Liver transplantation using organs from deceased organ donors: a single organ transplant center experience

BACKGROUND： In 2011, a pilot program for deceased organ donation was initiated in China. We describe the first successful series of liver transplants in the pilot program.METHODS： From July 2011 to August 2012, our center performed 26 liver transplants from a pool of 29 deceased donors. All organ donation and allograft procurement were conducted according to the national protocol. The clinical data of donors and recipients were collected and summarized retrospectively.RESULTS： Among the 29 donors, 24 were China Category II donors（organ donation after cardiac death）, and five were China Category III donors（organ donation after brain death followed by cardiac death）. The recipients were mainly the patients with hepatocellular carcinoma. The one-year patient survival rate was 80.8% with a median follow-up of 422（2-696） days. Among the five mortalities during the follow-up,three died of tumor recurrence. In terms of post-transplant complications, 9 recipients（34.6%） experienced early allograft dysfunction, 1（3.8%） had non-anastomotic biliary stricture,and 1（3.8%） was complicated with hepatic arterial thrombosis.None of these complications resulted in patient death. Notably,primary non-function was not observed in any of the grafts.CONCLUSION： With careful donor selection, liver transplant from deceased donors can be performed safely and plays acritical role in overcoming the extreme organ shortage in China.

Breath volatile organic compounds for the gut-fatty liver axis: promise, peril, and path forward

The worldwide interest in the gut microbiome and its impact on the upstream liver highlight a critical upside to breath research: it can uniquely measure otherwise unmeasurable biology. Bacteria make gases [volatile organic compounds(VOCs)] that are directly relevant to pathophysiology of the fatty liver and associated conditions, including obesity. Measurement of these VOCs and their metabolites in the exhaled breath, therefore, present an opportunity to safely and easily evaluate, on both a personal and a population level, some of our most pressing public health threats. This is an opportunity that must be pursued. To date, however, breath analysis remains a slowly evolving field which only occasionally impacts clinical research or patient care. One major obstacle to progress is that breath analysis is inherently and emphatically mutli-disciplinary: it connects engineering, chemistry, breath mechanics, biology and medicine. Unbalanced or incomplete teams may produce inconsistent and often unsatisfactory results. A second impediment is the lack of a well-known stepwise structure for the development of non-invasive diagnostics. As a result, the breath research landscape is replete with orphaned single-center pilot studies. Often, important hypotheses and key observations have not been pursued to maturation. This paper reviews the rationale and requirements for breath VOC research applied to the gut-fatty liver axis and offers some suggestions for future development.

Overview of organic anion transporters and organic anion transporter polypeptides and their roles in the liver

Organic anion transporters(OATs)and organic anion transporter polypeptides(OATPs)are classified within two SLC superfamilies,namely,the SLC22A superfamily and the SLCO superfamily(formerly the SLC21A family),respectively.They are expressed in many tissues,such as the liver and kidney,and mediate the absorption and excretion of many endogenous and exogenous substances,including various drugs.Most are composed of 12 transmembrane polypeptide chains with the C-terminus and the N-terminus located in the cell cytoplasm.OATs and OATPs are abundantly expressed in the liver,where they mainly promote the uptake of various endogenous substrates such as bile acids and various exogenous drugs such as antifibrotic and anticancer drugs.However,differences in the locations of glycosylation sites,phosphorylation sites,and amino acids in the OAT and OATP structures lead to different substrates being transported to the liver,which ultimately results in their different roles in the liver.To date,few articles have addressed these aspects of OAT and OATP structures,and we study further the similarities and differences in their structures,tissue distribution,substrates,and roles in liver diseases.

