Valerie Thiers - Academia.edu (original) (raw)
Papers by Valerie Thiers
Journal of Hepatology, 1991
European Journal of Epidemiology, 2000
Archives of Virology, 1997
We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglob... more We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglobulinemia (MC) with or without complicating B-cell Non-Hodgkin's lymphoma (NHL) in comparison with other immunological and lymphoproliferative disorders. The following groups of patients were studied: A) 25 patients with MC in 7 cases evolved into B-cell NHL; B) 25 healthy subjects; C) 22 patients with different systemic immune diseases; D) 24 patients with chronic HCV infection without MC; E) 25 patients with B-cell idiopathic NHL. Methods used included: i) Polymerase chain reaction (PCR) for HCV RNA detection in serum and peripheral blood mononuclear cells (PBMC) (uncultured or mitogen-stimulated); ii) Branched DNA (b-DNA) for HCV RNA quantification; iii) HCV genotyping by genotype-specific primers localized in the core region and by hybridization of amplification products of the 5 untranslated region (5UTR), obtained with universal primers, using genotype-specific probes. Serum anti-HCV and HCV RNA were detected in 88% and 73% of MC patients, respectively, and in a significantly lower percentage of healthy controls and patients with autoimmune diseases. HCV RNA concentration was significantly lower in supernatants than in corresponding whole sera (p:0.001). Plus-strand HCV RNA was detected in 81% of peripheral blood mononuclear cell (PBMC) samples and minus-strand in the majority of fresh or mitogen stimulated cells. All MC patients with NHL had HCV RNA sequences in PBMC. HCV genotype 2a/III was detected in MC patients with a prevalence that was significantly higher than in HCV infected patients without MC. Surprisingly, HCV markers (anti-HCV and/or HCV RNA) were found in 32% of patients with idiopathic NHL. These data suggest that HCV infection is involved in the pathogenesis of MC through both direct participation in the immune complex related vasculitis and by triggering the lymphoproliferative disorder underlying the disease. This latter disorder seems to be related to HCV lymphotropism which could also be responsible for the evolution of MC to malignant lymphoma. This study also suggests that HCV infection may be involved in the pathogenesis of idiopathic B-cell NHL through a similar pathogenetic mechanism.
Journal of Clinical Virology, 2011
Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatoc... more Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation.
Journal of Hepatology, 2011
Gut, 2008
Unsafe injections and transfusions used during treatments are considered to be responsible for ma... more Unsafe injections and transfusions used during treatments are considered to be responsible for many cases of transmission of hepatitis C virus (HCV) in developing countries, but cannot account for a substantial proportion of present infections. The aim of the present work was to investigate familial clustering of HCV infection in a population living in a highly endemic area. A large seroepidemiological survey was conducted on 3994 subjects (age range, 2-88 years) from 475 familial clusters in an Egyptian rural area. Epidemiological methods appropriate for the analysis of correlated data were used to estimate risk factors and familial dependences for HCV infection. A phylogenetic analysis was conducted to investigate HCV strain similarities within and among families. HCV familial correlations adjusted for known risk factors, similarities between viral strains. Overall HCV seroprevalence was 12.3%, increasing with age. After adjustment for relevant risk factors, highly significant intrafamilial resemblances in HCV seroprevalence were obtained between father-offspring (odds ratio (OR) = 3.4 (95% confidence interval (CI), 1.8 to 6.2)), mother-offspring (OR = 3.8 (95% CI, 2.5 to 5.8)), and sibling-sibling (OR = 9.3 (95% CI, 4.9 to 17.6)), while a weaker dependence between spouses (OR = 2.2 (95% CI, 1.3 to 3.7)) was observed. Phylogenetic analysis showed greater HCV strain similarity between family members than between unrelated subjects, indicating that correlations can be explained, in part, by familial sources of virus transmission. In addition, refined dissection of correlations between first-degree relatives supported the role of host genes predisposing to HCV infection. Current HCV infection in endemic countries has a strong familial component explained, at least partly, by specific modes of intrafamilial viral transmission and by genetic predisposition to infection.
