-10, and IL-1β in non-steatotic and steatotic grafts from DBDs.…”

“…It is also the case that steatosis is becoming even more prevalent, which means that more steatotic livers are discarded, particularly if the infiltration of fat is severe. Clearly, this exacerbates the current shortage of donors, which has already been described as critical ( 12 ). Thus, in order to reduce the LT waiting lists, we need therapeutic strategies that will reduce the post-LT risks of organ dysfunction or failure that are inherent to steatotic livers from DBDs.…”