Isabelle Cardeau-Desangles

Pegylated Interferon-α for Treating Chronic Hepatitis E Virus Infection after Liver Transplantation

This study assessed the effect of a 3-month course of pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) in 3 liver transplant patients with chronic active hepatitis E. A virological response was sustained for 6 and 5 months in 2 patients after Peg-IFN-alpha-2a therapy was completed. A relapse was observed in the third patient.

Hepatitis E virus and the kidney in solid-organ transplant patients.

Background. Hepatitis E virus (HEV) infection is an emerging disease in industrialized countries. Few data regarding genotype 3 HEV extrahepatic manifestations exist. Methods. We assessed kidney function and histology in solid-organ transplant patients during HEV infection. In all, 51 cases of genotype 3 HEV infections were diagnosed (34 kidney, 14 liver, and 3 kidney-pancreas transplant patients). Of these, 43.2% were cleared of the virus spontaneously within 6 months of infection, whereas 56.8% evolved to chronic hepatitis. Twelve of these patients completed a 3-month antiviral therapy and were followed up for 6 months posttreatment. Kidney function (estimated glomerular filtration rate [eGFR] obtained by the Modification of Diet in Renal Disease equation) and proteinuria were assessed before infection, during HEV infection and during follow-up. Kidney biopsies were obtained from patients with high proteinuria and decreased eGFR levels. Results. During HEV infection, there was a significant decrease in eGFR in both kidney- and liver-transplant patients. Glomerular diseases were observed in kidney biopsies obtained during the acute and chronic phases. This included membranoproliferative glomerulonephritis and relapses in IgA nephropathy. The majority of patients had cryoglobulinemia that became negative after HEV clearance. Kidney function improved and proteinuria decreased after HEV clearance. Conclusion. HEV-associated glomerulonephritis seems to be an HEV-related extrahepatic manifestation. Further studies are required to confirm these observations.

Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient

Hepatitis E virus (HEV) can induce chronic hepatitis in immunosuppressed patients. There is no established treatment for HEV infection. Pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) has been successfully used for treating HEV infection in liver transplant patients with chronic hepatitis. A kidney transplant patient with chronic HEV infection evolved to end-stage kidney disease and started haemodialysis. Three months after immunosuppressive therapy was stopped, HEV RNA was still detected both in serum and in stools. Before considering a retransplantation, we decided to initiate Peg-IFN-alpha-2a therapy to eradicate the virus. A 3-month course of Peg-IFN-alpha-2a was scheduled, and the latter was started at the weekly dose of 135 microg. Serum HEV RNA became negative by Week 3 of Peg-IFN-alpha-2a therapy, and remained negative until the last follow-up, i.e. 6 months after anti-viral therapy was stopped. Hence, we report the first known case of a 3-month course of Peg-IFN-alpha-2a inducing a sustained virological response in this HEV-positive and RNA-positive haemodialysis patient who had failed to be cleared of the virus after immunosuppressant withdrawal.

Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in maintenance liver transplant patients.

Although large retrospective studies have identified the presence of donor‐specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long‐term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixty‐seven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single‐antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min–max: 6–220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min–max: 2–45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28–11.05, p = 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody‐mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.

Donor-Specific Antibodies after Ceasing Immunosuppressive Therapy, with or without an Allograft Nephrectomy

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.

Incidence of donor‐specific antibodies in kidney transplant patients following conversion to an everolimus‐based calcineurin inhibitor‐free regimen

Scarce data exist regarding the incidence of donor‐specific antibodies (DSAs) in kidney transplant patients receiving everolimus‐based immunosuppression without calcineurin inhibitors (CNIs). The aim of this retrospective case–control study was to compare the incidence of de novo DSAs in patients converted to an everolimus‐based regimen without CNIs with that seen in patients maintained on CNIs. Sixty‐one DSA‐free kidney transplant patients who had been converted to an everolimus‐based regimen (everolimus group) were compared to 61 other patients maintained on CNIs‐based regimen (control group). Patients were matched according to age, gender, induction therapy, date of transplantation, and being DSA‐free at baseline. At last follow‐up, the incidence of DSAs was 9.8% in the everolimus group and 5% in the control group (p = ns). In the everolimus group, the increased incidence of DSAs between baseline and last follow‐up was statistically significant. Antibody‐mediated rejection occurred in 6.5% in the everolimus group and 0% in the CNIs group. The incidence of DSAs is numerically increased in kidney transplant patients treated with an everolimus‐based without CNIs. A study including a larger number of patients is required to determine whether a CNI‐free everolimus‐based immunosuppression significantly increases DSAs formation.

De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

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.

Risk factors of Pneumocystis pneumonia in solid organ recipients in the era of the common use of posttransplantation prophylaxis.

Pneumocystis pneumonia (PCP) in solid organ transplant (SOT) recipients becomes rare in the immediate posttransplantation period thanks to generalized prophylaxis. We aimed to identify the predictive factors for PCP in the era of universal prophylaxis and to propose a strategy for preventing PCP beyond the first year after transplantation. In a retrospective case–control study, 33 SOT cases with PCP diagnosed between 2004 and 2010 were matched with two controls each to identify risk factors for PCP by uni‐ and multivariate analysis. All the patients benefited from 6 months of posttransplantation trimethoprim–sulfamethoxazole prophylaxis. Most PCP in SOT patients occurred during the second year posttransplantation (33%). By univariate analysis, age, nonuse of tacrolimus, total and CD4 lymphocyte counts, gamma‐globulin concentration and cytomegalovirus (CMV) infection appeared to be PCP risk factors. In the final multivariate analysis, age (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI]: 1.3–10.4), CMV infection (OR: 5.2, 95% CI: 1.8–14.7) and total lymphocyte count (OR: 3.9, 95% CI: 1.4–10.7) were found to be independently associated with PCP. The second year posttransplantation appeared to be the new period of highest risk of PCP. Age, CMV viremia and lymphocytes were the most pertinent predictive criteria to evaluate the risk of PCP in clinical practice.

Anti-human leukocyte antigen immunization after early 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.

Impact of very early high doses of recombinant erythropoietin on anemia and allograft function in de novo kidney-transplant patients.

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.