Biomedical subjects

Jacques Izopet

Publications and source records attributed to Jacques Izopet.

68 records · Page 4Linked to original sources

PubMed2003

Hepatitis C virus infection among pregnant women in Yaounde, Cameroon: prevalence, viremia, and genotypes.

Central Africa is considered to be an area of high endemic hepatitis C infection. To determine the prevalence of anti-HCV antibodies, HCV RNA, and the genotype distribution in Cameroon, 1,494 pregnant women attending antenatal care units in Yaounde, Cameroon were screened for HCV infection. Anti-HCV antibodies were detected with a 3rd generation ELISA (Monolisa anti-HCV plus version 2, BioRad, Richmond, CA). All anti-HCV antibody-positive sera were then tested with another 3rd generation ELISA (AxSYM) HCV version 3, Abbott Laboratories, Abbott Park, IL) and subsequently for HCV RNA (Amplicor HCV, Roche Diagnostics, Basel, Switzerland). Genotype was determined by phylogenetic analysis of the NS5b gene. Seventy-three pregnant women were found to be anti-HCV antibody positive by the first ELISA, but only 28 were anti-HCV positive by both ELISA. The prevalence of anti-HCV antibodies was thus 1.9% (28/1,494) (95% CI: 1.3-2.7%). 21/28 (75%) of the positive samples by both ELISA were HCV RNA positive. The 45 samples that were HCV antibody negative by the second ELISA were also HCV RNA negative. The HCV subtypes identified were 1a (24%), 2f (38%) and 4f (38%). In contrast to previous studies, anti-HCV antibodies were rare among pregnant women in Cameroon. The percentage of HCV seropositive pregnant women who had circulating HCV RNA was similar to that observed in Europe. Several HCV genotypes were found in Cameroon.

Adolescent↗

PubMed2003

Evolution of hepatitis C virus quasispecies in renal transplant patients with de novo glomerulonephritis.

Long-term renal allograft survival in kidney transplant recipients infected by hepatitis C virus (HCV) may be influenced by the occurrence of de novo glomerulopathy associated with this virus. Therefore, we studied the evolution of HCV quasispecies in kidney transplant recipients infected by HCV with or without de novo glomerulopathy. The hypervariable region 1 (HVR-1) of the virus envelope was analyzed by cloning and sequencing 20 clones per sample to assess complexity and diversity from six kidney transplant patients who developed de novo glomerulopathy (group I) matched to six kidney transplant recipients without glomerular disease (group II), according to age, time since renal transplantation, and HCV genotype. Two sera were analyzed for each patient: one at the time of renal transplantation and the other at the time of appearance of de novo glomerulopathy, or after a similar duration since transplantation in group II. Overall, there was a significant increase of HCV viremia after the transplantation. This increase did not differ significantly between group I (+0.5 log copies/ml) and group II patients (+1 log copies/ml). The intersample diversity of HCV was similar in the two groups. Complexity and viral diversity were also similar at the time of transplantation. By contrast, complexity, diversity, and the proportion of nonsynonymous substitutions per nonsynonymous site were significantly higher after transplantation in group I patients. Our findings suggest a higher immune response and/or a particular cytokine production in patients developing de novo glomerulopathy rather than a direct effect of HCV on renal cells.

Adult↗

PubMed2003

High rate of hepatitis C virus infection and predominance of genotype 4 among elderly inhabitants of a remote village of the rain forest of South Cameroon.

To determine the prevalence of hepatitis C virus (HCV) infection and genotype distribution in a rural isolated area of Central Africa, plasma of 409 Bantous (mean age, 32 years; range, 2-78 years) living in a remote village of the rain forest of Southern Cameroon was screened for anti-HCV antibodies. HCV seropositive samples were also subjected to qualitative detection of viral RNA. HCV antibodies were detected in 70 (17.1%) individuals, 48 (68.8%) of whom had detectable viremia. The seroprevalence did not differ by gender (P = 0.37), but increased significantly with age (P < 0.05), with a strong increase in the oldest age groups. Indeed, nearly one-half (48%) of the adults >50 years old were HCV seropositive. The characterization of the viral genotypes indicated that most of the HCV strains were of genotype 4 (76%), while genotype 2 (16%), and 1 (8%) were marginally represented. The results suggest a cohort effect with an old, possibly iatrogenic, group exposure rather than a continuous exposure. A more in-depth population-based epidemiological study is needed to address this issue further.

Adolescent↗

PubMed2003

Long-term ribavirin therapy in hepatitis C virus-positive renal transplant patients: effects on renal function and liver histology.

