Impact of Switching From Immediate- or Prolonged-Release to Once-Daily Extended-Release Tacrolimus (LCPT) on Tremor in Stable Kidney Transplant Recipients: The Observational ELIT Study.

Once-daily extended-release tacrolimus (LCPT) exhibits increased bioavailability versus immediate-release (IR-TAC) and prolonged release (PR-TAC) tacrolimus. Improvements in tremor were previously reported in a limited number of kidney transplant patients who switched to LCPT. We conducted a non-interventional, non-randomized, uncontrolled, longitudinal, prospective, multicenter study to assess the impact of switching to LCPT on tremor and quality of life (QoL) in a larger population of stable kidney transplant patients. The primary endpoint was change in The Essential Tremor Rating Assessment Scale (TETRAS) score; secondary endpoints included 12-item Short Form Survey (SF-12) scores, tacrolimus trough concentrations, neurologic symptoms, and safety assessments. Subgroup analyses were conducted to assess change in TETRAS score and tacrolimus trough concentration/dose (C0/D) ratio by prior tacrolimus formulation and tacrolimus metabolizer status. Among 221 patients, the mean decrease of TETRAS score after switch to LCPT was statistically significant (p < 0.0001 vs. baseline). There was no statistically significant difference in change in TETRAS score after switch to LCPT between patients who had received IR-TAC and those who had received PR-TAC before switch, or between fast and slow metabolizers of tacrolimus. The overall increase of C0/D ratio post-switch to LCPT was statistically significant (p < 0.0001) and from baseline to either M1 or M3 (both p < 0.0001) in the mITT population and in all subgroups. In the fast metabolizers group, the C0/D ratio crossed over the threshold of 1.05 ng/mL/mg after the switch to LCPT. Other neurologic symptoms tended to improve, and the SF-12 mental component summary score improved significantly. No new safety concerns were evident. In this observational study, all patients had a significant improvement of tremor, QoL and C0/D ratio post-switch to LCPT irrespective of the previous tacrolimus formulation administered (IR-TAC or PR-TAC) and irrespective from their metabolism status (fast or slow metabolizers).

Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients.

RATIONALE & OBJECTIVE: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 32 patients with AFib amyloidosis diagnosed by genetic testing in France between 1983 and 2014, with a median follow-up of 93 (range, 4-192) months, were included. RESULTS: Median age at diagnosis was 51.5 (range, 12-77) years. Clinical presentation consisted of proteinuria (93%), hypertension (83%), and kidney failure (68%). Manifestations of kidney disease appeared on average at age 57 (range, 36-77) years in patients with the E526V variant, at age 45 (range, 12-59) years in those with the R554L variant (P<0.001), and at age 24.5 (range, 12-31) years in those with frameshift variants (P<0.001). KT was performed in 15 patients and LKT was performed in 4. In KT patients with the E526V variant, recurrence of AFib amyloidosis in the kidney graft was less common than with a non-E526V (R554L or frameshift) variant (22% vs 83%; P=0.03) and led to graft loss less frequently (33% vs 100%). Amyloid recurrence was not observed in patients after LKT. LIMITATIONS: Analyses were based on clinically available historical data. Small number of patients with non-E526V and frameshift variants. CONCLUSIONS: Our study suggests phenotypic variability in the natural history of AFib amyloidosis, depending on the FGA mutation type. KT appears to be a viable option for patients with the most common E526V variant, whereas LKT may be a preferred option for patients with frameshift variants.

Comparison of machine perfusion versus cold storage in kidney transplant recipients from expanded criteria donors: a cohort-based study.

