Liver Graft Recipients Research Articles

A simplified experimental model of large-for-size liver transplantation in pigs

OBJECTIVE:The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass.METHOD:Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected.RESULTS:The mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups.CONCLUSION:This transplant method is a feasible experimental model of large-for-size liver transplantation.

Lebertransplantation mit postmortalen Organen

Deceased donor liver transplantation is nowadays a routine procedure for the treatment of terminal liver failure and often represents the only chance of a cure. Under given optimal conditions excellent long-term results can be obtained with 15-year survival rates of well above 60 %.In Germany the outcome after liver transplantation has deteriorated since the introduction of an allocation policy, which is based on the medical urgency. At present 25 % of liver graft recipients die within the first year after transplantation. In contrast 1-year survival in most other countries, e.g. in the USA or the United Kingdom is around 90 % and therefore significantly better. Reasons for the inferior results in Germany are on the one hand an increasing number of critically ill recipients and on the other hand an unfavorable situation for organ donation. In comparison with other countries the organ donation rate is low and moreover the risk profile of these donors is above average. This combination of organ shortage and organ allocation represents a big challenge for the future orientation of liver transplantation and creates the potential for conflict. These cannot be solved on a medical basis but require a social consensus.Because of the present inferior results and because of the high expenses of the present system we suggest a discussion on future allocation policies as well as on future centre structures in Germany. In addition to the medical urgency the maximum benefit should also be considered for organ allocation.

High risk of cytomegalovirus infection following solid organ transplantation despite prophylactic therapy

Cytomegalovirus infection (CMV) in solid organ transplant recipients is a major clinical problem. The aim of this study was to evaluate the incidence of CMV infection and its association with mortality during the first year after transplantation in a large solid organ transplant cohort at the Royal Infirmary of Edinburgh between January 2006 and April 2009. Data including the use of CMV prophylaxis, nature of CMV disease, treatment and deceased date (when appropriate) was collected retrospectively using hospital databases and patient notes for all transplanted patients with detectable CMV viraemia. The outcomes between recipients of kidney and liver transplants in the four CMV donor/recipient serostatus categories (D+R+, D-R-, D+R-, D-R+) were compared. A total of 428 individuals were included. Despite the administration of valganciclovir prophylaxis, CMV disease (syndrome or end-organ involvement) was diagnosed within the year of transplantation in the D+R--group in 31.3% of liver and 19.2% of kidney recipients. All D+R- transplant recipients that received CMV-prophylaxis presented with late-onset CMV disease. Furthermore, the rate of CMV disease in the D+R+-group was markedly higher in renal graft recipients compared to liver recipients (22% vs. 5%). The highest mortality was observed among the D+R+ liver and kidney graft recipients with CMV infection. The high incidence of late-onset CMV disease in D+R- transplant recipients receiving CMV prophylaxis demonstrates that CMV disease remains an important problem after organ transplantation. Furthermore, the surprisingly high mortality in the D+R+-transplant patients with CMV viraemia highlights the need for proactive monitoring of this group.

Diagnostic Value of Ultrasound in Detection of Biliary Tract Complications After Liver Transplantation

BackgroundBiliary complications are significant source of morbidity after liver transplantation (LT). Cholangiography is the gold standard for diagnosis and specification of biliary complications.ObjectivesDetailed analyses of ultrasound (US) as a safe imaging method in this regard are still lacking. Therefore we analyzed systematically the diagnostic value of US in these patients.Patients and MethodsRetrospectively, 128 liver graft recipients and their clinical data were analyzed. All patients had a standardized US examination. The findings of US were compared to cholangiographic results in 42 patients. Following statistical analyses were performed: descriptive statistics, sensitivity, specificity, positive and negative predictive values (PPV, NPV).Results42 patients had 54 different biliary complications (Anastomotic stenosis (AS) n = 33, ischemic type biliary lesions (ITBL) n = 18 and leakage n = 3). US detected n = 22/42 (52%) patients with biliary complications. The sensitivity, specificity, PPV and NPV of US were: 61%, 100%, 100%, 79% (95CI, 36-86%) for ITBL and 24%, 100, 100%, 31% (95CI, 9-46 %) for AS, respectively.ConclusionsUS examination had no false positive rate. Therefore, it may be helpful as a first screening modality. But for the direct diagnosis of the biliary complication US is not sensitive enough.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis in a liver graft recipient: A case report

