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The immunogenicity of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccine was improved by the administration of a third dose. The aim of our retrospective study was to assess the evolution of binding and neutralizing antibody concentration until 3 months after the third dose in a large cohort of solid organ transplant (SOT) patients (n = 872). At 1 month after the third dose, anti-SARS-CoV-2 antibodies were detected by means of enzyme-linked immunosorbent assay tests in 578 patients (66.3%). In a subgroup of patients, 70% (180 out of 257) had anti-SARS-CoV-2 antibody concentrations ranging from 1.2 to 18 411 binding antibody units (BAU)/ml and 48.5% (115 out of 239) had a neutralizing antibodies titer that can confer clinical protection against SARS-CoV-2. Three-hundred ninety-three patients out of the 416 (94.5%) who were seropositive at month 1 and were tested at 3 months after vaccination remained seropositive. Between months 1 and 3 after vaccination, binding and neutralizing antibodies concentrations decreased significantly. The proportion of protected patients against the SARS-CoV-2 also slightly decreased. In conclusion, this study shows that although two-third of SOT develop anti-SARS-CoV-2 antibodies after three doses, one-third of them remain weak or non-protected. It is important to measure anti-SARS-CoV-2 antibodies to define the strategy that can optimize SOT protection against SARS-CoV-2., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The field of liver transplantation directly or indirectly embodies all liver diseases, in addition to specific ones related to organ rejection (cellular and humoral). The recommended non-invasive methods for determining the indication for liver transplantation are the Model for End-stage Liver Disease score, and the alpha-foetoprotein score in case of hepatocellular carcinoma. Radiological methods are the cornerstones for the diagnosis of vascular and biliary complications after liver transplantation. The possible diseases of the liver graft after transplantation are multiple and often intertwined. Non-invasive diagnostic methods have been poorly evaluated in this context, apart from the recurrence of hepatitis C. Liver biopsy remains the gold standard for evaluating graft lesions in the majority of cases, especially graft rejection., (Copyright © 2021. Published by Elsevier Masson SAS.)

Aim: To investigate the role of tacrolimus intra-patient variability (IPV) in adult liver-transplant recipients., Methods: We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies ( dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil (with or without steroids) were included., Results: Twenty-two patients (18.5%) experienced at least one acute-rejection episode (BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI (1.14-8.24), P = 0.03] or > 40% [OR = 4.16 (1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68 (1.3-10.4), P =0.014]. Thirteen patients (11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI (1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI (1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI (2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient- or graft-survival rates during the follow-up., Conclusion: Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver transplantation., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.

This is the case of a 56-year-old man who underwent heart transplantation. Within the first postoperative days, his respiratory and limb muscles weakened, which was attributed to critical illness polyneuromyopathy (CIPM). At day 70 post transplantation, he had increased liver enzyme levels and acute hepatitis E virus (HEV) infection was diagnosed. HEV RNA was found in the serum, stools, and cerebrospinal fluid. Results of further investigations suggested a possible HEV-related polyradiculoneuropathy. At transplantation, the patient was negative for immunoglobulin (Ig)G, IgM, and HEV RNA. A trace-back procedure identified the source of infection and concluded that HEV infection was contracted from blood transfusion 12 days prior to transplantation from an HEV RNA-positive donor. Tests of the organ donor for HEV were negative. Phylogenetic analysis revealed sequence homology between the HEV-3 strain of the patient and the HEV-3 strain of the blood donor. Despite ribavirin treatment, the patient died on day 153 post transplantation from multiorgan failure. In conclusion, patients with hepatitis or neuropathic illness who have received blood products should be screened for HEV., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Malignancies and lymphoma are common complications after kidney transplantation. However, no link has been made between the incidence of malignancies and hepatitis C virus (HCV) infection in this setting. This case-controlled study compared the incidence of malignancies, including lymphoma, between kidney transplant (KT) patients with or without HCV replication., Patients and Methods: A total of 99 HCV-positive RNA-positive KT patients were matched with 198 (1:2) anti-HCV-negative patients according to age, gender, and date of transplantation, and were followed for 145.8±78.4 months., Results: During the follow-up period, 28 HCV-positive (28%) cases developed at least one cancer, and 64 (32%) patients developed cancer in the HCV-negative group (P=not significant [ns]). Survival without a cancer was similar between both groups. Thirteen HCV-positive patients (13%) developed at least one solid cancer vs 29 (15%) HCV-negative patients (P=ns). Survival without a solid cancer was similar between both groups. Three patients from the HCV-positive and 4 from the HCV-negative group developed a lymphoma. Only 2 patients from the HCV group died from hepatocellular carcinoma. Survival without a skin cancer was similar between both groups. Patient and death-censored graft survival rates were significantly lower in the HCV group., Conclusion: The incidences and types of malignancies were similar in the HCV-positive and HCV-negative KT patients., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aim: Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known., Method: Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination., Results: Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03)., Conclusion: In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR., (© 2015 Steunstichting ESOT.)

