Hepatitis: Deny P

Zoulim F, Durantel D, Deny P. · INSERM, U871, Lyon, France. · Liver Int. · Pubmed #19207973 No free full text.

Abstract: The management of hepatitis B virus resistance to antivirals has evolved rapidly in recent years. The definition of resistance is now well established, with the importance of partial response and the improvement of assays to detect genotypic resistance and virological breakthrough. Data on phenotypic resistance have allowed to define the cross-resistance profile for the main resistant mutants, providing a rationale for treatment adaptation. Clinical studies have shown that an early treatment intervention in case of a virological breakthrough or a partial response with the addition of a second drug having a complementary cross-resistance profile allows one to maintain the majority of patients in clinical remission. The prevention of resistance should rely on the use of the most potent antivirals with a high genetic barrier to resistance as a first-line therapy. The future perspectives are to design strategies to hasten the HBsAg clearance, which should become a new treatment endpoint, to prevent drug resistance and to decrease the incidence of complications of chronic hepatitis B.

Sitruk V, Fain O, Gordien E, Ganne-Carrié N, Deny P, Beaugrand M, Trinchet JC. · Service d'Hépato-Gastroentérologie, Hôpital Jean-Verdier, Bondy Cedex, France. · Gastroenterol Clin Biol. · Pubmed #11845054 No free full text.

This publication has no abstract.

Abergel A, Ughetto S, Dubost S, Bonny C, Aublet-Cuvelier B, Delarocque-Astagneau E, Bailly JL, Bommelaer G, Casanova S, Delteil J, Deny P, Laurichesse H, Odent-Malaure H, Roussel J, Peigue-Lafeuille H, Henquell C. · CHU de Clermont-Ferrand, Service d'Hépato-Gastro-Entérologie, Hôtel-Dieu, Clermont-Ferrand, France. · Aliment Pharmacol Ther. · Pubmed #17900267 No free full text.

Abstract: BACKGROUND: We previously reported high prevalence of hepatitis C virus genotype 5a (HCV 5) (14%) in Central France. AIM: To identify the risk factors associated with HCV5 infection and to characterize local HCV5 lineages. METHOD: A case-control study and phylogenetic analysis were conducted. RESULTS: In all, 131 HCV5 and 343 HCV non 5 infected patients were enrolled. No HCV5 patient was born in sub-Saharan Africa and only two were injection drug user. HCV5 contamination was associated with living in a rural area called Vic le Comte (VLC) in non-transfused patients (OR = 17.7), with transfusion in patients living outside VLC (OR = 3.8) and with receiving injections in patients from VLC (OR = 3.1). More than 80% of the patients from outside VLC were contaminated by transfusion and those from VLC mainly by an iatrogenic factor - injections performed before 1972 by the local physician. Phylogenetic analysis of HCV5 isolates evidenced no distinct genetic cluster, but close relationships between the isolates of spouse pairs and between blood donors and recipients. CONCLUSIONS: Our results suggest that HCV5 spread in our district by iatrogenic route before 1972 and then via transfusion to the whole district. Collaborative studies are underway to study viral sequences from different parts of Africa and Europe to estimate the origin of our HCV 5a strains.

Roulot D, Bourcier V, Grando V, Deny P, Baazia Y, Fontaine H, Bailly F, Castera L, De Ledinghen V, Marcellin P, Poupon R, Bourlière M, Zarski JP, Roudot-Thoraval F, Anonymous00237. · Service d'Hépatogastroentérologie, Hôpital Jean Verdier, Bondy, France. · J Viral Hepat. · Pubmed #17576387 No free full text.

Abstract: Hepatitis C virus genotype 4 (HCV-4) infection is progressing in Europe, where epidemiology and sustained virological response (SVR) seem to be different than in the Middle East. We analysed epidemiological features and SVR rates in a retrospective study of 1532 HCV-4-infected patients, including 1056 patients infected in France, 227 immigrants infected in Egypt and 249 in sub-Saharan Africa. SVR rates were assessed in 242 naive patients of the 1532, who received peginterferon plus ribavirin for 48 weeks. HCV subtype 4a or 4d was the most common among patients infected in France, where the predominant route of transmission was intravenous drug abuse. The 4a subtype was largely predominant (93%) among patients infected in Egypt, where transmission was mostly because of parenteral treatment for schistosomiasis. More than seven different subtypes and no predominant route of infection were found in patients infected in sub-Saharan Africa. Liver fibrosis was significantly less severe in patients infected in France and Africa than in patients infected in Egypt. SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3% and 32.4%, respectively, P < 0.05). An overall better response was observed in patients infected with the 4a subtype. In multivariate analysis, two factors were associated independently with SVR: the Egyptian origin of transmission and the absence of severe fibrosis. In conclusion, the distribution of HCV-4 subtypes varies with the geographical origin of transmission and affects the SVR following antiviral treatment.

