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Biomedical subjects

Jacques Izopet

Publications and source records attributed to Jacques Izopet.

At least 37 records · Page 2Linked to original sources
PubMed2005

Decrease of Lewis frequency in HIV-infected patients: possible competition of fucosylated antigens with HIV for binding to DC-SIGN.

We explored the impact of human ABO glycosyltransferase and Lewis and secretor fucosyltransferase polymorphisms in HIV infection. We found that, compared with healthy blood donors, HIV-infected patients display a significant decrease in Le(a-b+) phenotype frequencies. We showed that HIV binding on DC-SIGN-transduced Jurkat cells was inhibited by fucosyl bovine serum albumin. Our results suggest a slight protective effect of Lewis b antigen on HIV infection, possibly by the competition of Lewis antigens with HIV for binding to DC-SIGN.

Cell Adhesion Molecules↗
PubMed2005

Factors accelerating liver fibrosis progression in renal transplant patients receiving ribavirin monotherapy for chronic hepatitis C.

In untreated hepatitis virus (HCV)-positive renal transplant patients, the rate of liver fibrosis progression is low. In contrast, in those treated by ribavirin monotherapy, liver fibrosis score increased significantly after only 1 year of ribavirin monotherapy. The aim of this study was to identify the factors that might contribute to accelerate liver fibrosis progression in this population. Eleven patients were included in the study. Intrahepatic transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA quantification determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) were similar before and after ribavirin therapy. The number of amino acid substitutions observed in the hypervariable region (HVR)-1 of the HCV genome between baseline and 1 year after ribavirin monotherapy was low, i.e., 3 (1-11) amino acid substitutions, suggesting the absence of a high selection pressure induced by ribavirin. In contrast, due to ribavirin-induced hemolysis, there was a significant increase in serum ferritin levels (P = 0.02) and in intrahepatic iron deposition (P = 0.04). Transferrin level and total iron-binding capacity decreased significantly during ribavirin monotherapy (P = 0.004). The increased liver fibrosis observed in renal transplant patients receiving ribavirin monotherapy could be related to ribavirin-induced anemia. Severe chronic hemolysis is responsible for iron overload, liver iron deposition, and an acceleration in the progression of liver fibrosis.

Adult↗
PubMed2005

Prevalence of complete resistance to at least two classes of antiretroviral drugs in treated HIV-1-infected patients: a French nationwide study.

The objective of the study was to estimate the prevalence of HIV-1 resistance to all drugs belonging to two or more antiretroviral drug (ARV) classes in treated patients in France. All genotyping assays performed in June 2001 and in November 2002 by the ANRS resistance laboratory network were analyzed by the ANRS algorithm. The 17 and 21 centers of the ANRS network participating in the study in 2001 and 2002, respectively, genotyped the viruses in plasma of 456 and 529 patients, respectively. In 2002, the proportions of patients harboring viruses fully resistant to one, two, and three ARV classes were 5.1%, 8.1%, and 2.5%, respectively. These results were similar to those obtained in 2001. In 2002, among the 56 patients with viruses completely resistant to at least two ARV classes, 98%, 96%, and 29% of patients had viruses with complete class resistance to NRTIs, NNRTIs, and PIs, respectively. Complete resistance to PIs was less frequent than full resistance to the other two ARV classes, and ritonavir-boosted amprenavir and lopinavir/r remained potentially active in respectively 71.4% and 42.9% of these 56 patients. In 2001 and 2002, respectively 30% of the 65 patients and 24% of the 56 patients with viruses completely resistant to at least two ARV classes were at an advanced stage of HIV disease, with CD4(+) cell counts below 200/microl and viral loads above 30 000 copies/ml. In France, the prevalence of HIV-1 viruses completely resistant to two or more ARV classes remained stable between 2001 and 2002. Resistance to RT inhibitors was more frequent than resistance to PIs in patients with viruses completely resistant to two or three classes of ARV.

Adolescent↗
PubMed2005

Intrahepatic cytokine profile in renal-transplant patients infected by hepatitis C virus.

