12 results on '"Zoulim, Fabien"'
Search Results
2. Significance of serum HBV RNA in non‐cirrhotic HBeAg ‐negative chronic hepatitis B patients who discontinue effective antiviral therapy
- Author
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Papatheodoridi, Margarita, primary, Papachristou, Eleni, additional, Moschidis, Zissis, additional, Hadziyannis, Emilia, additional, Rigopoulou, Eirini, additional, Zachou, Kalliopi, additional, Villeret, François, additional, Magiorkinis, Gkikas, additional, Lyberopoulou, Aggeliki, additional, Gatselis, Nikolaos, additional, Vlachogiannakos, Ioannis, additional, Manolakopoulos, Spilios, additional, Dalekos, George N., additional, Zoulim, Fabien, additional, Paraskevis, Dimitrios, additional, and Papatheodoridis, George V., additional
- Published
- 2022
- Full Text
- View/download PDF
3. Sequence characterization of extracellular HBV RNA in patient plasma.
- Author
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Chang, Silvia, Hedskog, Charlotte, Parhy, Bandita, Martin, Ross, Mo, Hongmei, Maiorova, Evguenia, and Zoulim, Fabien
- Subjects
HEPATITIS B virus ,RNA ,NUCLEOTIDE sequence ,HEPATITIS B ,VIRAL genomes ,RNA splicing ,PLANT viruses - Abstract
Antiviral nucleos(t)ide analogue therapies inhibit HBV replication and suppress the HBV DNA levels in patients with chronic HBV infection. Since HBV RNAs are expressed from cccDNA or HBV integrated sequences, independently of viral genome replication, levels of HBV RNAs in plasma may remain high following treatment with nucleos(t)ide analogue. Thus, HBV RNAs have been proposed to be used as a viral biomarker for treatment outcome and disease progression. Recent investigations of plasma HBV RNAs described the presence of full length as well as subgenomic forms of RNA. To support the usage of plasma HBV RNAs as a viral biomarker, further understanding of HBV RNA composition in clinical samples is needed. Here, sequence of extracellular HBV RNAs was characterized in plasma samples of patients with chronic HBV infection using two independent RNA amplification methods that do not use HBV‐specific primers for amplification: total RNA (NuGEN RNAseq) and mRNA (TruSeq RNAseq). Sequencing coverage was obtained across the full length of HBV genome for both methods, confirming the presence of full‐length HBV RNA in plasma. The sequence of HBV RNA was nearly identical to plasma HBV DNA sequence in each sample with only 0–14 (median 4) mismatches over 3 kb. Thus, sequence of HBV RNA plasma reflects the intrahepatic viral reservoir and can be used for monitoring of sequence variants such as resistance in clinical trials. Additionally, RNA splice forms, different polyA tails start positions and presence of HBV‐human chimeric transcript were identified. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Significance of serum HBV RNA in non-cirrhotic HBeAgnegative chronic hepatitis B patients who discontinue effective antiviral therapy.
- Author
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Papatheodoridi, Margarita, Papachristou, Eleni, Moschidis, Zissis, Hadziyannis, Emilia, Rigopoulou, Eirini, Zachou, Kalliopi, Villeret, François, Magiorkinis, Gkikas, Lyberopoulou, Aggeliki, Gatselis, Nikolaos, Vlachogiannakos, Ioannis, Manolakopoulos, Spilios, Dalekos, George N., Zoulim, Fabien, Paraskevis, Dimitrios, and Papatheodoridis, George V.
