D Ouzan

Institut Arnault Tzanck, Saint-Laurent, Provence-Alpes-Côte d'Azur, France

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Publications (198)647.07 Total impact

  • Journal of hepatology. 10/2014;
  • Gastroenterology 05/2014; 146(5):S-977. · 12.82 Impact Factor
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    ABSTRACT: Background The impact of the IL28B genotype on the real-life treatment decisions for patients infected with the hepatitis C virus (HCV) is unknown. Objective To prospectively analyze the impact of IL28B genotype in HCV genotype 1 (G1)- or 4 (G4)-infected patients using buccal epithelial cell samples in real-life clinical practices. Patients and methods From October 2011 to March 2013, 1007 CHC patients were included among 127 French clinical centers. Results The IL28B CC, CT, and TT genotype distribution was 252 (25%), 576 (57%), and 177 (18%), respectively. The treatment decisions were recorded and matched with the initial intentions for 433 patients. Multivariate analysis on intention to start treatment showed that patients with HCV G4 were less likely to be intended to be treated than HCV G1 patients (odds ratio [OR] = 0.43 [95% CI 0.19–0.97], P = 0.04); similarly HIV-HCV coinfected patients were less likely to be intended to be treated than HCV monoinfected patients (OR = 0.20 [0.09–0.41], P < .0001); conversely, F3–F4 patients were more likely to be intended to be treated than F0–F2 patients (OR = 2.24 [1.29–3.89], P = 0.004). Multivariate analysis on final decision to treat showed that Patients with F3–F4 were more likely to be treated than others (OR = 2.06 [1.26–3.38], P = 0.004). Conversely, although P-values are not significant, patients recruited in public hospitals tended to be less treated (OR = 0.65 [0.40–1.04], P = 0.069), similarly to HIV-HCV coinfected patients (OR = 0.55 [0.28–1.11], P = 0.095). Conclusion Our study showed that the IL28B genotype is used for the management of HCV-infected patients. In the context of future treatments, IL28B genotyping may remain useful if it can be used to develop individualized treatment strategies, identifying patients who can be successfully treated with shorter, simpler, or cheaper regimens.
    Clinics and Research in Hepatology and Gastroenterology. 01/2014;
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    ABSTRACT: Pre-treatment identification of patients likely to achieve a sustained virological response (SVR) with peginterferon alfa-2a/ribavirin would be useful for individualizing treatment choices. Devise a simple scoring system to identify patients with high probability of achieving an SVR with peginterferon alfa-2a/ribavirin. Using data from 2109 Caucasian treatment-naive HCV genotype 1 mono-infected patients from the PROPHESYS cohorts, the relationship between favourable baseline characteristics and SVR was explored using generalized additive model analysis, and a scoring system was devised to predict SVR. Points were assigned for: age (years) (≤35: 2; >35, ≤45: 1; >45; 0); body mass index (kg/m(2) ) (≤20: 2; >20, ≤22: 1; >22: 0); HCV RNA (IU/ml) (≤100000: 3; >100000-400000: 2; >400000-800000: 1; >800000: 0); platelets (>150 x 10(9) /l: 1; ≤150 x 10(9) /l: 0); ALT (x upper limit of normal [ULN]) (>3: 1; ≤3: 0); AST (x ULN) (≤1: 1; >1: 0). 1029, 698 and 382 patients had scores of 0-2, 3-4, and ≥5, respectively, among whom SVR rates were 35.0%, 54.9% and 76.7%. SVR in patients with scores ≥5 and undetectable HCV RNA by Week 4 was 86.7%. The score was tested against two databases of patients who received peginterferon alfa-2a/ribavirin in other clinical trials; similar high SVR rates in patients with scores ≥5 were reported. The scoring system can reliably identify treatment-naive HCV genotype 1 mono-infected Caucasian patients who have a high probability of achieving an SVR with peginterferon alfa-2a/ribavirin and will be particularly useful where protease inhibitors are not readily available. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 12/2013; · 3.87 Impact Factor
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    ABSTRACT: PROPHESYS is a large, multinational, non-interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on-treatment virological response (VR). This PROPHESYS subanalysis is restricted to treatment-naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono-infected patients who received peginterferon alfa-2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria. The likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA ≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non-RVR/EVR patients with HCV RNA >400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB-4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa-2a dose, but a high proportion received a higher-than-recommended ribavirin dose. Despite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.