Yazdanpanah Y, De Carli G, Migueres B, Lot F, Campins M, Colombo C, Thomas T, Deuffic-Burban S, Prevot MH, Domart M, Tarantola A, Abiteboul D, Deny P, Pol S, Desenclos JC, Puro V, Bouvet E. · Service des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing. · Rev Epidemiol Sante Publique. · Pubmed #17073127 No free full text.

Abstract: BACKGROUND: Factors that influence the risk for HCV infection after occupational exposure to hepatitis C virus (HCV) have not yet been determined. The objective of this study was to assess potential risk factors for Hepatitis C seroconversion after occupational exposure to HCV. METHODS: We conducted a European matched case-control study from 01/01/1991 through 31/12/ 2002. Cases were Health Care Workers (HCWs) who were HCV seronegative at the time of exposure, sustained a documented exposure to HCV, and present documented HCV seroconversion temporally associated with the exposure. Controls-HCWs had a documented exposure to HCV, were HCV seronegative at the time of exposure, and remained so at least 6 months later. Controls were matched to cases for the center and the time period of the exposure occurrence. RESULTS: 60 cases and 204 controls were included. All cases were exposed to HCV-infected materials through percutaneous injuries. Those for whom information was available (61.6%) were exposed to viremic source patients. Multivariate conditional logistic regression analysis, in which HCV viral load was not introduced because of missing values, identified needle placed in the source patient's vein or artery (Odds Ratio [OR]=100.1; 95% Confidence Interval [CI]=7.3-1365.7), deep injury (OR=155.2; 95%CI=7.1-3417.2), and HCW's gender (M vs. F: OR=3.1; 95%CI=1.0-10.0) as risk factors for HCV infection. In univariate unmatched analysis the risk of HCV transmission was increased 11-fold (C195%=1.1-114.1) in HCWs exposed to sources with a viral load>6 log10 copies/mL when compared to sources with a HCV viral load<4 log10 copies/mL. CONCLUSION: The risk of HCV transmission after percutaneous exposure increases with a larger volume of blood, and, a higher titer of HCV in the source patient's blood. The role of HCW's gender need to be further investigated. The results of this study have important implications for counselling and follow-up of HCWs after exposure.

Bonilla N, Barget N, Andrieu M, Roulot D, Letoumelin P, Grando V, Trinchet JC, Ganne-Carrié N, Beaugrand M, Deny P, Choppin J, Guillet J, Ziol M. · Cochin Institute, U567 INSERM, UMR8104 CNRS, Paris 5 University, Paris, France. · J Viral Hepat. · Pubmed #16792541 No free full text.

Abstract: Little is known about the role of specific hepatitis C virus (HCV) CD8+ T cells in liver damage, especially for the progression of fibrosis, during the highly variable course of chronic C hepatitis. The aim of this study was to investigate the presence of HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis and to examine their clinical significance by relating the response to liver fibrosis and progression rate, serum viral load, serum aminotransferase levels, inflammatory activity and in situ characteristics of the intrahepatic infiltrate. Fifteen patients were prospectively included in the study. Intrahepatic lymphocytes were tested for interferon gamma (IFNg) production in response to HCV class I-restricted epitopic peptides using enzyme-linked immunospot analysis. Liver biopsy samples were evaluated for fibrosis, fibrosis progression rate, activity, and in situ number of CD8+ cytotoxic lymphocytes and apoptotic cells. An IFNg-specific CD8+ T-cell response was detected in the liver samples of 47% of patients which was significantly related to a lower stage of fibrosis (P = 0.02) and a lower progression rate of fibrosis (P = 0.01). It was neither related to the number of cytotoxic lymphocytes infiltrating the liver nor to hepatocyte apoptosis. In conclusion, our results indicate that the presence of HCV-specific IFNg-secreting T cells in the liver of patients with chronic C hepatitis is associated with low liver fibrosis and fibrosis progression rate, suggesting that these IFNg-secreting T cells might limit the progression of liver damage.