- Subjects
CHRONIC hepatitis B ,HEPATITIS associated antigen ,HEPATITIS B virus ,RNA ,DISEASE relapse - Abstract
HBV RNA is considered as a promising predictor in patients who discontinue nucleos(t)ide analogues (NAs). We determined HBV RNA levels in non-cirrhotic HBeAg-negative patients who discontinued NAs and assessed their predictability for 12-month outcomes. Fifty-seven patients of DARING-B study were included. HBV RNA levels were determined in stored monthly serum samples drawn at 0–3 months after end of therapy (EOT). Other markers previously determined in the same cohort including hepatitis B core-related antigen (HBcrAg) were also assessed. HBV RNA at EOT was detectable in 7% of patients, who developed virological/clinical relapse and required retreatment at month 2; in patients with undetectable EOT HBV RNA, 12-month cumulative rates of virological relapse, clinical relapse and retreatment were 68%, 28% and 21%, respectively (p ≤ 0.008). HBV RNA at month-1 after EOT was detectable in 19% of patients being associated with higher probability only of virological relapse (p = 0.001). HBV RNA levels correlated significantly to HBV DNA, HBcrAg, ALT and interferon-induced protein-10, but not HBsAg levels. Combined EOT HBV RNA and HBcrAg detection and/or HBsAg >1000 IU/ml was associated only with higher probability of retreatment having higher sensitivity and lower specificity than HBV RNA alone. In conclusion, serum HBV RNA is detectable in a minority of non-cirrhotic HBeAgnegative patients under effective long-term NAs therapy offering low sensitivity but 100% specificity for early retreatment due to severe clinical relapses after NA discontinuation. The combinations of EOT HBV RNA with HBcrAg and/or high HBsAg levels increase sensitivity but decrease specificity for prediction of retreatment after NAs withdrawal [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
5. Hepatitis B virus genome diversity in adolescents: Tenofovir disoproxil fumarate treatment effect and HBeAg serocon version
- Author
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Combet, Christophe, primary, Bhardwaj, Neeru, additional, Hedskog, Charlotte, additional, Podlaha, Ondrej, additional, Gaggar, Anuj, additional, Murray, Karen F., additional, Mo, Hongmei, additional, Svarovskaia, Evguenia, additional, and Zoulim, Fabien, additional
- Published
- 2021
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- View/download PDF
6. Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B
- Author
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Papatheodoridi, Margarita, primary, Hadziyannis, Emilia, additional, Berby, Françoise, additional, Zachou, Kalliopi, additional, Testoni, Barbara, additional, Rigopoulou, Eirini, additional, Gatselis, Nikolaos K., additional, Lyberopoulou, Aggeliki, additional, Vlachogiannakos, Ioannis, additional, Manolakopoulos, Spilios, additional, Dalekos, George N., additional, Zoulim, Fabien, additional, and Papatheodoridis, George V., additional
- Published
- 2019
- Full Text
- View/download PDF
7. Biological basis for functional cure of chronic hepatitis B
- Author
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Martinez, Maria G., primary, Testoni, Barbara, additional, and Zoulim, Fabien, additional
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- 2019
- Full Text
- View/download PDF
8. Sofosbuvir‐Daclatasvir is suboptimal in patients with genotype 2 chronic hepatitis C infection: real‐life experience from the HEPATHER ANRS CO22 cohort.
- Author
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Lédinghen, Victor, Lusivika‐Nzinga, Clovis, Bronowicki, Jean‐Pierre, Zoulim, Fabien, Larrey, Dominique, Metivier, Sophie, Tran, Albert, Marcellin, Patrick, Samuel, Didier, Chazouillères, Olivier, Chevaliez, Stephane, Dorival, Celine, Fontaine, Hélène, Pawlotsky, Jean‐Michel, Carrat, Fabrice, and Pol, Stanislas
- Subjects
CHRONIC hepatitis C ,GENOTYPES ,TERMINATION of treatment ,RIBAVIRIN ,TREATMENT effectiveness - Abstract
Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real‐world data available for this regimen. To evaluate the real‐life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1‐1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real‐life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
9. Predictors of hepatitis B surface antigen loss, relapse and retreatment after discontinuation of effective oral antiviral therapy in noncirrhotic HBeAg‐negative chronic hepatitis B.
- Author
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Papatheodoridi, Margarita, Hadziyannis, Emilia, Berby, Françoise, Zachou, Kalliopi, Testoni, Barbara, Rigopoulou, Eirini, Gatselis, Nikolaos K., Lyberopoulou, Aggeliki, Vlachogiannakos, Ioannis, Manolakopoulos, Spilios, Dalekos, George N., Zoulim, Fabien, and Papatheodoridis, George V.