![Research paper thumbnail of [440] COMPARTMENTALIZATION OF HEPATITIS C VIRUS QUASISPECIES IN TUMORAL AND NON-TUMORAL HEPATOCYTES ISOLATED BY LASER-CAPTURE MICRODISSECTION](https://attachments.academia-assets.com/41723633/thumbnails/1.jpg)
](Journal of Hepatology, 2007
The non-random distribution of HCV quasispecies has been suggested between hepatocellular carcino... more The non-random distribution of HCV quasispecies has been suggested between hepatocellular carcinoma (HCC) and non-tumoral (NT) liver. HCV core protein seemed to interact with cellular functions. Point mutations of HCV core gene are suspected to play a role in multistep process of liver carcinogenesis. The Alternative Reading Frame Protein (ARFP/Flcore+l) coded by core region has never been studied in this setting. Aim: To test for an association between HCV core and/or ARFP heterogeneity and hepatocellular carcinoma. Methods: Seven patients with genotype 1 b HCV-related cirrhosis underwent surgery for HCC. Around 1500 hepatocytes were isolated by Laser capture microdissection (LCM) in the HCC and in 2 different non-tumoral cirrhotic nodules of resected livers. The entire HCV core cDNA was cloned and sequenced from each liver compartment and from plasma in 2 patients. Nucleotidic diversity, synonymous and nonsynonymous substitutions (dS-dN) were compared in core and ARFP within and between each compartment. The clustering of viral population was analyzed through phylogenetic analysis and multivariate matrix correlation tests (Mantel's test). Results: The viral load in HCC was low, relative to NT liver in all but one subject. An increased diversity and complexity of the quasispecies was observed in the tumor for 617 patients. Multivariate matrix correlation analysis demonstrated a strong compartmentalization of HCV core between HCC and NT hepatocytes for all 7 patients and also between the two cirrhotic nodules in 517 patients. Low dS-dN was observed for the ARFP for all compartment in 517 patients suggesting more selective pressure against this putative protein than against the core. In two analyzed subjects, plasma, tumoral and non tumoral hepatocytes contained different quasispecies. Conclusion: In tumoral hepatocytes, the HCV quasispecies had low replication, high diversity and are submitted to low selective pressures. Variants found through LCM in tumoral and non tumoral hepatocytes were distinct each others and to those found in plasma suggesting a topological likely cell-to-cell transmission of HCV within the liver. Overall, our study offers a first direct in situ evidence to support the role of core and ARFP gene mutations in hepatocellular carcinogenesis.
![Research paper thumbnail of [536] INTRAFAMILIAL AND HOUSEHOLD CLUSTERING OF HEPATITIS C VIRUS IN RURAL EGYPT: A PHYLOGENETIC AND MATRIX CORRELATION TESTS ANALYSIS](https://attachments.academia-assets.com/41918131/thumbnails/1.jpg)
](J Hepatol, 2007
POSTERS leptin, (3) in addition to iron overload and fat mass, high sTNFRl serum level is an inde... more POSTERS leptin, (3) in addition to iron overload and fat mass, high sTNFRl serum level is an independent risk factor of insulin resistance. These results suggest that insulin resistance associated with chronic HCV infection could be mediated through TNF-a.
Journal of Hepatology, Feb 1, 1991
1. J Hepatol. 1991;13 Suppl 4:S49-55. Hepatitis B virus DNA in HBsAg-negative patients. Molecular... more 1. J Hepatol. 1991;13 Suppl 4:S49-55. Hepatitis B virus DNA in HBsAg-negative patients. Molecular characterization and clinical implications. Bréchot C, Kremsdorf D, Paterlini P, Thiers V. INSERM U75, CHU Necker, Paris. PMID: 1822513 [PubMed - indexed for MEDLINE]. ...
Acta Endosc, 1989
... Le but de ce protocole est de tester l'efficacit6 d'une d6sinfection de fib... more ... Le but de ce protocole est de tester l'efficacit6 d'une d6sinfection de fibroscope par une machine de marque ~ Olympus ,. I. PRINCIPE DE L'I~TUDE Les particules du virus de l'h6patite B infec-tieuses sont appel6es particules de ~< Dane ~>. ...
The American journal of tropical medicine and hygiene
The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated ... more The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated in selected populations from Gabon using Polymerase Chain Reaction (PCR) and Enzyme Linked Immunosorbent Assay (ELISA) for anti-Envelop 2 (anti-E2) GBV-C/HGV antibodies. Among pregnant women, 29 of 229 (12.6%) were Hepatitis GB virus-C and Hepatitis G virus (GBV-C/HGV) RNA positive (+) and 32 of 81 (39.5%) anti-E2 + versus 8 of 39 (20.5%) TTV DNA +. Among sickle cell anemia patients, 9.7% (3/31) were GBV-C/HGV RNA + versus 22.5% (7/31) TTV DNA +. For tuberculosis patients, the figures were 11.5% (4/35) and 0%. A study of hepatocellular carcinoma cases (n = 27) versus controls (n = 66) did not show significant differences for GBV-C/HGV RNA (10.7% versus 12.1%) and TTV DNA (44.4% versus 30.3%). According to phylogenetic analysis, the 15 GBV-C/HGV strains investigated clustered in group 1, the most common in sub-Saharan Africa whereas TTV sequences (n = 4) mostly clustered in genotypes G1 a...