Background: Ribavirin is efficient at treating chronic hepatitis E virus infection in solid-organ transplant patients. However, the early kinetics of viral replication under therapy and the impact of immunosuppressant regimens on viral replication are unknown: thus, determining the aim of our study., Methods: Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA concentrations were determined before treatment, at days 7, 15, and 21 and at months 1, 2, and 3 during therapy and after ribavirin cessation., Results: A sustained virological response (SVR) occurred in 63%. Decreased viral concentration within the first week post-ribavirin therapy was an independent predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL or greater had an 88% positive predictive value. No correlation between ribavirin trough level on day 7 or at month 2 with a virological response or an SVR was observed. Before therapy, HEV RNA concentration was significantly greater in patients receiving mechanistic target of rapamycin inhibitor-based immunosuppression compared to patients given calcineurin inhibitors. The use of mycophenolic acid did not impact on the response to ribavirin., Conclusion: An early response to ribavirin can be used to define the optimal duration of therapy in the setting of HEV infection.

Background & Aims: Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis., Methods: Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study., Results: GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed., Conclusion: Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fibrosing cholestatic hepatitis (FCH) is a classical but rare and severe form of recurrent hepatitis C virus (HCV) after liver transplantation. Classical anti-HCV therapy, that is pegylated-interferon (peg-interferon) and ribavirin, has been shown to have limited efficacy in treating FCH. Herein, we report on the first case of successful use of peg-interferon, ribavirin, plus sofosbuvir to treat HCV-induced FCH in a combined liver-kidney transplant patient. Antiviral therapy was given for 24 weeks. HCV clearance occurred within 4 weeks after starting therapy and was maintained until 4 weeks after the end of therapy. Antiviral tolerance was good. We conclude that the use of sofosbuvir-based anti-HCV therapy can be successfully used to treat FCH after a liver or combined kidney-liver transplantation., (© 2014 Steunstichting ESOT.)