    Liver international: official journal of the International Association for the Study of the Liver 10/2013; · 3.87 Impact Factor
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    ABSTRACT: The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12-18 months of follow up. HBs seroconversion was observed in two patients.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 09/2013; · 3.12 Impact Factor
  • Journal of Hepatology 01/2013; · 9.86 Impact Factor
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    ABSTRACT: Dried blood spots (DBS) on filter paper have been successfully used to diagnose and monitor several infectious diseases. The aim was to investigate the performance of DBS in hepatitis B virus (HBV) diagnosis using commercial tests in comparison to standard methods. Paired DBS and plasma samples were collected from 200 patients: 100 patients with HBsAg negative status and 100 patients with HBsAg positive status. In the latter patient, HBeAg reactivity was tested. Ten samples of anti-HBs were collected from people vaccinated against HBV. We also studied 50 patients with positive HBV DNA viral load in plasma and 10 HBV DNA negative patients. HBV genotypes and gene polymerase mutations were determined in 10 randomly selected HBV-infected patients. The DBS sample consisted of 50 µL of whole blood, i.e. a 12-mm paper card. The sensitivity thresholds of HBsAg and anti-HBs antibody were 0.30±0.08 IU/mL and 18.11±6.05 IU/mL, respectively, for DBS with 98% sensitivity and 100% specificity. Sensitivity was 98% and specificity 100% for the detection of HBV DNA on a blotter, considering an HBV DNA threshold of 914.1±157.8 IU/ml. Ten patients had an HBeAg positive status in plasma, all were detected positive using DBS. HBV genotyping and mutation detection were successfully performed on DBS, with full concordance between the 10 paired DBS and plasma samples. This study shows DBS is a reliable alternative to plasma specimens for quantifying and detecting HBsAg, anti-HBs, HBeAg and genotyping. DBS may increase the opportunities for HBV testing and treatment follow-up in hard-to-reach individuals.
    PLoS ONE 01/2013; 8(4):e61077. · 3.53 Impact Factor
  • Denis Ouzan
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    ABSTRACT: The current treatment of patients with chronic HCV infection since ten years is pegylated interferon combined with ribavirin. This association allows a virological eradication in 55% of patients, all genotype and 40% of those infected with genotype 1, the most prevalent. Two protease inhibitors (telaprevir and boceprevir) were approved in 2011, in combination with pegylated interferon and ribavirin in both naïve and non-responder patients infected with HCV genotype 1. These new drugs allow obtaining a viral eradication in 70% of cases. Other direct acting antiviral drugs are also currently being tested and likely to radically change treatment strategies for patients with chronic hepatitis due to HCV.
    La Presse Médicale 09/2012; · 0.87 Impact Factor
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    ABSTRACT: The ability to predict which patients are most likely to achieve a sustained virologic response (SVR) with peginterferon/ribavirin would be useful in optimizing treatment for hepatitis C virus (HCV). The objective of this large international noninterventional cohort study was to investigate the predictive value (PV) of a virologic response (VR) by weeks 2, 4, and 12 of treatment on SVR. Treatment-naive HCV monoinfected patients (N = 7,163) age ≥18 years were prescribed peginterferon/ribavirin at the discretion of the treating physician according to country-specific requirements in accordance with the local label. The main outcome measure was the PV of a VR (HCV RNA <50 IU/mL) by weeks 2, 4, and 12 of treatment for SVR24 (HCV RNA <50 IU/mL after 24 weeks of untreated follow-up) by HCV genotype. The overall SVR24 rate was 49.4% (3,541/7,163; 95% confidence interval [CI]: 48.3-50.6%). SVR24 rates in patients with an HCV RNA titer <50 IU/mL by weeks 2, 4, and 12, respectively, were 66.2% (95% CI: 60.4-71.7%), 68.4% (95% CI: 65.7-71.0%), and 60.3% (95% CI: 58.5-62.1%) among genotype 1 patients; 82.0% (95% CI: 76.8-86.5%), 76.3% (95% CI: 73.3-79.1%), and 74.2% (95% CI: 71.3-76.9%) among genotype 2 patients; 67.3% (95% CI: 61.1-73.1%), 67.3% (95% CI: 64.2-70.3%), and 63.8% (95% CI: 61.0-66.6%) among genotype 3 patients; and 59.4% (95% CI: 40.6-76.3%), 63.3% (95% CI: 54.3-71.6%), and 54.3% (95% CI: 47.5-60.9%) among genotype 4 patients. The absence of a VR by week 12 had the highest negative PV across all genotypes. Conclusion: A VR by week 2 or 4 had the highest positive PV for SVR24 and differed according to HCV genotype. (HEPATOLOGY 2012).