BACKGROUND: Long-term renal transplant (RT) recipient mortality and graft loss increase significantly in hepatitis C virus positive (HCV-[+]ve) patients. Treatment with alpha-interferon in this population is associated with a high rate of acute rejection. The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+) RT patients (group A) matched to 32 HCV-(+) RT patients (group B) who did not receive ribavirin. METHODS: Ribavirin was started at a daily dose of 1,000 mg and then adapted to hemoglobin level. The study was scheduled for 1 year. RESULTS: Ribavirin monotherapy was associated with a decrease in liver enzymes and serum creatinine levels. When proteinuria was present, this decreased or disappeared. There were no significant changes in HCV viremia. There was a significant progression in liver fibrosis with no improvement in inflammation scores. Hemoglobin levels fall dramatically, despite an important support by recombinant erythropoeitin (median, 20,000 IU/wk). In 3 cases, ribavirin therapy had to be stopped. In the control group, after 1 year of follow-up, there was a significant increase in serum alanine aminotransferase and creatinine values. Proteinuria decreased in only 2 of 12 patients (P = 0.03 as compared with group A). CONCLUSION: One year of ribavirin monotherapy seems to have, at best, no beneficial effect on liver histology, although it improves liver enzyme levels. Despite its efficiency to dramatically decrease proteinuria, its impact on renal function remains unknown.

Adult↗

PubMed2003

Evidence that clearance of hepatitis C virus RNA after alpha-interferon therapy in dialysis patients is sustained after renal transplantation.

To date, there is no available treatment of hepatitis C virus (HCV) infection after renal transplantation (RT). Among 55 anti-HCV-positive/HCV RNA-positive hemodialysis patients who were treated with IFN-alpha (9 MU/wk during 6 or 12 mo), 21 of them (38%) had a sustained virologic response. Of these, 16 (76%) underwent RT 38 mo (range, 2 to 57 mo) after alpha-IFN therapy. There were 13 men and 3 women aged 46 yr (range, 27 to 68 yr). At RT, HCV serology was still positive in 15 patients, and HCV viremia was negative in all patients. Immunosuppression relied on anticalcineurin agents with or without steroids and/or antimetabolites; in addition, 12 of them received induction therapy with antithymocyte globulins. At the last follow-up after RT, at 22.5 mo (range, 2 to 88 mo), HCV viremia remained negative in all patients. Moreover, HCV RNA was not present in peripheral blood mononuclear cells when assessed in eight patients. HCV serology was found to be still positive in 13 patients. Three patients presented with acute rejection, one presented with a suppurative lymphocele, one died from a sepsis, and four presented with a cytomegalovirus infection. None of them developed posttransplant diabetes mellitus. In conclusion, hemodialysis patients waiting for a RT need to be treated with alpha-IFN because when HCV RNA clearance occurred, they experienced no relapse after transplantation despite chronic immunosuppressive treatment.

Adult↗

PubMed2003

Multicenter quality control for the detection of hepatitis C virus RNA in seminal plasma specimens.

The discrepant results available in the literature about the presence of hepatitis C virus (HCV) RNA in seminal plasma of men chronically infected by this agent are related, at least in part, to the molecular techniques used and particularly to the wide range of protocols dedicated to RNA extraction. In order to evaluate these protocols and to standardize the method of detection of HCV RNA in this fluid, a panel of coded specimens was tested blindly in 12 French laboratories; it included 14 seminal plasma specimens and four water controls spiked with HCV RNA ranging from 10 to 20000 IU/ml and two HCV-negative seminal plasma specimens. The extraction step was performed according to methods using either silica beads (NucliSens [Organon Teknika S.A., Fresnes, France]; RNA viral kit [Qiagen, Courtaboeuf, France]) or guanidinium thiocyanate (Amplicor HCV assay; Roche Diagnostics, Meylan, France), preceded or not by a centrifugation of the seminal plasma. For the amplification step, all the laboratories performed the same reverse transcription-PCR technique (Amplicor HCV Cobas assay). The percentage of correct results ranged from 53.3 to 100, the poorest results being obtained when no centrifugation step preceded the Amplicor extraction protocol. The rate of correct results was significantly higher in laboratories using a preliminary centrifugation of the specimen (P = 0.034 by chi-square test). By contrast, the overall number of correct results was not correlated to the initial volume of sample used for the test. These results allowed us to validate standardized techniques adapted to the performance of this test on a routine basis, especially in men infected with HCV and involved in programs of medically assisted reproduction.

Hepacivirus↗

PubMed2003

Predictive factors and selection of thymidine analogue mutations by nucleoside reverse transcriptase inhibitors according to initial regimen received.