Background: Kidney transplantation increases the chances for pregnancy and live birth for women with end-stage kidney disease. The aims of this study were to describe the outcomes of pregnancies in women with a kidney transplant and to evaluate the impact on anti-human leucocyte antigen (HLA) alloimmunization., Methods: We analysed 61 pregnancies that occurred in 46 patients after having excluded 10 miscarriages during the first trimester and 10 other pregnancies from which important data were missing. Anti-HLA antibodies were screened using the Luminex assay., Results: Overall, the live birth rate was 83% (94% after exclusion of miscarriages during the first trimester). Pre-eclampsia and gestational diabetes occurred in 26 and 21% of cases, respectively. The use of tacrolimus was an independent predictive factor for gestational diabetes. Twenty-four newborns (42%) were premature (<37 weeks). The median birth weight was 2720 (1040-3730) g. Nine newborns (15%) had low birth weights (<2.5 kg). At least one severe complication occurred in 56% of pregnancies. A high glomerular-filtration rate (GFR) before pregnancy was the sole independent protective factor that avoided a severe complication. Death-censored kidney-allograft survival was 80.4% at 6 years. De novo donor-specific anti-HLA antibodies were detected after only 5.9% of pregnancies: for two women, the father had the same HLA antigens as those from the deceased organ donor. The determination of the HLA of the father before pregnancy can better inform the woman about the possible impact of pregnancy on her kidney-allograft function., Conclusions: Despite many complications, the outcomes for pregnancy and kidney allografts are good. The risk of anti-HLA alloimmunization was low., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background and Aim: Liver transplantation remains the best option for treating type-1 hepatorenal syndrome (HRS1). The aim of this retrospective study was to determine whether the molecular adsorbent recirculation system (MARS) can improve renal function in HRS1 patients., Methods: Thirty-two patients with chronic liver disease and HRS1 were treated by MARS sessions which were performed every other day. The endpoint was renal function improvement by 28 days after diagnosis of HRS1 that was defined as a serum-creatinine level of < 133 μmol/L. Partial renal recovery was defined as a 10% decrease in baseline serum-creatinine level., Results: The mean number of MARS sessions required by each patient was 3.5 ± 1.5. The median time between admission and the start of MARS therapy was 3 (0-15) days. Of the total patients, 13 (40%) had improved renal function. Among these, nine (28%) had complete renal recovery. Among the patients that survived, only 40% (6/15) had improved renal function, and among the patients that died within the first month after the initiation of MARS, seven patients had a renal response. The 28-day survival rate was 47%. Seven patients received a liver transplant after diagnosis of HRS. Of these, four had complete or partial recovery after transplantation (57%) versus 9 of the 25 patients who did not undergo liver transplantation (36%), P = not significant., Conclusion: MARS therapy improved renal function in only very few patients with HRS1. Further controlled studies including large number of patients are required., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Histological renal lesions observed after liver transplantation are complex, multifactorial, and interrelated. The aims of this study were to determine whether kidney lesions observed at five yr after liver transplantation can predict long-term kidney function. Ninety-nine liver transplant patients receiving calcineurin inhibitor (CNI)-based immunosuppression, who had undergone a kidney biopsy at 60±48 months post-transplant, were included in this follow-up study. Kidney biopsies were scored according to the Banff classification. Estimated glomerular filtration rate (eGFR) was assessed at last follow-up, that is, 109±48 months after liver transplantation. eGFR decreased from 92±33 mL/min at transplantation to 63±19 mL/min after six months, to 57±17 mL/min at the kidney biopsy, to 54±24 mL/min at last follow-up (p<0.0001). At last follow-up, only three patients required renal replacement therapy. After the kidney biopsy, 13 patients were converted from CNIs to mammalian target of rapamycin inhibitors, but no significant improvement in eGFR was observed after conversion. Elevated eGFR at six months post-transplant and a lower fibrous intimal thickening score (cv) observed at five yr post-transplant were the two independent predictive factors for eGFR≥60 mL/min at nine yr post-transplant. Long-term kidney function seems to be predicted by the kidney vascular lesions., (© 2012 John Wiley & Sons A/S.)

Background and Objectives: Within the last few years, anti-human leukocyte antigen detection assays have significantly improved. This study asked, using the Luminex single-antigen assay, whether an allograft nephrectomy allowed donor-specific alloantibodies to appear that were not previously detected in the serum when the failed kidney was still in place., Design, Setting, Participants, & Measurements: After losing the kidney allograft and stopping immunosuppressive therapy, the proportions of donor-specific alloantibodies and nondonor-specific alloantibodies were compared in patients who had (n=48; group I) and had not (n=21; group II) undergone an allograft nephrectomy. Allograft nephrectomies were performed at 150 days after kidney allograft loss, and the time between allograft nephrectomy and last follow-up was 538 ± 347 days., Results: At kidney allograft loss, donor-specific alloantibodies were detected in three group II patients (14.2%) and six group I patients (12.5%). At last follow-up, donor-specific alloantibodies were detected in 11 patients (52.4%) without and 39 patients (81%) with an allograft nephrectomy (P=0.02). Anti-human leukocyte antigen class I donor-specific alloantibodies were positive in 23.8% of group II and 77% of group I patients (P<0.001); anti-human leukocyte antigen class II donor-specific alloantibodies were positive in 42.8% of group II and 62.5% of group I patients. Independent predictive factors for developing donor-specific alloantibodies after losing kidney allograft and stopping immunosuppressants were number of anti-human leukocyte antigen A/B mismatches at transplantation (zero versus one or more) and allograft nephrectomy., Conclusions: The development of donor-specific alloantibodies was significantly greater in patients with a failed kidney who had undergone an allograft nephrectomy compared with those patients who had not undergone allograft nephrectomy.

Introduction: The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs., Materials and Methods: Thirty-two patients, who experienced an early graft loss (<3 months after transplantation) and required an allograft nephrectomy, and who were considered for retransplantation, were included in the study. Anti-HLA antibodies were assessed, using the Luminex assay, before transplantation, on day 15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6 months until the last follow-up., Results: The median time between transplantation and allograft nephrectomy was 2.5 (0-81) days. The median follow-up was 335 (30-1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was 56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in 33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti-HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors' epitopes. Induction therapy (type and dose) and the time between transplantation and allograft nephrectomy did not influence the incidence of DSAs. No independent predictive factor for the development of DSAs was identified., Conclusion: Even after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may develop in more than 50% of patients whose immunosuppression has been stopped after an allograft nephrectomy.

