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Biomedical subjects

E Dussaix

Publications and source records attributed to E Dussaix.

At least 19 recordsLinked to original sources
PubMed2007

KSHV after an organ transplant: should we screen?

The incidence of Kaposi sarcoma (KS) related to Kaposi sarcoma-associated herpesvirus (KSHV/HHV-8) after organ transplantation is 500-1000 times greater than in the general population, and its occurrence is associated with immunosuppressive therapy. The reported incidence of posttransplant KS ranges from 0.5% to 5%, depending on the patient's country of origin and the type of organ received, mainly after renal transplantation. Posttransplant KS is caused by two possible mechanisms: KSHV reactivation in patients who were infected before the graft and KSHV contamination from the infected organ's donor to the recipient. KSHV reactivation appears to play a greater role in the risk of KS than incident infections. However, some studies, with findings based not only on serological data but also on molecular tracing of the viral infection, have shown that organ-related transmission of KSHV could be more common than previously thought and associated in some cases with severe KSHV-related disease. Precise estimates of KSHV seroprevalence in the organ donor and recipient populations in different countries are lacking. However, studies have reported seroprevalences among donors and recipients that are similar to those among the general population of the country considered. Many studies have suggested the potential utility of screening of KSHV antibodies among organ donors and recipients. However, to date the results of these studies have argued in favor of KSHV screening, even in low-KSHV infection prevalence countries, not to exclude the graft but to have the KSHV status information in order to have the opportunity to monitor, clinically and biologically, patients at risk for KSHV-related disease development. The detection of KSHV antibodies could be done in the days after the transplantation and the results transmitted to the physicians retrospectively. In conclusion, the question of screening donors and recipients for KSHV, even in low-KSHV infection prevalence countries, is still debated, and prospective studies are needed to evaluate the benefit of pre- and posttransplantation strategies.

Animals↗
PubMed2005

[HBs antigen mutants: prevalence, clinical and diagnostic implications].

The serological diagnosis hepatitis B (HBV) infections relies mainly on the detection of the small surface antigen (HBsAg). Immuno-enzymatic assays use antibodies directed against epitopes of the major hydrophilic region, in particular against a determinant. Genetic variants have been detected in vaccinated children, liver transplanted patients receiving anti-HBs immunoprophylaxis and chronic carriers with an occult infection (negative HBsAg). Substitutions in this region can induce conformational changes abolishing some diagnostic antibodies binding leading to false negative results. To estimate the prevalence of such substitutions, we studied 55 sequences of the gene S obtained between 2002 and 2004, carried out mainly in the search of changes of resistance to the lamivudine. The polymorphism of the major hydrophilic region (positions 102 to 169) was studied using Mutation Master software. Each sequence was compared with a consensus sequence of the same genotype. Genotype distribution is as follows: D, 40%; With, 20%; C, 16%; B, 11%; E, 9%; F, 2% and G, 2%. Changes I195 M and W196L, reflecting lamivudine resistance are present among 18 patients (33%). Substitutions of the major absorbent area are found among 31 patients (56%), of which a third associated with resistance mutations. The most frequent substitutions involved the following amino-acids: F/Y134 (7/31), M133 (6/31), D144 (6/31) and G145 (6/31). These two latter are known to be associated anti-HBs immunoglobulins or vaccine escape. BLOSUM scores are indicative of substitutions inducing important changes of physicochemical properties in 16 patients (29%). Such substitutions could thus potentially alter the binding of antibodies used in diagnostic assays. In conclusion, changes of the major hydrophilic loop of HBs antigen are not rare and could have an important implications for transfusion safety and diagnostic reliability.

Amino Acid Sequence↗
PubMed2003

[Liver transplantation: is it possible in HIV/HCV co-infected patients?].

The prognosis of HIV infection has been modified by antiretroviral therapy. However, the morbidity and the mortality of HCV co-infection increase and may be a major problem of health service. Up to now co-infected patients are excluded of transplantation due to complexity, the ethical aspects, the immunodeficiency and the co-infection. This study tries to estimate the feasibility in this population. Between December 1999 and March 2002, seven patients were transplanted. The average of CD4 was 332/ml; the viral load was <50 copies/ml. Before transplantation, no patient had experienced opportunist infection and all patients received antiretroviral therapy adapted to their history. The average follow-up is of 14 months: one patient died 3 months after transplantation, the other one presented a candida in oesophagus, the average of CD4 was 280/ml, and viral load was <50 copies/ml in five patients. A relapse of HVC was observed in all patients. Interferon/rivabirine therapy was proposed for four patients. Every patient received tacrolimus and corticoids. HAART were modified four times for toxicity and one time for virological failure. We observed two cases of transient renal insufficiency, two cases of diabetes, two cases of pancreatitis, and abnormalities of the respiratory mitochondrial chain in four patients. Finally, liver transplantation in HIV-HCV co-infected patients seems to be feasible when strict criteria of selection are taken into account. This still experimental strategy requires a multidisciplinary partnership.

