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Biomedical subjects

J Izopet

Publications and source records attributed to J Izopet.

At least 19 recordsLinked to original sources
PubMed2006

Does cyclosporine have a beneficial effect on the course of chronic hepatitis C infection after renal transplantation?

The aim of our study was to assess the long-term liver histology in renal transplant patients infected with hepatitis C virus (HCV) who were treated with a cyclosporine-based regimen. Among 55 anti-HCV+/RNA+ patients, liver biopsies (LB) were requested every 3 to 4 years after transplantation: two LBs (n=55); three LBs (n=44); four LBs (n=10). Overall, the rate of liver fibrosis progression was 0.07+/-0.03 Metavir U/y. Only three patients out of 55 (5.4%) developed cirrhosis. Liver fibrosis remained stable throughout follow-up in 21 patients; increased in 21 patients; and improved in the remaining 13 patients. The incidence of posttransplant diabetes mellitus was low (9%). We concluded that HCV infection is not harmful to liver histology in more than 50% of renal transplant patients with grafts functioning more than 6 years. Cyclosporine might have beneficial effects on the natural course of HCV infection after renal transplantation.

Adult↗
PubMed2006

Pilot study of interferon-alpha-ribavirin-interleukin-2 for treatment of nonresponder patients with severe liver disease infected by hepatitis C virus genotype 1.

The aim of this randomized prospective study was to assess the efficacy and safety of a triple therapy with interferon-alpha (IFN-alpha)-ribavirin-interleukin-2 (IL-2) for the treatment of patients with genotype 1 infection and high viral load nonresponsive to primary IFN-ribavirin therapy. Twenty hepatitis C virus (HCV) genotype 1 patients with high viral load and Metavir fibrosis score >or=2 without HIV co-infection who were previously nonviral responders to standard treatment with IFN plus ribavirin were intensively re-treated with IFN-alpha2a (3 millions (M) IU every 2 days) combined with ribavirin (1000-1200 mg/day) for a 24-week period. Patients were randomized to receive four cycles of subcutaneous injection of IL-2 (3 MIU/day, 5 days a week every 3 weeks) during either the first 12 weeks (group 1, n = 10) or the last 12 weeks (group 2, n = 10) of combination therapy. At the end of triple therapy, six patients (30%) achieved a biochemical response and 4 (20%) a viral response followed by a relapse after triple therapy withdrawal. After 12 weeks of therapy, no difference in viral load was observed between the groups. The decrease in viral load in group 2 was not raised after the addition of IL-2 to IFN plus ribavirin combination therapy. No serious adverse effects were observed. In conclusion, in patients with poor predictive factors of response, the addition of IL-2 to IFN ribavirin combination therapy does not exert a favourable impact on HCV treatment.

Antiviral Agents↗
PubMed2005

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Adult↗
PubMed2004

Hepatitis C virus genotype 5: epidemiological characteristics and sensitivity to combination therapy with interferon-alpha plus ribavirin.

Twenty-six patients living in the Midi-Pyrenees region of France who were infected with hepatitis C virus (HCV) genotype 5 were investigated. Most of these patients were of advanced age and had been infected nosocomially or by blood transfusion. Our case-control study, in which we treated patients with interferon- alpha plus ribavirin, indicated that, 24 weeks after the beginning of treatment, the virus response in patients infected with HCV genotype 5 was better than that in patients infected with HCV genotype 1 (100% of patients negative for detectable HCV RNA vs. 36.3%, respectively; P < .01); furthermore, 48 weeks after the end of treatment, the virus response in patients infected with HCV genotype 5 was better than that in patients infected with HCV genotype 1 (63.6% vs. 22.7%, respectively; P < .05) and was similar to that in patients infected with HCV genotype 2 or 3 (66.6%). These results show that HCV genotype 5 might have good intrinsic sensitivity to combination therapy with interferon- alpha plus ribavirin.

Adult↗
PubMed2004

Use of two real-time polymerase chain reactions (PCRs) to detect herpes simplex type 1 and 2-DNA after automated extraction of nucleic acid.

