We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103+ cells) principally due to reduced CD3+CD8+ cells, while CD103+CD3– cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3– IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3– IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3–CD127+ cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3– IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ+IL-22+ population was observed. Epithelial cell–depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3– IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56+, NKp44+, CCR6+, CD127–, cytotoxicity, and IFNγ secretion), ILC3 (CD56+, NKp44+, IL-23R+, CCR6+, RORγt+, and IL-22 secretion), and intermediate ILC1–ILC3 phenotypes (IFNγ+IL-22+). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets. We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103+ cells) principally due to reduced CD3+CD8+ cells, while CD103+CD3– cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3– IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3– IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3–CD127+ cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3– IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ+IL-22+ population was observed. Epithelial cell–depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3– IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56+, NKp44+, CCR6+, CD127–, cytotoxicity, and IFNγ secretion), ILC3 (CD56+, NKp44+, IL-23R+, CCR6+, RORγt+, and IL-22 secretion), and intermediate ILC1–ILC3 phenotypes (IFNγ+IL-22+). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.
Introduction: The acceptance of non-heart-beating donors (NHBD) emerges as a consequence of the shortage of organs and increased mortality in the waiting list. The use of these grafts implies a higher risk of primary graft dysfunction (PGD) as well as ischemic cholangiopathy (IC). Classically, liver function tests (LFT) (AST-ALT) and ischemia times, as well as the macroscopic aspect of the liver are used as determining factors in accepting these organs. Patients and methods: Between January 2006 and December 2011, we performed 380 OLT. 48 of these transplants were NHBD (Maastricht type II). We analyzed factors implied in relationship to LFT and the times with ECMO. Results: We present 48 liver recipients from uncontrolled NHBD, with a mean age of 58.1 ± 9.3 (36-71) years, and a male:female ratio of 3.8:1. The mean age of donor was 39 ± 9.3 years. The indications for transplant were: HCV infection + hepatocarcinoma (HCC) 27.1%, alcoholic cirrhosis (AC) 20.8%, HCV alone 20.8% with a total percentage of HCV of 60.4% and HCC of 43.8%. PGD was observed in 5 patients, and IC in 16. In relation to predictive factors for PGD, no statistical differences were found with respect to the mean values of cold ischemia and warm ischemia times in both groups. We also didn't find statistical differences with respect to times in ECMO, fluid flux in ECMO, nor in the transfusion of red blood cells and plasma in ECMO. No statistical differences were seen with respect to time of cardiac arrest, which paradoxically was lower in those with PGD, who also presented shorter time of cardiopulmonary resuscitation (CPR) and out-of-hospital CPR. We observed differences with respect to LFT: AST at start of ECMO: 503 U/l in PGD group vs 150 in non-PGD patients (p=0.000); ALT at the start of ECMO 462 vs 160 (p=0.000). No differences were observed with respect to total bilirrubin levels, prothrombin time (PT), activated partial thromboplastin time (aPTT) and blood pH. Considering the predictive factors for IC, no statistical differences were observed with respect to the mean values of cold ischemia times and warm ischemia times in both groups. Differences were observed with respect to a higher necessity of red blood cells in ECMO in patients with CI, although not statistically significant. No differences were observed with regard to flux parameters in ECMO, in the CPR times, nor in the analytical values. Conclusion: Taking into consideration these results, we should analyse the true value of these classical parameters in decision making, especially that only an association with elevated LFT was observed for dysfunction. Thus new parameters should be considered for the evaluation of these livers.
Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.
