Mauricio Sainz-Barriga

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co‐localized inside the thrombus.

Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty‐one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range = 25%‐91%, P = 0.001). Severe PHT (HVPG ≥ 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value ≥ 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT. Liver Transpl 17:836‐848, 2011.

A multicentre, randomized clinical trial comparing the Veriset™ haemostatic patch with fibrin sealant for the management of bleeding during hepatic surgery

BACKGROUND Bleeding during hepatic surgery is associated with prolonged hospitalization and increased morbidity and mortality. The Veriset™ haemostatic patch is a topical haemostat comprised of an absorbable backing made of oxidized cellulose and self-adhesive hydrogel components. It is designed to achieve haemostasis quickly and adhere to tissues without fixation. METHODS A prospective, randomized, multicentre, single-blinded study (n = 50) was performed to compare the use of a Veriset™ haemostatic patch with a fibrin sealant patch (TachoSil(®) ) (control) in the management of diffuse bleeding after hepatic surgery. Patients were randomized following the confirmation of diffuse bleeding requiring the use of a topical haemostat. Time to haemostasis was assessed at preset intervals until haemostasis was achieved. RESULTS Both groups were similar in comorbidities and procedural techniques. The median time to haemostasis in the group using the Veriset™ haemostatic patch was 1.0 min compared with 3.0 min in the control group (P < 0.001; 3-min minimum application time for the control patch). This result was independent of bleeding severity and surface area. Both products had similar safety profiles and no statistical differences were observed in the occurrence of adverse or device-related events. CONCLUSIONS Regardless of bleeding severity or surface area, the Veriset™ haemostatic patch achieved haemostasis in this setting significantly faster than the control device in patients undergoing hepatic resection. It was safe and easy to handle in open hepatic surgery.

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis >30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered.

Early Arterial Revascularization After Hepatic Artery Thrombosis May Avoid Graft Loss and Improve Outcomes in Adult Liver Transplantation

BACKGROUND Hepatic artery thrombosis (HAT) represents a devastating complication after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients. Treatments of HAT include thrombectomy and thrombolysis (with or without redo of the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver retransplantation, and clinical observation. METHODS We retrospectively analyzed data from 739 adult LTs between January 1992 and September 2009. HAT was classified as early (E-HAT), when occurring within the first 30 days after LT, or late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected clinically was confirmed by Doppler ultrasound and angiography in all cases. Attempted revascularization was defined as early (ER) if performed within the first 2 weeks after LT and late (LR) if performed between 15 and 30 days. RESULTS After a median follow-up (FU) of 62 months (range, 1-227 months), HAT occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L-HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to 62% graft salvage; it was 81% when the revascularization was performed within the first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The overall incidence of BC among rescued grafts was 54% without graft loss during FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E-HAT and L-HAT, respectively (P = ns). CONCLUSIONS Urgent revascularization in cases of early HAT may decrease graft loss, especially when performed within the first week after LT, with improved overall outcomes.

Flow competition between hepatic arterial and portal venous flow during hypothermic machine perfusion preservation of porcine livers.

Hypothermic machine perfusion (HMP) is regarded as a better preservation method for donor livers than cold storage. During HMP, livers are perfused through the inlet blood vessels, namely the hepatic artery (HA) and the portal vein (PV). In previous HMP feasibility studies of porcine and human livers, we observed that the PV flow decreased while the HA flow increased. This flow competition restored either spontaneously or by lowering the HA pressure (PHA). Since this phenomenon had never been observed before and because it affects the HMP stability, it is essential to gain more insight into the determinants of flow competition. To this end, we investigated the influence of the HMP boundary conditions on liver flows during controlled experiments. This paper presents the flow effects induced by increasing PHA and by obstructing the outlet blood vessel, which is the vena cava inferior (VCI). Flow competition was evoked by increasing PHA to 55–70 mmHg, as well as by obstructing the VCI. Remarkably, a severe obstruction resulted in a repetitive and alternating tradeoff between the HA and PV flows. These phenomena could be related to intra-sinusoidal pressure alterations. Consequently, a higher PHA is most likely transmitted to the sinusoidal level. This increased sinusoidal pressure reduces the pressure drop between the PV and the sinusoids, leading to a decreased PV perfusion. Flow competition has not been encountered or evoked under physiological conditions and should be taken into account for the design of liver HMP protocols. Nevertheless, more research is necessary to determine the optimal parameters for stable HMP.

