Nicolas Richter

Persistence Of Donor Lymphocytes In Liver Allograft Recipients

Occasional cases of graft-versus-host disease after liver transplantation indicate a transfer of donor lymphocytes by human liver grafts. However, little is known about the usual fate and potential function of passenger lymphocytes in clinical liver transplantation. In this study, we have analyzed liver graft recipients for the presence of donor lymphocytes in the early course after transplantation. The presence of such cells in blood, the graft, and, occasionally, the skin was studied by the use of mAb to polymorphic HLA class I determinants and double-staining techniques in flow cytometry and immunocytology. The findings were compared with the clinical courses and with the results of routine graft biopsies. Within the first week after transplantation, in all 16 patients, between 1% and 24% donor lymphocytes (T, NK, and B cells) were detectable in blood, and in 14 of 22 patients (64%), between 2% and 23% donor T cells were found in the graft. After more than 2 weeks, donor cells were still present in blood in 2 of 14 patients at very low numbers. The presence of donor lymphocytes in the graft was associated with intragraft immune activation in 5 of 15 patients, but no clinical rejection occurred in these cases; mild graft-versus-host disease was observed in one patient. These findings demonstrate that donor lymphocytes regularly persist in liver-grafted patients for some time; this transient mixed lymphoid chimerism is only rarely associated with clinical graft-versus-host disease and some evidence even suggests that these donor-derived lymphocytes may exert beneficial immunomodulatory properties.

Everolimus and Early Calcineurin Inhibitor Withdrawal: 3-Year Results From a Randomized Trial in Liver Transplantation

The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open‐label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI‐based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft‐Gault) at month 11 postrandomization. A 24‐month extension phase followed 81/114 (71.1%) of eligible patients to month 35 postrandomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval [CI] −1.3, 21.5 mL/min, p = 0.082) in favor of CNI‐free versus CNI using Cockcroft‐Gault, 9.4 mL/min/1.73 m2 (95% CI −0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four‐variable) and 9.5 mL/min/1.73 m2 (95% CI −1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI‐free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy‐proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI‐free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus‐based CNI‐free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.

Living donor liver transplantation: effect of the type of liver graft donation on donor mortality and morbidity

To investigate the influence of the type of liver graft donation on donor mortality and morbidity. The clinical course of 87 living liver donors operated on at our center between 2002 and 2009 was retrospectively analysed and data pertaining to all complications were retrieved. No donor mortality was observed and no donor suffered any life‐threatening complication. Four donors (4.6%) developed biliary leakage, nine (10.3%) had to be readmitted to hospital and six (6.9%) required some or other type of reoperation related to the previous liver donation. Reoperations included incisional or diaphragmatic hernia repair (n = 4), biliary leakage repair (n = 1) and segmental colon resection combined with diaphragmatic hernia repair (n = 1). There was a statistically significant difference in hospital stay (P < 0.001), autologous blood transfusions (P < 0.001) and operating time (P < 0.005) when right lobe donations (Segments V–VIII) were compared with left lobe (Segments II–IV) and left lateral lobe (Segments II–III) donations, whereas no difference was found between these groups regarding hospital readmission, operative revisions and the incidence or severity of complications. Right lobe donation was associated with prolonged hospital stay, increased blood transfusions and prolonged operating time when compared with left and left lateral lobe donation, whereas donor mortality and morbidity did not differ between these groups.

Diffusion-Weighted imaging and diffusion tensor imaging detect delayed graft function and correlate with allograft fibrosis in patients early after kidney transplantation.

To combine diffusion‐weighted imaging (DWI) and diffusion tensor imaging (DTI) for detection of allograft dysfunction in patients early after kidney transplantation and to correlate diffusion parameters with renal function and renal histology of allograft biopsies.