BACKGROUND: Most studies comparing the efficacy of hypothermic machine perfusion (HMP) versus static cold storage (SCS) are based on short-term outcomes. We aimed to better evaluate the mid-term impact of HMP in patients receiving expanded criteria donor (ECD) kidneys. METHODS: The analyses were based on the French Données Informatisées et VAlidées en Transplantation (DIVAT) observational cohort. Patients aged ≥45 years transplanted for the first or second times from an ECD donor since 2010 were studied. Our study reported the graft and/or patient survivals and the incidence of acute rejection episode. The Cox models and the Kaplan-Meier estimators, weighted on the propensity score, were used to study the times-to-events. RESULTS: Among the 2019 included patients, 1073 were in the SCS group versus 946 in the HMP group. The mean life expectancy with functioning graft was 5.7 years [95% confidence interval (CI) 5.4-6.1] for the HMP cohort followed-up for 8 years post-transplantation versus 6.0 years (95% CI 5.7-6.2) for the SCS group. These mid-term results were comparable in the patients receiving grafts from donors aged ≥70 years and in the transplantations with cold ischaemia time ≥18 h. CONCLUSIONS: Our study challenges the utility of using HMP to improve mid-term patient and graft survival. Nevertheless, the improvement of the short-term outcomes is indisputable. It is necessary to continue technological innovations to obtain long-term results.

The weekend effect in kidney transplantation outcomes: a French cohort-based study.

Numerous studies have reported a weekend effect on outcomes for diseases treated at hospitals. No study has been conducted in France for kidney transplantation. We therefore performed a cohort-based study to evaluate whether outcomes of kidney transplant recipients display a weekend effect. Data were extracted from the French DIVAT cohort. Patients aged 18 years and older, transplanted with a single kidney from deceased donors between 2005 and 2017 were studied. Linear regression, logistic regression, and cause-specific Cox model were used. Among the 6652 studied patients, 4653 patients were transplanted during weekdays (69.9%) versus 1999 during weekends (30.1%). The only statistically significant difference was the percentage of patients with vascular surgical complication(s) at 30 days: 13.3% in the weekend group versus 16.2% in the weekday group 0.79 (95% CI: 0.68; 0.92). We did not observe other significant differences for the other outcomes: patient or graft survival, the risk of acute rejection episodes, the 30-day percentage of urological complications, and the 1-year estimated glomerular filtration rate. Our study highlights a small protective weekend effect with less post-surgery vascular complications compared to weekdays. This paradox might be explained by a different handling of weekend transplantations.

Lack of impact of pre-emptive deceased-donor kidney transplantation on graft outcomes: a propensity score-based study.

BACKGROUND: A significant number of studies have compared graft outcomes between patients with Pre-emptive Kidney Transplantation (PreKT) and patients on Dialysis before their Kidney Transplantation (DiaKT). These studies have suffered from the limitation that the DiaKT group is composed of all the dialysed patients, including those placed on a waiting list at the time of their first dialysis session. This seriously questions the comparability of these patients with those placed on the waiting list a long time before the need for renal replacement therapy. The aim of this study was to precisely evaluate the causal effect of PreKT from deceased donors. METHODS: Data were extracted from the multicentric French DIVAT (Données Informatisées et VAlidées en Transplantation) cohort. The DiaKT group was composed of patients placed on the waiting list with an initial intention of pre-emptive transplantation. Cause-specific Cox models with propensity scores (inverse probability weighting) were used to study the patient and graft outcomes. RESULTS: Among the 1138 included patients, 554 patients were in the PreKT group. The outcomes of the PreKT group were similar compared with the DiaKT group. In particular, the life expectancy with a functioning graft was 8.51 years [95% confidence interval (CI) 8.20-8.81] for the PreKT recipients versus 8.49 years (95% CI 8.15-8.84) for the DiaKT recipients. CONCLUSIONS: Our results challenge the utility of PreKTs from deceased donors, especially with regard to the consequential increase in the waiting list.

Dynamic predictions of long-term kidney graft failure: an information tool promoting patient-centred care.