- Subjects
CHRONIC hepatitis B ,HEPATITIS associated antigen ,TERMINATION of treatment ,ENZYME-linked immunosorbent assay - Abstract
Reliable predictors of outcomes after treatment discontinuation in HBeAg‐negative chronic hepatitis B (CHB) patients have not been established. We investigated the role of hepatitis B surface antigen (HBsAg), interferon‐inducible protein‐10 (IP10) and hepatitis B core‐related antigen (HBcrAg) serum levels as predictors of HBsAg loss, relapse and retreatment in noncirrhotic HBeAg‐negative CHB patients who discontinued long‐term antiviral therapy. All HBsAg‐positive (n = 57) patients of the prospective DARING‐B study were included and followed monthly for 3 months, every 2/3 months until month‐12 and every 3/6 months thereafter. HBsAg, IP10 and HBcrAg levels were measured by enzyme immunoassays, and SCALE‐B score was calculated. Twelve patients achieved HBsAg loss before retreatment with 18‐month cumulative incidence of 25%. Independent predictors of HBsAg loss were baseline HBsAg and month‐1 IP10 levels. Of 10 patients with baseline HBsAg ≤100 IU/mL, 70% cleared HBsAg and 10% required retreatment. Of 23 patients with baseline HBsAg >1000 IU/mL, 4% cleared HBsAg and 43% required retreatment. Of 24 patients with intermediate baseline HBsAg (100‐1000 IU/mL), 17% cleared HBsAg and 21% required retreatment; in this subgroup, month‐1 IP10 was significantly associated with HBsAg loss, which occurred in 30% and 7% of cases with IP10 >150 and ≤150 pg/mL, respectively. Baseline HBcrAg was undetectable in all patients who cleared HBsAg and was associated with retreatment. SCALE‐B was associated with HBsAg loss but not with relapse or retreatment. In conclusion, HBsAg, IP10 and HBcrAg serum levels can be useful for the decisions and management of treatment discontinuation in noncirrhotic Caucasian patients with HBeAg‐negative CHB. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
10. Non‐virological factors are drivers of hepatocellular carcinoma in virosuppressed hepatitis B cirrhosis: Results of ANRS CO12 CirVir cohort.
- Author
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Brichler, Segolene, Nahon, Pierre, Zoulim, Fabien, Layese, Richard, Bourcier, Valerie, Audureau, Etienne, Sutton, Angela, Letouze, Eric, Cagnot, Carole, Marcellin, Patrick, Guyader, Dominique, Roulot, Dominique, Pol, Stanislas, Ledinghen, Victor, Zarski, Jean‐Pierre, Calès, Paul, Tran, Albert, Peron, Jean‐Marie, Mallat, Ariane, and Riachi, Ghassan
- Subjects
VIROLOGY ,HEPATITIS B treatment ,CIRRHOSIS of the liver ,IMMUNOSUPPRESSION ,CARCINOGENESIS ,LIVER cancer - Abstract
Summary: Worldwide, hepatocellular carcinoma (HCC) occurs mainly in Asian patients with hepatitis B virus (HBV) infection. This study aimed to decipher the environmental and virological factors associated with HCC occurrence and validate risk scoring systems in a French multicentre prospective cohort of HBV cirrhotic patients. Patients with biopsy‐proven Child‐Pugh A viral cirrhosis included in the ANRS CO12 CirVir cohort who were HBsAg(+) without hepatitis C coinfection were selected for: (a) interview through a standardized questionnaire reporting coffee consumption and HCC familial history; (b) HBsAg quantification using baseline and sequential 2‐year frozen sera; (c) baseline HBV genotype determination; and (d) assessment of risk factors and applicability of HCC risk scores (Kaplan‐Meier analysis, Cox models). Among 317 patients studied (261 men, median age 53 years, past or ongoing antiviral treatment 93.3% and baseline detectable HBV DNA in 88 patients), the baseline and 2‐year median HBsAg levels were 810 and 463 IU/mL, respectively. After a median follow‐up of 65.2 months, 27 HCC cases were diagnosed (annual incidence: 1.6%). Three factors were independently associated with HCC occurrence: age > 50 years, platelets ≤ 150 × 103/mm3 and body mass index ≥ 30 kg/m2. Two out of five risk scores were validated, and the most accurate was PAGE‐B at 1 year. Moreover, HCC in patients without maintained virological suppression seems more aggressive and less accessible to curative treatment. In conclusion, in French patients with HBV cirrhosis mostly virally suppressed, independent HCC risk factors were host‐related (age, obesity) or linked to the severity of cirrhosis (thrombopenia), and the European PAGE‐B score was the most accurate risk score. In the French prospective multicentre ANRS CO12 CirVir cohort, among 317 patients with biopsy‐proven compensated HBV‐related cirrhosis, host conditions, comorbidities and severity of liver disease were independent predictors of HCC occurrence. Only two out of five HCC risk scores were validated in those patients and the European PAGE‐B score was the most accurate. Moreover, HCC in patients without a maintained virological suppression seem more aggressive and less accessible to curative treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
11. Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues.