In order to examine the immunopathogenesis of hepatitis C virus (HCV)-related liver injury in renal-transplant patients, intra-hepatic cytokine profiles were examined in 38 liver biopsies from 38 patients by measuring messenger RNA (mRNA) concentrations by a real-time PCR method of a Th1 cytokine (i.e., interferon (IFN)-gamma), a Th2 cytokines (i.e., interleukine (IL)-10), a proinflammatory cytokine (i.e., IL-8), and a potent fibrogenic factor (transforming growth factor [TGF]-beta). There was no significant difference in TGF-beta, IFN-gamma, IL-10, or IL-8 levels of expression according to liver-activity grade, liver-fibrosis stage, the concentration of HCV RNA at liver biopsies, or the HCV genotype. However, IFN-gamma/beta-actin mRNA concentration was higher than the IL-10/beta-actin mRNA concentration in patients with F3 Metavir score. Median IFN-gamma/beta-actin mRNA concentration tended to be higher in patients with A3 and A4 Metavir activity grades compared with those with A0 and A1 activity grades. There was a significant correlation between the duration of HCV infection and both TGF-beta/beta-actin (r(2)=0.19, P=0.04) and IL-8/beta-actin mRNA concentrations (r(2)=0.19, P=0.03). IFN-gamma/beta-actin mRNA concentration also increased according to the duration of HCV (r(2)=0.19, P=0.07). Finally, there was a significant correlation between the duration of HCV infection and liver fibrosis stage (r(2)=0.17, P=0.045). Intrahepatic Th1 cytokine profile seems to be predominant in patients with extensive fibrosis and activity scores, suggesting that it might be responsible for liver injury in renal transplant patients.

Adult↗
PubMed2005

Pegylated interferon and ribavirin therapy for chronic hepatitis C virus genotype 4 infection.

Hepatitis C Virus (HCV) is classified into six genotypes. Genotype 4 is now spreading in Europe, especially among drug users, who are often infected with both HCV and the human immunodeficiency virus (HIV). Previous studies have shown that HCV-4 responds poorly to interferon. Pegylated interferon (peg-IFN) associated with ribavirin is now the most effective treatment for eradicating the virus. We have now studied the response of HCV-4 to peg-IFN and ribavirin and investigated the influence of HIV infection on anti-HCV therapy. Twenty-eight patients infected with HCV-4 were given peg-IFN plus ribavirin for 48 weeks. Patients infected with HCV alone tended to have a better initial response (66%) than patients infected with both HCV and HIV (30%, P = 0.06) and eradication was better (50%) than in doubly infected patients (15%, P = 0.06). After controlling for major factors influencing virus response, the virus response 12 weeks after the beginning of treatment in patients infected with HCV-4 (50%) was similar to that of patients infected with genotype 1 (53%) and lower than that of patients infected with genotypes 2 or 3 (82%, P < 0.05). The response 24 weeks after the end of therapy in patients infected with HCV-4 (32%) was similar to that of patients infected with HCV-1 (28%) and lower than that of patients with HCV-2 or HCV-3 (62% P < 0.05). These results indicate that HCV-4 patients should be considered to be difficult-to-treat.

Adult↗
PubMed2005

Incidence of HCV infection in French hemodialysis units: a prospective study.

A large prospective study was carried out from 1997 to 2000 in 25 French hemodialysis units including 1,323 patients to determine the incidence of hepatitis C virus (HCV) infection. Monthly testing of alanine aminotransferase (ALT) activity, and assessment of HCV RNA and anti-HCV antibodies if the ALT activity was elevated, identified 14 new infections in 7 different units, giving an incidence of 0.4% new HCV infections per year. Molecular analyses and epidemiological data indicated that five patients became infected with HCV outside the unit where they were dialyzed, while the nine remaining patients acquired HCV from infected patients on dialysis during the same shift at the same unit. HCV was cleared in six of the seven (85.7%) patients with acute hepatitis C who were given standard doses of alpha-interferon (alpha-IFN). The persistence of nosocomial transmission of HCV in hemodialysis units emphasizes the need to implement infection control practices. Identifying new infections is crucial because alpha-IFN treatment results in long term clearance of HCV RNA in a large proportion of patients.

Acute Disease↗
PubMed2005

Distribution and heterogeneity of hepatitis C genotypes in hepatitis patients in Cameroon.