Journal of clinical microbiology, 1997
PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G ... more PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.
Revue Française des Laboratoires, 2000
Molecular techniques (PCR, sequence analysis) have allowed to data that greatly contributed to th... more Molecular techniques (PCR, sequence analysis) have allowed to data that greatly contributed to the knowledge and understanding of the epidemiology of Hepatitis C virus (HCV). Genotyping assays provided informations on his worlwide distribution and on the distinct geographical repartition of some types. These molecular data allow to the reconstruction of virus origin and routes of transmission. Furthermore, they led to the identification of several large-scale outbreaks of HCV infection. Nucleotide sequence analysis has provided additional informations that strengths the first observations. In particular, the evaluation of HCV gene nucleotide mutation rates have led to calculation of divergence times between genotypes, and after extrapolation, to date the common ancestor of different types of HCV. These informations are in agreement with their present geographical distribution. Finally, information from nucleic acid sequences may be used to infer phylogenetic relationships among virus variants. This approach has been used to investigate possible transmission events between pair of individuals.
PROTEOMICS – Clinical Applications, 2007
Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide op... more Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.
PLoS ONE, 2013
Strains responsible for acute hepatitis B infections (AHB) in France have not been characterized.... more Strains responsible for acute hepatitis B infections (AHB) in France have not been characterized. This study was first designed to analyze the molecular epidemiology of AHB and second to describe the differences between AHB and chronic hepatitis B (CHB) exacerbations.
PLoS ONE, 2014
Background: We propose a new approach based on genetic distances among viral strains to infer abo... more Background: We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level.
Liver International, 2010
To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV tra... more To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.
Kidney International, 1995
Efficacy and tolerance of -2b interferon therapy on HCV infection of hemodialyzed patients. A hig... more Efficacy and tolerance of -2b interferon therapy on HCV infection of hemodialyzed patients. A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of n-2b Interferon therapy upon HCV infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed patients were given a standard a-2b interferon regimen (3 megaunits subcutaneously three times weekly, following each hemodialysis) over six months as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N = 3). Thirteen of these 19 had increased levels of aminotransferase at the time of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the polymerase chain reaction and the bDNA test,
Journal of Virological Methods, 1997
The distribution between the different hepatitis C virus genotypes and subtypes has potentially i... more The distribution between the different hepatitis C virus genotypes and subtypes has potentially important clinical and epidemiological i:mplications. With this view a simple restriction fragment length polymorphism (RFLP) based assay was developed to identify the three major genotypes, 1, 2 and 3 and distinguish subtype la from lb. This RFLP test uses a combination of three restriction endonuclease digestions, BstNl, BstUl and Sau3a, respectively. Comparison with a 5'UTR based assay (LiPA), showed a 98% concordance with the RFLP based assay. In addition, good concordance is shown between these data and those obtained with a serological assay based on NS4 peptides. 0 1997 Elsevier Science B.V.
