Carr Alice L J, Shah Rahi, Marfil-Garza Braulio A, Lam Anna, Dajani Khaled, Anderson Blaire, Owen Richard T J, O'Gorman Doug, Kin Tatsuya, Bigam David, Shapiro A M James, Senior Peter A
Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
Royal College of Surgeons in Ireland, University of Medicine and Health Sciences, Dublin, Ireland.
PLoS One. 2025 Jul 29;20(7):e0329074. doi: 10.1371/journal.pone.0329074. eCollection 2025.
Islet transplantation (ITx) is advancing rapidly, with clinical trials of stem cell derived islets demonstrating short-term insulin independence. However, long-term insulin independence may still require multiple infusions. We examined the effects of sequential ITx on portal venous pressure and factors influencing acute pressure changes across 693 intraportal ITx procedures in 298 adults (44% M); who received up to 5 procedures, at the University of Alberta Hospital over 24 years. We assessed acute portal pressure changes per infusion, using linear mixed-effects models to compare sequential pre-infusion pressures to baseline and assess relationships between pressure changes and packed cell volume (PCV), purity, islet dose (IE/kg) and estimated total liver volume (eTLV). Portal pressure transiently increased, similarly, after each infusion by an overall median 2.0 mmHg (IQR 1.0,4.0). PCV exhibited the strongest relationship with change in pressure, with1mmHg increase per 1 mL of PCV, when adjusted for other parameters (Coefficient = 1.0 [95%CI 0.81,1.21];p < 0.0001). Conversely, higher purity and larger eTLV were associated with smaller increases in pressure. A significant interaction term indicated that the effect that PCV has on pressure change may be moderated at higher purities. Our work provides insights from deceased-donor intraportal ITx that can inform the design of future clinical protocols for ITx.
胰岛移植(ITx)正在迅速发展,干细胞来源的胰岛的临床试验表明可实现短期胰岛素非依赖。然而,长期胰岛素非依赖可能仍需要多次输注。我们研究了序贯ITx对门静脉压力的影响,以及在24年期间于阿尔伯塔大学医院对298名成年人(44%为男性)进行的693次门静脉内ITx手术中影响急性压力变化的因素;这些患者接受了多达5次手术。我们使用线性混合效应模型评估每次输注时的急性门静脉压力变化,以比较序贯输注前压力与基线压力,并评估压力变化与血细胞比容(PCV)、纯度、胰岛剂量(胰岛当量/kg)和估计全肝体积(eTLV)之间的关系。每次输注后,门静脉压力均短暂升高,总体中位数为2.0 mmHg(四分位间距1.0,4.0)。在调整其他参数后,PCV与压力变化的关系最为密切,每1 mL PCV增加,压力升高1 mmHg(系数 = 1.0 [95%CI 0.81,1.21];p < 0.0001)。相反,较高的纯度和较大的eTLV与较小的压力升高相关。一个显著的交互项表明,PCV对压力变化的影响可能在较高纯度时受到调节。我们的研究为死体供者门静脉内ITx提供了见解,可为未来ITx临床方案的设计提供参考。