Zoulim F, Poynard T, Degos F, Slama A, El Hasnaoui A, Blin P, Mercier F, Deny P, Landais P, Parvaz P, Trepo C, Anonymous00622. · INSERM U271, Lyon, France. · J Viral Hepat. · Pubmed #16611195 links to  free full text

Abstract: Lamivudine resistance has been described in subjects with chronic hepatitis B infections, associated with mutations in the viral polymerase gene. The objective of this study was to estimate the emergence rate of lamivudine-resistant viral strains and their consequences over a 2-year period. We evaluated 283 lamivudine-naïve subjects with chronic hepatitis B. Clinical and virological features were assessed at inclusion and every 6 months thereafter. Viral DNA was characterized using polymerase chain reaction (PCR)-based sequencing. Potential risk factors for the emergence of lamivudine resistance mutations were assessed using logistic regression analysis. The annualized incidence rate for viral polymerase mutations was 22%. The only independent risk factor identified was high viral load, at inclusion. Detectable viral DNA and elevated transaminases were more frequent in subjects harbouring mutant viral strains, and these underwent a lower rate of hepatitis B e seroconversion. All subjects responded favourably to treatment, with no difference in symptoms between the two groups. This prospective cohort study identified lamivudine-resistant mutations emerging in 22% of subjects, yearly, which were apparently not associated with clinical aggravation over the study period.

Yazdanpanah Y, De Carli G, Migueres B, Lot F, Campins M, Colombo C, Thomas T, Deuffic-Burban S, Prevot MH, Domart M, Tarantola A, Abiteboul D, Deny P, Pol S, Desenclos JC, Puro V, Bouvet E. · Service des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Faculté de Médecine de Lille, Tourcoing, France. · Clin Infect Dis. · Pubmed #16231252 No free full text.

Abstract: BACKGROUND: Additional studies are required to identify risk factors for hepatitis C virus (HCV) transmission to health care workers after occupational exposure to HCV. METHODS: We conducted a matched case-control study in 5 European countries from 1 January 1991 through 31 December 2002. Case patients were health care workers who experienced seroconversion after percutaneous or mucocutaneous exposure to HCV. Control subjects were HCV-exposed health care workers who did not experience seroconversion and were matched with case patients for center and period of exposure. RESULTS: Sixty case patients and 204 control subjects were included in the study. All case patients were exposed to HCV-infected fluids through percutaneous injuries. The 37 case patients for whom information was available were exposed to viremic source patients. As risk factors for HCV infection, multivariate analysis identified needle placement in a source patient's vein or artery (odds ratio [OR], 100.1; 95% confidence interval [CI], 7.3-1365.7), deep injury (OR, 155.2; 95% CI, 7.1-3417.2), and sex of the health care worker (OR for male vs. female, 3.1; 95% CI, 1.0-10.0). Source patient HCV load was not introduced in the multivariate model. In unmatched univariate analysis, the risk of HCV transmission increased 11-fold for health care workers exposed to source patients with a viral load >6 log(10) copies/mL (95% CI, 1.1-114.1), compared with exposures to source patients with a viral load < or =4 log10 copies/mL. CONCLUSION: In this study, HCV occupational transmission was found to occur after percutaneous exposures. The risk of HCV transmission after percutaneous exposure increased with deep injuries and procedures involving hollow-bore needle placement in the source patient's vein or artery. These results highlight the need for widespread adoption of needlestick-prevention devices in health care settings, together with other preventive measures.

Poynard T, Zoulim F, Ratziu V, Degos F, Imbert-Bismut F, Deny P, Landais P, El Hasnaoui A, Slama A, Blin P, Thibault V, Parvaz P, Munteanu M, Trepo C. · Department of Hepatology and Gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris, France. · Am J Gastroenterol. · Pubmed #16128941 No free full text.

