Showing papers by "Fabien Zoulim published in 2005"
TL;DR: The results suggest that the emergence of the triple mutant may be delayed and associated with viral resistance in patients treated with 3TC+ADV, and provides a rationale for the clinical evaluation of de novo combination therapies.
265 citations
231 citations
TL;DR: 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.
130 citations
TL;DR: It is shown that HCV eradication has a positive impact on graft survival and no difference in patient survival was observed in the two groups.
102 citations
TL;DR: The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV–HBV-co-infected patients, regardless of HBV strains and their degree of replication.
Abstract: Background The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients. Methods We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models. Results The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P 10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations. Conclusion The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.
94 citations
TL;DR: Rheumatological symptoms are common in patients chronically infected with HCV and it is essential to individualize the role of treatment with interferon-alpha and to consider the use of methotrexate for difficult cases.
Abstract: 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.
56 citations
TL;DR: The treatment of HBV infected patients with analogues of nucleos(t)ides, including lamivudine and adefovir dipivoxil, has significantly increased the rate of anti-HBe seroconversion and therefore reduced the impact of chronic hepatitis B (CHB) on liver disease.
43 citations
TL;DR: The prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection.
39 citations
TL;DR: It is suggested that in patients who previously failed lamivudine therapy, proactive antiviral treatment may lead to a beneficial virological and clinical effect.
37 citations
TL;DR: It is provided the first evidence that PNAs targeting the bulge and upper stem of epsilon can efficiently and in a sequence-specific manner inhibit DHBV RT.
35 citations
TL;DR: The clinical impact of key issues concerning nucleoside analogues, cross-resistance patterns, and the effect of viral load suppression on the restoration of specific antiviral cellular responses is discussed in the perspective of new clinical trials.
Abstract: Owing to the persistence of hepatitis B virus (HBV) and the selection of drug-resistant mutants, a new concept of antiviral therapy for chronic hepatitis B relies on the combination of nucleoside analogues. In experimental models of HBV infection, several key points concerning these combinations were addressed. (i) Is it possible to achieve a synergic antiviral effect with polymerase inhibitors? (ii) Is it possible to impact on intracellular viral covalently closed circular DNA? (iii) What is the impact of the cross-resistance patterns of the different nucleoside analogues? (iv) What is the effect of viral load suppression on the restoration of specific antiviral cellular responses? The clinical impact of these key issues is discussed in the perspective of new clinical trials.
TL;DR: The patient appeared to have made a quasi-monoclonal humoral response to the y epitope, which means the virus could replicate, despite the high levels of anti-HBs.
Abstract: Hepatitis B virus (HBV) infections can be prevented or controlled by the host humoral immune response (anti-HBs) directed against the major surface antigen (HBsAg), elicited either naturally or by vaccination. A chronic HBV carrier was found to have high levels of both virus and anti-HBs. Full-length HBV genomes were amplified from the patient's serum, sequenced and cloned. The genome was ‘wild-type’ HBV of genotype C and serotype adr. The sequence has remained stable, with no signs of emergence of an immune-escape mutant population. To study what was recognized by the patient's serum, viral particles were 35S-labelled and then immunoprecipitated by using the patient's serum or control sera. The patient's serum immunoprecipitated the adr HBsAg encoded by his HBV genome poorly, but efficiently recognized HBsAg of serotype ayw. When his HBV genome was modified by a point mutation to express HBsAg of serotype ayr, the patient's serum could recognize the antigen, as well as the control anti-HBs-positive serum. The patient appeared to have made a quasi-monoclonal humoral response to the y epitope. By switching to the d epitope, which requires only a point mutation, the virus could replicate, despite the high levels of anti-HBs. This study underlines the subtleties of virus–host interactions. Implications for HBV vaccination are discussed.
TL;DR: Point mutations of the C61 codon may generate viable HBeAg-negative variants and secretion block of theC61R mutant could be overcome by co-expression of wild-type core protein.
Patent•
22 Dec 2005TL;DR: In this article, the use of an uridine derivative of formula (I) for the preparation of a drug having antiviral activity against a Flaviviridae is described, where the derivative is chosen from among hydrogen, hydroxyl, o-alkyl, O-polymorphosynthetic acid, OCO alkyl and halogen.
