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Poynard T.,University Pierre and Marie Curie | De Ledinghen V.,Bordeaux University Hospital Center | Zarski J.P.,Clinique University dHepato Gastroenterologie | Stanciu C.,Gastroenterology and Hepatology Institute | And 8 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Liver fibrosis stage is traditionally assessed with biopsy, an imperfect gold standard. Two widely used techniques, FibroTest®, and liver stiffness measurement (LSM) using Fibroscan® have been validated using biopsy, and therefore the true performances of these estimates are still unknown in the absence of a perfect reference. The aim was to assess the relative accuracy of FibroTest, LSM, and biopsy using methods without gold standard in patients with chronic hepatitis C (CHC) and controls. Methods: A total of 1289 patients with CHC and 604 healthy volunteers, with assessment of fibrosis stage by the three techniques, and alanine aminotransferase (ALT) taken as a control test, were analyzed by latent class method with random effects. In the volunteers, the false positive risk of biopsy was obtained from a large surgical sample of four normal livers. Results: The latent class model with random effects permitted to conciliate the observed data and estimates of test performances. For advanced fibrosis, the specificity/sensitivity was for FibroTest 0.93/0.70, LSM 0.96/0.45, ALT 0.79/0.78 and biopsy 0.67/0.63, and for cirrhosis FibroTest 0.87/0.41, LSM 0.93/0.39, ALT 0.78/0.08 and biopsy 0.95/0.51. The analysis of the discordances between pairs suggested that the variability of the model was mainly related to the discordances between biopsy and LSM (residuals >10; p <0.0001). Conclusions: A method without the use of a gold standard confirmed the accuracy of FibroTest and Fibroscan for the diagnosis of advanced fibrosis and cirrhosis in patients with chronic hepatitis C. The variability of the model was mostly due to the discordances between Fibroscan and biopsy. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Nascimbeni F.,University Pierre and Marie Curie | Nascimbeni F.,University of Modena and Reggio Emilia | Lebray P.,University Pierre and Marie Curie | Fedchuk L.,University Pierre and Marie Curie | And 9 more authors.
Clinical Gastroenterology and Hepatology | Year: 2015

Background & Aims: Transient elastometry is a noninvasive procedure used to measure fibrosis when patients are diagnosed with liver disease; it might be used to monitor changes over time. We investigated whether there are short-term variations in stiffness measurements that are not attributable to changes in fibrosis by studying patients with stable liver disease. Methods: We performed a retrospective analysis of 531 paired liver stiffness measurements made by Fibroscan when the study began (LSM1) and at follow-up (LSM2), more than 1 day and less than 1 year apart, from 432 stable (for body mass index, waist circumference, and alcohol consumption), untreated, immunocompetent patients with chronic liver disease (from January 2006 through March 2009). Variations between the first and follow-up measurements were expressed as absolute (LSM2-LSM1, kPa) or relative ([LSM2-LSM1]/LSM1*100) or as changes in fibrosis stage. Results: There was >20% variation in 49.7%, >30% in 34.3%, and >50% in 12.2% of paired measurements; this variation was constant across the spectrum of LSM1 values. The variations produced a 1-fibrosis stage difference in 31.5% of pairs and a ≥2-stage difference in 9.8% of pairs. Patients with LSM1 >7 kPa had increased probability of having a different stage of fibrosis at LSM2, compared with patients with LSM1 <7 kPa. Factors associated with variation included measurements made by 2 different operators or at least 1 non-senior operator, ratios of interquartile range:median values, significant fibrosis (≥7 kPa) at LSM1, baseline body mass index, or a 2-fold difference in level of alanine aminotransferase between measurements. When the analyses were restricted to measurements made by the same operator, the variation was slightly reduced; fibrosis stage differed between measurements for only 34.3% of cases. Conclusions: Operator-related and patient-related factors produce significant variations in liver stiffness measurements made by transient elastometry, limiting its use in monitoring patients. These variations are unrelated to disease progression. The lowest levels of variation occur in measurements made in patients with no or early-stage fibrosis or by a single experienced operator. © 2015 AGA Institute.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.5-1 | Award Amount: 7.81M | Year: 2010

Non-alcoholic fatty liver disease (NAFLD) has become one of the top concerns for the practising hepatogastroenterologist due to the obesity epidemic and its potential to progress to advanced liver disease which significantly impacts on overall and liver-related mortality. The aim of the FLIP (Fatty Liver: Inhibition of Progression) project is to understand and prevent the progression of liver disease in NAFLD. FLIP is a consortium of basic scientists and practising clinical hepatologists with an established track record and focus on research into the underlying mechanisms and management of patients with NAFLD. Therefore FLIP provides a unique opportunity to assemble the largest European cohort of patients with histologically diagnosed NAFLD with clinical and epidemiological data and with biobanks of DNA, frozen liver tissue and serum. These will be used in a wide range of collaborative inter-disciplinary research projects aimed at addressing key unanswered questions related to the mechanisms and consequences of liver injury in NAFLD and the development of novel preventive and therapeutic strategies. The main outcomes of FLIP will be new insights in the progression of liver disease in NAFLD in terms of initiating mechanisms and patients at risk, innovative diagnostic methods particularly adapted for large-scale screening and prognostic evaluation, improved implementation of lifestyle changes, collaboration with leading biotechnological or pharmaceutical companies in order to translate to the market diagnostic tests or newly identified molecular targets for pharmacological therapy. By disseminating the projects results, FLIP will further help the European Community to suggest guidelines on the management of this emerging liver disease. The long-term goal is to lay the foundations for the future of NAFLD research in Europe by creating a Collaborative Research Network on NAFLD that will continue the work initiated by the FLIP consortium.