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy is a potentially curative approach for peritoneal carcinomatosis of colonic origin. So far experience concerning the use of this treatment option in transplant recipients is lacking. We herein present the case of a 31-year-old man who had previously been liver transplanted for primary sclerosing cholangitis. Approximately 10 years after transplantation colon carcinoma with co-existing peritoneal carcinomatosis was diagnosed. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were conducted. Operative management under tacrolimus medication did not trigger infections, wound healing disorders or graft function impairment. At one year follow-up no tumor recurrence was detected. Recent literature suggests that proctocolectomy for colorectal cancer is considered feasible in liver graft recipients. Virtually all patients suffering from primary sclerosing cholangitis exhibit co-existing ulcerative colitis, rendering this subset of patient at risk for developing colonic malignancies. Furthermore chronic immunosuppression may facilitate malignant growth. The most feared complication in colorectal carcinomas is the occurence of peritoneal carcinomatosis, for which cytoreduction plus hyperthermic intraperitoneal chemotherapy may be a curative option. This, so far unique, case report suggests that even in this patient subset this treatment is feasible and for further cases this dual-approach for the management of PC in transplant recipients should be taken into account.

A Novel Organ Preservation for Small Partial Liver Transplantations in Rats: Venous Systemic Oxygen Persufflation With Nitric Oxide Gas

The prognosis for recipients of small liver grafts is poor. The aim of this study was to determine the impact of venous systemic oxygen persufflation (VSOP) with nitric oxide (NO) gas for 30% partial liver preservation and transplantation in rats. After we determined optimal NO concentration as 40 ppm in vitro with the isolated perfused rat liver model, we assessed liver injury and regeneration in vivo at 1, 3, 24 and 168 h after transplantation in the following three groups after 3 h-cold storage (n = 20 per group): control group = static storage; VSOP group = oxygen persufflation and VSOP+NO group = oxygen with NO persufflation. The liver graft persufflation was achieved with medical gas via the suprahepatic vena cava; In comparison with control group after transplantation, VSOP+NO preservation (1) increased portal circulation, (2) reduced AST and ALT release, (3) upregulated hepatic endothelial NO synthase, (4) reduced hepatocyte and bileductule damage and (5) improved liver regeneration. These results suggest that gaseous oxygen with NO persufflation is a novel and safe preservation method for small partial liver grafts, not only alleviating graft injury but also improve liver regeneration after transplantation.

Isolated increase in serum alkaline phosphatase after liver transplantation: Risk factors and outcomes analysis

BackgroundIsolated increase in serum alkaline phosphatase (IISAlp) is frequently observed in liver transplant recipients visiting outpatient clinics. However, whether the increase is associated with risk factors or poor survival is unknown. MethodsWe retrospectively reviewed the medical records of liver transplant recipients who were followed up during 1999–2009 and had IISAlp 1 month after liver transplantation, which was sustained for at least 6 months. Clinical parameters, survival, and risk factors were analyzed and compared between recipients who survived longer than 6 months after transplantation. ResultsAmong 307 liver transplant recipients, 44 had IISAlp. Compared with the control group, the patients with IISAlp were more frequently of the pediatric population, recipients of female donor or living-related partial liver grafts, and found to have biliary-related pretransplant disorders, lower body weight, and shorter warm ischemic time (P < 0.01). One patient with IISAlp died of acute myeloid leukemia during the follow-up period. The mean time to observation of IISAlp after liver transplantation was 6.3 ± 0.8 months. The mean follow-up duration was 5.5 ± 0.2 years. Stepwise multivariate analysis showed that being a pediatric or living-related liver transplant recipient was an independent risk factor for IISAlp, with adjusted hazard ratios (95% confidence interval) of 5.41 (2.59–11.28) and 3.0 (0.98–9.27), respectively. ConclusionsTherefore, being a pediatric or living-related liver transplant recipient was an independent risk factor for IISAlp. However, IISAlp was not associated with poor survival after liver transplantation. Hence, patients who have undergone liver transplantation do not require frequent routine examination of serum alkaline phosphatase levels.

