Nassim Kamar

Complement Mutation-Associated De Novo Thrombotic Microangiopathy Following Kidney Transplantation

Mutations in one or more genes encoding complement‐regulatory proteins predispose to atypical hemolytic uremic syndrome (aHUS) and its recurrence following kidney transplantation. We evaluated plasma complement level and performed a screening for mutations in genes encoding complement Factors H and I (CFH, CFI) and membrane cofactor protein (MCP) in 24 kidney transplant recipients experiencing de novo thrombotic microangiopathy (TMA). Six patients presented with low C3 and/or low Factor B levels suggestive complement alternative pathway. A mutation in the CFH or CFI gene was found in 7/24 patients (29%), two of whom had a mutation in both genes. On the contrary, no mutation was identified in a control kidney transplant patients group (n = 25) without TMA. Patients with or without mutations were similar with regard to clinical features. Eight out of 24 patients lost their graft within 1 year of posttransplantation including six patients with a CFH mutation or a decrease of C3 or CFB in plasma. To conclude, kidney transplant patients with de novo TMA exhibit an unexpectedly high frequency of CFH and CFI mutations. These results suggest that genetic abnormalities may represent risk factors for de novo TMA after kidney transplantation and raise the question of the best therapeutic strategy.

Acute autochthonous hepatitis E in western patients with underlying chronic liver disease: a role for ribavirin?

further observation and evaluation. Unfortunately, the objective parameters before discharge such as Post-Anesthetic Discharge Scoring System or Aldrete scoring system were not used. The long term follow up and side effects related to sedation were not done in our study. Regarding the hypoxemia events, all the subjects received supplementary oxygen by nasal prongs. The hypoxemia events, which were slight and transient, were noticed only in the cirrhotic group. The statement that this group might be more prone to develop desaturation could be true, albeit, with no statistical significance. The American Society of Anesthesiologists Physical Status (ASA) score was not calculated, although, this parameter may influence the recovery time [2]. In conclusion, we agree that it is better and safer to apply a multiple psychometric tests before discharging, but this can offset the advantage of the reduced recovery time in patients sedated with propofol. Longer follow up period can easily be taken even by a phone call 1–2 days after the procedure. According to this approach, MHE can be diagnosed and treated rapidly. Finally, a discharge from the hospital at 2 h post endoscopy seems to be very safe [3]. Conflict of interest

Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence – The ANRS CUPILT study

BACKGROUND & AIMSnHCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy.nnnMETHODSnFrom October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigators discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment.nnnRESULTSnThe SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs.nnnCONCLUSIONSnTreatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence.nnnLAY SUMMARYnThe recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.

Impact of Early or Delayed Cyclosporine on Delayed Graft Function in Renal Transplant Recipients: A Randomized, Multicenter Study

The benefit of delayed cyclosporine in reducing risk of delayed graft function (DGF) is not clearly established. This study compared early vs. delayed cyclosporine microemulsion (CsA‐ME) in de novo renal transplant patients. Patients were randomized to early (day 0, n = 97) or delayed (day 6, n = 100) CsA‐ME at an initial dose of 8 mg/kg/day with dose adjusted according to C2 level. All patients received enteric‐coated mycophenolate sodium (EC‐MPS), steroids and an anti‐interleukin‐2 receptor antibody. In both groups, 33% of patients were at high risk of DGF; 26 patients (26.8%) in the early CsA‐ME group and 23 patients (23.0%) in the delayed CsA‐ME group experienced DGF (n.s.). Renal function at 3 months was comparable (creatinine clearance 51.1mL/min with early CsA‐ME and 53.8 mL/min with delayed CsA‐ME), and remained similar to 12 months. Treatment failure, defined as biopsy‐proven acute rejection, graft loss or death, did not differ significantly at 12 months (23.7% with early CsA‐ME vs. 29.0% with delayed CsA‐ME). Biopsy‐proven acute rejection occurred in 15.5% of early CsA‐ME and 26.5% of delayed CsA‐ME patients (n.s.). Both regimens were well tolerated. These data suggest that early or delayed introduction of CsA‐ME results in similar renal function in renal transplant patients regardless of DGF risk level.

Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study

Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid‐organ‐transplant recipients with chronic HEV infection. We hypothesized that early short‐term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy.

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.

Rituximab therapy prevents focal and segmental glomerulosclerosis recurrence after a second renal transplantation.

