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C Trépo

Publications and source records attributed to C Trépo.

At least 19 recordsLinked to original sources
PubMed2006

Primary and memory T cell responses induced by hepatitis C virus multiepitope long peptides.

To develop a vaccine against hepatitis C virus, we synthesized four long peptides from nonstructural proteins NS3, NS4 and NS5B containing HLA-class I and class II epitopes mainly inducing responses in natural infection. In HLA-A2.1 transgenic mice, the four peptides primed higher CTL responses to 6:7 minimal HLA-A2 epitopes than those induced by the minimal epitopes. HLA-A2.1/HLA-DR1 transgenic mice immunized with one peptide, containing a class II epitope implicated in viral resolution, developed IFNgamma-producing CD4+-T and CD8+-T cells. These peptides recalled HCV-specific IFNgamma-producing cells from HCV-infected patients' PBMC. This support the selection of these domains for inclusion in a vaccine formulation.

Adult↗
PubMed2005

Rheumatological manifestations of hepatitis C: incidence in a rheumatology and non-rheumatology setting and the effect of methotrexate and interferon.

OBJECTIVES: To evaluate hepatitis C virus (HCV)-positive patients followed in a rheumatology department and to compare them with a similar population of HCV-positive patients who had never seen a rheumatologist, in order to describe the rheumatological symptoms present and the effects of methotrexate and interferon-alpha therapy. METHODS: We performed a retrospective study of clinical, radiological and biological data on 21 rheumatology patients (Group I) presenting symptoms consistent with a chronic inflammatory arthritis with a known HCV infection and compared them with 41 members of an HCV support association (Group II). RESULTS: Symptoms of myalgia, sicca syndrome, Raynaud's phenomenon or paraesthesias were similarly frequent in the two groups. However, inflammatory joint pain and joint swelling were more common in Group I. In this group rheumatoid factor was positive in 48%, antinuclear antibodies in 26%, cryoglobulin in 44% and a reduced complement level in 63%. The majority of patients from Group I treated with methotrexate demonstrated an amelioration of the rheumatological symptoms with few negative outcomes. Regarding interferon-alpha therapy and rheumatological symptoms-in Groups I and II respectively 50 and 66% demonstrated a deterioration, 33 and 30% showed no change and 17 and 4% showed an amelioration. CONCLUSION: Rheumatological symptoms are common in patients chronically infected with HCV. It is essential to individualize the role of treatment with interferon-alpha and to consider the use of methotrexate for difficult cases.

Adult↗
PubMed2005

Clinical impact of occult HBV infections.

HBV infection in the absence of HBsAg has been a matter of debate for years, but its existence and clinical relevance are now supported by many publications, editorials and reviews. HBV DNA without HBs antigenemia was detected in the following clinical situations: (1) Chronic, presumably viral, hepatitis unrelated to HCV, atypical alcoholic hepatitis and hepatocellular carcinoma (HCC); (2) viral reactivation following immunosuppression; (3) Transmission through transplantation, transfusion or experimental transmission to chimpanzees. Occult HBV infections are not restricted to areas of high HBV endemicity. Indeed, such cases have been described in Western countries including France. It is now established that occult HBV infection among non-HCV patients suffering from chronic hepatitis varies from 20% to 30% in Europe, and in the context of HCV infection it varies from 20% in France up to 80% in Japan. The percentage of occult HBV infections among non A-E cases depends on several parameters: (1) The method of detection, including PCR primer selection; (2) patient recruitment; (3) patients from countries highly endemic for HBV are more likely to develop occult HBV infections; (4) prevalence may also vary depending on the nature of biological material tested, with a higher proportion for liver compared to serum specimen. The mechanisms leading to HCC in occult HBV infection seem similar to those overt cases, patients with low-grade but diagnosable HBV replication that retains its pro-oncogenic properties. During the course of HCV infection, occult HBV infection may worsen liver damage induced by HCV and reduce the response to HCV antiviral treatment. Occult HBV infection is a frequent phenomenon and HBV DNA testing with highly sensitive PCR in the clinical setting is therefore becoming of paramount importance.

Carcinoma, Hepatocellular↗
PubMed2004

Genetic immunization and comprehensive screening approaches in HLA-A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen.