Adult↗
PubMed2002

Performance of TRUGENE hepatitis C virus 5' noncoding genotyping kit, a new CLIP sequencing-based assay for hepatitis C virus genotype determination.

The performance of the recently developed, standardized direct sequencing assay for hepatitis C virus (HCV) genotyping [TRUGENE HCV 5'-NC (noncoding)] was assessed in comparison with the reverse hybridization-based assay INNO-LIPA HCV II. Both assays allow HCV genotyping starting from amplification products generated by the diagnostic Roche AMPLICOR HCV test. HCV amplicons from 205 patients were used for this study: 34 were tested prospectively by both methods, while 171 had been stored at -20 degrees C for up to 2 years after LiPA genotyping. The TRUGENE procedure failed to determine a genotype in six low-titered samples (3.5 +/- 0.3 log UI/mL vs. 5.2 +/- 0.5 UI/mL for typable samples). Type and subtype could be determined by sequencing for 199 samples (97%). Among them, five were considered as coinfections by the LiPA method. Three LiPA patterns suggesting type 1 and 4 coinfection were not supported by sequence analysis while one 1a/2b and one 1a/3a coinfection was backed up by direct sequencing. For the remaining 194 samples, type assignment was concordant in 100% of the cases. LiPA subtyping was available for 162 samples (83.5%). Sub-typing results concurred in 128 cases (79%). NS5B sequencing of discrepant samples underscored the limitation of the 5'-noncoding region (NCR) in correct subtype assignment. In conclusion, the TRUGENE HCV 5'-NC genotyping kit appeared to be a specific and reliable method that can be used in the current indication of HCV genotyping.

5' Untranslated Regions↗
PubMed2002

Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors.

BACKGROUND AND AIMS: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. PATIENTS: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. RESULTS: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4-39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1-23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. CONCLUSION: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.

Antiviral Agents↗
PubMed2001

Genetic clustering of hepatitis C virus strains and severity of recurrent hepatitis after liver transplantation.

The influence of viral factors on the severity of hepatitis C virus (HCV)-related liver disease is controversial. We studied 68 liver transplant patients with recurrent hepatitis C, of whom 53 were infected by genotype 1 strains. Relationships between core sequences, serum HCV RNA levels, and fibrosis scores for each patient were analyzed in pairwise fashion 5 years after transplantation. We used Mantel's test, a matrix correlation method, to evaluate the correspondence between measured genetic distances and observed phenotypic differences. No clear relationship was found when all 68 patients were analyzed. In contrast, when the 53 patients infected by genotype 1 strains were analyzed, a strong positive relationship was found between genetic distance and differences in 5-year fibrosis scores (P = 0.001) and differences in virus load (P = 0.009). In other words, the smaller the genetic distance between two patients' viral core sequences, the smaller the difference between the two patients' fibrosis scores and viral replication levels. No relationship was found between genetic distance and differences in age, sex, or immunosuppression. In multivariate analysis, the degree of fibrosis was negatively related to the virus load (r = -0.68; P = 0.003). In the particular setting of liver transplantation, and among strains with closely related phylogenetic backgrounds (genotype 1), this study points to a correlation between the HCV genetic sequence and the variability of disease expression.

Genotype↗
PubMed2001

Residual hepatitis B virus particles in liver transplant recipients receiving lamivudine: PCR quantitation of HBV DNA and ELISA of preS1 antigen.

Lamivudine, an antiviral agent, has a potential role in the treatment of recurrent or acquired de novo hepatitis B virus (HBV) infection after liver transplantation. During lamivudine therapy, residual HBV particles in serum, PBMC, and liver were quantified in 7 patients in whom hepatitis B occurred de novo (n = 4) or recurred (n = 3). HBV DNA and preS1 antigen were measured using a sensitive PCR technique and an in-house ELISA method, respectively. The genetic and antigenic properties of HBV variants that emerged during lamivudine treatment were also examined. One month after the outset of lamivudine treatment, all 7 patients remained positive for both HBV DNA and preS1 antigen in serum, reflecting residual HBV replication. At the end of therapy, four patients were considered to be lamivudine responders, including one who seroconverted to anti-HBs but remained HBV DNA positive in the liver (> 10(3) copies/microg of DNA). Among the three patients who did not respond to lamivudine, one had pol mutations (L450P and S550C) that had not been described previously, in addition to the common mutations within the YMDD locus and B domain. Defective core and preS viral proteins and atypical sedimentation profiles of HBV DNA-positive particles were observed in all three lamivudine-resistant patients. These findings confirm the persistence of HBV in liver transplant recipients despite strong inhibition of replication by lamivudine, and show abnormal viral transcription and/or morphogenesis in lamivudine-resistant patients.