Preventive treatment of focal and segmental glomerusclerosis (FSGS) allograft recurrence in high risk recipients having a prior history of graft loss caused by FSGS recurrence is still a challenging question. We retrospectively identified four patients who underwent a second renal transplantation because of recurrent FSGS and who received Rituximab therapy as a prophylactic treatment. Loss of their first allograft was directly related to an early (<3u2003months) recurrence of FSGS that was either resistant to plasmapheresis therapy in two cases or had escaped to this therapeutic management in the two others. After the second renal transplantation, all patients were free of FSGS recurrence during follow‐ups that were between 12 and 54u2003months long. These preliminary results demonstrate for the first time that Rituximab therapy may constitute an attractive prophylactic option for patients being considered for a second renal transplantation because of recurrent FSGS in their first graft.

Renal Transplantation in Patients With AA Amyloidosis Nephropathy: Results From a French Multicenter Study

Although end‐stage renal disease related to AA amyloidosis nephropathy is well characterized, there are limited data concerning patient and graft outcome after renal transplantation. We performed a multicentric retrospective survey to assess the graft and patient survival in 59 renal recipients with AA amyloidosis. The recurrence rate of AA amyloidosis nephropathy was estimated at 14%. The overall, 5‐ and 10‐year patient survival was significantly lower for the AA amyloidosis patients than for a control group of 177 renal transplant recipients (p = 0.0001, 0.028 and 0.013, respectively). In contrast, we did not observe any statistical differences in the 5‐ and 10‐ year graft survival censored for death between two groups. AA amyloidosis‐transplanted patients exhibited a high proportion of infectious complications after transplantation (73.2%). Causes of death included both acute cardiovascular events and fatal septic complications. Multivariate analysis demonstrated that the recurrence of AA amyloidosis on the graft (adjusted OR = 14.4, p = 0.01) and older recipient age (adjusted OR for a 1‐year increase = 1.06, p = 0.03) were significantly associated with risk of death. Finally, patients with AA amyloidosis nephropathy are eligible for renal transplantation but require careful management of both cardiovascular and infectious complications to reduce the high risk of mortality.

Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.

BackgroundnChronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients].nnnMethodsnFifty patients (36 males, mean age ± standard deviation 60.5 ± 7.5 years) with chronic HCV infection (G1: 28/56%, cirrhosis: 27/54%) and severe renal failure [i.e. MDRD estimated glomerular filtration rate (eGFR) <35 mL/min], including 35 on HD, were enrolled. Antiviral treatment consisted of SOF/ribavirin (RBV) (n = 7), SOF/RBV/pegylated interferon (n = 2), SOF/daclatasvir ± RBV (n = 30) or SOF/simeprevir ± RBV (n = 11) for 12 or 24 weeks. A reduced dose of SOF (400 mg three times a week or 400 mg every other day) was given to all HD patients. Initial dose of RBV (n = 12) ranged from 400 to 4200 mg/week.nnnResultsnOn an intent-to-treat-based analysis, sustained virological response rate was 86% at 12 weeks. During therapy, haemoglobin levels were not significantly modified, but recombinant erythropoietin (rEPO) dose significantly increased in patients treated with RBV. Two patients (4%) required blood transfusion. No patient had treatment discontinuation due to side effects. Dose of RBV was reduced in two patients (16.7%) during antiviral therapy. Dose of SOF was reduced in two non-HD patients because of side effects. In non-HD patients, median eGFR was not significantly modified during treatment.nnnConclusionsnOur results strongly suggest that SOF-based antiviral therapy, with a reduced dose of SOF, is safe and effective for the treatment of HCV patients with ESRD, including HD patients.

Nepali earthquakes and the risk of an epidemic of hepatitis E

HRD received travel, accommodation costs, and consultancy fees from GlaxoSmithKline, Wantai, and Roche; travel, accommodation, and lecture fees from Merck, Gilead, and GFE Blut GmBh; travel and accommodation fees from the Gates Foundation. NK received travel, accommodation costs, and consultancy fees from Novartis and Merck; travel, accommodation, and lecture fees from Gilead, Novartis, Astellas, BMS, Amgen, and Fresenius; travel and accommodation fees from the Gates Foundation. PP received support from Gates Foundation, IMI, and UNAIDS, and is a board member of Biocartis. The other authors declare no confl icts of interest.