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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 169-172

Is the Institute Georges Lopez-1 solution an equally effective, cheaper alternative to the University of Wisconsin solution in liver transplantation?


1 Department of Liver Diseases and Transplantation, Manipal Hospitals; Department of Surgical Gastroenterology, Manipal Hospital Whitefield, Bengaluru, Karnataka, India
2 Department of Liver Diseases and Transplantation, Manipal Hospitals, Bengaluru, Karnataka, India

Date of Submission01-Oct-2018
Date of Decision02-Dec-2018
Date of Acceptance10-Jan-2019
Date of Web Publication17-Sep-2019

Correspondence Address:
Dr. Magnus Mansard
Department of Liver Diseases and Transplantation, Manipal Hospitals, Old Airport Road, Bengaluru - 560 017, Karnataka; Department of Surgical Gastroenterology, Manipal Hospital Whitefield, Bengaluru - 560 066, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_61_18

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  Abstract 


Aim: To compare the outcomes of deceased donor liver transplantation (DDLT) using either the University of Wisconsin solution (UW) or the Institute Georges Lopez-1 (IGL-1) solution. Materials and Methods: Adult patients who underwent DDLT between November 2015 and March 2018 were included in the study. All patients received grafts from brain-dead donors. In 30 patients, the UW solution was used to preserve the liver and in 53 patients, the IGL-1 solution was used. The data of these two groups of the patients were analyzed and compared. Results: Between the two groups of patients, donor and recipient demographics and surgery-related variables were found to be similar. No difference was observed in the incidence of postreperfusion syndrome, number of days of hospitalization, and in the 30-day mortality. Early graft dysfunction was observed in 9 (16.98%) patients in the IGL-1 group and in 7 (23.33%) patients in the UW group (P = 0.48). One patient had primary nonfunction in each group. The postoperative levels of the liver transaminases were also not found to be significantly different. Conclusions: The efficacies of liver preservation by the IGL-1 and UW solutions were found to be comparable.

Keywords: Economics, liver allograft function/dysfunction, organ perfusion and preservation


How to cite this article:
Mansard M, Siddachari R, Govil S, Doraiswamy S, Kumar G, Subramanian N, Arikichenin O. Is the Institute Georges Lopez-1 solution an equally effective, cheaper alternative to the University of Wisconsin solution in liver transplantation?. Indian J Transplant 2019;13:169-72

How to cite this URL:
Mansard M, Siddachari R, Govil S, Doraiswamy S, Kumar G, Subramanian N, Arikichenin O. Is the Institute Georges Lopez-1 solution an equally effective, cheaper alternative to the University of Wisconsin solution in liver transplantation?. Indian J Transplant [serial online] 2019 [cited 2019 Dec 9];13:169-72. Available from: http://www.ijtonline.in/text.asp?2019/13/3/169/266951




  Introduction Top


It is well recognized that the success of liver transplantation strongly depends on effective organ preservation resulting in the maintenance of functional, biochemical, and morphological integrity of the graft.[1] A better organ preservation solution will reduce the posttransplant morbidity and mortality and as well increase the donor pool. The University of Wisconsin (UW) solution is currently the most widely used preservation medium for liver transplantation worldwide. The Institute Georges Lopez (IGL-1) solution has been proposed as an alternative to the UW solution for liver transplantation. Its composition is similar to that of the UW solution: the hydroxyethyl starch (HES) in UW is replaced by polyethylene glycol (PEG) in IGL-1, making IGL-1 less viscous.[2] Furthermore, the concentrations of sodium and potassium are reversed in IGL-1 when compared to that in UW. The composition of IGL-1 solution overcomes the two main limitations of UW solution which are its high viscosity and high potassium levels in the solution.[3] The aim of this study is to compare the efficacy of IGL-1 solution for liver preservation to that of the standard UW solution.


  Materials and Methods Top


Consecutive patients who underwent deceased donor liver transplantation (DDLT) at Manipal Hospitals since the inception of the liver transplant program in November 2015 till January 2018 have been included in this study. The data collected prospectively on these patients have been retrospectively analyzed. All patients studied were aged above 18 years and have undergone their first liver transplants. The grafts were procured from brain dead. All patients received whole grafts. Patients receiving combined grafts were excluded from the study. The choice of perfusion solution depended on its availability and the surgeon's preference. As a routine policy, 4 L of Histidine–tryptophan–ketoglutarate solution was used to flush the arterial system through the aortic cannulation. Two liters of either IGL-1 or UW solution was used to flush the portal venous system in situ and 2 more liters of the same solution was used to flush the graft in the back table. Immediately before use, the following were added to each liter of the UW solution: 200,000 units of penicillin G, 40 units of regular insulin, and 16 mg of dexamethasone, as per the instructions from the manufacturer of the solution. Nothing was added to the IGL-1 solution before use.