Abstract: OBJECTIVES: The noninvasive serum markers, FibroTest-ActiTest (FT-AT), are an alternative to liver biopsy in patients with chronic hepatitis C and B. The aim was to use these markers in a prospective study of patients treated with lamivudine in order to assess the impact of treatment, as well as the factors associated with fibrosis progression. METHODS: Two hundred and ninety-eight patients were included in a prospective longitudinal study in 50 hospitals across France. FT-AT were measured at baseline, and then after 6, 12, and 24 months of lamivudine 100-mg treatment. Epidemiological, clinical, and virologic characteristics were analyzed by univariate and multivariate analysis. RESULTS: Two hundred and eighty-three patients were included for analysis. The accuracy of FT-AT versus biopsy was validated with the area under the ROC curve, 0.77 (SE = 0.03) for bridging fibrosis and 0.75 (SE = 0.06) for severe activity (A3). At baseline, bridging fibrosis (METAVIR stages F2-F3-F4) was highly associated (p < 0.001) in multivariate analysis with male gender and age and marginally associated with anti-HBe presence (p= 0.05) and non-Asian ethnic origin (p= 0.046). Lamivudine treatment had a very significant impact overall. FT decreased significantly from 0.51 at baseline to 0.37 at 24 months (p < 0.001), and 85% of patients had improvement at 24 months. AT also decreased significantly from 0.56 to 0.13 (p < 0.0001), and 91% of patients had improvement at 24 months. A three-phase kinetics was observed for both fibrosis and activity; there was a marked improvement during the first 6 months, followed by a plateau between 6 and 12 months, and another improvement between 12 and 24 months. The occurrence of a YMDD variant does not entirely explain these three-phase variations. The first phase impact on fibrosis rates was higher in Asian patients (p= 0.01) and in patients younger than 40 yr (p < 0.001). CONCLUSIONS: In patients with chronic hepatitis B, a 24-month course of lamivudine treatment leads to a significant decrease in necroinflammatory grades and fibrosis stages as assessed by noninvasive markers, with the occurrence of a three-phase kinetics. FT-AT should be useful in the noninvasive follow-up of lamivudine treatment.

Lebarbier C, Williams V, Garandeau C, Bellaiche G, Deny P, Maisonneuve L, Gordien E. · Laboratoire de biologie médicale, hôpital Robert-Ballanger, Aulnay-sous-bois, France. · Pathol Biol (Paris). · Pubmed #15531112 No free full text.

Abstract: Our purpose is to assess the question of the definition of hepatitis B virus pre-C-C mutant-chronic infection, according to the level of the viral load at the era of very sensitive techniques of quantification of HBV DNA.

Martial J, Morice Y, Abel S, Cabié A, Rat C, Lombard F, Edouard A, Pierre-Louis S, Garsaud P, Béra O, Chout R, Gordien E, Deny P, Césaire R. · Laboratoire de Virologie-Immunologie. Service de Maladies Infectieuses et Tropicales, Université Paris 13, Bobigny, France. · J Clin Microbiol. · Pubmed #14766854 links to  free full text

Abstract: Molecular epidemiological studies of hepatitis C virus (HCV) in the Caribbean may help to specify the origin and spread of HCV infection. Indeed, the Caribbean population is intermixed from European and African origins and geographically close to the American continent. We characterized HCV genotypes in the Caribbean island of Martinique. HCV genotypes were analyzed by sequencing or reverse hybridization in the 5' noncoding region (5'NC) in 250 HCV-monoinfected and 85 HCV-human immunodeficiency virus (HIV)-coinfected patients. In addition, sequencing in the nonstructural 5B (NS5B) gene was required to determine the subtype or to perform phylogenetic analysis in selected samples. Genotypes 1 to 6 were found, respectively, in 84.4, 6.8, 5.2, 2.8, 0.4, and 0.4% of 250 HCV-monoinfected patients and in 71.7, 7.1, 15.3, 5.9, 0, and 0% of 85 HCV-HIV-coinfected patients. HCV-1b was found in 66.4% of the HCV-monoinfected patients and was associated with blood transfusion, whereas HCV-1a was detected in 41.2% of the HCV-HIV-coinfected patients and was associated with intravenous drug use (IVDU). The HCV-3 strains belonged to subtype 3a and were linked to IVDU. Phylogenetic analyses were focused on HCV-2 and HCV-4, which are common in Africa. Two opposite patterns were evidenced. NS5B sequences from 19 HCV-2 isolates were affiliated with many different subtypes described either in Europe or in West Africa, suggesting an ancient radiation. In contrast, seven of the nine HCV-4 NS5B sequences ranged within HCV-4a and HCV-4d clusters spreading in continental France by the IVDU route. Epidemiological data demonstrate the recent introduction of HCV-4a and -4d subtypes into the Caribbean.