Hepatitis C virus infects humans world-wide. The virus genome varies greatly and it has several genotypes. HCV infection is highly prevalent in Central Africa and Cameroon. Initial studies on the genetic variability of HCV showed infection with HCV genotypes 1, 2, and 4. We have now sequenced the NS5b and E2 regions of 156 HCV isolates collected from patients presenting for diagnosis in Yaounde and used the data to describe the distribution of HCV genotypes and subtypes in patients with hepatitis in Cameroon. Genotype 1 was more frequent than Genotypes 4 and 2. Genotypes 1 and 4 were highly heterogeneous, containing many subtypes described previously (1b, 1c, 1e, 1h, 1l, 4f, 4t, 4p, 4k) and unsubtyped groups. There was a systematic phylogenetic concordance between NS5b and E2 sequence clustering. The Genotype 2 sequences did not vary. Neither subject age nor gender influenced HCV distribution. HCV Genotypes 1 and 4 are very heterogeneous in Cameroon, perhaps due to ancient infections. The homogeneity of HCV Genotype 2 indicates its more recent introduction from western Africa.

Adult↗
PubMed2005

Follow-up of 28 HCMV seropositive renal-transplant recipients: comparison of clinical, biological and virological parameters in the groups of treated versus untreated infected patients.

BACKGROUND: A pre-emptive strategy for prevention of Human Cytomegalovirus (HCMV) disease depends on accurate detection of HCMV infection and clinical and/or biological abnormalities. OBJECTIVES: The aim of our study was to evaluate a therapeutic strategy based on the presence of either minimal clinical and/or biological symptoms or high HCMV viral load assessed by quantitative real-time PCR from whole blood as previously described. STUDY DESIGN: Between June 2002 and July 2003, 70 HCMV seropositive patients underwent a renal transplantation. Virological monitoring was performed every 2 weeks until day 90 then every 3-4 weeks until day 180. Biochemical and haematological parameters were also prospectively monitored. RESULTS: Twenty-eight patients (40%) showed at least one positive HCMV DNA in whole blood. Based on the following criteria: HCMV viral load greater than 4log(10)/ml, or the persistence of a HCMV DNAemia in two consecutive blood samples, or fever, or leucopenia or neutropenia, or increase in alanine aminotransferase level, 14 of the 28 patients received IV ganciclovir as a pre-emptive treatment. Immunosuppressive therapy and demographical data were comparable in both groups. As far as virological, haematological and biochemical parameters are concerned, no statistical significant difference was observed between treated and untreated patients. Moreover no adverse outcome was observed among untreated patients always having a HCMV viral load below 4log(10)/ml. CONCLUSIONS: This study reinforces the need of monitoring of HCMV seropositive renal-transplant recipients based on HCMV diagnosis and quantification by real-time PCR. The results showed that HCMV viraemic patients may benefit of absence of antiviral treatment when they have a low viral load (below 4log(10)/ml) and absence of clinical and/or biological abnormalities. Further studies are required now to validate the threshold value at which we should begin pre-emptive therapy.

Antibodies, Viral↗
PubMed2005

Clinical performance of the LCx HCV RNA quantitative assay.

This study was conducted to assess the performance of the Abbott laboratories LCx HCV RNA Quantitative Assay (LCx assay) in the clinical setting. Four clinical laboratories measured LCx assay precision, specificity, and linearity. In addition, a method comparison was conducted between the LCx assay and the Roche HCV Amplicor Monitor, version 2.0 (Roche Monitor 2.0) and the Bayer VERSANT HCV RNA 3.0 Assay (Bayer bDNA 3.0) quantitative assays. For precision, the observed LCx assay intra-assay standard deviation (S.D.) was 0.060-0.117 log IU/ml, the inter-assay S.D. was 0.083-0.133 log IU/ml, the inter-lot S.D. was 0.105-0.177 log IU/ml, the inter-site S.D. was 0.099-0.190 log IU/ml, and the total S.D. was 0.113-0.190 log IU/ml. The specificity of the LCx assay was 99.4% (542/545; 95% CI, 98.4-99.9%). For linearity, the mean pooled LCx assay results were linear (r=0.994) over the range of the panel (2.54-5.15 log IU/ml). A method comparison demonstrated a correlation coefficient of 0.881 between the LCx assay and Roche Monitor 2.0, 0.872 between the LCx assay and Bayer bDNA 3.0, and 0.870 between Roche Monitor 2.0 and Bayer bDNA 3.0. The mean LCx assay result was 0.04 log IU/ml (95% CI, -0.08, 0.01) lower than the mean Roche Monitor 2.0 result, but 0.57 log IU/ml (95% CI, 0.53, 0.61) higher than the mean Bayer bDNA 3.0 result. The mean Roche Monitor 2.0 result was 0.60 log IU/ml (95% CI, 0.56, 0.65) higher than the mean Bayer bDNA 3.0 result. The LCx assay quantitated genotypes 1-4 with statistical equivalency. The vast majority (98.9%, 278/281) of paired LCx assay-Roche Monitor 2.0 specimen results were within 1 log IU/ml. Similarly, 86.6% (240/277) of paired LCx assay and Bayer bDNA 3.0 specimen results were within 1 log, as were 85.6% (237/277) of paired Roche Monitor 2.0 and Bayer specimen results. These data demonstrate that the LCx assay may be used for quantitation of HCV RNA in HCV-infected individuals.