The recipient variables that were observed were age, sex, height, weight, body mass index (BMI), presence of hypertension, presence of diabetes, preoperative bilirubin, preoperative international normalized ratio (INR), preoperative creatinine, the Model for End-Stage Liver Disease (MELD) score, the Child-Turcotte-Pugh (CTP) score, etiology, and the presence of hepatocellular carcinoma (HCC). The donor characteristics observed in both groups were age, sex, estimated donor weight, peak sodium levels, the estimated steatosis of the graft and the number of inotropes, and the donor was on before donation. The surgery-related variables that were recorded include type of arterial anatomy of the graft, the number of blood transfusions required, the need for portal vein thrombectomy, and the ischemia times.

The following outcomes were studied postreperfusion syndrome (PRS), early allograft dysfunction (EAD), mortality within the first 30 days after the transplantation and postoperative trend in the production of serum hepatic enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). PRS was defined as a decrease in mean arterial pressure >30% below the baseline value, lasting for at least 1 min, occurring during the first 5 min after reperfusion of the liver graft (unclamping of the portal vein).[4] EAD was defined as a peak value of aminotransferases >2000 IU/mL during the 1st week or an INR of ≥1.6 and/or bilirubin ≥10 mg/dL at day 7.[5]

All analyses were performed using the Statistical software package STATA version 15.0 (StataCorp., Lakeway Drive College Station, Texas, USA). Continuous variables were described by either means and standard deviations, or median and interquartile range, and categorical variables by frequencies and percentages. Comparisons between groups IGL-1 and UW were performed by Student's t-test for continuous variables. The Pearson's Chi-square test was used for categorical variables, and the Fisher's exact test was used when the variables were small. The nonparametric Mann–Whitney U-test was used to compare the liver enzymes, peak bilirubin, and peak INR values between the groups. For all analyses, P < 0.05 was considered as statistically significant.


  Results Top


A total of 83 patients underwent DDLTs in the study period. The IGL-1 preservation solution was used in 53 (63.86%) patients and the UW solution was used in 30 (36.14%) patients. Recipient, donor, and graft baseline characteristics according to each group are presented in [Table 1]. There were no differences in terms of recipient's age, sex, height, weight, BMI, presence of hypertension, presence of diabetes, preoperative bilirubin, preoperative INR, preoperative creatinine, the MELD score, the CTP score, and the etiology of liver disease. The IGL-1 group had more number of patients with HCC than the UW group (P = 0.03).
Table 1: Recipient and donor characteristics and surgery variables

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A significantly higher proportion of female donors were found in the IGL1 group (P = 0.02). The following other donor characteristics were comparable: age, peak sodium levels, estimated weight of the donor, the number of donors on high (three or more) inotropic support, and the proportion of patients with >30% steatosis of the graft. The proportion of patients who underwent portal vein thrombectomy, the proportion of grafts which had accessory/replaced hepatic arteries, the ischemia times, and the number of blood transfusions required were also comparable.

The outcome parameters are presented in [Table 2]. The peak AST levels, bilirubin levels, and the INR in the postoperative period were comparable between the two groups. The incidence of PRS, EAD, and 30-day mortality were not found to be significantly different between the two groups. The period of hospitalization was also not different between patients of the two groups.
Table 2: Outcome parameters

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[Figure 1] and [Figure 2] show the postoperative trends of the liver enzymes (AST and ALT respectively). The enzyme levels measured on postoperative days 1, 4, and 7 were not found to be significantly different between the two groups.
Figure 1: Postoperative trends in aspartate aminotransferase levels

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Figure 2: Postoperative trends in alanine aminotransferase levels

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  Discussion Top


Studies have demonstrated that UW preservation solution presents two major limitations. The presence of HES, as an oncotic agent, has a hyperaggregating effect on red blood cells.[6] This can potentially result in microcirculatory disturbances resulting in ischemia-type biliary complications.[7] The other limitation is its high potassium concentration that can provoke vasoconstriction and damage cells. It carries a risk of hyperkalemic cardiac arrest, and therefore, requires a flush of the organ in the recipient before transplantation. The other limitations are its high viscosity, requirement for additives, and high cost.

IGL-1 is a new solution with two main characteristics: inversion of potassium and sodium concentrations resulting in a lower concentration of potassium compared to UW solution and substitution of HES by a biopolymer, the PEG, resulting in a lower viscosity of IGL-1 when compared to UW solution.[2] These physical and biochemical properties could improve liver washout during procurement, thus preventing intrahepatic microcirculatory changes.[3] The low viscosity of the IGL-1 solution results in a better washout of blood at the capillary level. This can potentially result in better preservation of the hepatic microcirculation and thereby leading to a lesser chance of ischemic cholangiopathies in the graft.[3] The low potassium content of the fluid also averts the risk of hyperkalemic cardiac arrest and the need to flush the graft.