Objectives: This retrospective single-center study evaluated long-term renal function after conversion from calcineurin inhibitors to sirolimus-based immunosuppression in kidney transplant recipients., Materials and Methods: From 2001 to 2009, one hundred fifty kidney transplant recipients were converted from calcineurin inhibitors to sirolimus at least 3 months after transplant., Results: After a mean follow-up of 171 weeks, 56.7% of converted patients remained on sirolimus. The 5-year survival rate of the patients (including intent-to-treat) and grafts was 85.5% and 83.6%. Patients on sirolimus showed significant improvement in renal function with a creatinine clearance of 50.9 ± 20.7 and 52.9 ± 20.8 mL/minute at month 0 and month 24. Independent predictive factors associated with a stable estimated glomerular filtration rate at the last follow-up of sirolimus patients were (1) having a living donor, (2) absence of anti-HLA alloantibodies at month 0, and (3) cyclosporine versus tacrolimus used before conversion. Adverse effects were reported in 134 patients (89.3%). They included (1) hospitalization for infection (n=52), (2) de novo proteinuria (n=40), and (3) eight patients with biopsy-proven acute rejection. Sirolimus was stopped and replaced by calcineurin inhibitors in 37 patients after a mean of 16 months treatment. After stopping sirolimus, renal-allograft function remained stable at 2 years., Conclusions: Conversion of calcineurin inhibitors to sirolimus in kidney transplant recipients was associated with improved renal function. The reintroduction of calcineurin inhibitors was safe in patients who were withdrawn from sirolimus owing to adverse effects.

Background: Chronic kidney disease is a common complication after liver transplantation. However, few reports regarding kidney histology exist for this setting., Methods: Inulin clearance was measured and a kidney biopsy was performed in 99 patients at 60 ± 48 months after liver transplantation. Kidney biopsies were scored according to the Banff classification, and interstitial fibrosis was measured by a computerized quantitative method., Results: There was a steep decrease in kidney function within the first 6 months following transplantation, but this lessened thereafter. At kidney biopsy, inulin clearance and estimated glomerular filtration rate (eGFR) (using the abbreviated Modification of Diet in Renal Disease equation) were highly correlated (r(2) = 0.47, P < 0.0001). A decrease in eGFR at 6 months post-transplant was the sole predictive factor for inulin clearance of < 60 mL/min/1.73 m(2) at 5 years post-transplant. Few patients had a specific pattern of kidney histopathology and all patients had complex primary lesions. Lowered eGFR at 6 months post-transplant was a predictive factor for > 50% sclerotic glomeruli on the kidney biopsy. The duration of tacrolimus therapy, as compared to cyclosporine A, was a protective factor for < 20% interstitial fibrosis on the kidney biopsy., Conclusion: In the setting of liver transplantation, this is the largest kidney-histology study to confirm that histological kidney lesions are complex, multiple and interrelated. Kidney function at 6 months post-transplant can predict long-term kidney function and histology.

Background: Tenofovir therapy has been found to be efficient in treating hepatitis B virus (HBV) in nontransplant patients. However, in the setting of solid-organ transplantation, the efficacy of tenofovir has not been tested. The aim of this pilot study was to assess the clinical and biologic response and tolerance to tenofovir therapy in HBV-positive organ transplant recipients., Methods: Seven patients, three kidney, three liver, and one cardiac transplant recipients, with chronic HBV infection were partial responders to adefovir (n=7), lamivudine (n=7), or entecavir (n=5) therapy. Consequently, they were placed on tenofovir therapy (245 mg daily, which was adapted to renal function) alone (n=4) or in combination with lamivudine (n=3). Tenofovir therapy was assessed at 1, 3, 6, and 12 months postinitiation or at the last follow-up., Results: HBV DNA viral load (4.16 [2.03-5.56] log10 copies/mL at baseline) became significantly decreased to 3.15 (1.08-5.17), 2.88 (1.3-4.3), 3.53 (1.3-5.75), 3.33 (1.3-7.57), and 2.31 (1.3-4.81) log copies/mL at 1, 3, 6, and 12 months posttenofovir initiation and at last follow-up, respectively (P=0.02). Three patients were HBV DNA negative at the last follow-up. Liver enzyme levels did not change significantly throughout the follow-up period. Clinical and biologic tolerance was excellent., Conclusions: Even though HBV DNA clearance was not achieved in all patients, the results of this pilot study are encouraging and demonstrate that tenofovir therapy is safe and efficacious in treating HBV-positive organ transplant patients. However, a larger trial is needed to confirm these preliminary results., (© 2011 by Lippincott Williams & Wilkins)