Herpes simplex virus infections may be diagnosed by several techniques, including conventional cell culture and the polymerase chain reaction (PCR). This prospective study compares the analytical performances and usefulness of an in-house real-time PCR method and the Light Cycler HSV (1/2) detection kit (Roche Diagnostics, Mannheim, Germany). The results of both PCRs were then compared to those obtained by conventional cell culture. A total of 313 samples were tested (70 dermal samples, 81 cerebrospinal fluids (CSF), 47 ocular, 42 anogenital, 34 throat swabs, and 33 oral samples, 3 whole blood, 2 biopsies, and 1 bronchoalveolar lavage). Samples for molecular assays were extracted twice with the MagNa Pure instrument (Roche Molecular Biochemicals, Mannheim, Germany) and tested blind in parallel by the two PCR methods. Most (226) samples were also examined by cell culture. Forty three samples were found positive by both PCRs, whereas 267 were negative. The HSV-1 and -2 typing of positive samples was identical. Three of the samples were positive in the in-house PCR and negative in the Light Cycler HSV (1/2) detection kit. There was no statistically significant difference between the two tests. Only one sample gave an invalid result due to negative PCR and negative internal control result. Seven samples were positive by both real-time PCRs and negative in conventional culture. The PCRs were significantly (P < 0.05) more sensitive. The results show good agreement between the two real-time PCR methods, with the molecular tests being more sensitive than cell culture.

Base Sequence↗
PubMed2004

Virological exploration of individuals with discordant HIV screening tests.

Screening for HIV infection can use many algorithms. When two different HIV antibody assays are used, discordant results may occur. To discriminate between HIV seroconversion, HIV variant infection and false positive reactivity, 30 consecutive subjects with two discordant HIV antibody-screening assays were extensively investigated for HIV infection. No subject had HIV seroconversion or reached HIV seropositivity criteria after a follow-up of 3 months. By contrast 36% became HIV negative by the use of both HIV screening assays. p24 Antigen, HIV-1 RNA, HIV-1 DNA, HIV-2 DNA assays and HIV isolation by sensitive culture were unable to identify HIV infection in the 30 subjects with discordant HIV screening assays. The data suggest that the use of two HIV screening assays increase false-positive HIV results without increasing clinical sensitivity. To compliment follow-up of HIV screening, early testing for HIV RNA could be useful to identify or eliminate a recent infection.

Adolescent↗
PubMed2004

Efficacy and safety of induction therapy with 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). However, in recent years, the long-term results of OLT in this setting are worsening, possibly due to the powerful immunosuppressants in use. The aim of our study was to assess the safety and efficacy of induction therapy using rabbit antithymocyte globulin antibodies (RATG). METHODS: Over an 18-month period from January 2000 to June 2001, 16 patients underwent OLT for HCV-related ESLD and survived more than 1 month posttransplantation. They received induction therapy based on RATG (Thymoglobulins, Sangstat, France) at 1 mg/kg per day for 3 consecutive days, and it was then adjusted to maintain a CD2 count below 50/mm(3). Overall, RATG was given for a median of 5 days for a total dose of 406 +/- 45 mg. Steroids were started pretransplant and tacrolimus on day 1. The primary end-points were patient and graft survivals at 6 months posttransplantation, incidence of rejection, infectious complications (bacterial, viral, and fungal) and recurrence of HCV infection based on biochemical, virological, and histologic criteria. RESULTS: The survival rates were 100% for patients and 93.7% for grafts. The acute rejection rate was 37.5%. The median time to acute rejection was 15.5 days. There was only one serum sickness case. Cytomegalovirus infections occurred in 25% of patients. The rate of de novo diabetes that required insulin therapy was at 50%. The rate of HCV recurrence was 56.25%. In addition, HCV RNA serum concentrations increased significantly posttransplantation (>1 log). In conclusion, RATG induction therapy is safe and efficient in HCV-positive liver recipients.

Adult↗
PubMed2004

[Hepatitis C virus infection in renal-transplant patients].