Journal of Medical Virology, 2008
Journal of Hepatology, 1991
European Journal of Epidemiology, 2000
Archives of Virology, 1997
We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglob... more We investigated the pathogenetic relevance of hepatitis C virus (HCV) infection in mixed cryoglobulinemia (MC) with or without complicating B-cell Non-Hodgkin's lymphoma (NHL) in comparison with other immunological and lymphoproliferative disorders. The following groups of patients were studied: A) 25 patients with MC in 7 cases evolved into B-cell NHL; B) 25 healthy subjects; C) 22 patients with different systemic immune diseases; D) 24 patients with chronic HCV infection without MC; E) 25 patients with B-cell idiopathic NHL. Methods used included: i) Polymerase chain reaction (PCR) for HCV RNA detection in serum and peripheral blood mononuclear cells (PBMC) (uncultured or mitogen-stimulated); ii) Branched DNA (b-DNA) for HCV RNA quantification; iii) HCV genotyping by genotype-specific primers localized in the core region and by hybridization of amplification products of the 5 untranslated region (5UTR), obtained with universal primers, using genotype-specific probes. Serum anti-HCV and HCV RNA were detected in 88% and 73% of MC patients, respectively, and in a significantly lower percentage of healthy controls and patients with autoimmune diseases. HCV RNA concentration was significantly lower in supernatants than in corresponding whole sera (p:0.001). Plus-strand HCV RNA was detected in 81% of peripheral blood mononuclear cell (PBMC) samples and minus-strand in the majority of fresh or mitogen stimulated cells. All MC patients with NHL had HCV RNA sequences in PBMC. HCV genotype 2a/III was detected in MC patients with a prevalence that was significantly higher than in HCV infected patients without MC. Surprisingly, HCV markers (anti-HCV and/or HCV RNA) were found in 32% of patients with idiopathic NHL. These data suggest that HCV infection is involved in the pathogenesis of MC through both direct participation in the immune complex related vasculitis and by triggering the lymphoproliferative disorder underlying the disease. This latter disorder seems to be related to HCV lymphotropism which could also be responsible for the evolution of MC to malignant lymphoma. This study also suggests that HCV infection may be involved in the pathogenesis of idiopathic B-cell NHL through a similar pathogenetic mechanism.
Journal of Clinical Virology, 2011
Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatoc... more Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting. Objectives: Potential association between HCV genetic mutations or strain variability and HCC incidence has been examined through a comparative genetic analysis merely focused on a single HCV subtype (genotype 4a) in a single country (Egypt). Study design: The study focused on three HCV sequence datasets with explicit sampling dates and disease patterns. An overlapping HCV Core/E1 domain from three datasets was used as the target for comparative analysis through genetic and phylogenetic approaches. Results: Based on partial Core/E1 domain (387 bp), genetic and phylogenetic analysis did not identify any HCC-specific viral mutations and strains, respectively. Conclusions: The Core/E1 domain of HCV genotype 4a in Egypt does not contain HCC-specific mutations or strains. Additionally, sequence errors resulting from the polymerase chain reaction, together with a strong evolutionary pressure on HCV in patients with end-stage liver disease, have significant potential to bias data generation and interpretation.
Journal of Hepatology, 2011
Gut, 2008
Unsafe injections and transfusions used during treatments are considered to be responsible for ma... more Unsafe injections and transfusions used during treatments are considered to be responsible for many cases of transmission of hepatitis C virus (HCV) in developing countries, but cannot account for a substantial proportion of present infections. The aim of the present work was to investigate familial clustering of HCV infection in a population living in a highly endemic area. A large seroepidemiological survey was conducted on 3994 subjects (age range, 2-88 years) from 475 familial clusters in an Egyptian rural area. Epidemiological methods appropriate for the analysis of correlated data were used to estimate risk factors and familial dependences for HCV infection. A phylogenetic analysis was conducted to investigate HCV strain similarities within and among families. HCV familial correlations adjusted for known risk factors, similarities between viral strains. Overall HCV seroprevalence was 12.3%, increasing with age. After adjustment for relevant risk factors, highly significant intrafamilial resemblances in HCV seroprevalence were obtained between father-offspring (odds ratio (OR) = 3.4 (95% confidence interval (CI), 1.8 to 6.2)), mother-offspring (OR = 3.8 (95% CI, 2.5 to 5.8)), and sibling-sibling (OR = 9.3 (95% CI, 4.9 to 17.6)), while a weaker dependence between spouses (OR = 2.2 (95% CI, 1.3 to 3.7)) was observed. Phylogenetic analysis showed greater HCV strain similarity between family members than between unrelated subjects, indicating that correlations can be explained, in part, by familial sources of virus transmission. In addition, refined dissection of correlations between first-degree relatives supported the role of host genes predisposing to HCV infection. Current HCV infection in endemic countries has a strong familial component explained, at least partly, by specific modes of intrafamilial viral transmission and by genetic predisposition to infection.