Antiviral Drugs in the Prophylaxis of HBV Infection

Reactivation of hepatitis B infection (HBV) is known to occur in liver graft recipients and in chronic carriers of the surface antigen of HBV who receive immunosuppressive therapy. The use of hepatitis B immune globulin alone or in combination with antiviral agents such as lamivudine, adefovir, tenofovir, entecavir, famciclovir, ganciclovir, as prophylaxis in HBV liver transplants, has been well documented. In terms of HBV positive carriers undergoing cytotoxic chemotherapy, the preemptive use of nucleoside or nucleotide analogues seems to be effective. Monotherapy or combination of antiviral drugs, as well as the optimal duration of HBV prophylaxis, is to be determined.

Prevention of de novo hepatitis B with adefovir dipivoxil in recipients of liver grafts from hepatitis B core antibody-positive donors

Lamivudine has been shown to prevent de novo hepatitis B virus (HBV) infections in liver transplantation (LT) patients receiving hepatitis B core antibody-positive (HBcAb(+)) grafts, but it may produce long-term resistance. Adefovir dipivoxil (ADV) might be effective in preventing de novo hepatitis and resistance. A single-center, prospective trial was conducted with 16 adults (10 men and 6 women, mean age = 54 ± 11 years) who underwent LT with HBcAb(+) grafts between September 2007 and October 2009. After LT, patients were given ADV [10 mg daily (adjusted for renal function)]. No hepatitis B immune globulin was administered. At LT, all graft recipients were hepatitis B surface antigen-negative (HBsAg(-)), 38% were surface antibody-positive (HBsAb(+)), and 50% were HBcAb(+). The median follow-up after LT was 1.8 years (range = 1.0-2.6 years). All recipients had undetectable HBV DNA (<40 IU/mL) after LT until the end of follow-up. One recipient (6%) who was HBsAb(-) and HBcAb(-) before LT became HBsAg(+) after 52 weeks. One recipient was switched from ADV to entecavir for chronic renal insufficiency, and 19% of the patients had renal dose adjustments. There was a nonsignificant trend of increasing creatinine levels over time (1.2 mg/dL at LT, 1.3 mg/dL 1 year after LT, and 2.0 mg/dL 2 years after LT, P = 0.27). A comparison with a control cohort of LT recipients with hepatitis C virus who did not receive ADV showed no difference in the creatinine levels at LT or 1 year after LT. In conclusion, ADV prophylaxis prevents HBV replication in recipients of HBcAb(+) livers but does not fully protect recipients from de novo HBV. Long-term follow-up is needed to better determine the risk of de novo infection.

Limitations of Use of the Noninvasive Clearance of Indocyanine Green as a Prognostic Indicator of Graft Function in Liver Transplantation

AimTo assess the prognostic value of noninvasive indocyanine green (ICG) clearance (ICG-pulse-densitometric method [PDR]) for the outcome of liver grafts after transplantation. MethodsICG-PDR, hepatic artery resistance index, cardiac output, transaminases, prothrombin time, bilirubin, albumin, hematocrit at 48 to 72 hours after transplantation were analyzed with reference to outcome among 59 liver graft recipients. ResultsTwo grafts were lost at 10 and 88 days during the initial hospitalization. These two patients only differed from the other recipients in the need for packing (1/2 versus 3/57) and degree of hypoproteinemia (46 ± 0 versus 51 ± 7.8 g/L), whereas they had similar ICG-PDR values (16.7%/min and 21.8%/min versus 17.3%/min ± 7.2%/min). Seven patients showed an ICG-PDR ≤ 8.8%/min, a previously identified cutoff for early postoperative complications. These patients versus the other 52 significantly differed in prothrombin index (47.9% ± 15.9% versus 64.3% ± 11.7%, P = .001) and bilirubin (8.3 ± 3.2 versus 3.3 ± 2.9 mg/dL, P = .0001). Early postoperative complications—primary graft nonfunction, hepatic artery thrombosis, or septic shock— responsible for an ICG-PDR ≤ 8.8%/min were observed in 2/7 patients. Interestingly, six cases developed an early (range: 3–15 days) rejection episode. In all the cases rejection suspected by analytical abnormalities was confirmed by liver biopsy. Among the overall series of patients, ICG-PDR significantly correlated with serum albumin (r = 0.345; P = .007), bilirubin (r = −0.514; P = .0001), and hematocrit (r = 0.462; P = .0001) but not with transaminases, prothrombin index, cardiac output, or hepatic artery resistance index. Actuarial 72-month probability of graft survival was 75%. Overall, 14 grafts were lost over a median follow-up of 78 months (range 1–99 m). There were no significant differences among early ICG-PDR values among grafts lost vs retained upon follow-up. ConclusionICG-PDR measured once early after liver transplantation did not offer relevant information to predict individual patient outcomes in the immediate postoperative phase. This lack of prognostic value may have been due to the multiple confounding factors involved in ICG metabolism after liver transplantation.