Chronic hepatitis C virus (HCV) infection is the first cause of liver disease after renal transplantation. The prevalence of HCV infection in dialysis and in renal-transplant patients remains high. Mortality of HCV-positive renal-transplant patients is higher than that of HCV-negative ones. Liver disease and sepsis seem to be the main causes of death. Graft survival is also lower in HCV-positive renal-transplant patients. This seems to be due in part to the occurrence of de novo glomerulopathy. The effect of HCV infection upon liver fibrosis in renal-transplant patients receiving immunosuppressive treatment remains controversial. To date, there is no efficient treatment of HCV infection after renal transplantation. Consequently, it is mandatory to treat by alpha-interferon all HCV-positive/RNA-positive dialysis patients waiting for renal transplantation.

Antiviral Agents↗
PubMed2003

Screening for hepatitis B virus DNA in serum of organ donors and renal transplant recipients.

In order to determine the impact of screening potential organ donors for hepatitis B virus DNA using a standardized test, the serum of 145 donor candidates was tested. All of the candidates were negative for hepatitis B virus DNA, but the status of one donor was doubtful for hepatitis B virus surface antigen and seven donors tested positive for hepatitis B virus core antibody without hepatitis B virus surface antigen. Nine transplant recipients tested positive for hepatitis B virus surface antibody; they were given kidneys from the donor with a doubtful hepatitis B virus surface antigen result and from four of the seven donors who tested positive for hepatitis B core antibody. Follow-up revealed no case of hepatitis B transmission. In this study, screening for hepatitis B virus DNA was useful and did not lead to donor organ shortage. Patients with hepatitis B virus surface antibodies can safely be given kidneys from donors who are positive for hepatitis B core antibody but negative for hepatitis B virus DNA.

DNA, Viral↗
PubMed2003

Determining hepatitis C genotype by analyzing the sequence of the NS5b region.

Assays to determine the hepatitis C virus (HCV) genotype have recently become useful for clinical decision making and may be suitable for epidemiological investigations, such as identifying HCV outbreaks in a given population. Molecular assays are the most common diagnostic tools for HCV genotyping. This study compares two genome typing assays, one, the Trugene 5'NC genotyping kit, uses the sequence of the 5' non-coding (5'NC) region and the other, a non-commercial assay, uses the non-structural 5b (NS5b) region. Serum samples from 203 chronically HCV-infected patients were tested. The 5'NC and the NS5b assays were both very effective in identifying the genotype (99 and 98.5%) and the results with the two methods were always concordant for the genotype. The NS5b analysis permitted the identification of the subtype in all samples, whereas the 5'NC region assay did not in 33% of samples. The NS5b analysis showed that one patient had a mixed infection with HCV subtypes 1a and 2c, while the 5'NC assay did not. It is concluded that phylogenetic analysis using both the 5'NC and the NS5b regions are reliable and convenient methods for HCV typing in clinical practice. But analysis of the NS5b region may be more useful for tracing the source of an HCV infection.

5' Untranslated Regions↗
PubMed2003

Automated extraction and quantification of human cytomegalovirus DNA in whole blood by real-time PCR assay.

The measurement of human cytomegalovirus (HCMV) DNA in blood is becoming the standard method for monitoring HCMV infection in immune-suppressed and unsuppressed patients. As various blood compartments can be used, we have compared the HCMV DNA measured in whole blood (WB), peripheral blood leukocytes (PBL), and plasma by real-time PCR. We tested 286 samples: HCMV DNA was extracted automatically from WB and PBL with the MagNA Pure instrument (Roche Molecular Biochemicals) and manually from plasma samples. The HCMV DNA from WB, PBL, and plasma was measured by real-time Light Cycler PCR. Primers and probe were located in the UL 83 region. HCMV DNA was detected more frequently in WB (88.5%) than in the PBL (65.7%) (P < 0.0001) or the plasma (55.2%) (P < 0.0001). There was a good correlation between the positive results in WB and in PBL (r = 0.68; P < 0.0001), and 3.15 log(10) genome copies in 200000 PBL, equivalent to the threshold value of 50 pp65-positive polymorphonuclear cells per 200000 leukocytes, was equivalent to 3.4 log(10) genome copies in 200 microl of WB. WB was shown to be suitable for automated extraction and the quantitation of HCMV DNA by real-time Light Cycler PCR by analysis of serial samples from representative patients of various populations. This system may be very useful for monitoring of immune-suppressed and unsuppressed patients.

Adult↗
PubMed2003

[Is there a place for ribavirin in the treatment for renal transplant patients infected by hepatitis C virus?].