High-dose erythropoietin has no effect on short- or long-term graft function following deceased donor kidney transplantation

We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuEPO or placebo. The primary study end point was kidney function 6 weeks after transplantation with secondary end points of incidence of delayed graft function and kidney function 12 months after transplantation. Six weeks or 12 months after transplantation, the difference between estimated glomerular filtration rates was not significant comparing 44 patients who received rHuEPO to 44 patients receiving placebo. There was no significant difference regarding the incidence of delayed graft function (10 of 44 with rHuEPO compared with 14 of 44 on placebo). Protocol biopsies at 6 weeks and 6 months post transplant showed no significant differences in all assessed histological indices. The number and severity of adverse events were comparable between groups, as was patient and graft survival after 12 months. Thus, treatment with high-dose rHuEPO after kidney transplantation, although well tolerated, had no effect on long-term graft function or histology.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF.

Long-term follow-up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study

The 12‐month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)‐based immunosuppression to a CNI‐free everolimus (EVR)‐based regimen showed numerically better renal function. Here, we present the five‐yr follow‐up data.

Ligation of left renal vein for spontaneous splenorenal shunt to prevent portal hypoperfusion after orthotopic liver transplantation.

We report a case of recovered portal flow by ligation of the left renal vein on the first postoperative day after orthotopic liver transplantation of a 54-year-old female with alcoholic liver cirrhosis, chronic kidney failure, and spontaneous splenorenal shunt. After reperfusion, Doppler ultrasonography showed almost total diversion of the portal flow into the existing splenorenal shunt, but because of severe coagulopathy and diffuse bleeding, ligation of the shunt was not attempted. A programmed relaparotomy was performed on the first postoperative day, and the left renal vein was ligated just to the left of the inferior vena cava. Portal flows subsequently increased to 37 cm/sec, and the patient presented a good and stable liver function. We conclude that patients with known preoperative splenorenal shunts should be closely monitored, and if the portal flow becomes insufficient, ligation of the left renal vein should be attempted in order to optimize the portal perfusion of the liver.

Adaptive Personality Traits and Psychosocial Correlates among Living Kidney Donors

Since living kidney donors have repeatedly been shown to be mentally more healthy compared to the general population, they might also exhibit more adaptive personality characteristics. We investigated the personality traits of 315 living kidney donors (202 female and 113 male donors) on average 7.1 years after donation using the NEO-Five Factor Inventory, a frequently used personality inventory measuring the “big five” dimensions of personality (neuroticism, extraversion, openness, agreeableness, and conscientiousness). In addition, levels of depression, anxiety, and fatigue were assessed with the Patient Health Questionnaire-Depression Scale, GAD-7, and Multidimensional Fatigue Inventory. Kidney donors showed more adaptive personality traits with higher agreeableness and lower neuroticism scores compared to the German general population. This was even more pronounced in living kidney donors with a high motivation to donate again (non-regreters). Scores for depression, anxiety, and fatigue did not differ from general population values and were significantly correlated with most personality dimensions. The more adaptive personality characteristics of living kidney donors might either be a selection effect or the consequence of the experience of donation and improved health of the close relative. Regardless of the causal relationship, adaptive personality traits might positively influence both physical and psychosocial well-being of the donor. Longitudinal studies should investigate if living donation might lead to persistent adaptive changes in personality traits.

Chronic Bile Duct Stenosis after Hepaticojejunostomy Requiring Re-OperationLeading to Liver TransplantationâÂÂA Case Report

Background: Stenosis of a biliodigestive anastomosis is a rare complication of mid- and long-term survival after hepatobiliary surgery. First line therapy is endoscopic intervention. Only if this option is not successful or not possible a surgical approach is indicated. Case Report: A 40 year old male patient presented with recurrent episodes of cholangitis after hepaticojejunostomy due to neuroendocrine tumor in the common bile duct more than 17 years ago. Advanced endoscopic techniques and percutaneous drainage failed to overcome this disorder resulting in subsequent surgical therapy. During the first operation the bile duct could not be found in order to create sufficient bile drainage. However, during preparation of the liver hilum the portal vein was inadvertently hurt. Following vessel reconstruction the patient suffered from recurrent thrombosis of the vein in the course and since the bile duct could not be identified and arrosion bleeding caused acute liver failure the patient was listed for liver transplantation. The latter was successfully performed allowing complete recovery of the patient. Conclusion: In case of stenosis of a billiodigestive anastomosis and unsuccessful reconstruction of sufficient bile drainage despite extended surgical efforts or following complications during revision liver transplantation might be a good option for the treatment of patients in exceptional cases.