In a randomized controlled trial, Dondéro et al. compared IGL-1 preservation solution with UW solution in liver transplantation. The rates of primary nonfunction, early retransplantation, incidence of biliary nonanastomotic strictures, and hepatic artery thrombosis were found to be similar in both the groups.[8] A European liver transplant registry study evaluating long-term outcomes of >40000 liver grafts also revealed that IGL-1 and UW provide similar results.[9]

The Liver Transplantation Department, at Manipal Hospitals in India, procured the IGL-1 solution and started using it for the first time in the country. The ease of use of the solution due to the lack of requirement of additives and the lack of need for flushing of the graft made this the preferred solution for allograft preservation during transplants. However, the UW solution, the current standard worldwide, was preferred when the ischemia times were expected to be higher or when the graft was considered marginal. This can be seen in [Table 1], where the proportion of steatotic grafts were higher and the cold ischemia times were longer in the UW group, though not statistically significant.

In India, deceased organ donation has been increasing every year. While previously most of the liver grafts were from living donors, increasingly DDLTs are being carried out.[10] The high volumes of preservative solutions needed for DDLT has resulted in a prohibitive cost to patients. Using 8 L of the UW solution for organ retrieval at the cost of 36,000 rupees/L will incur a cost of 288,000 rupees (nearly 15% of the total average cost of the transplantation including postoperative hospital stay). One of the main advantages of the IGL-1 solution in India is its lower cost. It is 40% less costly than UW solution.[8] In India, liver transplantation is probably the costliest surgery performed, and it is not covered under most of the insurance plans.[11] The use of IGL-1 can potentially reduce the cost of the surgery by a large margin, thereby decreasing the financial burden on the patient.


  Conclusions Top


IGL-1 has been shown to be safe and effective to be used as a preservation solution for liver transplantation. Posttransplant graft function was comparable to that observed with UW solution. Further studies are required to compare the efficacy of the two solutions when used to preserve marginal grafts with longer ischemia times.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation 1988;45:673-6.  Back to cited text no. 1
    
2.
Wiederkehr JC, Igreja MR, Nogara MS, Goncalves N, Montemezzo GP, Wiederkehr HA, et al. Use of IGL-1 preservation solution in liver transplantation. Transplant Proc 2014;46:1809-11.  Back to cited text no. 2
    
3.
Ben Abdennebi H, Elrassi Z, Scoazec JY, Steghens JP, Ramella-Virieux S, Boillot O, et al. Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model. World J Gastroenterol 2006;12:5326-30.  Back to cited text no. 3
    
4.
Aggarwal S, Kang Y, Freeman JA, Fortunato FL, Pinsky MR. Postreperfusion syndrome: Cardiovascular collapse following hepatic reperfusion during liver transplantation. Transplant Proc 1987;19:54-5.  Back to cited text no. 4
    
5.
Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010;16:943-9.  Back to cited text no. 5
    
6.
Morariu AM, Vd Plaats A, V Oeveren W, 'T Hart NA, Leuvenink HG, Graaff R, et al. Hyperaggregating effect of hydroxyethyl starch components and university of wisconsin solution on human red blood cells: A risk of impaired graft perfusion in organ procurement? Transplantation 2003;76:37-43.  Back to cited text no. 6
    
7.
Olschewski P, Hunold G, Eipel C, Neumann U, Schöning W, Schmitz V, et al. Improved microcirculation by low-viscosity histidine- tryptophan-ketoglutarate graft flush and subsequent cold storage in University of Wisconsin solution: Results of an orthotopic rat liver transplantation model. Transpl Int 2008;21:1175-80.  Back to cited text no. 7
    
8.
Dondéro F, Paugam-Burtz C, Danjou F, Stocco J, Durand F, Belghiti J, et al. A randomized study comparing IGL-1 to the University of Wisconsin preservation solution in liver transplantation. Ann Transplant 2010;15:7-14.  Back to cited text no. 8
    
9.
Adam R, Delvart V, Karam V, Ducerf C, Navarro F, Letoublon C, et al. Compared efficacy of preservation solutions in liver transplantation: A long-term graft outcome study from the European Liver Transplant Registry. Am J Transplant 2015;15:395-406.  Back to cited text no. 9
    
10.
Nagral S, Nanavati A, Nagral A. Liver transplantation in India: At the crossroads. J Clin Exp Hepatol 2015;5:329-40.  Back to cited text no. 10
    
11.
Narasimhan G, Kota V, Rela M. Liver transplantation in India. Liver Transpl 2016;22:1019-24.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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