Andreu M, Gordien E, Lhote F, André MH, Deny P, Guillevin L. · Service de Médecine Interne, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Université Paris-Nord, Bobigny. · Ann Med Interne (Paris). · Pubmed #14593309 No free full text.

Abstract: In polyarteritis nodosa (PAN) due to hepatitis B virus (HBV) infection, the insidious nature of the infection makes very difficult to establish the chronology which often remains unknown. PN occurs in the majority of patients during the year following infection. Simultaneous occurrence or occurrence immediately after infection with the HBV is exceptional. We report here three cases of this form of simultaneous HBV infection and PN and describe the particular clinical, virological and evolutive features of the disease.

Sandres-Sauné K, Deny P, Pasquier C, Thibaut V, Duverlie G, Izopet J. · Service de Virologie, Hôpital Purpan, CHU, Toulouse, France. · J Virol Methods. · Pubmed #12711062 No free full text.

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

Nunes H, Deny P, Raphael M, Valeyre D. · Service de pneumologie et réanimation respiratoire, UPRES EA 2705 Maladies vasculaires pulmonaires, hôpital Antoine-Béclère, 157, rue de la Porte-de-Trivaux, 92140 Clamart, France. · Rev Mal Respir. · Pubmed #11468586 No free full text.

Abstract: A role for viruses in the development or course of the main idiopathic chronic infiltrative lung disease has been suggested for a long time. Viruses that have usually been incriminated in cryptogenic fibrosing alveolitis are hepatitis C virus, whose role has not been accurately proven, and latent viruses including Epstein-Barr virus and adenovirus. These latent viruses might be re-activated in the lung of patients immunocompromised by treatments and might be accountable for disease progression. However, published studies have been very conflicting and the only clinical trial testing ribavirin has failed to demonstrate a beneficial effect. In sarcoidosis, the responsibility of human herpesvirus 6 and 8 and retroviruses has not been proven. Finally, data in the literature do not support a link between Langerhans cell histiocytosis and human herpesvirus 6 and 8. These viruses may act by several mechanisms: viral proteins may be antigens driving an appropriate immune response; they may also behave as transactivating factors to control the expression of various genes involved in immune response, cell growth or synthesis of matrix proteins.

Bécheur H, Harzic M, Colardelle P, Deny P, Coste T, Dubeaux B, Chochon M, Roussin-Bretagne S, Doll J, Andrieu J. · Service d'Hépato-Gastroentérologie, Centre Hospitalier de Versailles, Le Chesnay. · Gastroenterol Clin Biol. · Pubmed #11084427 No free full text.

Abstract: BACKGROUND: Procedures such as digestive endoscopy may explain some unclear contaminations by HCV. AIMS: The aims of this study were to detect HCV genome on endoscopes and biopsy-forceps used in patients with known chronic HCV infection and to determine its presence in their gastric juice and saliva. METHODS: A gastroscopy with antral biopsies was performed in 48 patients with non-treated replicative chronic hepatitis C. Samples were obtained after pushing 10 mL of sterile water through the biopsy-suction channel and after immersing the brush used to clean this channel. The biopsy-forceps were also immersed and their tips brushed in 10 mL of sterile water. This sampling technique was repeated three times: immediately after the endoscopic procedure (T0), after washing with a detergent (T1) and after immersion for 20 minutes in a 2% glutaraldehyde solution (T2). The HCV genome was detected by polymerase chain reaction (PCR, Amplicor - Roche Diagnostics Systems). For the last 15 patients, samples of gastric juice and saliva were obtained before antral biopsies and used to detect HCV genome. RESULTS: HCV genome was detected in the biopsy-suction channel in 13 cases (27%) at T0 and in one case (2%) at T1. It was undetectable after completion of the disinfection procedure (T2). Three biopsy-forceps (6%) were PCR positive immediately after the endoscopy but none at T1 and T2. HCV genome was found in the gastric juice in three cases. In all of them, it was also found at T0 in the biopsy-suction channel but not on the biopsy-forceps. When saliva contained HCV genome (4 cases), it was present in the biopsy-suction channel in only one case. In this case, the gastric juice was also PCR positive. CONCLUSIONS: HCV genome is detected in 27% of cases in the biopsy-suction channel after an endoscopic procedure performed on patients with chronic HCV infection. The biopsy-forceps are PCR positive in 6% of cases. The infected gastric juice may play a role in the contamination of the endoscopes. The complete disinfection procedure seems effective to eliminate HCV.