Excessive alcohol consumption after liver transplantation impacts on long-term survival, whatever the primary indication

Beyond 5 years, poorer survival, related to alcohol relapse, is observed in patients with liver transplant for alcohol-related liver disease (ALD). However, alcohol consumption has been significantly understudied in non-ALD transplant recipients. We aimed at analyzing the impact of alcohol consumption on long-term survival irrespective of the indication for transplantation. This observational study included consecutive adult recipients of a primary liver graft between 1991 and 2007 in our hospital, who survived >6 months. Patients without ALD as primary indication, but with a history of excessive alcohol consumption before transplantation, were classified as secondary indication ALD. We studied the impact on survival of excessive consumption of alcohol after transplantation and several other variables. The 441 patients had mean follow-up of 81.7 months. Among the 281 patients with excessive alcohol consumption before transplantation, 206 had ALD as primary indication. After transplantation, alcohol consumption was reported by 32.3% of the study population, 43.7% in primary indication ALD, and 24.3% in non-ALD patients. Survival was 82% at 5 years and 49% at 10 years for patients with excessive alcohol relapse, compared with 86% and 75%, respectively, for patients without persistent excessive alcohol relapse. By multivariable analysis, the independent risk factors of death were: excessive alcohol relapse, age >51 years, post-transplantation diabetes mellitus, cyclosporine-based immunosuppression, and non-hepatic cancer. Excessive alcohol consumption has a negative impact on long-term survival after liver transplant, irrespective of the primary indication. Death is mainly due to recurrence of liver disease and non-hepatic cancer.

Lymphoproliferative disorders in pediatric liver allograft recipients: a review of 212 cases

Due to the limited incidence of posttransplant lymphoproliferative disorders (PTLD) in pediatric liver graft recipients, there is a scarcity of data on the characteristics of the disease in this population. We aimed to analyze the special features and behavior of PTLD arising after pediatric liver transplantation. A comprehensive search of the literature was conducted for the available data on PTLD in pediatric liver recipients pediatric PTLD through a search of Pubmed and Google Scholar using appropriate terms. We sought data on liver recipients younger than 18 years of age at the time of transplantation. From 51 reports, 43 fulfilled the inclusion criteria. Overall 250 cases of PTLD (212 pediatric PTLD) were found from 43 reports. Data on pediatric patients was compared to adults. Pediatric PTLD lesions were more likely of the polymorphic type (P=.004) and polyclonal (when age cut-off was defined at 12 years; P=.023). Remission rates, metastasis frequency and organ involvements were not different between the groups (P>.1 for all). Survival analysis showed no disparity between pediatric PTLD and adult patients (P>.1); but when data was reanalyzed for patients surviving at least 4 months post diagnosis, the log rank test showed that pediatric patients have a superior outcome compared to adults (P=.045). Pediatric liver recipients developing PTLD have relatively better disease presentation and behavior than that in adults. Stomach involvement was also more frequently seen in patients younger than 12 years, and should be more intensively evaluated. Future studies with a prospective approach and larger population size are needed for confirming our results.