Dosimetry calculations of involved and noninvolved organs in proton therapy of liver cancer:a simulation study

Radiation for targeting liver tumors can be challenging because of the damage that it can cause to sensitive organs such as heart and kidney.To calculate the dose received by noninvolved organs,a modeling of the patient’s entire body is necessary.Therefore,in this study,a human Oak Ridge National Laboratory-Medical Internal Radiation Dose phantom was used for liver proton therapy simulation.The results show that the optimum proton energy interval covering the whole tumor was in the range of 90-120 MeV.A spread-out Bragg peak was built by adding Bragg peaks to cover the liver tumor volume,and beam parameters recommended by the International Commission on Radiation Units and Measurements(ICRU) were evaluated.The flux of secondary particles was calculated on the surface of the tumor,and two-dimensional dose distributions for protons,neutrons and photons were shown.Finally,the total doses of protons,photons and neutrons in tumor and 14 noninvolved organs were calculated.The results indicated that the ratio of received dose to the normal tissue of the liver concerning the spherical tumor of 2 cm in radius was approximately0.01.This ratio for organs such as gall bladder,heart and kidney was approximately 8.4×10-5,5.1×10-5 and2.34×10-5.Secondary particles such as neutrons andphotons deposit their energies to organs located far from the treatment volume,thus increasing the risk of secondary cancers.The research results indicated that the secondary particles dose was quite small in liver proton therapy.All the calculations were performed using Monte Carlo N-Particle Transport Code (MCNP).

Clinical analysis of different periods of liver transplantation at an organ transplantation centre

Objective To summarize our clinical experience in liver transplantation while considering the background in this filed in China. Methods Ninety-five patients who had received liver transplantation from April 1993 to March 2002 were analyzed retrospectively. Three periods were defined objectively as period Ⅰ(1993-1997),Ⅱ(1999) and Ⅲ(2000 -2002). Operative techniques, recipients, original diseases, complications and survival rates were compared among the three periods. Results Malignant liver lesions were the main cause for liver transplantation in period Ⅰ and Ⅱ. The ratio of number of malignant disease to total recipients decreased gradually from period Ⅰ to Ⅱ (100%, 53% and 35%, respectively). The 1-year survival rate in patients with benign liver disease was 85 % and the total operative mortality was 5% in period Ⅲ. The incidence of hepatitis B virus reactivation or reinfection was 24% twelve months after liver transplantation. Vascular complication decreased but biliary complications did

Liver plays a central role in asymmetric dimethylargininemediated organ injury

Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.

Split liver transplantation: Current developments

In 1988, Rudolf Pichlmayr pioneered split liver transplantation(SLT), enabling the transplantation of one donor liver into two recipients-one pediatric and one adult patient. In the same year, Henri Bismuth and colleagues performed the first full right/full left split procedure with two adult recipients. Both splitting techniques were rapidly adopted within the transplant community. However, a SLT is technically demanding, may cause increased perioperative complications, and may potentially transform an excellent deceased donor organ into two marginal quality grafts. Thus, crucial evaluation of donor organs suitable for splitting and careful screening of potential SLT recipients is warranted. Furthermore, the logistic background of the splitting procedure as well as the organ allocation policy must be adapted to further increase the number and the safety of SLT. Under defined circumstances, in selected patients and at experienced transplant centers, SLT outcomes can be similar to those obtained in full organ LT. Thus, SLT is an important tool to reduce the donor organ shortage and waitlist mortality, especially for pediatric patients and small adults. The present review gives an overview of technical aspects, current developments, and clinical outcomes of SLT.

Desferrioxamine in warm reperfusion media decreases liver injury aggravated by cold storage