Poynard T.,University Pierre and Marie Curie | Moussalli J.,University Pierre and Marie Curie | Munteanu M.,BioPredictive | Thabut D.,University Pierre and Marie Curie | And 12 more authors.
Journal of Hepatology | Year: 2013

Background & Aims Chronic hepatitis C is both a virologic and fibrotic disease and complications can occur in patients with sustained virologic response (SVR) with residual fibrosis. Due to the limitations of repeated biopsies, no studies have assessed the dynamic of fibrosis before and after treatment. Using biopsy as reference, FibroTest™ has been validated as a biomarker of fibrosis progression and regression, with similar prognostic values. The aim was to estimate the impact of SVR on the dynamic of fibrosis presumed by FibroTest™. Methods In a prospective cohort, the main end point was the 10-year regression rate of fibrosis, defined as a minimum 0.20 decrease in FibroTest™, equivalent to one METAVIR stage. Results A total of 933 patients with both repeated FibroTest™ and transient elastography were included. At 10 years, among the 415 patients with baseline advanced fibrosis, 49% (95% CI 33-64%) of the 108 SVR had a regression, which was greater than in the 219 non-responders [23% (14-33%; p <0.001 vs. SVR)] and not lower than in the 88 non-treated [45% (10-80%; p = 0.39 vs. SVR)] patients. In all 171 SVR, cirrhosis regressed in 24/43 patients, but 15 new cirrhosis cases occurred out of 128 patients, that is only a net reduction of 5.3% [(24-15) = 9/171); (2.4-9.8%)]. Four cases of primary liver cancer occurred in SVR [4.6% (0-9.8)], and 13 in non-responders [5.6% (1.5-9.8); p = 0.07]. Conclusions In patients with chronic hepatitis C, and as presumed by FibroTest™, virological cure was associated with slow regression of fibrosis 10 years later, a disappointing 5% decrease in cirrhosis cases, and a remaining 5% risk of primary liver cancer. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Poynard T.,University Pierre and Marie Curie | Ngo Y.,Biopredictive | Munteanu M.,Biopredictive | Thabut D.,University Pierre and Marie Curie | Ratziu V.,University Pierre and Marie Curie
Current Hepatitis Reports | Year: 2011

A serum biomarker (FibroTest; Biopredictive, Paris, France; FibroSure; LabCorp, Burlington, USA) and liver stiffness measurement (LSM) by Fibroscan (Echosens, Paris, France) have been extensively validated in chronic hepatitis C. This review updates the clinical validation of serum biomarkers and LSM in patients with chronic hepatitis B (CHB). One meta-analysis combined all published studies and another used a database combining FibroTest individual data. Sensitivity analysis assessed the impact of several factors, including authors' independence, length of biopsy, ethnicity, hepatitis B early antigen status, viral load, and alanine aminotransferase value. Only two biomarkers had several validations: FibroTest (8 studies, 1,842 patients), and Fibroscan (5 studies, 618 patients). For the diagnosis of advanced fibrosis, the standardized area under the receiver operating curve was 0.84 (0.79-0.86) for FibroTest and 0.89 (0.83-0.96) for LSM, without significant difference. No significant factors of variability were identified for FibroTest's performance. In conclusion, FibroTest and LSM were the most validated biomarkers of fibrosis in CHB. However, the reliability of Fibroscan must be better assessed. © 2011 The Author(s).

Houot M.,BioPredictive | Ngo Y.,BioPredictive | Munteanu M.,BioPredictive | Marque S.,Capionis | And 2 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2016