Adult↗
PubMed2000

JC virus genotypes in France: molecular epidemiology and potential significance for progressive multifocal leukoencephalopathy.

JC virus (JCV) induces progressive multifocal leukoencephalopathy (PML), especially in human immunodeficiency virus (HIV)-infected patients. Although JCV genotypes have primarily been associated with geographic patterns, a distinctive neuropathogenicity was recently attributed to genotype 2. A multicenter study was conducted to describe the distribution of JCV genotypes in France and to investigate correlations between genotypes and PML. Genotypes were determined by sequencing 494 bp in the VP1 capsid gene. Peripheral JCV was studied in 65 urine samples from 43 HIV-infected patients and from 22 control subjects. Genotypes 1, 4, 2, and 3 were detected in 52.3%, 30.8%, 12.3%, and 4.6% of the samples, respectively. In 56 brain or cerebrospinal fluid samples, PML-associated JCV of genotypes 1, 2, 4, and 3 was found in 66%, 19.7%, 8.9%, and 5.4%, respectively. Infection with JCV genotypes 1 or 2 was correlated with PML (odds ratio, 3.29). On the other hand, infection with JCV genotype 4 could represent a lower risk for PML.

AIDS-Related Opportunistic Infections↗
PubMed2000

Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group.

OBJECTIVE: To describe the spontaneous course, before the introduction of highly active antiretroviral therapy (HAART), of HIV-1 RNA during the AIDS-free period of the disease. To assess the predictive value of changes in HIV-1 RNA levels. DESIGN: A total of 330 patients with a known date of infection followed in the SEROCO cohort. METHODS: HIV-1 RNA levels (threshold, 200 copies/ml) were evaluated from 2243 frozen sera obtained from enrolment until the onset of AIDS or until February 1996. Lowess curves were used to describe the variations of viraemia during follow-up. A Cox regression model was used to assess the predictive value of early and updated CD4 cell count and viral load. RESULTS: In addition to a lower early viral load, patients who remained AIDS-free had, on average, a longer period of viral load decrease after infection (36 versus 18 months), followed by a slower viral load increase compared with those who progressed to AIDS. A true plateau-phase after the seroconversion period, lasting approximately 4 years, was identified only in patients who remained AIDS-free for at least 90 months. In multivariate analysis, both early viral load and later changes were significant predictors of progression to AIDS. A decrease in the CD4 cell count to less than 200 cells/microl and the onset of a group B condition remained significant predictors of progression. CONCLUSION: Our study extends to the early post-seroconversion phase the prognostic value of extracellular HIV-1 RNA levels. Moreover, our data suggest that, in most HIV-infected individuals, a progressive loss of control of viral replication arises during the early years of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Lessons from a multicentre study of the detectability of viral genomes based on a two-round quality control of GB virus C (GBV-C)/hepatitis G virus (HGV) polymerase chain reaction assay.

The aim of this study was to determine whether multicentre quality controls for the detectability of viral genomes could contribute to the improvement of diagnostic performance in the participating laboratories. The study was carried out during two successive rounds, during which 18 laboratories specialized in nucleic acid testing analyzed, through a polymerase chain reaction (PCR) assay, a common panel of GB virus C (GBV-C)/hepatitis G virus (HGV) RNA-positive and -negative samples. During the first round, the laboratories used either an 'in-house' PCR procedure or a partly standardized commercial test. After decoding the results of the first round, the procedures of the participating laboratories were compared in order to establish a consensus procedure deduced from those of the laboratories which provided the best results. During the second round, each participating laboratory could use the resulting consensus procedure, or its own procedure, or both. The results of this quality control study indicated that, whatever method used, even specialized and trained laboratories may give false-negative or false-positive results. The commercial assay did not guarantee a systematic high quality level of results. The striking heterogeneity of results observed among laboratories using the same commercial assay confirm that molecular biology methods need skilled technicians. The results of this quality control study suggest that full standardization of viral genome detection, including all steps of the procedure, is necessary and that the laboratories performing PCR should participate in repeated quality control studies, whatever technique is being used.

Flaviviridae↗
PubMed2000

Performance of an automated system for quantification of hepatitis C virus RNA.

The Amplicor HCV Monitor test for quantitative determination of serum or plasma hepatitis C virus (HCV) RNA was modified recently and introduced onto the Cobas Amplicor instrument to automate fully amplification, detection and calculation of results. This new version (v2.0) was evaluated in a routine diagnostic laboratory. The sensitivity and reproducibility were assessed on well-characterized panels (Eurohep) and clinical samples. HCV RNA levels measured by the v2.0 Monitor test were about 1log(10) higher than those detected by the previous version test, and genotypes 1 and 3 were quantified with equal sensitivity. Within the linear dynamic range of 10(3) to 10(6) copies/ml, the coefficients of variation for both intra- and inter-assay reproducibility ranged from 1.9 to 2.95%. This test system was found to be a reliable and labor saving assay for the quantification of HCV RNA.