Split liver transplantation with extended right grafts under patient-oriented allocation policy. Single center matched-pair outcome analysis.

Abstract: Background:  Split liver transplantation (SLT) is an established technique developed to optimize the number of available grafts. Few data are available on SLT with extended right liver grafts (eRLG) in the context of patient‐oriented allocation policy.

Implication of stem cell factor in human liver regeneration after transplantation and resection

The stem cell factor (SCF), besides regulating hemopoietic stem cells homing and proliferation, has proliferative effects on hepatocytes and may be involved in liver regeneration. We investigate if liver transplantation (LT) and hepatic resection (HR) modify the concentration of soluble SCF (s-SCF) in peripheral blood of 15 LT and 7 HR. s-SCF was measured by ELISA as ng/ml. s-SCF basal levels were higher in LT that in HR (818 ± 349 vs. 479 ± 79, p = 0.005). A significant increase of s-SCF, peaking at postoperative day +3, was seen after LT (from 818 ± 349 to 1212 ± 461, p = 0.01) and HR (from 479 ± 79 to 698 ± 122, p = 0.004). s-SCF peak levels were higher after LT than HR (p = 0.0008). At day +7 s-SCF concentration returned to baseline values. LT have a higher basal s-SCF level than HR. These data show for the first time that liver injury affects s-SCF level and suggest that SCF may be involved also in clinical liver regeneration.

Living donor liver transplantation in Europe

Living donor liver transplantation (LDLT) sparked significant interest in Europe when the first reports of its success from USA and Asia were made public. Many transplant programs initiated LDLT and some of them especially in Germany and Belgium became a point of reference for many patients and important contributors to the advancement of the field. After the initial enthusiasm, most of the European programs stopped performing LDLT and today the overall European activity is concentrated in a few centers and the number of living donor liver transplants is only a single digit fraction of the overall number of liver transplants performed. In this paper we analyse the present European activities and highlight the European contribution to the advancement of the field of LDLT.

Successful transplantation of small‐for‐size grafts: A reappraisal

The outcomes of adult living donor liver transplantation (ALDLT) are equivalent to the outcomes of deceased donor liver transplantation in similar patient populations at experienced centers. Because of the organ shortage, most transplant centers are confronted with the need to perform transplantation for patients on the waiting list before they die or become too ill. Ultimately, it is the combined mortality of patients on the waiting list and posttransplant mortality, which determines the efficacy of liver replacement therapy. With the current ALDLT crisis in Western countries, it is imperative to develop reliable strategies that lead to successful outcomes and, at the same time, reduce the risks for living donors. On the basis of donor morbidity data for ALDLT from American and Asian surveys (1957 patients), we can calculate a reduced morbidity rate for left lobe donors versus right lobe donors (21% versus 11.5%). Data from the European Liver Transplant Registry show similar results. The widespread use of left lobes has been limited because they are smaller and are potentially insufficient for the metabolic demands of recipients. Currently, a donor liver is considered a small-for-size graft (SFSG) when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. Nevertheless, the graft size is only one of the factors required for successful ALDLT. Because of the vast potential pool of living donors and the inferior risk associated with left liver donation, a strategy for transplanting SFSGs safely into adult recipients could effectively address the donor shortage and potentially reduce mortality on the waiting list. Despite the statistically significant negative impact of SFSGs on graft prognosis and patient outcomes, success with these grafts was observed in early reports. Nishizaki et al. recorded no graft losses in 5 patients receiving SFSGs with graft volume to standard liver volume ratios of 26% to 29% in 2001. Likewise, in 2003, Kiuchi et al. reported 4 successful instances in which SFSGs were used in recipients with various pretransplant statuses; the lowest graft-to-recipient weight ratio was 0.59. These findings suggest that although recipients of SFSGs are at higher risk for worse outcomes, the small size of the grafts is not always solely responsible. Factors other than the graft volume can potentially influence the outcome; these include recipient-related factors (disease clinical status and portal hypertension), graft-related factors (donor age, steatosis, cold and warm ischemia times, ischemia/reperfusion injury, and immunological factors), and technical factors (vascular reconstruction and adequate outflow, vascular inflow, and pressure gradients). All these factors contribute to the concept of functional graft size, and even a larger graft can fail when multiple risk factors are present. During the last decade, controversial results have been reported about outcomes with SFSGs. The lowest 1-year graft survival rates have ranged from 33% to 65%, and the highest rates have ranged from 75% to 100%. Graft failure due to the use of SFSGs has been described as small-for-size syndrome (SFSS).