AIM:To evaluate whether desferrioxamine decreases ischemia and perfusion injury aggravated by cold storage(CS)in a rat liver perfusion model. METHODS:Isolated rat livers were kept in CS in University of Wisconsin Solution for 20 h at 4℃,then exposed to 25 min of warm ischemia(WI)at 37℃ followed by 2 h of warm perfusion(WP)at 37℃with oxygenated(95%oxygen and 5%carbon dioxide) Krebs-Henseleit buffer.Desferrioxamine(DFO),an iron chelator,was added at different stages of storage,ischemia and perfusion:in CS only,in WI only,in WP only, in WI and perfusion,or in all stages.Effluent samples were collected after CS and after WI.Perfusate samples and bile were collected every 30 min(0,0.5,1,1.5 and 2 h)during liver perfusion.Cellular injury was assessed by the determination of lactate dehydrogenase(LDH) and aspartate aminotransferase(AST)in the effluent and perfusate samples.Total iron was analysed in the perfusate samples.After WP,the liver was collected for the determination of liver swelling(wet to dry ratio) and liver morphological examination(hematoxylin and eosin staining). RESULTS:Increased CS time caused increased liver dysfunction during WP.After 2 h of WP,liver injury was indicated by increased release of AST(0.5 h CS:9.4± 2.2 U/g liver vs 20 h CS:45.9±10.8 U/g liver,P<0.05) and LDH(0.5 h CS:59±14 U/g liver vs 20 h CS:297 ±71 U/g liver,P<0.05).There was an associated increase in iron release into the perfusate(0.5 h CS:0.11 ±0.03μmoL/g liver vs 20 h CS:0.58±0.10μmoL/g liver,P<0.05)and reduction in bile flow(0.5 h CS: 194±12μL/g vs 20 h CS:71±8μL/g liver,P<0.05). When DFO was added during WI and WP following 20 h of CS,release of iron into the perfusate was de- creased(DFO absent 0.58±0.10μmoL/g liver vs DFO present 0.31±0.06μmoL/g liver,P<0.05),and liver function substantially improved with decreased release of AST(DFO absent 45.9±10.8 U/g liver vs DFO present 8.1±0.9 U/g liver,P<0.05)and LDH(DFO absent 297±71 U/g liver vs DFO present 56±7 U/g liver,P<0.05),and increased bile flow(DFO absent 71±8μL/g liver vs DFO present 237±36μL/g liver, P<0.05).DFO was also shown to improve liver morphology after WP.Cellular injury(the release of LDH and AST)was significantly reduced with the addition of DFO in CS medium but to a lesser extent compared to the addition of DFO in WP or WI and perfusion.There was no effect on liver swelling or bile flow when DFO was only added to the CS medium. CONCLUSION:DFO added during WI and perfusion decreased liver perfusion injury aggravated by extended CS.

The role of graft reperfusion sequence in the development of non-anastomotic biliary strictures following orthotopic liver transplantation: A meta-analysis

Background: Liver transplant is a potential cure for liver failure and hepatic malignancy but there are many techniques which have been described for vascular reconstruction. This study was to compare the prevalence of non-anastomotic biliary stricture and other surgical complications based on Clavien-Dindo scoring system, in initial portal reperfusion(sequential) versus simultaneous or initial artery reperfusion. Data sources: Meta-analysis of published studies comparing the outcomes of both techniques was carried out. Data search was conducted across the major databases and studies were selected under the guidance of the Cochrane guidelines for systematic reviews and meta-analysis. Results: Seven studies were included to address the primary and the secondary outcomes. No statistical difference was found in the incidence of non-anastomotic biliary strictures(OR = 0.40; P = 0.14), regardless of reperfusion technique. The pooled estimate of the Clavien-Dindo grading of complications was not significantly different between the techniques, though Clavien-Dindo II complications were higher in the simultaneous or initial artery reperfusion group than the initial portal reperfusion group(OR = 2.73; P = 0.01). Similarly, there was no difference in the operative time, hospital stay and other outcomes addressed in this report. Conclusions: The available evidence suggests that there is no significant difference demonstrated in the rate of non-anastomotic biliary strictures or other complications, between the two techniques, except for Clavien-Dindo II complications.

Current developments in pediatric liver transplantation

In 1953, the pioneer of human orthotopic liver transplantation(LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT(p LT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, p LT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and postoperative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of p LT, with a focus on alternatives to full-size deceased-donor organ transplantation.