Transforming Growth Factor-β1-Gene Polymorphism in the Development of Kidney Disease After Liver Transplantation

The development of kidney dysfunction is one of the most important after liver transplantation (LT). Genetic variants of pathogenetically relevant cytokines may influence the development and course of the disease. The aim of our study was to evaluate the role of transforming growth factor-β1 (TGF-β1) polymorphism in this context. Four hundred eighty-six liver graft recipients were genotyped for TGF-β1 codon 25 (guanine → cytosine, G → C) by polymerase chain reaction. Renal function before and after LT was characterized by estimation of glomerular filtration rate (GFR) using four-parameter-modification of diet in renal disease formula on defined dates. GFR was compared among TGF-β1-genotype groups of the entire cohort within the median observation period of 7 years. For the assessment of renal function recovery after LT, patients were divided into three groups by GFR difference (ΔGFR = ± 10 mL/min). Mean pretransplant GFR differed significantly among TGF-β1-genotype groups (GG: 85.0 mL/min vs. GC/CC: 75.3 mL/min; P=0.016). The significance disappeared in the follow-up period. Although GG genotype demonstrated higher mean GFR levels, patients with GC/CC genotype tended to improve kidney function compared with GG genotype (P=0.013). Interestingly, lower mean GFR rates were observed among female compared with male recipients before (P=0.002), separately at all dates and cumulatively after LT (P<0.001). Genetic variants of one of the most important cytokine TGF-β1 at codon 25 may have an impact on kidney function, suggesting an unfavorable effect of C allele in pretransplant setting and serve as marker for the recovery of renal function after LT. The identification of further confounders seems to be promising.

Immunophyllin Ligands Show Differential Effects on Alcohol Self-Administration in C57BL Mice

High abstinence rates characterize alcohol-dependent liver graft recipients. The immunosuppressants cyclosporine A (CsA) and tacrolimus (TRL) also inhibit calcineurin (CLN) in the brain. Previously, we found that CsA reduces alcohol consumption in C57BL/6J mice. The goals of the present study were: 1) to compare the ethanol preference effects of CsA against TRL, as well as sirolimus (SRL), an immunosuppressant without CLN inhibition and 2) to establish that reduction of alcohol consumption is not caused by caloric reinforcement from these ligands. C57BL/6J mice trained to imbibe ethanol consumed ethanol or sucrose in a modified limited-access drinking-in-the-dark paradigm; test groups received vehicle or doses of CsA (5-50 mg/kg), TRL (0.5-2.5 mg/kg), or SRL (1.0-5.0 mg/kg) for 5 consecutive days, 30 min before each 2-h limited-access session. Brain CsA, TRL, and SRL concentrations were measured. CsA (p < 0.001) and TRL (p < 0.01) each decreased ethanol consumption, whereas SRL showed no significant effects at any dose. Effective doses included CsA at 10 mg/kg and above and TRL at 2.5 mg/kg. CsA (50 mg/kg) did not reduce sucrose consumption. Both CsA and TRL reached significant brain concentrations compared with very low values of SRL. These data suggest that CsA and TRL may reduce alcohol preference through central CLN inhibition rather than by immunosuppression.

The Influence of Pharmacological Preconditioning with Sevoflurane on Incidence of Early Allograft Dysfunction in Liver Transplant Recipients

Background. Pharmacological preconditioning is one of the tools used to diminish preservation injury. We investigated the influence of sevoflurane preconditioning of liver grafts on postoperative graft function. Methods. Consecutive 60 deceased brain donors were randomized into sevoflurane group or control group. In sevoflurane group donors were treated with endexpiratory 2,0 volume% of sevoflurane during procurement. Primary endpoint was postoperative liver injury. Secondary endpoint was incidence of early allograft dysfunction (EAD). Results. The groups were not different in median DRI, donor age, graft steatosis, and MELD score. Peak AST and ALT levels were lower in sevoflurane group than in control group: 792 and 1861 (P = 0, 038) for AST and 606 and 1191 for ALT (P = 0, 117). Incidence of EAD was 16,7% in sevoflurane group and 50% in control group (Fisher test, P = 0, 013). In subgroups without steatosis preconditioning with sevoflurane did not have influence on incidence of EAD. In subgroups with mild and moderate steatosis incidence of EAD was lower in recipients of liver grafts treated with sevoflurane. Conclusions. Preconditioning with sevoflurane during organ procurement improves graft function by lowering incidence of early allograft dysfunction, particularly in recipients of steatotic liver grafts.