After kidney transplantation, occurrence of anemia in the early post-transplant period (<1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single-center study to assess whether delivery of high doses of erythropoietin-stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post-transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety-nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post-transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged >50 years, being a recipient aged >50 years, not treated for hypertension at pretransplant, and no post-transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post-transplant.

Background: Hepatitis-E virus (HEV) infection can be responsible for chronic hepatitis in solid-organ transplant patients., Methods: We identified 33 cases of autochthonous acute HEV infection in solid-organ transplant patients., Results: Among 27 HEV-positive patients, who had a follow-up of more than 6 months, 16 (59.25%) evolved to chronic HEV infection, defined by persisting elevated liver-enzyme levels and positive serum HEV RNA 6 months after diagnosis. Serial liver biopsies showed progression in liver activity and liver fibrosis. Three patients developed liver cirrhosis. The proportion of patients receiving tacrolimus compared with cyclosporine A was significantly higher in patients who evolved to chronic disease. Immunosuppressive therapy was reduced in patients with chronic hepatitis; however, those who had a dramatic decrease in tacrolimus trough levels were more likely to clear the virus. Four chronic liver transplant patients were cleared off the virus at 14, 16, 22, and 23 months after diagnosis. At last follow-up, their tacrolimus trough levels and daily steroid doses were significantly lower than those who remained viremic. These four patients had lower liver-enzyme levels and lower activity scores on liver biopsies, and their peripheral blood CD3- and CD4-positive cell counts were also significantly higher., Conclusions: The rate of chronic HEV-related hepatitis is approximately 60% in solid-organ transplant patients. When possible, the reduction of immunosuppressive drugs targeting T cells should be considered as a first-line therapeutic option.

Therapeutic drug monitoring of mycophenolate mofetil (MMF) was found to be beneficial in preventing acute rejection after kidney transplantation. The aim of this pilot prospective study was to evaluate the efficacy of MMF dose adjustment in de novo liver transplant patients receiving MMF at fixed versus concentration-controlled doses [ie, adapted to mycophenolic acid (MPA) AUC0-12h] and tacrolimus during the first 12 months posttransplant. Twenty-nine patients received steroids only up to day 10, induction therapy by lymphoglobulins followed by tacrolimus and MMF. In all patients, MPA AUC0-12h were measured on posttransplant days 7 and 14 and at months 1, 2, 3, 6, and 12. From March 2006 to March 2007, 15 patients received MMF at a fixed dose of 1 g twice a day for 12 months. From April 2007 to December 2007, MMF was given to 14 patients at a dose of 1 g twice a day until day 7 and was then adapted to reach an MPA AUC0-12h target of 30-60 mg x h/L. The proportion of MPA AUC0-12h values within the target range was similar in both groups. The proportion of patients with MPA AUC0-12h below 30 mg x h/L tended to be higher in the fixed dose group within the first month posttransplant. However, MMF dose did not differ significantly between the 2 groups at any period except month 1. MPA AUC0-12h tended to be higher in the concentration-controlled group at day 14 and month 2 and was significantly so at month 1. Tacrolimus trough concentrations tended to be lower in the concentration-controlled group at all study periods and was significantly so at month 3. At 12 months posttransplant, patient and graft survivals, acute rejection rate, and adverse events were similar in both groups. We concluded that adapting the dose of MMF resulted in a significant increase in MPA AUC0-12h at month 1. There was a trend toward a lower proportion of patients with MPA AUC0-12h below 30 mg x h/L in the concentration-controlled group. No difference in outcome was found between both groups.