Liver protection strategies in liver transplantation

BACKGROUND： Liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver protection.DATA SOURCES： Databases such as PubM ed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words： ＂ischemia reperfusion injury＂, ＂graft preservation＂, ＂liver transplantation＂, ＂machine perfusion＂ and ＂conditioning＂. Of the 146 studies identified,only those with cutting edge strategies were analyzed.RESULTS： A variety of therapeutic approaches were proposed to alleviate graft ischemia/reperfusion injury, which included static cold storage, machine perfusion （hypothermic, normothermic and subnormothermic）, manual conditioning （pre,post and remote）, and pharmacological conditioning. Evidences from animal experiments and clinical trials suggested that all these strategies could potentially protect liver graft; however, their clinical applications are limited partially due to their own disadvantages.CONCLUSIONS： There are a plenty of methods suggested to decrease the degree of donor liver transplantation-related injury. However, none of these approaches is perfect in clinical practice. More translational researches （molecular and clinical studies） are needed to improve the techniques in liver graft protection.

New strategies for prevention and treatment of splenic artery steal syndrome after liver transplantation

AIM: To explore a prophylactic procedure to prevent splenic artery steal syndrome (SASS), as well as a therapeutic intervention to correct it.

Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury?

Longstanding research describes the mechanisms whereby the restoration of blood flow and reoxygenation(reperfusion) aggravates the ischaemic injury caused by a period of anoxia to a donor liver. This phenomenon, called ischaemia-reperfusion injury(IRI), leads to parenchymal cell death,microcirculatory failure, and inflammatory immune response. Clinically, IRI is the main factor responsible for the occurrence of posttransplant graft dysfunction and ischaemic-type biliary lesions. While extended criteria donor livers are more vulnerable to IRI, their utilisation is required to address the shortfall in donor organs. Thus, the mitigation of IRI should drive the setting of a new benchmark for marginal organ preservation. Herein, strategies incorporating different modalities of machine perfusion of the liver to alleviate IRI are discussed in conjunction with advantages and disadvantages of individual protocols.Techniques leading to reperfusion of the liver during machine perfusion(in situ normothermic regional perfusion and ex situ normothermic machine perfusion)may mitigate IRI by shortening the ischaemic period of the organs. This benefit potentially escalates from the minimum level, obtained following just partial alleviation of the ischaemic period, to the maximum level, which can be potentially achieved with ischaemia-free organ transplantation. Techniques that do not lead to reperfusion of the liver during machine perfusion(hypothermic,subnormothermic, and controlled-oxygenated rewarming) optimise mitochondrial oxidative function and replenish cellular energy stores, thereby lowering reactive oxygen species production as well as the activation ofdownstream inflammatory pathways during reperfusion. Further mechanistic insights into IRI may guide the development of donor-specific protocols of machine perfusion on the basis of the limitations of individual categories of extended criteria donor organs.

Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure:A systematic review

BACKGROUND Orthotopic liver transplantation(OLT)is the only treatment for end-stage liver failure;however,graft shortage impedes its applicability.Therefore,studies investigating alternative therapies are plenty.Nevertheless,no study has comprehensively analyzed these therapies from different perspectives.AIM To summarize the current status of alternative transplantation therapies for OLT and to support future research.METHODS A systematic literature search was performed using PubMed,Cochrane Library and EMBASE for articles published between January 2010 and 2018,using the following MeSH terms:[(liver transplantation)AND cell]OR[(liver transplantation)AND differentiation]OR[(liver transplantation)AND organoid]OR[(liver transplantation)AND xenotransplantation].Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation.Among them,we selected articles including in vivo transplantation.RESULTS A total of 89 studies were selected.There are three principle forms of treatment for liver failure:Xeno-organ transplantation,scaffold-based transplantation,and cell transplantation.Xeno-organ transplantation was covered in 14 articles,scaffold-based transplantation was discussed in 22 articles,and cell transplantation was discussed in 53 articles.Various types of alternative therapies were discussed:Organ liver,25 articles;adult hepatocytes,31 articles;fetal hepatocytes,three articles;mesenchymal stem cells(MSCs),25 articles;embryonic stem cells,one article;and induced pluripotent stem cells,three articles and other sources.Clinical applications were discussed in 12 studies:Cell transplantation using hepatocytes in four studies,five studies using umbilical cord-derived MSCs,three studies using bone marrow-derived MSCs,and two studies using hematopoietic stem cells.CONCLUSION The clinical applications are present only for cell transplantation.Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations,which warrants future research to find relevant clinical applications.

Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation

Background: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma(HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points(exceptional MELD, ex MELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional(neoadjuvant) treatment(LRT) is used. For patients unlikely to timely receive an organ via primary allocation,“extended critera donor(ECD) organs” are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. Methods: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42(84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients(82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. Results: One-and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached( P = 0.487). LRT had no impact on overall survival( P = 0.629). Median waiting time was shorter if no LRT was performed(4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival( P = 0.663). Conclusions: Patients with an expected waiting time to transplantation of > 6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.

Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature

Mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is fulfilling all normal activities. Adult giant MHL is extremely rare. Symptoms, physical signs, laboratory results, and radiographic imaging are nonspecific and inconclusive. Surgical excision of the lesion is imperative to make a definite diagnosis and as a cure. Liver transplantation should be considered as an option in the treatment of a non-resectable MHL.

Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure(ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis(type A), cirrhosis(type B) and cirrhosis with previous decompensation(type C).RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in typesB and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate(85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate(55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different(85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02).CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF.

Intra-abdominal desmoid tumor after liver transplantation: A case report

We are reporting the first documented case of an abdominal desmoid tumor presenting primarily after liver transplantation. This tumor, well described in the literature as occurring both in conjunction with familial adenomatous polyposis as well as in the postsurgical patient, has never been noted after solid organ transplantation and was therefore not included in our differential upon presentation. Definitive diagnosis required the patient to undergo surgical excision and immunochemical staining of the mass for confirmation. A review of the literature showed no primary tumors after transplantation. In a population of patients who received a small bowel transplant after they developedshort gut post radical resection of aggressive fibromatosis, only rare recurrences were seen. No connection of tumor development with immunosuppression or need to decrease immunosuppressant treatment has been demonstrated in these patients. Our case and the literature show the risk of this tumor presenting in the post-transplantation patient and the need for a high index of suspicion in patients who present with a complex mass after transplantation to prevent progression of the disease beyond a resectable lesion. Results of a thorough search of the literature are detailed and the medical and surgical management of both resectable and unresectable lesions is reviewed.

Apoptosis of rat liver in cold preservation with custom-designed KYL solution

BACKGROUND: A suitable perfusate is very important in reducing various problems in liver preservation, prolonging the time of organ preservation and enhancing the quality of donor tissue. University of Wisconsin (UW) solution is the most successful solution for preserving multiple organs at present, but it has many shortcomings. We set out to develop a new liver preservation solution (KYL solution) and study its effects on apoptosis in rat liver undergoing cold preservation. METHODS: Using non-circulated isolated perfused rat liver (IPRL), we randomly preserved Sprague-Dawley rat livers for 0, 4, 8, 16, 24, and 48 hours with KYL solution or UW solution. The effects were assessed by measuring the content of free radicals in Krebs-Henseleit solution and the intracellular calcium content of hepatocytes, assessing hepatocellular apoptosis and related-gene expression, and observing the morphological changes in liver. To evaluate the protection by KYL and UW solutions in rat liver perfusion and preservation, we chosed normal saline for negative comparison. RESULTS: The intracellular calcium content of the liver preserved in KYL solution was less than that preserved in UW solution. At every different period of preservation, the malonaldehyde and superoxide dismutase content in Krebs-Henseleit solution, the percentage of apoptotic cells and the expression patterns of apoptosis-related-genes were similar in livers preserved in KYL and UW solutions. Morphological changes in the two groups were almost the same. The variables in both groups were better than those of livers preserved in normal saline. Both KYL and UW solutions protected rat liver from ischemia-reperfusion injury. CONCLUSIONS: KYL solution is superior to UW solution in preventing calcium overload. More severe hepatocyte damage may appear in the KYL group than in the UW group and the effect of KYL solution on apoptosis in rat liver preservation is similar to that of UW solution.

Warm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation

BACKGROUND： Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.