Pregnancy after living related liver transplantation – a report of two cases

Living related liver transplantation (LRLT) is currently the only available alternative to orthotopic liver transplantation that is of use in children with acute liver failure. There are reports of long-term survival in liver graft recipients who had been transplanted in childhood. In female patients of reproductive age it may also mean ability to conceive. We report 2 cases of successful pregnancies in women after living related liver transplantation. During the 6-month follow-up, no obstetric complications during pregnancy, delivery and postpartum period, and no deterioration of graft function were noted. The neonates were delivered full-term in good general condition, with no signs of intrauterine hypotrophy, congenital malformations or infection, and their psycho-motor development is perfectly normal. These 2 cases of pregnancies with favorable perinatal outcomes in women after living related liver transplantation, who delivered in our Department with no deterioration of graft function, may be regarded as evidence of full recovery in women after the LRTL procedure.

The status of dental and jaw bones in children and adolescents after kidney and liver transplantation

Systemic complications in patients after renal or liver transplantation may be localized in the oral cavity. Calcium-phosphate disturbances may affect the structure and metabolism of mandible bones, promote calcification of dental pulp, and in children may cause developmental defects of teeth. The aim of this study was to evaluate the incidence of dental and bone abnormalities in children and adolescents after kidney and liver transplantation with respect to the type of the transplanted organ and maintenance immunosuppression. Overall, 23 kidney and 25 liver recipients (mean age: 13.95±4.2 yrs) were evaluated. Twenty patients received ciclosporin A (CsA) and 28 tacrolimus (TAC). Twenty-one kidney and 14 liver recipients were treated with steroids. Mean time after transplantation was 3.62±2.98 years. The severity of caries and percentage of odontogenic abnormalities (76.0% vs. 60.86%) was higher in liver transplant recipients. Positive correlations were found between discoloration of the deciduous teeth and liver transplantation, between enamel hypoplasia and kidney transplantation, and between treatment with CsA and its dose and blood concentration (p<0.05). Pulp stones were present in 13.04% of kidney vs. 8.0% in liver recipients, more often in those treated with CsA than with TAC. Jaw bone abnormalities were present in 30.43% kidney recipients vs. 12% liver recipients. Both kidney and liver recipients present dental and bone abnormalities. The incidence of specific types of oral lesions is different in renal and liver graft recipients; however, it is also correlated with specific immunosuppression.

The Hepatoprotective Effect of Sodium Nitrite on Cold Ischemia-Reperfusion Injury

Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR) solution or University of Wisconsin (UW) solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Logistic regression models were used in the univariate and multivariate analyses of predictors for the development of IC. Additional analyses using Cox regression models were performed to identify predictors of graft survival and to compare outcomes for DCD and DBD graft recipients. In our series, the patient survival rates for the DCD and DBD groups at 1, 3, and 5 years was 92.6%, 85%, and 80.9% and 89.8%, 83.0%, and 76.6%, respectively (P = not significant). The graft survival rates for the DCD and DBD groups at 1, 3, and 5 years were 80.9%, 72.7%, and 68.9% and 83.3%, 75.1%, and 68.6%, respectively (P = not significant). In the DCD group, 5 patients (2.5%) had primary nonfunction, 7 patients (3.5%) had hepatic artery thrombosis, and 3 patients (1.5%) experienced hepatic necrosis. IC was diagnosed in 24 patients (12%), and 11 of these patients (5.5%) required retransplantation. In the multivariate analysis, the asystole-to-cross clamp duration [odds ratio = 1.161, 95% confidence interval (CI) = 1.021-1.321] and African American recipient race (odds ratio = 5.374, 95% CI = 1.368-21.103) were identified as significant factors for predicting the development of IC (P < 0.05). This study has established a link between the development of IC and the asystole-to-cross clamp duration. Procurement techniques that prolong the nonperfusion period increase the risk for the development of IC in DCD liver grafts.

How Regenerative Medicine May Contribute to the Achievement of an Immunosuppression-Free State

How Regenerative Medicine May Contribute to the Achievement of an Immunosuppression-Free State