Treatment of chronic hepatitis C in renal-transplant (RT) recipients with alpha-interferon is associated with a high rate of acute rejection. We therefore evaluated the biochemical, virological, histological efficacies, as well as the safety of one year ribavirin monotherapy in 16 HCV-(+) RNA (+) RT patients (group A) matched to 32 HCV-(+) RNA (+) RT patients (group B) who did not receive ribavirin. Ribavirin was initially started at a daily dose of 1000 mg and then adapted to hemoglobin level. Ribavirin monotherapy was associated with a significant decrease in AST, ALT and gamma glutamyl transpeptidase levels. Serum creatinine decreased as well. When proteinuria was present (n = 5), this decreased or disappeared. There was no significant changes in HCV viremia. The histological analysis of liver biopsies revealed a significant progression in liver fibrosis with no improvement in inflammation scores. There was a significant decrease in hemoglobin levels, despite an important support by recombinant erythropoeitin. However, in three cases, ribavirin therapy had to be stopped. In group B, after 1 year of follow up, there was a significant increase in serum ALT and creatinine values. Proteinuria decreased in only 2 of 12 patients. In conclusion, one year ribavirin therapy in HCV-(+) RNA (+)ve RT has no impact upon liver histology, although it improves liver enzyme levels. It impact upon renal function remains unknown. Nevertheless when proteinuria is present it disappears.

Adult↗
PubMed2003

[Hepatitis C infection among patients receiving hemodialysis].

In France, the prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients is high, about 15 to 42%. Although the incidence and the prevalence of HCV infection decreased during the last decade, de novo cases of HCV infection still occur in hemodialysis units. To date the nosocomial transmission is the principal cause of contamination. The strict application of universal precautions and the separation of chronic hemodialysis patients according to their virological status may decrease the incidence of HCV infection in hemodialysis units. The transaminase level and HCV viremia are lower in chronic hemodialysis patients than that in the general population. Liver disease seems also to be less aggressive. Chronic hemodialysis patients presenting acute hepatitis C infection and those waiting for renal transplantation have to be treated by interferon-alpha (IFN-alpha), since the virological response is elevated and sustained. In case of cirrhosis or severe liver disease, a combined liver-kidney transplantation can be proposed after IFN-alpha therapy. Finally, in chronic hemodialysis who are not candidate for renal transplantation IFN-alpha therapy can be discussed according the patients' age and general health status.

Antiviral Agents↗
PubMed2001

Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation.

Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIV-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed.

Amino Acid Sequence↗
PubMed2001

Prevalence of resistance mutations in antiretroviral-naive chronically HIV-infected patients in 1998: a French nationwide study.

OBJECTIVE: To estimate the prevalence of resistance-conferring mutations to antiretroviral drugs in previously untreated patients with chronic HIV-1 infection as a basis for French recommendations on viral genotyping before antiretroviral treatment initiation. DESIGN: Resistance mutations were sought in samples from 404 patients seen in 23 specialized centres throughout metropolitan France in 1998. METHODS: The protease and reverse transcriptase (RT) genes of plasma virions were sequenced. Primary and secondary protease and RT gene mutations were identified from the International AIDS Society resistance testing - USA panel. RESULTS: The prevalence of patients with primary and secondary mutations were 3.7% (95% CI 1.7-5.7) and 50.3% (95% CI 45.0-55.6), respectively. The prevalence of patients with mutations associated with resistance to nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors was 3.3% (95% CI 1.5-5.1) and 0.8% (95% CI 0.0-1.7), respectively. The prevalence of patients with NRTI primary mutations differed according to whether seropositivity had been diagnosed more or less than one year previously (0.2 versus 2.2% P = 0.023). Primary mutations associated with protease inhibitor resistance occurred at a prevalence of 1.9% (95% CI 0.5-3.4) with no difference according to the duration of known seropositivity. CONCLUSION: In France, in 1998, the prevalence of patients with primary mutations associated with resistance to antiretroviral drugs was low. Genotyping before the initiation of therapy was not recommended in chronically HIV-1-infected naive patients. A national sentinel survey of resistance in this clinical setting is performed regularly to update the recommendations for resistance testing.

Adult↗