BACKGROUND: Informing kidney transplant recipients of their prognosis and disease progression is of primary importance in a patient-centred vision of care. By participating in decisions from the outset, transplant recipients may be more adherent to complex medical regimens due to their enhanced understanding. METHODS: We proposed to include repeated measurements of serum creatinine (SCr), in addition to baseline characteristics, in order to obtain dynamic predictions of the graft failure risk that could be updated continuously during patient follow-up. Adult recipients from the French Données Informatisées et VAlidées en Transplantation (DIVAT) cohort transplanted for the first or second time from a heart-beating or living donor and alive with a functioning graft at 1 year post-transplantation were included. RESULTS: The model was composed of six baseline parameters, in addition to the SCr evolution. We validated the dynamic predictions by evaluating both discrimination and calibration accuracy. The area under the receiver operating characteristic curve varied from 0.72 to 0.76 for prediction times at 1 and 6 years post-transplantation, respectively, while calibration plots showed correct accuracy. We also provided an online application tool (https://shiny.idbc.fr/DynPG). CONCLUSION: We have created a tool that, for the first time in kidney transplantation, predicts graft failure risk both at an individual patient level and dynamically. We believe that this tool would encourage willing patients into participative medicine.

Comparison of graft and patient survival according to the transplantation centre policy for 1-year screening biopsy among stable kidney recipients: a propensity score-based study.

BACKGROUND: The clinical utility of screening biopsies (SBs) at 1 year post-transplantation is still debated, especially for stable kidney graft recipients. Given the heterogeneity in practices between transplantation centres, the objective of this study was to compare graft and patient survival of stable patients according to whether they were followed up in a transplantation centre with or without a policy for having an SB at 1 year post-transplantation. MATERIALS: From a French multicentre cohort, we studied 1573 kidney recipients who were alive with stable graft function at 1 year post-transplantation, with no acute rejection in their first year post-transplantation. RESULTS: Using propensity score-based analyses, we did not observe any significant difference in the relative risk for graft failure between patients from centres with a 1-year SB policy and those from other centres [hazard ratio = 1.15, 95% confidence interval (CI) 0.86-1.53]. The corresponding adjusted survival probability at 8 years post-transplantation was 69% (95% CI 61-74%) for patients from centres with a 1-year SB policy versus 74% (95% CI 67-79%) for those from other centres. CONCLUSION: A 1-year SB policy for stable patients may not lead to therapeutical benefits for improved graft and patient survival. Further studies examining the benefits versus the risks of a 1-year SB policy are warranted to demonstrate the long-term utility of this intervention.

Preemptive second kidney transplantation is associated with better graft survival compared with non-preemptive second transplantation: a multicenter French 2000-2014 cohort study.

The impact of preemptive second kidney transplantation (2KT) on graft and patient survival is poorly established. The association between preemptive 2KT (p2KT, N = 93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314) recipients using propensity score methods. During the follow-up, there were 274 returns to dialysis and 134 deaths. p2KT was associated with lower death-censored graft loss (HR = 0.39 [0.18-0.88], P = 0.024) and graft failure from any cause including death (HR = 0.42 [0.22-0.80], P = 0.008). Similar associations were observed for death with a functioning graft, although not reaching statistical significance (HR = 0.47 [0.17-1.26], P = 0.13). There was a significant interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT was not significantly associated with the risk of graft failure from any cause including death in living donor 2KT (P = 0.39), whereas the association was substantial in the deceased donor subset (HR = 0.30 [0.14-0.64], P = 0.002). Of note, the adjusted graft survival of p2KT with deceased donor paralleled that of 2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and 76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study analyzed using propensity scores suggests that p2KT is associated with better graft prognosis.

Ribavirin for chronic hepatitis E virus infection in transplant recipients.

BACKGROUND: There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia. METHODS: We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less. RESULTS: All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%. CONCLUSIONS: This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.

Renal graft intolerance syndrome in late graft failure patients: efficacy and safety of embolization as first-line treatment compared to surgical removal.

Although renal graft percutaneous embolization was introduced to avoid the risk associated with graft nephrectomy, there is no universal consensus about its indications and results. In order to evaluate the efficacy of graft embolization in the treatment of graft intolerance syndrome as well as its safety compared to surgical removal with respect to complications and other morbidity measures, We performed a retrospective observational study comparing two groups of patients treated for graft intolerance syndrome: Group 1: patients who had embolization as first-line treatment and Group 2: patients directly treated by surgical removal. 72 patients were included, (32 in Group 1 and 40 in Group 2); the postintervention follow-up continued for 12 months. Patients in Group 1 are older than those in Group 2. Otherwise, the two groups are similar concerning sex, manifestations of graft intolerance syndrome, diabetes and nutritional and functional status. The overall success rate of embolization in complete resolution of graft intolerance syndrome and ultimately avoidance of surgical removal was 84.37%. The surgical removal group had more serious complications, a longer hospital stay and needed more blood transfusions. We conclude that embolization of symptomatic renal grafts has considerable efficacy with less morbidity, and no serious complications compared to the standard surgical graft removal.