Interferon-gamma (IFN gamma)-producing CD8+ T cells have been shown to play a key role in the control or eradication of hepatitis C virus (HCV) infections. In particular, T cells specific of the non-structural protein 3 (NS3) are often associated with control of viremia. The aim of the study was to identify novel HLA-A2 restricted CD8+ T cell epitopes specific of NS3 using a combination of comprehensive approaches. HLA-A2.1 transgenic mice were immunized with a DNA vaccine optimized for NS3 specific epitope presentation and induced CD8+ T cell reactivity was screened using 42 algorithm-predicted peptides as well as a library of 78 overlapping 15-mer peptides spanning the whole protein. Three epitopes mapping within the NS3 protease (GLL: aa 1038-1047) or helicase (ATL: aa 1260-1268 and TLH: aa 1617-1625) were identified. These epitopes, which display similar and high in vitro binding capacities to soluble HLA-A2 molecules, are able to induce either cytotoxic T lymphocytes (CTL) and/or IFN gamma-producing T cells. Comparative in vitro target cell sensitization studies revealed a higher immunogenicity of the GLL peptide as compared with both ATL and TLH peptides. This peptide was capable to recall in vitro HCV-specific IFN gamma and IL-10-producing T cells from peripheral blood mononuclear cells (PBMC) of chronically infected patients. These data increase the pool of NS3-specific CD8+ T cell epitopes available to analyze HCV associated immunity and could contribute to the design and evaluation of candidate vaccines.

Amino Acid Sequence↗
PubMed2004

[Hepatitis G virus and labile blood products: role of transfusional transmission].

The GBV-C/HGV (HGV) virus was discovered a few years ago. This virus is known to be parenterally as well as sexually transmitted. However, no study has found some pathogenic roles for HGV so far. In the present study, we aimed to investigate the transmission of HGV by blood components transfused to 284 patients hospitalized in surgery unit in 1995. We tested two parameters of infection in blood components transfused to infected recipients: viral RNA by PCR and anti-E2 antibodies by ELISA. We tried to suspect some potent hepatocyte impacts by assessing the levels of two enzymes in serums: alanine aminotransferase (ALT) and alpha-glutathion S-transferase (alpha-GST). We found that HGV-RNA was detectable in 3.6% of recipients prior to transfusion and 7.5% post-transfusion. For each infected recipient, we retrospectively did a search for HGV-RNA in each transfused blood component, and we found at least one blood component as HGV-RNA-positive for each transfusional infected recipient. Anti-E2 antibody prevalence standing for a former and cured infection was 39.6% in all the recipients. In viremic recipients, ALT levels were mostly normal, while alpha-GST levels were found more commonly elevated than in non-viremic recipients although non-significantly (20% vs. 6.3%; P = 0.07). The present study underlines that HGV transmission is mostly transfusional in surgery units, and that infectiosity of blood components can be anticipated by detection of the viral RNA by PCR. Furthermore, the possible relationship between the serum activity of alpha-GST and the hepatotropism of HGV, although non-admitted as pathogenic, should be investigated.

Aged↗
PubMed2004

Evolution of hepatitis B viral load and viral genome sequence during adefovir dipivoxil therapy.

Phase II and III clinical trials of adefovir dipivoxil (ADV) for the treatment of chronic hepatitis B have shown that this hepadnavirus polymerase inhibitor is well tolerated and effectively suppresses hepatitis B virus (HBV) replication. We therefore analysed the evolution of viral load and the emergence of HBV polymerase mutants in a 22-patient subgroup from a phase III clinical trial of ADV for the treatment of HBeAg-positive chronic hepatitis B. HBV DNA serum titres were quantified using a real-time polymerase chain reaction (PCR) assay with molecular hybridization probes. Emergence of polymerase mutants was assessed by direct sequencing of the viral reverse transcriptase domain after PCR amplification of HBV DNA isolated from serum. Our results indicated that ADV therapy effectively suppressed HBV replication in these patients (median serum HBV decrease at week 48 of treatment = 4.3 log10 copies/mL). The initial drop of HBV DNA titres in serum at week 12 of ADV therapy seemed to be predictive of subsequent HBe seroconversion (P = 0.059). Neither viral breakthrough nor the selection of drug resistant mutants were observed during the study period. Our results showed that ADV administration for 48-72 weeks effectively suppresses HBV replication without the emergence of resistant viral mutants.

Adenine↗
PubMed2004

Survival in HIV-infected patients is associated with hepatitis C virus infection and injecting drug use since the use of highly active antiretroviral therapy in the Lyon observational database.

