Project description:BackgroundDeceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.MethodsUsing the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist.ResultsOne hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis.ConclusionsIn a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.
Project description:Toxoplasmosis may be transferred by organ transplantation. The most common clinical presentation is with multisystem disease, although isolated ocular toxoplasmosis has been described. Many centers have suggested that universal use of co-trimoxazole prophylaxis obviates the need for specific Toxoplasma testing. We report a case of donor-acquired ocular toxoplasmosis after liver transplantation despite co-trimoxazole prophylaxis. The diagnosis was confirmed by Toxoplasma polymerase chain reaction assay in conjunction with seroconversion. The fact that the infection was donor acquired was confirmed by serological mismatch and the absence of sporozoite-specific antigen antibody in the recipient.
Project description:BackgroundMyosteatosis is associated with perioperative outcomes in orthotopic liver transplantation (OLT). Here, we investigated the effects of body composition and myosteatosis on long-term graft and patient survival following OLT.MethodsClinical data from 225 consecutive OLT recipients from a prospective database were retrospectively analysed (May 2010 to December 2017). Computed tomography-based lumbar skeletal muscle index (SMI) (muscle mass) and mean skeletal muscle radiation attenuation (SM-RA) (myosteatosis) were calculated using a segmentation tool (3D Slicer). Patients with low skeletal muscle mass (low SMI) and myosteatosis (low SM-RA) were identified using predefined and validated cut-off values.ResultsThe mean donor and recipient age was 55 ± 16 and 54 ± 12 years, respectively. Some 67% of the recipients were male. The probability of graft and patient survival was significantly lower in patients with myosteatosis compared with patients with higher SM-RA values (P = 0.011 and P = 0.001, respectively). Low skeletal muscle mass alone was not associated with graft and patient survival (P = 0.273 and P = 0.278, respectively). Dividing the cohort into quartiles, based on the values of SMI and SM-RA, resulted in significant differences in patient but not in graft survival (P = 0.011). Even though multivariable analysis identified low SM-RA as an important prognostic marker (hazard ratio: 2.260, 95% confidence interval: 1.177-4.340, P = 0.014), myosteatosis lost its significance when early mortality (90 days) was excluded from the final multivariable model. Patients with myosteatosis showed significantly higher all-cause mortality and in particular higher rates of deaths due to respiratory and septic complication (P = 0.002, P = 0.022, and P = 0.049, respectively).ConclusionsPreoperative myosteatosis may be an important prognostic marker in patients undergoing deceased donor liver transplantation. The prognostic value of myosteatosis seems to be particularly important in the early post-operative phase. Validation in prospective clinical trials is warranted.
Project description:We aimed to characterize patterns of differences in liver graft failure rates by recipient sex, accounting for the modifying effects of donor sex and recipient age.MethodsWe evaluated 144 212 first deceased donor liver transplant recipients [1988-2019; Scientific Registry of Transplant Recipients (SRTR)]. We used multivariable time-varying Cox models, considering a recipient sex by donor sex by recipient age (0-12, 13-24, 25-44, ≥45 y) interaction.ResultsAmong recipients of male donors, females <45 y had higher graft failure rates than males of the same age, but none of these differences were statistically significant [0-12 y: adjusted hazard ratio (aHR) 1.17 (0.98, 1.40); 13-24 y: aHR 1.18 (0.96, 1.46); 25-44 y: aHR 1.11 (0.96, 1.28)]; there was no material or statistically significant difference between female and male recipients ≥45 y [aHR 1.01 (0.97, 1.06)]. When the donor was female, recipients <45 y showed no statistically significant differences in graft outcomes by recipient sex [0-12 y: aHR 0.91 (0.74, 1.11); 13-24 y: aHR 0.98 (0.77, 1.25); 25-44 y: aHR 0.86 (0.73, 1.01)], whereas female recipients ≥45 y had significantly lower graft failure rates [aHR 0.85 (0.81, 0.89)] than males of the same age.ConclusionsAmong recipients of female donors, female recipients ≥45 y had significantly better outcomes than males of the same age; there were no clear differences by recipient sex in younger recipients. When the donor was male, there was no material or statistically significant difference in graft failure rates between males and females ≥45 y; among younger recipients point estimates suggested higher failure rates in females than males recipients, but confidence intervals were wide making firm conclusions impossible. Larger studies combining multiple datasets are needed.