Acute humoral rejection (AHR) is uncommon after ABO-compatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab. Liver enzymes returned to within normal range 18 d after diagnosis. Liver biopsies, at 3 and 9 mo post-transplant, showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

Background: In the setting of kidney transplantation, cinacalcet has been given, mainly, once daily, but also twice daily. The aims of this prospective study were to assess the acute pharmacodynamic effect of cinacalcet administrated once or twice daily to kidney transplant patients with normal renal function and persisting hypercalcaemia due to hyperparathyroidism and to evaluate 1-year efficacy and tolerance of cinacalcet given at a dose of 30 mg b.i.d., Methods: Eleven patients, who received a transplant 6 (6-59) months previously, were included in the study. A first kinetic was done after administration of 60 mg of cinacalcet at 8 a.m. After a washout period of 1 week, the second kinetic was performed with cinacalcet given at 30 mg b.i.d within a 12-h period., Results: During both kinetics, serum calcium (sCa), ionized calcium (sCa(2+)), albumin-corrected Ca and parathyroid hormone (PTH) levels decreased significantly. At 24 h after the second kinetic, sCa(2+) was significantly lower. After 1 year of cinacalcet treatment, given at the dose of 30 mg b.i.d., there was a significant decrease in sCa, sCa(2+), PTH levels and calcium x phosphorus (Ph) product. In contrast, Ph levels increased significantly. There was no significant change in renal function., Conclusion: Once- or twice-daily acute administration of cinacalcet to kidney-transplant patients has similar efficacy. One-year administration of cinacalcet, given as two daily doses, is safe and efficient.

The aim of our study was to assess the efficacy and safety of entecavir in kidney- and liver-transplant recipients with chronic hepatitis B virus (HBV) infection. Ten male transplant patients with chronic HBV infection (eight kidney- and two liver-transplant patients), who have become adefovir (n=9) or lamivudine-resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After a median follow-up of 16.5 months, entecavir therapy was associated with a significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10 copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-) patients. There were no significant changes in renal function or hematological parameters. This study demonstrates that entecavir therapy is safe and efficient in HBV(+) organ-transplant patients.

The aims of this prospective, open-label, single-center pilot study were to assess the efficacy and safety of human cytomegalovirus (HCMV) prophylaxis using valganciclovir in HCMV- seropositive kidney-transplant patients to prevent HCMV infection and disease. Fifty-one HCMV seropositive kidney-transplant patients recipients who received transplants between 1 December 2005 and 30 November 2006 were included in the study. Valganciclovir was given from transplantation up to 114 (37-329) days, and was adapted to renal function, i.e., 900 mg/d if calculated creatinine clearance was >60 ml/min, or 450 mg/day if it was <60 ml/min. HCMV DNAemia was assessed every 2 weeks during prophylaxis, and on the same basis for 3 months post-prophylaxis. Immunosuppression was based on calcineurin inhibitors (ciclosporine A=22; tacrolimus=11), with mycophenolate mofetil (n=51), and low-dose steroids. Eighteen patients received no calcineurin-inhibitors, but Belatacept instead. During valganciclovir prophylaxis, asymptomatic HCMV DNAemia was observed in one patient, and no case of HCMV disease occurred. Within 252 days (45-425) post-valganciclovir prophylaxis, HCMV DNAemia was detected in 23.5% (n=12) of patients, of whom two had two or more consecutive HCMV DNAemias. Valganciclovir prophylaxis in HCMV-seropositive kidney-transplant patients is effective for preventing cytomegalovirus disease.

The aims of the present study were to assess the incidence of cytomegalovirus (CMV) reactivation, and to determine the predictive factors for CMV reactivation in CMV seropositive kidney-transplant patients. One hundred ninety CMV seropositive kidney-transplant patients were included in this study; of these, 39 patients had received CMV prophylaxis. CMV DNAemia was assessed by real-timepolymerase chain reaction assay every 2 weeks until day 120, then every 3-4 weeks until day 180, and then every month until day 365. One hundred seven patients (56.3%) had at least one positive CMV DNAemia within the first year. The time between renal transplantation and the first positive CMV DNAemia was 59 +/- 5 days. The number of positive CMV DNAemia/patient was 3.28 +/- 0.22. CMV viral load at first positive CMV DNAemia was 704 (10-742,000) copies/ml. The donor CMV seropositivity, the absence of CMV prophylaxis, and the occurrence of acute rejection before CMV reactivation were independent factors associated with CMV reactivation within the first year after kidney transplantation. Hence, CMV reactivation is frequent after kidney transplantation. CMV prophylaxis in CMV seropositive kidney-transplant patients should be offered to avoid CMV-related side-effects.