Biography:

In the past Nassim Kamar has collaborated on articles with Agnes Debout and Yohann Foucher. One of their most recent publications is Clinical—Liver, Pancreas, and Biliary TractRibavirin Therapy Inhibits Viral Replication on Patients With Chronic Hepatitis E Virus Infection. Which was published in journal Gastroenterology.

More information about Nassim Kamar research including statistics on their citations can be found on their Copernicus Academic profile page.

Nassim Kamar's Articles: (18)

Clinical—Liver, Pancreas, and Biliary TractRibavirin Therapy Inhibits Viral Replication on Patients With Chronic Hepatitis E Virus Infection

Background & AimsHepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients. Pegylated α-interferon can effectively treat chronic HEV infection after liver transplantation but is contraindicated for kidney transplantation. We assessed the antiviral effect of ribavirin monotherapy in patients with chronic HEV infection following kidney transplantation.MethodsIn a pilot study performed at Toulouse University Hospital, 6 patients that received kidney transplants who were positive for HEV RNA (infected with HEV for 36.5 months; [range, 11–46 months]) were given ribavirin monotherapy for 3 months. Ribavirin was given at 600–800 mg/day in 2 separate doses, based on the patient's ability to clear creatinine.ResultsMedian serum concentration of HEV RNA at baseline was 5.77 log copies/mL (range, 4.35–7.35 log copies/mL). Three months after ribavirin therapy commenced, HEV RNA was undetectable in serum samples from all patients. A sustained virologic response was observed in 4 patients; the other 2 patients relapsed at 1 and 2 months after ribavirin therapy ended. At the end of the study, all patients had normal levels of alanine and aspartate aminotransferase. Anemia was the main side effect caused by ribavirin therapy.ConclusionsRibavirin monotherapy inhibits the replication of HEV in vivo and might induce a sustained virological response in patients with chronic HEV infections. Further studies are required to determine the optimal duration of ribavirin therapy.

Basic ResearchEach 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.

Original ArticleA clinical scoring system highly predictive of long-term kidney graft survival

Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Données Informatisées et VAlidées en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver–operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.

CommentaryCan we prevent donor-specific antibodies from developing after ABO-incompatible kidney transplantation?

The burden of chronic kidney disease is increasing worldwide and its costs are skyrocketing, particularly for those with end-stage kidney disease (ESKD). Thus, kidney transplantation needs to be available to as many as ESKD patients as possible. In countries where a donor swap or a donor-chain program is not feasible, ABO-incompatible (ABO-i) and/or HLA incompatible (HLAi) programs have been developed. In the setting of ABOi kidney transplantation, pretransplant desensitization is mandatory; this is based on the removal of isoagglutinins by plasmapheresis or immunoadsorption, and often using splenectomy (SPx) or, more recently, rituximab (RTx) infusion instead. Because RTx and SPx interfere with B-cell function, one wonders whether these desensitization protocols alter the occurrence of post-transplant donor-specific alloantibodies.

Pharmacokinetics and Pharmacodynamics of Once-daily Prolonged-release Tacrolimus in Liver Transplant Recipients

AbstractPurposeLimited published data are available regarding the pharmacokinetic (PK) and pharmacodynamic (PD) variables of prolonged-release tacrolimus (PRT) after liver transplantations. The goal of this study was to compare the PK and PD profiles of PRT in early and stable liver transplant recipients by developing a population PK model of PRT and investigating the profile of calcineurin activity (CNA) in the peripheral blood mononuclear cells.MethodsA conversion from BID immediate-release tacrolimus (IRT) to once-daily PRT based on a one-to-one daily dose was performed at day 7 (D7) and D90 posttransplantation in groups A (n = 12) and B (n = 12), respectively. Extensive PK samplings, including whole-blood tacrolimus (TAC) concentration, and CNA assessments were performed at D14 and D104 in groups A and B, respectively. TAC concentration–time data (N = 221) were analyzed by using nonlinear mixed effects modeling.FindingsA 2-compartment model with linear elimination and a delayed first-order absorption characterized by 2 transit compartments best described the PK data. Model-predicted dose-normalized (6.0 mg/d) area under the TAC concentration–time curve over the dosing interval in groups A and B was similar (geometric mean, 235.6 ng/mL · h [95% CI, 139.6–598.7] vs 224.6 ng/mL · h [95% CI, 117.6–421.5], respectively; P = 0.94). Area under the CNA versus time curve over the dosing interval did not differ between groups (4897 [3437] and 4079 [1008] pmol/min/106 cells; P = 0.50). In group A, trough CNA at D14 posttransplantation was statistically higher than that measured just before the switch to PRT (ie, D7 posttransplantation) (198 [92] vs 124 [72] pmol/min/106cells, n = 8; P = 0.048); no statistical difference in TAC concentration was observed (P = 0.11). In group B, no statistical difference between D90 and D104 was observed in either trough CNA (149 [78] vs 172 [82] pmol/min/106 cells, n = 6; P = 0.18) or TAC (P = 0.17) concentration. No graft rejection was observed in either of the groups.ImplicationsThis study suggests that one-to-one dosage conversion to once-daily PRT during the early posttransplantation period could result in significant CNA variations but without causing graft rejection. Further investigations in larger cohorts are warranted to confirm these results. ClinicalTrials.gov identifier: NCT02105155.