DNA, Viral↗
PubMed2005

Acute 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.

Acute Disease↗
PubMed2005

A large nosocomial outbreak of hepatitis C virus infections at a hemodialysis center.

OBJECTIVE: To identify modes of HCV transmission during an outbreak of HCV infection in a hemodialysis unit. DESIGN: An epidemiologic study, virologic analysis, assessment of infection control practices and procedures, and technical examination of products and dialysis machines. SETTING: A private hemodialysis unit treating approximately 70 patients. PATIENTS: Detection of HCV RNA by PCR was performed among patients receiving dialysis in 2001. Case-patients were patients who had a first positive result for HCV RNA between January 2001 and January 2002 and either acute hepatitis, a seroconversion for HCV antibodies, or a previous negative result. Three control-patients were randomly selected per case-patient. RESULTS: Of the 61 patients treated in the unit in 2001 and not infected with HCV, 22 (36.1%) became case-patients with onset from May 2001 to January 2002 for an incidence density rate of 70 per 100 patient-years. Phylogenic analysis identified four distinct HCV groups and an index case-patient for each with a similar virus among patients already known to be infected. No multidose medication vials or material was shared between patients. Connection to a dialysis machine by a nurse who had connected an HCV-infected patient "just before" or "one patient before" increased the risk of HCV infection, whereas using the same dialysis machine after a patient infected with HCV did not. Understaffing, lack of training, and breaches in infection control were documented. Direct observation of practices revealed frequent flooding of blood into the double filter on the arterial pressure tubing set. CONCLUSIONS: During this outbreak, HCV transmission was mainly patient to patient via healthcare workers' hands. However, transmission via dialysis machines because of possible contamination of internal components could not be excluded.

Adult↗
PubMed2005

Heterogeneity of hepatitis C virus genotype 4 strains circulating in south-western France.

Hepatitis C virus (HCV) is a major cause of liver disease. Knowledge of HCV variability is crucial for clinical and epidemiological analysis. HCV genotype 4 (HCV-4) has become increasingly prevalent in European countries, including France, in recent years. The present study investigates the heterogeneity of HCV-4 in south-western France by phylogenetic analysis of NS5B sequences from 166 patients. The E2 region of 90 strains was also analysed. Genotype 4 accounts for 7.4 % of HCV infections in this area. Analysis of the NS5B region revealed 12 subtypes and the NS5B and E2 phylogeny data were congruent, except for one strain. The epidemiological data indicated two main groups of patients. One included intravenous drug users (IVDUs) of French origin, who were infected by homogeneous strains of subtypes 4a or 4d. The second group comprised non-IVDU patients who were infected with heterogeneous strains. This group was subdivided into patients of French origin, who were infected with eight subtypes, and patients from non-European countries (Central Africa or the Middle East), who were mainly infected with 4f, 4k, 4r and other subtypes; they showed the greatest genetic heterogeneity. This study of a large cohort of patients shows the great diversity of HCV-4 strains, and that these subtypes have spread differently.

Adult↗
PubMed2005

Induction therapy with either anti-CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C.

