The growing demand for liver transplantation and the concomitant scarcity of cadaveric livers have increased the need for living donor liver transplantation (LDLT). Ensuring the safety of donors and recipients is critical. The preoperative identification of the vascular and biliary tract anatomy with 3-dimensional (3D) printing may allow better preoperative surgical planning, avert unnecessary surgery in patients with potentially unsuitable anatomy, and thereby decrease the complications of liver transplant surgery. We developed a protocol and successfully 3D-printed synthetic livers (along with their complex networks of vascular and biliary structures) replicating the native livers of 6 patients: 3 living donors and 3 respective recipients who underwent LDLT. To our knowledge, these are the first complete 3D-printed livers. Using standardized preoperative, intraoperative, and postoperative assessments, we demonstrated identical anatomical and geometrical landmarks in the 3D-printed models and native livers. Three-dimensional (3D) printing is a process for making a solid 3D object of virtually any shape from a digital model. A 3D printer works as an ordinary office printer, but instead of placing a single layer of ink on paper, the machine lays down successive thin layers of a material to form a 3D object that replicates the original one. 1 The growing demand for liver transplantation and the concomitant shortage of cadaveric livers have led to a rise in living donor liver transplantation (LDLT), in which resection of the right or left liver lobe is performed for the purpose of liver transplantation. 2 Living donors are healthy individuals, so ensuring their safety is of paramount importance. There have been a number of reported donor deaths worldwide and a substantial number of donor morbidities, so there is a need for measures to optimize donor safety. 3 Many of these morbidities are attributable to incomplete preoperative anatomical characterization of vascular and biliary structures and inaccurate estimates of the liver volume; these data are needed to determine the extent of the resection. This information provides a road map, and its accuracy has improved with the introduction of radiological software able to provide 3D visualization of liver structures. 4,5 3D imaging has the ability to better demonstrate the 3D relationships between vital vascular and biliary structures and the surrounding parenchyma in comparison with conventional computed tomography (CT) or magnetic resonance imaging (MRI). 3D imaging Additional Supporting Information may be found in the online version of this article.
The effect of normothermic machine perfusion (NMP) on post-reperfusion hemodynamics and extrahepatic biliary duct histology of donors after cardiac death (DCD) livers after transplantation has not been addressed thoroughly and represented the object of this study. Ten livers (n=5/group) with 60’ of warm ischemia were preserved by cold storage (CS) or sanguineous NMP for 10 hours, and then reperfused for 24 hours with whole blood in an isolated perfusion system to simulate transplantation. In our experiment, arterial and portal venous flows were stable in NMP group during the entire simulated reperfusion, while decreased dramatically in CS group after 16 hours post-reperfusion (P<.05), findings consistent with severe parenchymal injury. Similarly, significant differences existed between CS and NMP group on hepatocellular enzyme release, bile volume produced, and enzyme released into bile (P<.05). On histology CS livers presented with diffuse hepatocyte congestion, necrosis, intraparenchymal hemorrhage, denudated biliary epithelium and submucosal bile duct necrosis, while NMP liver showed very mild injury in liver parenchyma and biliary architecture. Most importantly, Ki67 staining in extrahepatic bile duct showed biliary epithelial regeneration. Our findings advance the knowledge of post-reperfusion events that characterize DCD livers and propose NMP as a beneficial preservation modality able to improve biliary regeneration after a major ischemic event, which may prevent in clinical transplantation the development of ischemic cholangiopathy.
Ischemic-type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD-LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m 2 , p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBSrelated graft failure in DCD-LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.
Background and Aims Hepatitis C virus (HCV)‐viremic organs are underutilized, and there is limited real‐world experience on the transplantation of HCV‐viremic solid organs into recipients who are HCV negative. Approach and Results Patients listed or being evaluated for solid organ transplant after January 26, 2018, were educated and consented by protocol on the transplantation of HCV‐viremic organs. All recipients were HCV nucleic acid test and anti‐HCV antibody negative at the time of transplant and received an HCV‐viremic organ. The primary outcome was sustained virological response (SVR) at 12 weeks after completion of direct‐acting antiviral (DAA) therapy (SVR12). Seventy‐seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. No patients had evidence of advanced hepatic fibrosis. Treatment regimen and duration were at the discretion of the hepatologist. Sixty‐four patients underwent kidney transplant (KT), and 58 KT recipients had either started or completed DAA therapy. Forty‐one achieved SVR12, 10 had undetectable viral loads but are not eligible for SVR12, and 7 remain on treatment. One KT recipient was a nonresponder because of nonstructural protein 5A resistance. Four patients underwent liver transplant and 2 underwent liver‐kidney transplant. Three patients achieved SVR12, 1 has completed DAA therapy, and 2 remain on treatment. Six patients underwent heart transplant and 1 underwent heart‐kidney transplant. Six patients achieved SVR12 and 1 patient remains on treatment. Conclusions Limited data exist on the transplantation of HCV‐viremic organs into recipients who are HCV negative. Our study is the largest to describe a real‐world experience of the transplantation of HCV‐viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV‐viremic grafts in the DAA era appears to be efficacious and well tolerated.
With increasing demand for donor organs for transplantation, machine perfusion (MP) promises to be a beneficial alternative preservation method for donor livers, particularly those considered to be of suboptimal quality, also known as extended criteria donor livers. Over the last decade, numerous studies researching MP of donor livers have been published and incredible advances have been made in both experimental and clinical research in this area. With numerous research groups working on MP, various techniques are being explored, often applying different nomenclature. The objective of this review is to catalog the differences observed in the nomenclature used in the current literature to denote various MP techniques and the manner in which methodology is reported. From this analysis, we propose a standardization of nomenclature on liver MP to maximize consistency and to enable reliable comparison and meta‐analyses of studies. In addition, we propose a standardized set of guidelines for reporting the methodology of future studies on liver MP that will facilitate comparison as well as clinical implementation of liver MP procedures.
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