Kidney transplantation in patients with systemic sclerosis: a nationwide multicentre study.

Kidney transplantation is one of the therapeutic options for end-stage renal disease (ESRD) in systemic sclerosis (SS). Current evidence demonstrates poorer patient and graft survival after transplantation in SS than in other primary kidney diseases. All the patients presenting ESRD associated with SS who had received a kidney allograft between 1987 and 2013 were systematically included from 20 French kidney transplantation centres. Thirty-four patients received 36 kidney transplants during the study period. Initial kidney disease was scleroderma renal crisis in 76.4%. Extrarenal involvement of SS was generally stable, except cardiac and gastrointestinal involvements, which worsened after kidney transplantation in 45% and 26% of cases, respectively. Patient survival was 100%, 90.3% and 82.5% at 1, 3 and 5 years post-transplant, respectively. Pulmonary involvement of SS was an independent risk factor of death after transplantation. Death-censored graft survival was 97.2% after 1 and 3 years, and 92.8% after 5 years. Recurrence of scleroderma renal crisis was diagnosed in three cases. In our study, patient and graft survivals after kidney transplantation can be considered as excellent. On this basis, we propose that in the absence of extrarenal contraindication, SS patients presenting with ESRD should be considered for kidney transplantation.

Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation.

Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy.

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.

Similar patient survival following kidney allograft failure compared with non-transplanted patients.

Data from the national French Renal Epidemiology and Information Network (REIN) registry were used to compare survival between transplant recipients under age 65 who resumed dialysis after graft failure during 2007-2009 and transplant-naïve incident dialysis patients matched for age, gender, diabetes mellitus, and year of starting dialysis. Among 911 transplant patients who returned to dialysis, 103 had died by 1 January 2011. Multivariate analysis showed that age over 48 years, coronary artery disease, peripheral artery disease, and inability to walk unassisted were significant predictors of death. In the case-control analysis, the observed mortality rates in 778 transplant failure and 778 transplant-naïve dialysis patients were 11.8 and 10.8%, respectively. Kaplan-Meier estimates of survival after transplant failure vs. the transplant-naïve controls were 95.2 vs. 94.1% at 1 year, 90.3 vs. 88.8% at 2 years, and 84.2 vs. 80.2% at 3 years (log rank P=0.197 overall). Dialysis in transplant failure vs. transplant-naïve patients was not associated with significantly increased mortality. At the start of dialysis, the serum creatinine levels and the rate of unplanned dialysis were significantly lower in transplant failure patients compared with transplant-naïve controls. Thus, in patients under 65 years of age in France, survival of dialysis patients after graft loss is similar to that of incident dialysis patients who have not undergone transplantation.

A useful scoring system for the prediction and management of delayed graft function following kidney transplantation from cadaveric donors.

Delayed graft function (DGF) is a common complication in kidney transplantation and is known to be correlated with short- and long-term graft outcomes. Here we explored the possibility of developing a simple tool that could predict with good confidence the occurrence of DGF and could be helpful in current clinical practice. We built a score, tentatively called DGFS, from a French multicenter and prospective cohort of 1844 adult recipients of deceased donor kidneys collected since 2007, and computerized in the Données Informatisées et VAlidées en Transplantation databank. Only five explicative variables (cold ischemia time, donor age, donor serum creatinine, recipient body mass index, and induction therapy) contributed significantly to the DGF prediction. These were associated with a good predictive capacity (area under the ROC curve at 0.73). The DGFS calculation is facilitated by an application available on smartphones, tablets, or computers at www.divat.fr/en/online-calculators/dgfs. The DGFS should allow the simple classification of patients according to their DGF risk at the time of transplantation, and thus allow tailored-specific management or therapeutic strategies.