Highly active antiretroviral therapy (HAART) has reduced the incidence of death in HIV-infected patients but various rates of survival have been reported due to the infection with hepatitis C virus (HCV) and the use of injecting drugs (IDU). A survival analysis was performed to estimate and compare the death rates in HIV-positive patients infected by IDU and/or positive for HCV antibodies in the pre-HAART and HAART periods in Lyon (France) between 1992 and 2002. Patients were stratified into four groups (G): HCV-/IDU-(G1), HCV+/IDU-(G2), HCV+/IDU-(G3), HCV+/IDU+ (G4) and adjusted death rates in the pre-HAART era (< 1996) and the HAART era (> or = 1996) were compared. The aHR of progression to death was 1.05 (95% CI 0.75-1.47, P = 0.75) for G2, 1.09 (95% CI 0.54-2.22, P = 0.81) for G3 and 0.90 (95% CI 0.65-1.24, P =0.51) for G4 compared with G1 in the pre-HAART era. The aHR of progression to death was 0.76 (95% CI 0.28-2.08, P = 0.59) for G2, 1.23 (95% CI 0.17-8.86, P = 0.84) for G3 and 2.90 (95% CI 1.62-5.20, P < 0.001) for G4, compared with G1 in the HAART era. HAART management of HCV+/IDU+ patients needs to be optimized for them to achieve a similar benefit as observed among other individuals.

Adult↗
PubMed2003

[Is GB virus C alias "hepatitis" G virus involved in human pathology?].

GB virus-C alias "hepatitis" virus G was discovered in 1995 as a putative causative virus of non A-E hepatitis. It is a very common virus found in 1 to 5% of eligible blood donors in developed countries. Numerous studies over seven years led to the exclusion of its role as a significant etiological agent of hepatitis. Its in vivo replication site is still unknown. Its direct involvement in the induction of significant hepatic or extra-hepatic diseases could not be demonstrated. However, coinfections with other viruses may contribute to changes in the evolution of both liver disease (negatively) and HIV/AIDS (favourably). Today, no country has decided to screen GBV-C in blood donors. However, more studies are necessary before the absence of influence of GBV-C infection on human health in the context of other viral infections could be confirmed definitely. This article is a review of the literature on a possible involvement of GBV-C in pathologies whether associated or not to other infections.

Acquired Immunodeficiency Syndrome↗
PubMed2003

The risk of hospital-acquired GB virus C infection: a pilot case-control study.

The risk of hospital-acquired infection with GB virus C (GBV-C) was explored among 42 patients. The factors independently associated with detection of GBV-C RNA in serum were bronchoscopic examination [adjusted odds ratio (OR)=18.1 (95% confidence interval 1.3-255.3), P=0.03] and a history of illicit drug use [OR=14.5 (1.0-218.7), P=0.05]. In this cohort of patients, invasive procedures appear to be associated with GBV-C infection but not with hepatitis C virus (HCV) infection.

Adult↗
PubMed2001

Role of silent hepatitis B virus in chronic hepatitis B surface antigen(-) liver disease.

Despite a number of studies documenting hepatitis B virus (HBV) infection in the absence of hepatitis B surface antigen (HBsAg) a causal relationship between silent HBV infection and liver disease remain difficult to establish. In particular, both the prevalence and clinical significance of this observation are poorly understood. Why is HBV replication apparently so low in these patients? A number of studies have tried to elucidate the mechanism of HBsAg negative infections, and considerable data documenting HBV infectivity or reinfection in the absence of detectable HBsAg support the hypothesis that in some of these cases, HBV is undergoing low-level replication in the liver and this, in several situations including: (1) chronic liver disease, alcoholic liver disease, hepatocellular carcinoma; (2) viral reactivation following cancer chemotherapy or immunosuppression and (3) transmission via transfusion or from human serum to chimpanzees. In a recent study including 50 patients with chronic liver disease of unknown etiology we could detect serum HBV DNA by nested polymerase chain reaction (PCR) in 15/50 patients (50% at the cirrhosis stage) in the absence of HBsAg; in the liver of the 15 patients both HBcAg and/or HBsAg can be detected at very low-level. Viral host factors allowing HBV persistence in the absence of HBsAg can depend on several mechanisms. Coinfections with HCV can explain only a proportion of HBsAg(-) HBV infections. Secondly, HBV mutations in the core promotor region leading to a minimal viral replication, or mutations in the HBsAg-encoding region might explain the absence of serological recognition. Finally, it is possible that in some cases host immune mechanisms can maintain HBV infection in a latent state until transmission to another individual who subsequently develops a more active infection especially when immunosuppressive therapy is employed. Existence of HBsAg(-) HBV infections should be taken into account by the use of sensitive PCR tests for prevention of viral transmission in the settings of blood donations and organ transplants.