- Author
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Chevaliez, Stéphane, Rodriguez, Christophe, Poiteau, Lila, Soulier, Alexandre, Donati, Flora, Darty‐Mercier, Mélanie, Pioche, Corinne, Leroy, Vincent, Brodard, Véronique, Zoulim, Fabien, Brouard, Cécile, Larsen, Christine, Semaille, Caroline, Roudot‐Thoraval, Françoise, and Pawlotsky, Jean‐Michel
- Subjects
HEPATITIS B virus ,NUCLEOSIDES ,NUCLEOTIDES ,LAMIVUDINE ,ANTIVIRAL agents - Abstract
Summary: Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long‐term administration as monotherapies. The prevalence of resistance‐associated substitutions (RASs) and fitness‐associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment‐naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full‐length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment‐naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next‐generation sequencing at baseline who were treatment‐eligible and treated with currently recommended drugs achieved a virological response. The presence of pre‐existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
12. Sofosbuvir-Daclatasvir is suboptimal in patients with genotype 2 chronic hepatitis C infection: real-life experience from the HEPATHER ANRS CO22 cohort.
- Author
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de Lédinghen V, Lusivika-Nzinga C, Bronowicki JP, Zoulim F, Larrey D, Metivier S, Tran A, Marcellin P, Samuel D, Chazouillères O, Chevaliez S, Dorival C, Fontaine H, Pawlotsky JM, Carrat F, and Pol S
- Subjects
- Antiviral Agents adverse effects, Carbamates, Drug Therapy, Combination, Genotype, Hepacivirus genetics, Humans, Imidazoles, Prospective Studies, Pyrrolidines, Sofosbuvir adverse effects, Valine analogs & derivatives, Hepatitis C drug therapy, Hepatitis C, Chronic drug therapy
- Abstract
Sofosbuvir plus daclatasvir with or without ribavirin has demonstrated a high efficacy and an acceptable safety profile in clinical trials of patients infected with genotype 2 hepatitis Cvirus (HCV); however, there are currently no real-world data available for this regimen. To evaluate the real-life safety and efficacy of sofosbuvir/daclatasvir with or without ribavirin in genotype 2 HCV patients in the French cohort ANRS CO22 HEPATHER(NCT01953458). In this ongoing, national, multicentre, prospective, observational study, we observed patients with HCV genotype 2 infection who initiated treatment with sofosbuvir (400 mg/d) plus daclatasvir with or without ribavirin (1-1.2 g/d). Patients were divided into two treatment groups: sofosbuvir/daclatasvir with or without ribavirin (12 weeks/24 weeks). The primary end point was a sustained virological response at week 12 following the end of therapy. Overall, 88% and 91% of patients achieved a sustained virological response following 12 and 24 weeks of treatment with sofosbuvir/daclatasvir with or without ribavirin, respectively. The most common adverse events were asthenia (29%), headache (15%) and fatigue (20%), and ribavirin addition was associated with a higher rate of adverse events and treatment discontinuation. Sofosbuvir/daclatasvir with or without ribavirin was associated with lower rates of sustained virological response in the real-life setting compared with the clinical setting and demonstrated suboptimal efficacy for the treatment of patients with genotype 2 chronic HCV., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2020
- Full Text
- View/download PDF
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