Project description:BackgroundThe reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.MethodsRecipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.ResultsEarly reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7-96.4), and 85.2% (95%CI, 66.5-94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0-98.2), and 92.9% (95%CI, 85.0-96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9-99.5), and 88.3% (95%CI, 69.3-96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7-94.3) and 88.0% (95%CI, 79.2-93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).ConclusionsObserved graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.
Project description:BackgroundNatural immunity against cytomegalovirus (CMV) can control virus replication after solid organ transplantation; however, it is not known which components of the adaptive immune system mediate this protection. We investigated whether this protection requires human leukocyte antigen (HLA) matching between donor and recipient by exploiting the fact that, unlike transplantation of other solid organs, liver transplantation does not require HLA matching, but some donor and recipient pairs may nevertheless be matched by chance.MethodsTo further investigate this immune control, we determined whether chance HLA matching between donor (D) and recipient (R) in liver transplants affected a range of viral replication parameters.ResultsIn total, 274 liver transplant recipients were stratified according to matches at the HLA A, HLA B, and HLA DR loci. The incidence of CMV viremia, kinetics of replication, and peak viral load were similar between the HLA matched and mismatched patients in the D+/R+ and D-/R+ transplant groups. D+/R- transplants with 1 or 2 mismatches at the HLA DR locus had a higher incidence of CMV viremia >3000 genomes/mL blood compared to patients matched at this locus (78% vs. 17%; P = 0.01). Evidence was seen that matching at the HLA A locus had a small effect on peak viral loads in D+/R- patients, with median peak loads of 3540 and 14,706 genomes/mL in the 0 and combined (1 and 2) mismatch groups, respectively (P = 0.03).ConclusionOverall, our data indicate that, in the setting of liver transplantation, prevention of CMV infection and control of CMV replication by adaptive immunity is minimally influenced by HLA matching of the donor and recipient. Our data raise questions about immune control of CMV in the liver and also about the cells in which the virus is amplified to give rise to CMV viremia.
Project description:Background: Delayed graft function (DGF) is a common complication after kidney transplantation (KT) with a poor clinical outcome. There are no accurate biomarkers for the early prediction of DGF. Macrophage migration inhibitory factor (MIF) release during surgery plays a key role in protecting the kidney, and may be a potential biomarker for predicting post-transplant renal allograft recovery. Methods: Recipients who underwent KT between July 2020 and December 2020 were enrolled in the study. Plasma MIF levels were tested in recipients at different time points, and the correlation between plasma MIF and DGF in recipients was evaluated. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000035596). Results: Intraoperative MIF levels were different between immediate, slowed, and delayed graft function groups (7.26 vs. 6.49 and 5.59, P < 0.001). Plasma MIF was an independent protective factor of DGF (odds ratio = 0.447, 95% confidence interval [CI] 0.264-0.754, P = 0.003). Combining plasma MIF level and donor terminal serum creatinine provided the best predictive power for DGF (0.872; 95%CI 0.795-0.949). Furthermore, plasma MIF was significantly associated with allograft function at 1-month post-transplant (R 2 = 0.42, P < 0.001). Conclusion: Intraoperative MIF, as an independent protective factor for DGF, has excellent diagnostic performance for predicting DGF and is worthy of further exploration.
Project description:BACKGROUND:The high demand for livers for transplantation has led to organs of limited quality being accepted to expand the donor pool. This is associated with inferior outcomes due to more pronounced preservation injury. Accordingly, recent research has aimed to develop preservation modalities for improved preservation as well as strategies for liver viability assessment and liver reconditioning. METHODS:The PubMed database was searched using the terms 'perfusion', 'liver', 'preservation', and 'reconditioning' in various combinations, and the according literature was reviewed. RESULTS:Several perfusion techniques have been developed in recent years with the potential for liver reconditioning. Preclinical and first emerging clinical data suggest feasibility, safety, and superiority over the current gold standard of cold storage. CONCLUSION:This review outlines current advances in the field of liver preservation with an emphasis on liver reconditioning methods.
Project description:AIM:To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS:This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS:Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ? 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION:Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.