Conventional and innate lymphocytes response at the acute phase of HEV infection in transplanted patients

Highlights•Alterations in γδ cells were observed in HEV-infected transplanted patients.•γδ had elevated expression of CD69 and γδ memory subsets were depleted.•Specific adaptive immune responses differentiated resolutive from chronic evolution.

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

Background & AimsHCV 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.MethodsFrom 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 investigator’s discretion. The primary efficacy end point was a sustained virological response (SVR) 12 weeks after the end of treatment.ResultsThe SVR rate 12 weeks 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.ConclusionsTreatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence.Lay summaryThe 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.

Research ArticleControl of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation

Highlights•Chronic HBV infection no longer influences 10-year patient or graft survival in kidney transplant recipients.•Chronic HCV infection still negatively impacts 10-year patient and graft survival.•The negative effect of chronic HCV infection is removed by sustained viral suppression.•Antiviral therapy should be systematically proposed for HBV- and/or HCV-infected kidney transplant recipients/candidates.

Case reportsAcute hepatitis and renal function impairment related to infection by hepatitis E virus in a renal allograft recipient

Clinicians often are faced with an increase in liver enzyme levels. In the majority of cases, the cause is found rapidly. Conversely, in a few cases, the etiologic agent remains unknown and requires either liver biopsy or drug-medication modification. We report a case of acute icteric hepatitis associated with renal function impairment related to infection caused by primary hepatitis E virus (HEV) in a renal transplant recipient who lived in a nonclassic endemic area and had not traveled abroad. Clinicians must be aware that in cases of unexplained hepatitis in organ transplant recipients and in the absence of evident drug hepatotoxicity, HEV should be considered as an etiologic agent for hepatitis. Subsequently, HEV serological tests should be performed, HEV RNA should be looked for in acute-phase serum and stool samples, and liver parameters should be monitored closely because HEV might be responsible, in some cases, for fulminant hepatitis.

Case ReportSuccessful Retransplantation of a Kidney Allograft Affected by Thrombotic Microangiopathy Into a Second Transplant Recipient

The donor organ shortage has compelled transplant centers to use organs from nontraditional sources. One example is the reuse of a previously transplanted organ, such as a kidney or liver retrieved from a brain-dead allograft recipient. For the first time, we reused a previously transplanted kidney that experienced intractable recurrent thrombotic microangiopathy (TMA) from a living allograft recipient. Within a few weeks posttransplantation, a deceased kidney allograft recipient developed intractable severe recurrent idiopathic TMA in the allograft despite intensive plasma exchanges and steroid and rituximab therapy. This required nephrectomy to cure TMA. The index recipient was believed to have a well-functioning allograft despite TMA (serum creatinine, 1.36 mg/dL [120 μmol/L]) and microalbuminuria with albumin of 1.2 g/dL [12 g/L]), and it appeared mildly damaged on biopsy examination. After donor and recipient informed consents were obtained and after approval of the French Agency of Biomedicine, the TMA allograft was reused and transplanted into a recipient whose original kidney disease was polycystic kidney disease. The retransplantation was uneventful, and at 6 months posttransplantation, the ultimate recipient's serum creatinine level was 1.06 mg/L (97 μmol/L) and albuminuria was 0.5 g/dL (5 g/L). A routine kidney biopsy showed mild glomerular lesions. After allograft nephrectomy, the donor's hematologic TMA symptoms dissipated within 10 days. We conclude that a kidney allograft with TMA recurrence can be successfully retransplanted into another recipient with excellent kidney function while still curing the first recipient of recurrent TMA. This might increase the number of kidney allografts from extended criteria donors.