BACKGROUND: Hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti-CD25 monoclonal antibodies. METHODS: From January 2000 to January 2003, 31 patients underwent OLT for HCV-related ESLD, and survived more than 1 month post-transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 +/- 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end-points were at 6 months post-transplantation. RESULTS: Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post-transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated. CONCLUSION: RATG induction therapy is as efficient and as safe as induction with anti-CD25 monoclonal antibodies.

Adult↗
PubMed2005

Natural history of hepatitis C virus-related liver fibrosis after renal transplantation.

The aim of our study was to assess hepatitis C virus (HCV) evolution and long-term liver histology outcome in anti-HCV(+)/RNA(+) renal transplant (RT) patients. A total of 51 anti-HCV(+)/RNA(+) RT patients underwent liver biopsies (LB) every 3-4 years after transplantation (two LBs, n = 51; three LBs, n = 42; four LBs, n = 9). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.09 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (n = 21), those with progressing liver fibrosis (n = 21) and those with a regression in liver fibrosis (n = 10). In the last two groups, the progression and the regression of liver fibrosis were gradual during follow-up. Ferritin levels and hepatosiderosis were significantly higher in fibrosers. Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in the current study, more than 10 years after renal transplantation, HCV infection was not harmful upon liver histology in more than 50% of patients. The diversification of the HVR-1 might be used to predict liver fibrosis outcome.

Adult↗
PubMed2005

Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients.

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.

Adult↗
PubMed2005

Comparison of hepatitis C virus NS5b and 5' noncoding gene sequencing methods in a multicenter study.

A national evaluation study was performed in 11 specialized laboratories with the objective of assessing their capacities to genotype hepatitis C virus (HCV) and define the applicability of a given genotyping method. The panel consisted of 14 samples positive for HCV RNA of different genotypes (including 3 samples with two different artificially mixed genotypes) and 1 HCV-negative sample. Seventeen sets of data were gathered from the 11 participating laboratories. The sensitivities ranged from 64.3 to 100% and from 42.7 to 85.7% for the methods that used sequencing of the NS5b region and the 5' noncoding (5' NC) region, respectively. When the data for the artificially mixed samples were excluded, NS5b genotyping gave correct results for 80% of the samples, 1.7% of the samples were misclassified, and 18.3% of the samples had false-negative results. By 5' NC-region genotyping methods, 58.3% of the results were correct, 29.7% were incomplete, 8.3% were misclassifications, 1.2% were false positive, and 2.4% were false negative. Only two procedures based on NS5b sequencing correctly identified one of the three samples with mixtures of genotypes; the other methods identified the genotype corresponding to the strain with the highest viral load in the sample. Our results suggest that HCV 5' NC-region genotyping methods give sufficient information for clinical purposes, in which the determination of the subtype is not essential, and that NS5b genotyping methods are more reliable for subtype determination, which is required in epidemiological studies.

5' Untranslated Regions↗
PubMed2005

Evolution of hepatitis C virus quasispecies during therapy with IL2 combinated to alpha interferon and ribavirin.

This study analyses the impact of interleukin 2 (IL2) combined with alpha interferon (IFN-alpha) and ribavirin on the heterogeneity of hepatitis C virus (HCV). We studied 10 patients who took part in a clinical trial that assessed the effects of retreatment with IL2, IFN-alpha and ribavirin in patients who failed to clear the virus after a previous bitherapy. The heterogeneity of HCV quasispecies was assessed by cloning and sequencing the hypervariable region 1 (HVR1) in samples obtained at baseline (W0), after 12 weeks of treatment with IFN-alpha and ribavirin (W12), after a cycle of administration of IL2 in combination with the classical bitherapy (W21 and W24) in the eight patients who failed to clear the virus under treatment. The mean viral load at W21 and at W24 was not different from that at W12. The heterogeneity of HVR1 quasispecies after the administration of IL2 was not different from that at baseline or after 12 weeks of bitherapy. Furthermore, the proportion of nonsynonymous substitutions was unchanged after the IL2 cycles. Thus, the efficacy of the tritherapy with IL2, IFN-alpha and ribavirin is similar to that of the classical bitherapy. Treatment with IL2 in combination with IFN-alpha and ribavirin had no effect on the selective pressure on HCV quasispecies. IL2 is not the best option to treat hepatitis C.

Adult↗