    Hepatology 06/2012; · 12.00 Impact Factor
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    ABSTRACT: Point mutations in the coding region of the interleukin 28 gene (rs12979860) have recently been identified for predicting the outcome of treatment of hepatitis C virus infection. This polymorphism detection was based on whole blood DNA extraction. Alternatively, DNA for genetic diagnosis has been derived from buccal epithelial cells (BEC), dried blood spots (DBS), and genomic DNA from serum. The aim of the study was to investigate the reliability and accuracy of alternative routes of testing for single nucleotide polymorphism allele rs12979860CC. Blood, plasma, and sera samples from 200 patients were extracted (400 µL). Buccal smears were tested using an FTA card. To simulate postal delay, we tested the influence of storage at ambient temperature on the different sources of DNA at five time points (baseline, 48 h, 6 days, 9 days, and 12 days). There was 100% concordance between blood, plasma, sera, and BEC, validating the use of DNA extracted from BEC collected on cytology brushes for genetic testing. Genetic variations in HPTR1 gene were detected using smear technique in blood smear (3620 copies) as well as in buccal smears (5870 copies). These results are similar to those for whole blood diluted at 1/10. A minimum of 0.04 µL, 4 µL, and 40 µL was necessary to obtain exploitable results respectively for whole blood, sera, and plasma. No significant variation between each time point was observed for the different sources of DNA. IL28B SNPs analysis at these different time points showed the same results using the four sources of DNA. We demonstrated that genomic DNA extraction from buccal cells, small amounts of serum, and dried blood spots is an alternative to DNA extracted from peripheral blood cells and is helpful in retrospective and prospective studies for multiple genetic markers, specifically in hard-to-reach individuals.
    PLoS ONE 01/2012; 7(3):e33000. · 3.53 Impact Factor
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    ABSTRACT: The aim of this study was to document in real life the characteristics and management of hepatitis C patients treated with pegylated interferon-α2a and ribavirin, and the efficacy of treatment (sustained virological response [SVR]). This observational study enrolled hepatitis C patients initiating pegylated interferon-α2a and ribavirin treatment. A total of 2,066 patients were included, of which 70% were treatment-naive, 53% had genotype (G) 1 and 38% G2 or G3 infection, and 35% had an F3-F4 Metavir score. In total, 18% of patients treated for 24 weeks and 39% of patients treated for 48 weeks prematurely stopped treatment, mainly because of side effects. The SVR rate (intent-to-treat population) was 39%: 43% in naive patients and 31% in treatment-failure patients. In the complete case analysis population, this was 49%: 54% in naive patients and 37% in treatment-failure patients. Among naive patients, the SVR rate was 42% in G1 carriers and 69% in G2 or G3 carriers. The SVR rate was 69% in naive G1 patients without fibrosis (F0; versus 44% in F1-F2 versus 31% in F3-F4; P<0.001). In naive patients, G2 or G3, low viral load (<800,000 IU/ml) and age ≤40 years were predictive factors for SVR. In treatment-failure patients, low viral load, no or low fibrosis stage (F0-F1) and no treatment modification were predictive factors of SVR. In patients treated in a real-life setting, adherence to therapy, SVR rates, predictive factors of SVR and safety results were close to those observed in randomized trials. A high SVR in G1 naive patients with no fibrosis warrants further study and might suggest earlier treatment.