Introduction The scarcity of grafts for liver transplantation (LT) from brain death donors (BDD), as well as the increasing mortality on waiting list have led us to look for other alternatives to achieve more liver grafts, being those from controlled and uncontrolled cardiac death (uDCD) the most attractive sources. However, intraoperative bleeding during LT has been higher when using uDCD donors, also related with higher morbi-mortality and lower patient and graft survival. Our aim is to compare the necessity of hemoderivates in uDCD and DBD groups. Materials and Methods Between January 2006 and December 2016 we performed 783 LT in adult recipients, excluding retransplants or patients undergoing OLT for acute liver failure. Liver grafts from uDCD donors (Group A) were used in 75 patients, and livers from BDD donors (Group B) were used in 708 patients. Results The mean age in group A was 59±8 years vs B 55±10 years in Group B (p=0.000). There were no significant differences in terms of sex, BMI and Child score. HCV cirrhosis was the indication for LT in 60% of cases in Group A vs 50.2% in group B (p=0.541). Hepatocellular carcinoma was present in 54.7% of patients in group A vs 38.9% in Group B (p=0.07). The mean of MELD score was 14.4±5 in Group A vs 14.5±6 in Group B (p=NS).The mean ICU stay was 6.8±7 days in Group A versus 6.3±9 days in group B (p=0.638). The mean transfusion of units of hemoderivates was as follows: 1) Packed red blood cells (PRBC): 12.3±13 units in Group A vs 8.6±10 Group B (p=0.008). 2) Fresh frozen plasma (FFP): 16.2±12 units in group A vs 10.7±8.8 in Group B (p=0.000). 3) Platelets: 2.29±2 units in group A vs 1.7±2 in group B (p=0.014). Using a logistic regression for multiple predictor variables, the only two factors with statistical significance related with MBT (>6 units of RBC) were uDCD condition (OR 2.3; CI 95%: 1.2-4.9; p=0.024), and higher Meld score (OR 2.75; CI 95%: 1.7-4.4; p=0.000) Survival at 1, 3 and 5 years was 81.3%, 70.2% and 68.6%, respectively, in group A vs 89%, 83.7% and 78.8%, respectively, in Group B (p= 0.070) Discussion. Conclusion The use of liver grafts from uDCD donors is associated with increased necessity of transfusion of hemoderivates in comparison with the use of BDD donors.
Introduction: Currently, pancreas transplantation is the only treatment option that allows us to keep a diabetic patient in normoglycaemia. It also increases the survival of these patients and improves their quality of life. However, postoperative complications increased their morbidity and mortality which may be considered. One of these complications is the anastomotic leak. The aim of this study is to find out the incidence of anastomotic leak and relaparotomies in our recipients as well as patients and graft survivals. Patients and methods: We analyzed 142 recipients who underwent pancreatic transplant from March 1995 to December 2010, all of them with more than one year of follow up.132 of these patients were simultaneous pancreas-kidney transplants, 2 pancreas after kidney and 8 retransplants. The average follow up was 35.96 months (± 24.43). Results: Twelve of 142 recipients (8.4%) had an anastomotic leak. Enteric drainage was performed in seven of these patients (58.3%) and bladder drainage in five (41.6%). 75% had shunt complications, such as: pancreatitis, lithiasis, abscess and urinary tract infections. Of these 12 patients, 8 (66.6%) required relaparotomy. In two cases (16.7%) a drainage conversion was needed. Three cases (25%) underwent transplantectomy, one of them (8.3%) as a direct result of the anastomotic leak, and the others due to chronic rejection and graft thrombosis. The overall patient and graft survival at 1, 3 and 5 years was 91.7%, 91.7%, 91.7% and 75%, 66.7%, 66.7%, respectively. Conclusions: Anastomotic leak is a severe postoperative complication in pancreas transplant recipients which may be take into account especially during the immediate postoperative period. In our serie the anastomotic leak was the direct cause of graft loss in one case. The anastomotic leak percentage in our serie was higher in those who underwent enteric drainage technique, but this difference was not statistically significant.
Introduction: Sarcoidosis is a rare disease characterized by the formation of epitheloid non-caseating granulomas and can affect various organs of the body. The liver is usually affected by the formation of these granulomas (70-90%), but it usually silent, although in rare occasions it can produce complications sucha as jaundice, liver failure, cirrhosis, and portal hypertension. A liver transplantation can be performed in patients with cirrhosis secondary to an intrahepatic cholestasis due to sarcoidosis. We present a case of hepatic sarcoidosis transplated in “12 de Octubre” University Hospital. Patient and methods: A 53-year old woman with diagnosis of pulmonary sarcoidosis in 1999, with personal history of type-2 diabetes melliuas, esophageal varices and hepatic encephalopathy with associated hepatopulmonary syndrome, is admitted for liver transplantation (liver cirrhosis Chil-Pugh B7). An orthotopic liver transplantation is performed with a graft from a brain-dead donor. The pathology of the recipient liver showed micronodular cirrhosis associated with epitheloid non-caseating granulomas and ductopenia compatible with sarcoidosis. The postoperative evolution was uneventful, and the patient was dismissed at tenth postoperative day. Conclusions: Liver transplantation is a valid option in patients with liver cirrosis due to sarcoidosis. The survival after transplantation is similar to patients with liver transplants due to other causes, with good recipient and graft survival at long term. Although liver recurrence in the graft is not well known, it seems to have a little impact in long term results.