Acute renal failure associated with the new BRAF inhibitor vemurafenib: a case series of 8 patients.

BACKGROUND: Vemurafenib is a BRAF inhibitor that has become the cornerstone of metastatic or inoperable melanoma therapy since its approval in 2011 in the United States and 2012 in Europe. This targeted therapy has shown impressive results in terms of increased progression-free and overall survival as compared to dacarbazine. The safety profile did not include any renal manifestations at that time. METHODS: This report is the first case series of 8 patients who experienced significant to severe renal insufficiency under vemurafenib treatment. RESULTS: This case series shows that vemurafenib may induce potentially severe acute renal failure, including renal sequelae and persistent kidney disease in some cases. CONCLUSIONS: Further studies are needed to investigate the effects of vemurafenib on the kidneys. Meanwhile, renal function should be closely monitored in treated patients for early detection of any renal dysfunction occurrence. Cancer 2014;120:2158-2163. © 2014 American Cancer Society.

An alternative approach to estimate age-related mortality of kidney transplant recipients compared to the general population: results in favor of old-to-old transplantations.

Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased-donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10-year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease.

Impact of graft nephrectomy on outcomes of second kidney transplantation.

OBJECTIVES: To determine the impact of renal graft nephrectomy on second kidney transplantation survival. METHODS: We carried out a retrospective single-center study by analyzing cases performed from January 2000 to December 2011. Retransplanted patients who underwent previous allograft nephrectomy more than 3 months post-transplantation (group 1) were compared with those who did not (group 2) in terms of graft survival, incidences of acute rejection and delayed graft function. Multivariate Cox proportional hazard models were used to assess risk factors of graft loss after retransplantation. RESULTS: Overall, 146 patients were analyzed, including 52 (35.6%) in group 1 and 94 (64.4%) in group 2. Group 1 patients presented a significantly shorter first graft survival (0.8 vs 8.6 years, P < 0.001) and more anti-class I antibodies (90.5% vs 74.2%, P = 0.03). A total of 10 patients (19%) in group 1 and 16 patients (17%) in group 2 had at least one acute rejection episode (P = 0.74). Delayed graft function was observed in 13 patients (25%) in group 1 and 17 patients (18%) in group 2 (P = 0.32). Graft survival at 1, 5 and 10 years was, respectively, 94%, 81% and 58% in group 1, and 99%, 93% and 66% in group 2 (P = 0.10). Graft survival was decreased by increased donor age and serum creatinine, and tended to be associated with post-transplantation presence of anti-class I and II antibodies. Graft nephrectomy was not associated with graft survival in multivariate analysis. CONCLUSIONS: Graft nephrectomy, probably a marker of high immunological risk patients, is not a risk factor of increased retransplant failure.

Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs. METHODS: We studied data from 85 recipients of solid organ transplants who were infected with HEV. Chronic HEV infection was defined by the persistent increases in levels of liver enzymes and polymerase chain reaction evidence of HEV in the serum and/or stool for at least 6 months. RESULTS: Fifty-six patients (65.9%) developed chronic hepatitis. Univariate analysis associated liver transplant, shorter times since transplant, lower levels of liver enzymes and serum creatinine, lower platelet counts, and tacrolimus-based immunosuppressive therapy (rather than cyclosporin A) with chronic hepatitis. On multivariate analysis, the independent predictive factors associated with chronic HEV infection were the use of tacrolimus rather than cyclosporin A (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.49-1.97; P = .004) and a low platelet count at the time of diagnosis with HEV infection (OR, 1.02; 95% CI, 1.001-1.1; P = .04). Of patients with chronic hepatitis, 18 (32.1%) achieved viral clearance after the dose of immunosuppressive therapy was reduced. No HEV reactivation was observed after HEV clearance. CONCLUSIONS: HEV infection causes chronic hepatitis in more than 60% of recipients of solid organ transplants. Tacrolimus therapy is the main predictive factor for chronic hepatitis. Dose reductions of immunosuppressive therapy resulted in viral clearance in more than 30% of patients.

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation.

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.