Abstract: The invention relates to the use of an uridine derivative of formula (I) : wherein - R1 represents monohalogenated alkynyl or dihalogenated alkenyl; - R2 is chosen from among hydrogen, hydroxyl, O-alkyl, O-CO alkyl and halogen; - R3 is chosen from among hydrogen, hydroxyl, O-alkyl, O-CO alkyl, halogen, SH, S-alkyl and N3; and - R4 is chosen from among hydroxyl, O-alkyl, O-CO alkyl, O-phosphate, O-diphosphate, O-triphosphate and O phosphonate, as well as its possible tautomers, its possible pharmaceutically acceptable addition salts with an acid or a base, and its N-oxide forms, for the preparation of a drug having antiviral activity against a Flaviviridae.
TL;DR: The synthesis of hitherto unknown 5-haloethynyl and 5-(1,2-dihalo)vinyluracil nucleosides in the 2'-deoxy, 3-deoxy- and ribosyl series is reported and their in vitro anti-HIV and anti-HCV activities and cellular toxicitites are discussed.
TL;DR: Although preliminary biological assays have revealed the ability of 1 to inhibit in vitro the HCV IRES-dependent translation in a dose-dependent manner, the linear analog has shown a slightly higher activity.
01 Dec 2005
TL;DR: Auteur(s) : F Zoulim, C Trepo Inserm U 271 et Hotel Dieu, Service d’ hepatogastroenterologie, Lyon Epidemiologie de l’hepatite B.
Abstract: Auteur(s) : F Zoulim, C Trepo Inserm U 271 et Hotel Dieu, Service d’hepatogastroenterologie, Lyon Epidemiologie de l’hepatite B Malgre la disponibilite d’un vaccin efficace contre l’hepatite B, cette infection virale demeure un probleme majeur de sante publique a l’echelon mondial [1]. On estime que 350 millions de personnes sont porteuses chroniques du virus de l’hepatite B dans le monde. On estime que, aux Etats-Unis, environ 1,25 million de personnes sont porteuses [...]
Journal Article•
TL;DR: New therapeutic approaches should be based on the combination of PEG IFN and specific inhibitors of HCV replication to increase the rate of sustained response.
Abstract: Hepatitis C virus (HCV) infects approximately 3 % of the global population and represents a major public health problem worldwide. Treatment of chronic hepatitis C is based on the combination of pegylated interferon alpha (PEG IFN) with ribavirin. With this treatment, sustained virological response is obtained in around 80% of patients infected with HCV genotype 2 or 3 and 50% of patients infected with HCV genotype 1. The most frequent adverse events are the flu-like syndrome and psychiatric disorders for PEG IFN, and anaemia for ribavirin; they need a careful follow-up. Determination of viral load and genotype is essential for the indication of therapy and the follow-up during treatment. Patients infected with HCV genotype 2 or 3 should be treated for 24 weeks. In patients infected with HCV genotype 1, a decrease in viral load by 2 log after 12 weeks of treatment (early virological response) is needed to take the decision to continue treatment, for a total duration of 48 weeks. A poor response to treatment is associated with host factors (age, alcohol consumption, cirrhosis) and viral factors (genotype 1, high viral load, co-infection with HBV or HIV). New therapeutic approaches should be based on the combination of PEG IFN and specific inhibitors of HCV replication to increase the rate of sustained response.
Patent•
22 Dec 2005
TL;DR: In this paper, l'invention concerne l'utilisation d'un derive d'uridine de formule (I), ainsi que de ses tautomeres eventuels, ses sels d'addition d'acides pharmaceutiquement acceptables eventusels avec un acide ou une base, aini que ses formes N-oxyde, pour preparer un medicament possedant une activite antivirale contre un virus de la famille des Flaviv
Abstract: L'invention concerne l'utilisation d'un derive d'uridine de formule (I), ainsi que de ses tautomeres eventuels, ses sels d'addition d'acides pharmaceutiquement acceptables eventuels avec un acide ou une base, ainsi que ses formes N-oxyde, pour preparer un medicament possedant une activite antivirale contre un virus de la famille des Flaviviridae. Dans ladite formule (I), R1 represente un groupe alcynyle monohalogene ou alcenyle dihalogene, R2 est choisi parmi un atome d'hydrogene, un groupe hydroxyle, un groupe -O-alkyle, un groupe -O-CO-alkyle et un atome d'halogene, R3 est choisi parmi un atome d'hydrogene, un groupe hydroxyle, un groupe -O-alkyle, un groupe -O-CO-alkyle, un atome d'halogene, un groupe -SH, un groupe -S-alkyle et N3 et R4 est choisi parmi les groupes hydroxyle, -O-alkyle, -O-CO-alkyle, -O-phosphate, -O-diphosphate, -O-triphosphate et -O-phosphonate.