Journal of Hepatology, 2007
The non-random distribution of HCV quasispecies has been suggested between hepatocellular carcino... more The non-random distribution of HCV quasispecies has been suggested between hepatocellular carcinoma (HCC) and non-tumoral (NT) liver. HCV core protein seemed to interact with cellular functions. Point mutations of HCV core gene are suspected to play a role in multistep process of liver carcinogenesis. The Alternative Reading Frame Protein (ARFP/Flcore+l) coded by core region has never been studied in this setting. Aim: To test for an association between HCV core and/or ARFP heterogeneity and hepatocellular carcinoma. Methods: Seven patients with genotype 1 b HCV-related cirrhosis underwent surgery for HCC. Around 1500 hepatocytes were isolated by Laser capture microdissection (LCM) in the HCC and in 2 different non-tumoral cirrhotic nodules of resected livers. The entire HCV core cDNA was cloned and sequenced from each liver compartment and from plasma in 2 patients. Nucleotidic diversity, synonymous and nonsynonymous substitutions (dS-dN) were compared in core and ARFP within and between each compartment. The clustering of viral population was analyzed through phylogenetic analysis and multivariate matrix correlation tests (Mantel's test). Results: The viral load in HCC was low, relative to NT liver in all but one subject. An increased diversity and complexity of the quasispecies was observed in the tumor for 617 patients. Multivariate matrix correlation analysis demonstrated a strong compartmentalization of HCV core between HCC and NT hepatocytes for all 7 patients and also between the two cirrhotic nodules in 517 patients. Low dS-dN was observed for the ARFP for all compartment in 517 patients suggesting more selective pressure against this putative protein than against the core. In two analyzed subjects, plasma, tumoral and non tumoral hepatocytes contained different quasispecies. Conclusion: In tumoral hepatocytes, the HCV quasispecies had low replication, high diversity and are submitted to low selective pressures. Variants found through LCM in tumoral and non tumoral hepatocytes were distinct each others and to those found in plasma suggesting a topological likely cell-to-cell transmission of HCV within the liver. Overall, our study offers a first direct in situ evidence to support the role of core and ARFP gene mutations in hepatocellular carcinogenesis.
J Hepatol, 2007
POSTERS leptin, (3) in addition to iron overload and fat mass, high sTNFRl serum level is an inde... more POSTERS leptin, (3) in addition to iron overload and fat mass, high sTNFRl serum level is an independent risk factor of insulin resistance. These results suggest that insulin resistance associated with chronic HCV infection could be mediated through TNF-a.
Journal of Hepatology, Feb 1, 1991
1. J Hepatol. 1991;13 Suppl 4:S49-55. Hepatitis B virus DNA in HBsAg-negative patients. Molecular... more 1. J Hepatol. 1991;13 Suppl 4:S49-55. Hepatitis B virus DNA in HBsAg-negative patients. Molecular characterization and clinical implications. Bréchot C, Kremsdorf D, Paterlini P, Thiers V. INSERM U75, CHU Necker, Paris. PMID: 1822513 [PubMed - indexed for MEDLINE]. ...
Acta Endosc, 1989
... Le but de ce protocole est de tester l'efficacit6 d'une d6sinfection de fib... more ... Le but de ce protocole est de tester l'efficacit6 d'une d6sinfection de fibroscope par une machine de marque ~ Olympus ,. I. PRINCIPE DE L'I~TUDE Les particules du virus de l'h6patite B infec-tieuses sont appel6es particules de ~< Dane ~>. ...
The American journal of tropical medicine and hygiene
The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated ... more The distribution of Hepatitis GB-C/HG (GB-C/HG) and TT viruses (TTV) infections was investigated in selected populations from Gabon using Polymerase Chain Reaction (PCR) and Enzyme Linked Immunosorbent Assay (ELISA) for anti-Envelop 2 (anti-E2) GBV-C/HGV antibodies. Among pregnant women, 29 of 229 (12.6%) were Hepatitis GB virus-C and Hepatitis G virus (GBV-C/HGV) RNA positive (+) and 32 of 81 (39.5%) anti-E2 + versus 8 of 39 (20.5%) TTV DNA +. Among sickle cell anemia patients, 9.7% (3/31) were GBV-C/HGV RNA + versus 22.5% (7/31) TTV DNA +. For tuberculosis patients, the figures were 11.5% (4/35) and 0%. A study of hepatocellular carcinoma cases (n = 27) versus controls (n = 66) did not show significant differences for GBV-C/HGV RNA (10.7% versus 12.1%) and TTV DNA (44.4% versus 30.3%). According to phylogenetic analysis, the 15 GBV-C/HGV strains investigated clustered in group 1, the most common in sub-Saharan Africa whereas TTV sequences (n = 4) mostly clustered in genotypes G1 a...
Journal of clinical microbiology, 1997
PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G ... more PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.