Thymidine analogue mutations were determined and compared in patients who received zidovudine monotherapy and added didanosine or zalcitabine, and in patients who started with one of these dual nucleoside combinations. Although patients who started in the era of zidovudine monotherapy had a longer duration of therapy compared with the other group, there was no statistical difference in the number of mutations between the two groups. However, thymidine analogue mutations were more frequent in patients who added didanosine to zidovudine monotherapy compared with those who added zalcitabine. Patients who started with a dual nucleoside combination developed 215Y/F first, followed by 215Y/F+41L, then 215Y/F+41L+210W, then 215Y/F+67N+70R+41L or 219Q/E, and then 215Y/F+41L+67N+70R+219Q/E. Patients who started with zidovudine monotherapy had a different pathway with the mutation at codon 70 appearing first, followed by 215Y/F+70R or 210W, then 215Y/F+41L+210W, then 215Y/F+67N+70R+219Q/E, and then 215Y/F+41L+67N+70R+210W. Medication adherence was associated with the number of mutations in both groups of patients. Two distinct mutational patterns were noted. The first pattern involved mutations at codons 41, 210 and 215, while the second involved mutations at codons 67, 70 and 219.

Anti-HIV Agents↗

PubMed2002

Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine or stavudine, each in combination with lamivudine and indinavir.

The authors studied the effect of zidovudine (ZDV) resistance mutation on virologic response to treatment with ZDV or stavudine (d4T) each in combination with lamivudine and indinavir. Viral genotyping was performed on plasma HIV-1 RNA at study entry and concerned 155 patients previously treated with ZDV, didanosine, or zalcitabine and enrolled in the NOVAVIR (Agence National de Recherche sur le SIDA [ANRS] 073) trial. Three virologic responses were investigated: early response (<50 copies/mL at week 24), late response (<500 copies/mL at week 80), and virologic failure (two HIV-1 RNA >5000 copies/mL). Patients were classified as resistant or susceptible to ZDV according to the ANRS algorithm. Plasma viral RNA from 123 of 155 patients had two or more ZDV resistance mutations. The number of ZDV resistance mutations was positively correlated with the duration of prior antiviral therapy (p <.001). At week 24, 74% and 77% of patients with virus classified as resistant were responders in the d4T and ZDV arm, respectively. Similar results were found at week 80. Virologic failure was reached in 7 of 24 patients with virus classified as susceptible and in 26 of 131 patients with resistant virus (p =.29). In the ZDV arm, patients classified as resistant had longer times to virologic failure than those classified as susceptible (p =.003). In conclusion, sustained virologic response despite presence of ZDV resistance mutations implies that these mutations do not preclude an early and durable response to treatment with a potent three-drug regimen in these patients. Patients susceptible to ZDV had lower median mean corpuscular volumes and lower random indinavir levels, suggesting that adherence was the main reason for failure.

Anti-HIV Agents↗

PubMed2002

Evolution of total and integrated HIV-1 DNA and change in DNA sequences in patients with sustained plasma virus suppression.

Blood samples from patients with plasma HIV-1 RNA <20 copies/ml for more than 2 years were studied. Significant decreases in total and integrated HIV-1 DNA were observed during the first 15 months of suppressive therapy before the concentrations became stable. Clonal analysis of HIV-1 pol demonstrated that the proportions of resistance mutations in DNA sequences after 2 years were lower than those in baseline DNA and RNA sequences. The changes in the clonal composition of HIV-1 env populations in three patients with evidence of changes in HIV-1 pol populations indicated a shift from predominantly R5-like viruses to predominantly X4-like viruses in two patients and the persistence of predominantly X4-like viruses in the third. Our analyses indicate the reemergence of ancestral sequences from long-lived cells or the residual production of wild-type virus from anatomic sites with limited access to antiretroviral drugs and the preferential infection of cells expressing CXCR4.

Amino Acid Sequence↗

PubMed2002

Evolution of human immunodeficiency virus type 1 populations after resumption of therapy following treatment interruption and shift in resistance genotype.

Conventional genotyping of human immunodeficiency virus type 1 often reveals a shift from a drug-resistant genotype to a wild-type genotype after treatment interruption. A real-time polymerase chain reaction-based technique was used to detect minority resistant populations in 13 patients who showed genotype reversion after interruption of treatment for 3 months. Sixty-two percent of patients in whom the V82A and L90M protease mutations were no longer detectable by conventional genotyping still harbored minority resistant variants, in proportions ranging from 0.1% to 21%. None of the patients with these minority resistant variants who received a protease-inhibitor regimen on resumption of therapy had a response to treatment. However, population sequencing and clonal analysis of plasma samples obtained 1-2 months after resumption of treatment revealed the presence of wild-type virus during the initial decline in plasma virus load, which indicates that minority resistant variants were not rapidly selected.

Amino Acid Sequence↗

PubMed2002

Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus after a second course of interferon-alpha.