Tabebuia avellanedae extracts inhibit IL-2-independent T-lymphocyte activation and proliferation

AbstractIn order to identify new, immune modulating compounds, aqueous extracts of plants pre-selected on ethno-pharmacological knowledge were screened for inhibitory effects in an anti-CD3 driven lymphocyte proliferation assay (MTT-assay). We found for the extract of the inner bark of Tabebuia avellanedae (Tabebuia) dose dependent and reproducible inhibitory effects on lymphocyte proliferation. We further analyzed Tabebuia in flow cytometry based whole blood T-cell function assays. We found that Tabebuia inhibited dose dependent ConA stimulated T-cell proliferation. Decreased T-lymphocyte proliferation was associated with dose dependent reduction of CD25 and CD71 expression on T-lymphocytes. In contrast Tabebuia exerted no effects on cytokine expression (Il-2 and TNF-α) by PMA/Ionomycin stimulated T-lymphocytes. Concentrations of Tabebuia used were not toxic for lymphocytes as verified by trypan blue exclusion assay. Further experiments showed that the immune inhibitory effects by Tabebuia were not mediated by its pharmacological lead compound β-lapachone and only observed in aqueous but not in ethanol plant extracts.

In vitro mitogen-stimulated T-cell from hepatitis C virus-positive liver transplantation candidates, increases T-cell activation markers and T-cell proliferation

AbstractThe incidence of acute rejection is significantly higher in hepatitis C virus (HCV) liver-transplant patients than in patients who have received a graft for other liver diseases, i.e., mainly alcoholic cirrhosis. The aim of this study was to assess T-cell function, i.e., intralymphocyte cytokine expression (IL-2 and TNF-α), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 α-chain (CD25) expression], and T-cell proliferation using a flow-cytometry whole-blood assay in patients waiting for a liver transplantation (n = 49). Our data suggest that, in mitogen-stimulated T-cells, (i) intra-lymphocyte cytokine expression is significantly higher in patients with liver disease than in healthy volunteers (n = 25); (ii) the expression of T-cell activation markers is decreased in patients with liver cirrhosis compared to healthy volunteers, and (iii) the expression of T-cell activation markers and T-cell proliferation are increased in patients with HCV infection (n = 15) compared to those without HCV infection (n = 34), particularly compared to patients with alcoholic liver disease (n = 19). Circulating CD19-positive cells count was also significantly higher in HCV-positive patients. In conclusion, in vitro, mitogen-stimulated T-cell seem to induce a higher immune response in the blood from patients waiting for a liver transplant for HCV-related liver disease than those without HCV infection, and particularly those with alcoholic liver disease.

Amantadine therapy in renal transplant patients with hepatitis C virus infection

AbstractBackground: To date, there is no safe and efficient treatment of hepatitis C virus (HCV) infection after renal transplantation. Recently, there were encouraging reports after using amantadine in HCV-positive immunocompetent patients. Objectives: In an open pilot study, we evaluated the efficacy and the safety of amantadine monotherapy in 8 HCV positive renal-transplant patients with chronic active hepatitis and increased alanine aminotransferase (ALT) levels. Results: After 6 months of amantadine therapy (200 mg per day), there were no decrease in HCV viremia (5.87±0.37 log copies/ml at M6 versus 5.71±0.5 log copies/ml at baseline; P>0.05). However, we found a significant decrease in ALT activity (71±17 IU/l at M6 versus 100±9 IU/l at baseline; P=0.04), whereas the decrease in aspartate aminotransferase activity did not reach statistical significance. There were no significant changes in liver histology. The clinical and biological tolerance was very good. Finally, there were a significant decrease in cyclosporine A whole blood trough levels during therapy. Conclusions: Our study is the first one to demonstrate that amantadine monotherapy lack of efficacy in HCV renal-transplant patients. It is able to improve liver enzymes but it has no impact neither upon HCV viremia nor upon liver histology.

Performance of a commercial assay for detecting and quantifying HEV RNA in faeces

Highlights•No commercial HEV RNA assay is validated for use in faecal samples.•Monitoring HEV faecal excretion is recommended for managing chronic HEV infection in solid-organ transplant recipients.•We evaluated the Altona assay by testing patients on ribavirin therapy.