Carcinoma, Hepatocellular↗
PubMed2001

Preliminary results of interferon-alpha therapy on woodchuck hepatitis virus-induced hepatocarcinogenesis: possible benefit in female transgenic mice.

BACKGROUND: C-myc activation is a potent oncogenic event in hepatocarcinogenesis. The aim of this study was to test the preventive effect of interferon-alpha (IFN-alpha) on the development of dysplasia and subsequent hepatocellular carcinoma (HCC) in transgenic (Tg) mice overexpressing c-myc in the liver. METHODS: The WHV/c-myc Tg mice recapitulating woodchuck hepatitis virus-induced hepatocarcinogenesis were treated with IFN-alpha, starting early in life until sacrifice at pre-neoplastic or neoplastic stages. Transgene expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR), hepatocyte proliferation was assessed by bromodeoxyuridine incorporation and RT-PCR for proliferating cell nuclear antigen, and apoptosis was assessed by in situ nick-end-labeling of DNA. RESULTS: C-myc expression and hepatocyte proliferation were significantly reduced in treated female mice, without modification of apoptosis, correlating with a lower severity of dysplasia in 9/12 treated animals at pre-neoplastic stages. At the neoplastic stage, 2/3 treated females neither exhibited carcinoma nor dysplasia, while all 6/6 untreated mice and 3/3 treated males developed carcinomas. CONCLUSIONS: Inhibition of c-myc and hepatocyte proliferation by long-term administration of IFN-alpha was associated with a decrease, or a delay, of oncogenesis in the mouse Tg HCC model. Whether c-myc and hepatocyte proliferation down-regulation could be relevant parameters of IFN-alpha efficiency for hepatocarcinogenesis prevention in cirrhotic patients should be established.

Animals↗
PubMed2001

Schistosomiasis mansoni and viral B hepatitis in woodchucks.

BACKGROUND/AIMS: An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections. This study explores the relevance of this unique model regarding hepatitis/schistosomiasis interactions. METHODS: Woodchucks (Marmota monax and Marmota marmota) were infected with: (a), S. mansoni; (b), WHV; or (c), both S. mansoni and WHV. RESULTS: Following the experimental parasitic infection of woodchucks, with or without WHV, schistosomiasis presented a peculiar and severe course in early infection, involving mostly the intestines. Subsequently, the intestinal and hepatic lesions underwent considerable modulation and the periovular granulomas decreased in size and number, while the parasitic infection tended to self-cure within the 9 months following infection. Nine woodchucks inoculated with the hepatitis virus alone presented with several degrees of acute and chronic hepatitis, with one of them dying of hepatocarcinoma 1 year after inoculation. Four woodchucks with concomitant viral and schistosome infections presented with a simple additive pattern of lesions, without any evidence of modification or aggravation of either one of the two infections. Similarly, no significant impact of schistosomiasis on WHV serum markers could be seen. CONCLUSIONS: Schistosomiasis and viral hepatitis in woodchucks run parallel courses, with neither apparent special histological features derived from the association of the two conditions, nor modulation of WHV replication. Schistosomiasis itself, however, was observed to run a peculiar course in the woodchuck. The present data are important for consideration in further experiments exploring the interplay between schistosomiasis and viral hepatitis induced liver damage in this unique experimental host.

Animals↗
PubMed2001

Duck hepatitis B virus polymerase gene mutants associated with resistance to lamivudine have a decreased replication capacity in vitro and in vivo.

BACKGROUND/AIMS: Hepatitis B virus mutants of the polymerase gene are frequently selected during lamivudine therapy for chronic hepatitis B. To study the biology of these mutants, we analyzed their replication capacity in the duck hepatitis B virus (DHBV) infection. METHODS: The B and C domain polymerase mutants corresponding to the clinical isolates were engineered by site directed mutagenesis in the DHBV genome in different expression vectors. RESULTS: The study of the enzymatic activity of the mutated viral polymerase polypeptides analyzed in a cell free system demonstrated a lower priming activity and a decreased capacity of elongation of viral minus strand DNA that was consistent with the lower replication capacity of these mutants in transfected leghorn male hepatoma cells compared to wild type genome. These mutants had a lower replication capacity in primary hepatocytes and in in vivo transfected ducklings. Although resistant to lamivudine, these mutants remained sensitive to PMEA. CONCLUSION: YMDD mutants of the DHBV reverse transcriptase have a decreased replication capacity both in vitro and in vivo, and are not cross-resistant to PMEA. These results may be important to design new antiviral strategies to combat the replication of the lamivudine resistant viral strains.

