225-OR: Sequential Islet Transplants for Type 1 Diabetes Do Not Cumulatively Increase Hepatic Portal Venous Pressure

The future of islet transplantation (ITx) is rapidly moving towards stem-cell based therapies, which have led to short term insulin independence when delivered into the hepatic portal vein. It is likely that multiple infusions will be needed to maintain insulin independence long term. We examined the effects of sequential ITx on portal pressures and if features of the transplanted preparation influence acute changes in portal pressure. We include data from adults undergoing intraportal ITx at the University of Alberta Hospital between May 1999 to April 2023. We assessed, by pairwise comparison, acute changes in portal pressure at each ITx infusion and used linear mixed-effects models to: 1) compare sequential pre-infusion portal pressure with reference to pre-first ITx infusion and 2) assess the relationship between change in portal pressure and packed cell volume (PCV), purity and islet equivalents per kilogram (IEQ/kg). We include 299 adults (44% M) who received up to 5 (median of 2 [IQR 2-3]) ITx infusions and a median total 15,220 IEQ/kg [IQR 11,324, 19,700]. The median purity across all ITx infusions was 55% [IQR 45, 70] with a median PCV of 3ml [IQR 2.5, 4]. The total time to final ITx was a median 11m [IQR 2-50]. Portal pressure acutely increased after each ITX infusion (p<0.001) by a median 2.0 mmHg [IQR 1.0-4.0]. This acute rise was not sustained however, with sequential pre-infusion portal pressure returning to similar levels (p>0.1) as that pre-first ITx infusion (median 11.0 mmHg [IQR 8.0-14.0]). PCV had the strongest correlation with post-infusion change in portal pressure, with a 1 mmHg increase in portal pressure per 1 ml of PCV (Slope: 1.09 [95% CI0.93,1.26]; p<0.001). Sequential ITx do not increase portal pressure or amplify changes during supplementary infusions. Higher PCV may exacerbate acute rises in portal pressures. Insights from deceased-donor intraportal ITx can inform safe implementation of future stem-cell based therapies in people living with diabetes.