    Antiviral therapy 01/2012; 17(1):101-10. · 3.07 Impact Factor
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    ABSTRACT: Recent studies have suggested that host genetics may be useful for predicting drug response and have supported the recommendation that single polynucleotide polymorphisms (SNPs) of IL28B should be investigated when treating hepatitis C virus (HCV)-1 infected patients. The aim of this study was to determine whether a single IL-28B genotype SNP rs8099917 or rs12979860 determination is sufficient to predict treatment failure in patients with chronic HCV. A total of 198 patients were included; mean (±standard deviation) age was 47±12 years and 140 (71%) were men. One hundred and fifty-six (79%) patients were infected with HCV genotype 1 and 42 (21%) with HCV genotypes 2 or 3. One hundred and eight (55%) patients had sustained virologic response (SVR). Two SNPs in the IL-28B were analyzed (rs8099917 and rs12979860). A total of 115 (58%) patients had rs8099917 TT genotype and 61 (31%) had rs12979860 CC genotype. Rs8099917 TT and rs12979860 CC genotypes were associated with SVR in HCV genotype 1 patients [odds ratio=2.60 (1.36-5.00), P=0.004 and odds ratio=3.30 (1.58-6.90), P=0.03 respectively]. No association was found between SNPs and SVR in HCV genotype 2 or 3 patients. This study confirms that SNPs rs8099917 and rs12979860 used alone may be useful for predicting the outcome of HCV treatment. In a rational and cost-effective approach, determination of only one of these two SNPs is sufficient for predicting SVR. Because of the highest predictive SVR associated with rs12979860 CC compared with the rs8099917 TT (respective positive predictive value: 72% vs. 63%, P=ns), rs12979860 determination alone is sufficient for predicting interferon response.
    European journal of gastroenterology & hepatology 10/2011; 23(10):931-5. · 1.66 Impact Factor
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    ABSTRACT: Adherence is important for therapy of chronic diseases, but has still not been well studied in real life in chronic hepatitis C. To assess adherence to hepatitis C combination therapy in routine clinical practice and to identify factors associated with imperfect adherence. This cohort study included unselected chronic hepatitis C patients initiating peginterferon α-2b plus ribavirin. 100% adherence was defined by taking all the prescribed doses of both drugs for the full initially intended duration, as declared by the patient or believed by the physician. Quality of life was assessed using the short-form health survey (SF-36) questionnaire. 1860 patients were analysed, including 72% treatment-naive, 36% genotype 2/3, 23% psychiatric, 44% drug addicts and 3% human immunodeficiency virus (HIV)-positive patients. Early treatment discontinuation occurred in 30% of patients. Overall, 38% of patients reported 100% adherence. Patient- and physician-reported adherences were discordant, with a 20-30% overestimation by physicians. HIV co-infection [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.36-4.67], no drug use during follow-up (2.37, 1.30-4.31), genotype 3 (1.55, 1.20-2.00) and treatment-naive (1.32, 1.03-1.69) were associated with 100% adherence. Quality of life worsened during treatment but returned to baseline after the end of treatment. Imperfect adherence to combination therapy is common in routine patients. Adherence is markedly overestimated by physicians and is associated with some patient's baseline characteristics. Knowledge of these factors might help identify patients who are most in need of intervention and plan more frequent and accurate follow-up.