Adenine↗
PubMed2001

Successful combination therapy of polyarteritis nodosa associated with a pre-core promoter mutant hepatitis B virus infection.

BACKGROUND/AIMS: To describe the clinical and virological evolution of a polyarteritis nodosa (PAN) case associated with a hepatitis B virus (HBV) pre-core promoter mutant infection that was successfully treated with plasma exchanges, corticosteroids, and interferon alpha (IFN-alpha). METHODS: Viral markers were used, including HBV DNA quantified by the branched DNA assay and detected by PCR, the HBV genome sequence, pre-S1Ag and anti-HBC IgM which were studied throughout the treatment period and the entire follow-up in the serum, while the presence of virus in extrahepatic sites was detected by immuno-staining. RESULTS: The patient was infected with a typical pre-core promoter mutant harboring four point mutations. Pre-S1Ag was cleared rapidly from serum, most likely via the formation of immune complexes since HBV DNA declined more progressively. Viral infection was then cleared after a second episode of hepatocyte lysis. This was accompanied by a recovery from all clinical manifestations. CONCLUSIONS: The favorable treatment outcome observed in this first case of pre-core promoter HBV mutant associated PAN underlines that combination therapy based on IFN-alpha can clear pre-core promoter HBV infection and cure PAN. It also provides new insight in the pathogenesis of HBV associated PAN.

Adrenal Cortex Hormones↗
PubMed2001

High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology.

BACKGROUND/AIMS: In approximately 5% of chronic liver disease cases, no aetiology can be identified. We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to define potential clinical outcomes. METHODS: Patients' sera were screened with highly sensitive polymerase chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus. Sera were also retested for antibodies against the core antigen of HBV. RESULTS: Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%) patients. Immunostaining for HBV antigens on biopsies from patients positive for HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples. Eleven of the fifteen patients were anti-HBc positive. With one exception, all patients carried HBV genomes at low levels (10(4) copies/ml or less). Histological signs of chronic liver disease were observed in all patients. CONCLUSION: Unrecognised HBV infections may account for a high proportion of chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which appear mandatory for the diagnosis and management of non-A non-E hepatitis as well as for improved safety of transfusions and transplantations are needed.

Adult↗
PubMed2001

Removal of cell-bound lipoproteins: a crucial step for the efficient infection of liver cells with hepatitis C virus in vitro.

Hepatitis C virus (HCV) is of major social, medical and economic importance. The prevalence of HCV is approximatively 1% in most developed countries, and much higher in developing countries. HCV infection is the second major cause, after hepatitis B virus infection, for the generation of chronic liver disease and hepatocellular carcinoma. To date, the only reliable model for the study of HCV infection is the chimpanzee. Indeed, there is no robust in vitro infection system, yet. There is thus an urgent need for such an in vitro infection system in order to evaluate therapeutic agents. Here, a process is provided for infecting hepatocyte cell lines with hepatitis C virus in vitro. It is strongly suggested that cell-bound lipoproteins are playing a crucial role during the infection process. In order to obtain a robust infection, the cell-bound lipoproteins have first to be removed from their cellular receptor prior to the addition of viral inocula originating from human sera, the latter being made originally of a virus-lipoprotein complex.

Carcinoma, Hepatocellular↗
PubMed2001

Prevalence of hepatitis C infection among general practice patients in the Lyon area, France.

STUDY OBJECTIVE: To estimate the prevalence of hepatitis C virus (HCV) infection among patients in general practices. DESIGN AND PARTICIPANTS: A screening campaign requested by the French Health Insurance Fund and involving 271 general practitioners (GPs) and 96% of the 95 medical laboratories was conducted in the Lyon area. Each GP participated for one week and offered an HCV screening to all patients aged 18-69 years during this period. Risk factors were estimated by a medical questionnaire (MQ) filled in by the physician. MAIN RESULTS: From May to October 1997, 11,805 subjects were recruited into the study. Among them, 101 were known HCV positive. The MQ was filled up in 86% of the 11,704 remaining patients. Only 59% of those (6876/11,704) went to a laboratory to be tested. Fifty-one were ELISA positive of whom 30 were confirmed by RIBA or PCR. If we add 101 patients that were known HCV positive and estimate the prevalence among patients who did not go to the laboratory, this study gives a total estimated prevalence of 1.3%. CONCLUSIONS: The prevalence of HCV infection among patients of GPs is about 1.3%, very close to the estimate in the French general population. The substantial number of patients known HCV positive is probably related to the participation of GPs sensitised to HCV issues and who already have screened most of their HCV patients.

Adolescent↗