Background Blood tests and transient elastography (TE), proposed as alternatives to biopsy for identifying advanced fibrosis (METAVIR-stage-F2 or greater) or cirrhosis, have never been compared using an intention to diagnose approach, with direct comparisons only, and Bayesian approach. Aim To permit more appropriate comparisons. Methods From an overview of articles (2002-2014), we selected studies that directly compared the diagnostic accuracy of FibroTest, aspartate aminotransferase-platelet ratio index (APRI), FIB4 or TE, with biopsy as a reference, in patients with chronic hepatitis C (CHC) or B (CHB). Investigators abstracted and checked study details and quality by using pre-defined criteria. Bayesian method in intention to diagnose was the primary outcome. Results Of 1321 articles identified, 71 studies including 77 groups according to aetiology (All-CB) were eligible: 37 Only-C, 28 Only-B and 12 Mixed-C-B. There were 185 direct comparisons between the area under the ROC curves (AUROCs), 99 for the diagnosis of advanced fibrosis and 86 for cirrhosis. In All-CB, Bayesian analyses revealed significant AUROCs differences in identifying advanced fibrosis in favour of FibroTest vs. TE [credibility interval: 0.06(0.02-0.09)], FibroTest vs. APRI [0.05 (0.03-0.07)] and for identifying cirrhosis TE vs. APRI [0.07 (0.02-0.13)] and FIB4 vs. APRI [0.04(0.02-0.05)]. No differences were observed between TE and FibroTest, for identifying cirrhosis in All-CB, and in sub-groups (Only-C, Only-B, Mixed-CB) for both cirrhosis and fibrosis. Conclusions In CHC and CHB, APRI had lower performances than FIB-4, TE and FibroTest. TE had lower performance than FibroTest for identifying advanced fibrosis in All-CB, without significant difference for identifying cirrhosis in all groups. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Poynard T.,University Pierre and Marie Curie | Thabut D.,University Pierre and Marie Curie | Munteanu M.,Biopredictive | Ratziu V.,University Pierre and Marie Curie | And 2 more authors.
PLoS ONE | Year: 2010

Background: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. We hypothesized that publications with a first author having a higher Hirsch' index value (h-I), which quantifies and predicts an individual's scientific research output, should have a longer half-life. Methods and Results: 474 original articles concerning cirrhosis or hepatitis published from 1945 to 1999 were selected. The survivals of the main conclusions were updated in 2009. The truth survival was assessed by time-dependent methods (Kaplan Meier method and Cox). A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%) were considered obsolete and 100 (21%) false. The median of the h-I was = 24 (range 1-85). Authors with true conclusions had significantly higher h-I (median= 28) than those with obsolete (h-I = 19; P = 0.002) or false conclusions (h-I = 19; P = 0.01). The factors associated (P<0.0001) with h-I were: scientific life (h-I = 33 for >30 years vs. 16 for,30 years), -methodological quality score (h-I = 36 for high vs. 20 for low scores), and -positive predictive value combining power, ratio of true to not-true relationships and bias (h- I = 33 for high vs. 20 for low values). In multivariate analysis, the risk ratio of h-I was 1.003 (95%CI, 0.994-1.011), and was not significant (P = 0.56). In a subgroup restricted to 111 articles with a negative conclusion, we observed a significant independent prognostic value of h-I (risk ratio = 1.033; 95%CI, 1.008-1.059; P = 0.009). Using an extrapolation of h-I at the time of article publication there was a significant and independent prognostic value of baseline h-I (risk ratio = 0.027; P = 0.0001). Conclusions: The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-index was associated with true conclusions, methodological quality of trials and positive predictive values. © 2010 Poynard et al.

Poynard T.,University Pierre and Marie Curie | Munteanu M.,Biopredictive | Deckmyn O.,Biopredictive | Ngo Y.,Biopredictive | And 5 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Time-dependent statistics have been used to assess liver fibrosis progression (LFP) in liver diseases from birth to first biopsy, in a limited number of patients. Non-invasive biomarkers such as FibroTest (FT) should allow the estimation of LFP on larger populations. We aimed at validating this concept by comparing LFP using FT vs. biopsy (P1) and then at applying the non-invasive method to a large population (P2). Methods: In P1, LFP was assessed using biopsy and FT in 2472 untreated patients: 770 with chronic hepatitis C, 723 with hepatitis B, 761 with non-alcoholic fatty liver disease (NAFLD), and 218 with alcoholic fatty liver disease (ALD). In P2, 342,346 interpretable FT prospectively measured were used. LFP was estimated using transition rates (cumulative hazard rate) to cirrhosis (F4) or to minimal fibrosis (>F0). Results: In P1, there was a significant concordance between FT and biopsy estimates of hazards with intraclass correlation (ICC) = 0.961 (95% CI 0.948-0.970) and 0.899 (95% CI 0.135-0.969) for F4 and >F0, respectively. This concordance persisted according to the disease and the gender. The more rapid LFP to F4 (biopsy/FT) was observed for men with ALD (1.44/1.62), and the slower for women with NAFLD (0.09/0.02). In P2, the LFP started to increase for men at the age of 30 years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the "man curve" around the age of 80 years. The following factors were associated with LFP to F4 (all p <0.0001): male gender (Relative Risk = 3.29), HIV co-infection (2.33), and residency in Middle East (2.67) or Eastern Europe (2.15). Conclusions: Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors. © 2012 European Association for the Study of the Liver.

Biopredictive | Date: 2013-06-05

The present invention relates to a new diagnosis method in the field of hepatology, combining measurement of serum markers and of liver elasticity.

Biopredictive | Date: 2012-11-30

The present invention relates to a new diagnosis method in the field of hepatology, combining measurement of serum markers and of liver elasticity.

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