Automation↗
PubMed2000

Is cytomegalovirus infection a co-factor in HIV-1 disease progression?

The influence of cytomegalovirus (CMV) infection as a co-factor in HIV-1 disease progression has mainly been studied in haemophiliacs and remains controversial. Based on the files of 1683 HIV-1-infected patients in the Seropositive Cohort (SEROCO) and Haemophiliacs Cohort (HEMOCO) cohorts, we studied the role of CMV infection in progression to CD4+ cell counts of less than 200 microl, AIDS onset and death, in various HIV exposure groups. Adjusted relative risk (aRR) of progression to AIDS and to death was respectively 1.30 (P = 0.05) and 1.58 (P = 0.007). In the sexual exposure group the influence of CMV infection on the risk of progression to AIDS was of borderline significance (aRR = 1.50; P = 0.07) and was more marked on the risk of death (aRR = 2.00; P = 0.03). No such influence of CMV infection was observed in the transfusion and intravenous drug use exposure groups. When we studied the influence of CMV infection according to the stage of HIV disease, the main effect was on progression from AIDS to death, probably because CMV disease is a late event. Sexual CMV transmission and frequent re-exposure to CMV may explain why CMV infection emerged as an important co-factor for HIV progression only in the sexual exposure group.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation.

AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND RESULTS: Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter > or = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04). CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.

Carcinoma, Hepatocellular↗
PubMed1999

Nonrandom distribution of hepatitis C virus quasispecies in plasma and peripheral blood mononuclear cell subsets.

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences in quasispecies composition between the liver, peripheral blood mononuclear cells, and serum. We studied HCV RNA compartmentalization in the plasma of nine patients, in CD19(+), CD8(+), and CD4(+) positively selected cells, and also in the negatively selected cell fraction (NF). HCV RNA was detected in all plasma samples, in seven of nine CD19(+), three of eight CD8(+), and one of nine CD4(+) cell samples, and in seven of eight NF cells. Cloning and sequencing of HVR1 in two patients showed a sequence grouping: quasispecies from a given compartment (all studied compartments for one patient and CD8(+) and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartment. The characteristics of amino acid and nucleotide substitutions suggested the same structural constraints on HVR1, even in very divergent strains from the cellular compartments, and homogeneous selection pressure on the different compartments. These findings demonstrate the compartmental distribution of HCV quasispecies within peripheral blood cell subsets and have important implications for the study of extrahepatic HCV replication and interaction with the immune system.

Amino Acid Sequence↗
PubMed1999

Differences in kinetics of human cytomegalovirus cell-free viral release after in vitro infection of human microglial cells, astrocytes and monocyte-derived macrophages.

Microglial cells and astrocytes isolated from human embryonic proencephalon were compared to monocyte-derived macrophages (MDM) for their ability to replicate human cytomegalovirus (HCMV) in vitro. A specific cytopathic effect was observed in microglial cells and astrocytes, but not in MDM. A high percentage of glial cells but a low percentage of MDM expressed immediate-early and late viral antigens. The ability of HCMV-infected microglial cells and astrocytes to release viral particles in their supernatants was significantly higher than that of infected MDM. Human microglial cells and astrocytes at an early stage of development are highly susceptible to HCMV infection.

Antigens, Viral↗
PubMed1999

Prolonged survival without neurological improvement in patients with AIDS-related progressive multifocal leukoencephalopathy on potent combined antiretroviral therapy.

To evaluate the benefit of combined antiretroviral therapy including protease inhibitors (CART) on survival time and neurological progression in patients with AIDS-related progressive multifocal leukoencephalopathy (PML), 81 consecutive PML cases, collected between January 1990 and June 1998, were reviewed. Fifteen patients were neuropathologically proven. JC virus detection in CSF was positive in 59 patients. At PML diagnosis, median CD4 cell count was low (median, 35 cells/microL) and plasma HIV load, determined in 41 patients, was high (median, 4.8 log10 copies/ml). Following PML diagnosis, there was a significant difference (P<10(-4)) in survival between patients who were untreated or treated with nucleoside analogs (n=50, median: 80 days) and patients who were started early on CART (n=23, median: 246 days). A third group of eight patients who received CART late during the course of PML was considered separately. At the study endpoint, 18 of all the CART-treated patients (n=31) were still alive. Plasma HIV load was undetectable in 67% of them. The median increase in CD4 cell count was 112 cells/microL from CART onset. In contrast, no significant improvement in neurological status was observed. Our results demonstrate a benefit of CART on survival of AIDS-related PML patients and suggest the need for an early, specific anti-JC virus treatment to limit the neurological deterioration.

AIDS-Related Opportunistic Infections↗