ORIGINAL RESEARCHErectile Dysfunction in End-Stage Liver Disease Men

ABSTRACTIntroductionIn men, erectile dysfunction (ED) is an important issue. Data concerning ED in men with end-stage liver disease (ESLD) is limited, and the risk factors for ED in this population are still unknown.AimsTo determine the prevalence, timescale, and risk factors for ED in ESLD patients candidates to liver transplantation.MethodsPatients candidates for a liver transplantation were asked to participate in a mailed survey about sexual function. Among the 123 eligible men, 98 (84%) agreed to complete the questionnaire.Main Outcome MeasuresThe quality of erection was evaluated using the five-item International Index of Erectile Function (IIEF-5) score, and satisfaction for sexuality, using the patient-baseline Treatment-Satisfaction Scale (TSS) score. Other questions also focused on patient perception of changes over time.ResultsOn the overall population, 28 patients (29%) were nonsexually active. Among the 70 patients who were sexually active, 52 patients (74%) had ED. Regarding the development of ED, 50% of the patients perceived that a deterioration of erectile function occurred within the six previous months. The absence of sexual activity was more frequent in hepatitis B or C patients (P = 0.02). The risk factors for ED were alcohol intake (P = 0.03), tobacco use (P = 0.03), and cardiovascular disease (P = 0.004). The significant risk factors for having a low TSS score were having viral hepatitis (P = 0.01), and cardiovascular disease (P = 0.01).ConclusionPopulation of men with ESLD who are candidates for a liver transplantation is characterized by a high frequency of lack of sexual activity, and by a high prevalence of ED and should be targeted by interventions to improve sexual functioning. These preliminary data need further validation in prospective trial using more comprehensive questionnaires. Huyghe E, Kamar N, Wagner F, Capietto A-H, El-Kahwaji L, Muscari F, Plante P, and Rostaing L. Erectile dysfunction in end-stage liver disease men. J Sex Med 2009;6:1395–1401.

Article originalLa diversification de la région hypervariable-1 du virus de l'hépatite C pourrait prédire l'évolution de la fibrose hépatique après transplantation rénaleThe evolution of the hypervariable region-1 of hepatitis C virus may predict liver fibrosis outcome after renal transplantation

RésuméLe but de notre travail était d'évaluer l'évolution à long terme de la fibrose hépatique et d'étudier l'évolution du virus de l'hépatite C (VHC) chez des transplantés rénaux (TR) antiVHC (+)/ARN (+). Cinquante-cinq patients ont bénéficié d'une ponction biopsie hépatique (PBH) tous les trois à quatre ans après la transplantation (2 PBH, n = 55 ; 3 PBH, n = 44 ; 4 PBH, n = 10). La région hypervariable (HVR)-1 du génome du VHC a été caractérisée lors de la transplantation et lors des deux premières biopsies. Le taux de progression de la fibrose hépatique était de 0,07 ± 0,03 unité Métavir/année. Nous avons identifié trois groupes de patients : ceux dont le score de fibrose était resté stable au cours du suivi (groupe I, n = 21), ceux qui ont présenté une progression (groupe II, n = 21), et enfin ceux qui ont présenté une régression (groupe III, n = 13) de la fibrose hépatique. Le stade initial de fibrose et la diversification de HVR-1 du génome du VHC étaient deux facteurs indépendants associés à la régression de la fibrose hépatique. En conclusion, dans cette étude, après transplantation rénale, l'infection par le VHC n'avait pas d'effet néfaste sur l'histologie hépatique chez plus de 50 % des patients. La diversification de HVR-1 pourrait être utilisée pour prédire l'évolution de la fibrose hépatique après greffe rénale chez des TR VHC (+).

Revue générale/Mise au pointPlace de la transplantectomie après échec de greffe rénaleKidney nephrectomy after allograft failure

RésuméLe nombre de patients transplantés rénaux retournant en dialyse après échec de greffe ne cesse d’augmenter. Ces patients représentent une population distincte de celle des dialysés qui n’ont jamais eu de greffe rénale, et sont à haut risque de morbi-mortalité, en particulier cardiovasculaire et infectieuse. L’attitude concernant la gestion de l’immunosuppression après l’arrêt de fonction du greffon rénal n’est pas codifiée. De même, la question de la transplantectomie reste entière : certains proposent de ne réserver ce geste qu’aux patients présentant un syndrome d’intolérance du greffon, alors que d’autres en proposent une ablation systématique afin de démasquer des anticorps anti-HLA qui seraient adsorbés par le greffon, et, de fait, non détectables dans le sang. L’évolution dans les techniques de détection des anticorps anti-HLA amène un flou supplémentaire quant à ces questions.

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