The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon-alpha (IFN-alpha). To assess the factors leading to virus eradication by IFN-alpha, patients whose first treatment by IFN-alpha failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2-PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN-alpha therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment.

Adult↗

PubMed2002

Virological and immunological effects of salvage therapy following treatment interruption and a shift in HIV-1 resistance genotype.

The circulating human immunodeficiency virus type 1 (HIV-1) population of patients in whom many prior therapy regimens have failed often undergo a shift from a drug-resistant virus to a wild-type virus following interruption of treatment. This study analyses the virological and immunological effects of salvage therapy following treatment interruption and a shift from a drug-resistance genotype. Twenty-one HIV-1 infected patients who had genotype reversion by population-based sequencing after 3 months of treatment interruption were given a new salvage regimen consisting of 3-5 drugs selected according to their treatment history. Seven (33%) of 21 patients who had fewer than 200 HIV-1 RNA copies/ml until month 12 were defined as virological responders. Four patients were transient responders and 10 were nonresponders. The virological responders were more frequently CDC group A and had higher CD4 + T lymphocyte counts at the time of treatment resumption. The peripheral blood T CD4 + and T CD8 + lymphocyte populations of the patients declined significantly during treatment interruption. Only virological responders showed significant increases in their CD4 + T lymphocyte count 12 months after treatment resumption and these counts rapidly returned to pre-interruption baseline values in most of these patients. Treatment interruption could be useful for optimising salvage therapy for patients previously given many failing regimens. However, controlled trials are needed to assess the clinical benefit of this strategy.

Adult↗

PubMed2002

Screening of blood from potential organ and cornea donors for viruses.

Prospective nucleic acid tests were carried out for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) using the COBAS Amplicor HIV-1 and HCV tests (Roche Diagnostics, Meylan, France) on potential organ (n=113) and cornea (n=368) donors in France to evaluate their performance and suitability for use as a complement to routine serological tests. Blood samples were collected from organ donors with preserved cardiac function after verification of cerebral death. Blood samples were collected from cornea donors post-mortem within 48 hr after death. An internal control was added to the samples before extraction to monitor each individual polymerase chain reaction (PCR). The nucleic acid tests were always interpretable in organ donors and negative in all except in 2 anti-HCV positive patients. One had an indeterminate HIV p24 antigen but was negative for HIV RNA. HIV and HCV RNA were not found in cornea donors with a negative serology but indeterminate molecular results were frequent in this group (17.6%). Cornea donors also gave significantly more (14.4%) indeterminate serological results than organ donors (1.8%) (P<0.001). This was due to the poor quality of the blood samples collected post-mortem. However, there was no correlation between indeterminate results of serological and molecular tests. There were 16/19 (84%) indeterminate serological results for HIV and 4/4 (100%) for HCV that were negative by PCR. Thus, nucleic acid tests could be useful for qualifying a donor whose serological results are indeterminate. The extraction procedures on post-mortem specimens and/or blood collection must be changed to improve the performance of nucleic acid tests.

Cornea↗

PubMed2002

Long-term impact of renal transplantation on liver fibrosis during hepatitis C virus infection.

BACKGROUND & AIMS: During hepatitis C virus (HCV) infection, liver fibrosis progression after renal transplantation remains controversial. The aim of this cohort study with controls was to compare liver histopathologic features during HCV infection between renal transplant recipients and matched groups of hemodialyzed patients or controls without renal disease and untreated for HCV. METHODS: Each renal transplant recipient (group 1, n = 30) was matched at first liver biopsy (LB) using the main factors known to influence progression of fibrosis with one HCV hemodialyzed patient (group 2, n = 30) and one HCV-infected patient (nonhemodialyzed, nontransplanted; group 3, n = 30). Patients from group 1 were also matched with those of group 3 on the time between 2 consecutive LBs performed 37 months apart. LBs were evaluated according to the Knodell index, METAVIR score, and rate of fibrosis progression per year (fibrosis unit). RESULTS: The rate of fibrosis progression per year between the first and second LBs was significantly lower (P = 0.03) in group 1 (0.067; 95% confidence interval: -0.05, 0.18) than group 3 (0.20; 95% confidence interval: 0.13, 0.26). At the second LB, the Knodell index and activity or fibrosis in METAVIR were lower in group 1 than group 3 (4.2 +/- 0.4 vs. 7.5 +/- 0.6, 0.5 +/- 0.1 vs. 1.3 +/- 0.2, and 1.4 +/- 0.2 vs. 2.3 +/- 0.2 respectively, P < 0.01). CONCLUSIONS: Our study suggests that liver fibrosis progression is low in most HCV-infected renal transplant recipients with moderate liver disease at baseline.

Adult↗