    Liver international: official journal of the International Association for the Study of the Liver 04/2011; 31(4):516-24. · 3.87 Impact Factor
  • Journal of Hepatology 04/2010; 52. · 9.86 Impact Factor
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    ABSTRACT: Injection drug users are often excluded from hepatitis C virus (HCV) treatment. This study compares sustained virological response, adherence, and quality of life in patients with or without a history of illicit drug use in routine clinical practice. This is a post-hoc analysis of a prospective, observational study conducted in 1860 patients who received peginterferon alpha-2b/ribavirin combination therapy. Nondrug users (NDUs) were defined as patients without a history of drug addiction; former drug users (FDUs) as patients who had stopped using illicit drugs or opioid maintenance therapy and active drug users (ADUs) as patients using illicit drugs or on opioid maintenance therapy. Virological response, adherence, and the health-related quality of life were assessed by the measure of HCV RNA in the serum, self-report and 36-item short-form health survey Questionnaire, respectively. The analyzed population included 1038 (56%) NDUs, 578 (31%) FDUs, and 244 (13%) ADUs. About 85% of ADUs were on opioid maintenance therapy and 25% used illicit drugs. Although ADUs had a more chaotic lifestyle and more psychiatric disorders, sustained virological response of ADUs (58%) did not differ from that of NDUs (49%) and FDUs (51%) (P=0.133). Adherence rates were 39% in NDUs and FDUs, and 37% in ADUs (P=0.883). Health-related quality of life was improved in the three groups after the end of treatment. Our study suggests that HCV therapy in ADUs on opioid maintenance therapy is as effective as in other HCV patients. The effectiveness of HCV therapy in illicit drug users needs to be evaluated in further studies.
    European journal of gastroenterology & hepatology 03/2010; 22(9):1050-7. · 1.66 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
  • Journal of Hepatology 01/2010; 52(1):S108-S108. · 9.86 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
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    ABSTRACT: Hepatitis C antiviral therapies have significant psychiatric side effects. It is therefore believed that they might exacerbate mental illness in patients with pre-existing psychiatric disorders, resulting in poor adherence and response to antiviral treatment. We aimed to assess adherence to treatment, virological outcomes and mental safety in psychiatric patients, compared with non-psychiatric patients, treated for hepatitis C. A cohort study involved unselected hepatitis C patients on scheduled therapy with pegylated interferon-alpha2b and ribavirin, between 2002 and 2005 in France, and followed-up until 6 months after the end of treatment. Virological response was reported by the physician according to standard definitions and adverse events were monitored. Adherence to treatment was assessed by patient report. Among 1,860 patients, 403 (22%) had pre-existing psychiatric disorders, mostly depressive and anxiety disorders. Strict adherence was similar in psychiatric and non-psychiatric patients (35% versus 39%; P=0.20) as was the rate of sustained virological response (52% versus 51%; P=0.75). Conversely the rate of mental adverse events was higher in psychiatric patients (78% versus 57%; P<0.001). Baseline characteristics independently associated with the risk of later mental adverse events were history of depression, initial pegylated interferon-alpha2b dose and female gender. Antiviral therapy in hepatitis C patients with associated psychiatric disease appears as effective as in other patients but results in a higher rate of mental adverse events, emphasizing the need for close monitoring of these psychiatric patients.
    Antiviral therapy 01/2010; 15(4):599-606. · 3.07 Impact Factor

Publication Stats

2k Citations
647.07 Total Impact Points


  • 1990–2014
    • Institut Arnault Tzanck
      • Department of Hepato-Gastroenterology
      Saint-Laurent, Provence-Alpes-Côte d'Azur, France
  • 2013
    • Institut Paoli Calmettes
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2007–2011
    • Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine
      Clicy, Île-de-France, France
    • Centre hospitalier Laennec de Creil
      Creil, Picardie, France
  • 2008–2009
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
    • Hôpital Saint Joseph
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1997–2009
    • Alphabio
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1998–2004
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France
  • 2002
    • CCI Nice Cote d'Azur
      Provence-Alpes-Côte d'Azur, France
    • Hôpital Ambroise Paré – Hôpitaux universitaires Paris Ile-de-France Ouest
      Billancourt, Île-de-France, France
  • 1992–1999
    • University of Nice-Sophia Antipolis
      • Faculté de Médecine
      Valbonne, Provence-Alpes-Cote d'Azur, France
  • 1987
    • CHU de Lyon - Hôpital Gériatrique des Charpennes
      Lyons, Rhône-Alpes, France