Revue Française des Laboratoires, 2000
Molecular techniques (PCR, sequence analysis) have allowed to data that greatly contributed to th... more Molecular techniques (PCR, sequence analysis) have allowed to data that greatly contributed to the knowledge and understanding of the epidemiology of Hepatitis C virus (HCV). Genotyping assays provided informations on his worlwide distribution and on the distinct geographical repartition of some types. These molecular data allow to the reconstruction of virus origin and routes of transmission. Furthermore, they led to the identification of several large-scale outbreaks of HCV infection. Nucleotide sequence analysis has provided additional informations that strengths the first observations. In particular, the evaluation of HCV gene nucleotide mutation rates have led to calculation of divergence times between genotypes, and after extrapolation, to date the common ancestor of different types of HCV. These informations are in agreement with their present geographical distribution. Finally, information from nucleic acid sequences may be used to infer phylogenetic relationships among virus variants. This approach has been used to investigate possible transmission events between pair of individuals.
PROTEOMICS – Clinical Applications, 2007
Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide op... more Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide. Proteomic studies provide opportunities to uncover targets for the diagnosis and treatment of this disease. However, in HCC developing in a setting of cirrhosis, the detection of proteome alterations may be hampered by the increased cellular heterogeneity of tissue when analysing global liver homogenates. The aim of this study was to evaluate whether the identification of proteome alterations in these HCC cases was improved when the differential protein profile between tumour and non-tumour areas of liver was determined using hepatocytes isolated by laser microdissection (LM). Differential profiles established with LM-hepatocytes and liver section homogenates using 2-DE and MS exhibited noticeable differences: 30% of the protein spots with deregulated expression in tumorous LM-samples did not display any modification in homogenates; conversely 15% of proteins altered in tumorous homogenates were not impaired in LM-hepatocytes. These alterations resulted from the presence in cirrhotic liver of fibrotic stroma which displayed a protein pattern different from that determined in LM-hepatocytes. In conclusion, our data demonstrate the interest of LM in distinguishing between fibrotic and hepatocyte proteome alterations and thus the benefit of LM to proteome studies of HCC developing in a context of cirrhosis.
PLoS ONE, 2013
Strains responsible for acute hepatitis B infections (AHB) in France have not been characterized.... more Strains responsible for acute hepatitis B infections (AHB) in France have not been characterized. This study was first designed to analyze the molecular epidemiology of AHB and second to describe the differences between AHB and chronic hepatitis B (CHB) exacerbations.
PLoS ONE, 2014
Background: We propose a new approach based on genetic distances among viral strains to infer abo... more Background: We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level.
Liver International, 2010
To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV tra... more To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.
Kidney International, 1995
Efficacy and tolerance of -2b interferon therapy on HCV infection of hemodialyzed patients. A hig... more Efficacy and tolerance of -2b interferon therapy on HCV infection of hemodialyzed patients. A high frequency (25%) of anti-hepatitis C virus (HCV) antibodies is observed in French hemodialyzed patients; this is associated with detectable viremia in 85% and results in chronic hepatitis in more than 90%. We conducted a pilot study to examine the tolerance and efficacy of n-2b Interferon therapy upon HCV infection in hemodialyzed patients. Nineteen anti-HCV positive hemodialyzed patients were given a standard a-2b interferon regimen (3 megaunits subcutaneously three times weekly, following each hemodialysis) over six months as a treatment of biopsy-proven chronic hepatitis (N = 16) or acute hepatitis (N = 3). Thirteen of these 19 had increased levels of aminotransferase at the time of treatment. Serum HCV RNA was tested qualitatively and quantitatively by the polymerase chain reaction and the bDNA test,
Journal of Virological Methods, 1997
The distribution between the different hepatitis C virus genotypes and subtypes has potentially i... more The distribution between the different hepatitis C virus genotypes and subtypes has potentially important clinical and epidemiological i:mplications. With this view a simple restriction fragment length polymorphism (RFLP) based assay was developed to identify the three major genotypes, 1, 2 and 3 and distinguish subtype la from lb. This RFLP test uses a combination of three restriction endonuclease digestions, BstNl, BstUl and Sau3a, respectively. Comparison with a 5'UTR based assay (LiPA), showed a 98% concordance with the RFLP based assay. In addition, good concordance is shown between these data and those obtained with a serological assay based on NS4 peptides. 0 1997 Elsevier Science B.V.
Journal of Medical Virology, 2008