Does the Presence of a Measurable Blood Alcohol Level in a Potential Organ Donor Affect the Outcome of Liver Transplantation?

The widespread application of hepatic transplantation has created a tremendous demand for donor organs. An assessment of donor parameters is thought to be important in selecting good donors; however, the criteria utilized have not been standardized. This study was performed to determine the effect of a measurable donor blood alcohol level on graft survival. Fifty‐two patients who underwent orthotopic liver transplantation at the University of Pittsburgh were included in the study. Twenty‐five patients received liver grafts from donors having a blood alcohol level between 0.04 and 0.4 g/I with a mean of 0.17 g/I. Twenty‐seven patients received a liver graft from a donor who had no measurable blood alcohol. There were no differences between these two groups of donors regarding the time of initial hospitalization until the time of donation. Graft failure within the first 30 days was 24% for those receiving an organ from an alcohol‐positive donor as compared with 22.2% in those receiving an organ from an alcohol negative donor. The recipient mortality rate was 16% and 11%, respectively. No relationships between the donor blood alcohol level and organ performance, frequency of primary graft nonfunction, or number of episodes of acute cellular rejection were evident. Based upon these data, the presence of a measurable blood alcohol level in a donor should not mitigate against organ donation. Copyright © 1991, Wiley Blackwell. All rights reserve

Hemodynamic and biochemical changes during normothermic and hypothermic sanguinous perfusion of the porcine hepatic graft

Using an ex vivo liver sanguinous perfusion system, hemodynamic and biochemical changes of the porcine livers were studied, which were preserved cold (4°C) for 24 hr in University of Wisconsin solution and reperfused with normothermic (37°C) (n=8) or hypothermic (32°C) (n=8) blood for 3 hr. Six more livers were reperfused with normothermic blood (37°C) immediately after procurement as controls. The total hepatic blood flow was adjusted to 1 ml/min/g liver weight, in which hepatic artery and portal vein flows were administered at a 1:2 ratio. In livers stored cold for 24 hr in UW solution and perfused normothermically, a statistically higher hepatic artery resistance was exhibited at 30 an 60 min after reperfusion (P<0.05), and there was lower bile output (P<0.05) at 90 and 120 min as compared to the controls. In livers stored cold for 24 hr in UW solution and perfused hypothermically, as compared to ones perfused normothermically, statistically higher hepatic- artery and portal-vein resistances (P<0.05) were observed throughout the perfusion period and 60 min= after reperfusion, respectively. In addition, bile output and oxygen consumption of these livers were statistically lower than those of ones perfused normothermically (P<O.05). In contrast, chemistries of the perfusat of livers perfused hypothermically were comparable to ones perfused normothermically. Histologic examination of the liver perfused hypothermically demonstrated hepatic arterial and/or portal venous congestion and mild-to-moderate hemorrhage in the portal triads. This study suggests that livers preserved for a prolonged period of time demonstrate a high hepatic arterial resistance shortly after revascularization, and that recipient hypothermia after revascularization may be a risk factor for the development of hepatic arterial thrombosis following liver transplantation. © 1990 by Williams & Wilkins

Significance of lecithin:cholesterol acyltransferase activity as a prognostic indicator of early allograft function in clinical liver transplantation

Rapid and accurate assessment of allograft function in the early postoperative period is critical for successful liver transplantation. This study evaluated the efficacy of lecithin:cholesterol acyltransferase (LCAT) activity as an indicator of early allograft function in human orthotopic liver transplantation (OLTx). During a three-month period between September and November 1987, 9 of 11 adult OLTx recipients whose graft exhibited poor function were studied. Poor graft function was defined as primary nonfunction, need for retransplantation within a week after OLTx, or elevation of the prothrombin time over 20 sec early after OLTx. Plasma LCAT activities (measured pretransplant and at 0, 6, 12, 18, and 24 hr, as well as 3 days, after OLTx) and pretransplant clinical variables were compared with those of 15 control patients whose graft exhibited good function. A significant correlation was found between mean LCAT activities during the first 24-hr after OLTx and early allograft function (P < 0.05, χ2 = 5.23). When pretransplant histological findings of the 6 grafts with poor function and the 15 controls together were correlated with the mean LCAT activity within 24 hr following OLTx, a significant association was demonstrated (P < 0.05). This study suggests that plasma LCAT activity is an effective and practical method for assessing early allograft function following OLTx

A new liver perfusion and preservation system for transplantation Research in large animals

A kidney perfusion machine, model MOX-100 (Waters Instruments, Ltd, Rochester, MN) was modified to allow continuous perfusion of the portal vein and pulsatile perfusion of the hepatic artery of the liver. Additional apparatus consists of a cooling system, a membrane oxygenator, a filter for foreign bodies, and bubble traps. This system not only allows hypothermic perfusion preservation of the liver graft, but furthermore enables investigation of ex vivo simulation of various circulatory circumstances in which physiological perfusion of the liver is studied. We have used this system to evaluate the viability of liver allografts preserved by cold storage. The liver was placed on the perfusion system and perfused with blood with a hematocrit of approximately 20% and maintained at 37°C for 3 h. The flows of the hepatic artery and portal vein were adjusted to 0.33 mL and 0.67 mL/g of liver tissue, respectively. Parameters of viability consisted of hourly bile output, oxygen consumption, liver enzymes, electrolytes, vascular resistance, and liver histology. This method of liver assessment in large animals will allow the objective evaluation of organ viability for transplantation and thereby improve the outcome of organ transplantation. Furthermore, this pump enables investigation into the pathophysiology of liver ischemia and preservation. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Pretransplant assessment of human liver grafts by plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors.

In spite of the improved outcome of orthotopic liver transplantation (OLTx), primary graft nonfunction remains one of the life-threatening problems following OLTx. The purpose of this study was to evaluate plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors as a predictor of liver allograft viability prior to OLTx. Thirty-nine donors were studied during a 5-month period between April and August 1988. Allograft hepatectomy was performed using a rapid technique or its minor modification with hilar dissections, and the allografts were stored cold (4 degrees C) in University of Wisconsin (UW) solution. Early post-transplant allograft function was classified as good, fair, or poor, according to the highest SGOT, SGPT, and prothrombin time within 5 days following OLTx. Procurement records were reviewed to identify donor data, which included conventional liver function tests, duration of hospital stay, history of cardiac arrest, and graft ischemic time. Blood samples from the donors were drawn immediately prior to aortic crossclamp, and from these plasma LCAT activity was determined. Plasma LCAT activity of all donors was significantly lower than that of healthy controls (12.4 +/- 8.0 vs 39.2 +/- 13.3 micrograms/ml per hour, P less than 0.01). LCAT activity (16.4 +/- 8.3 micrograms/ml per hour) in donors of grafts with good function was significantly higher than that in those with fair (8.6 +/- 4.5 micrograms/ml per hour, P less than 0.01) or poor (7.3 +/- 2.4 micrograms/ml per hour, P less than 0.01) function.(ABSTRACT TRUNCATED AT 250 WORDS

Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection

In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection