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Thierry Poynard - One of the best experts on this subject based on the ideXlab platform.

  • performance of the steatotest actitest nashtest and FibroTest in a multiethnic cohort of patients with type 2 diabetes mellitus
    Journal of Investigative Medicine, 2019
    Co-Authors: Fernando Bril, Thierry Poynard, Michael J Mcphaul, Michael P Caulfield, Jeanmarie Castille, Consuelo Soldevilapico, Virginia Clark, Roberto J Firpimorell, Jinping Lai, Kenneth Cusi
    Abstract:

    Fibromax is a diagnostic tool composed of the combination of 4 non-invasive biomarker panels for the diagnosis of steatosis (SteatoTest), necrosis and inflammation (ActiTest and NashTest-2) and fibrosis (FibroTest). The purpose of this study was to assess the performance of these biomarker panels in patients with type 2 diabetes mellitus (T2DM). All patients underwent routine labs, a 75 g oral glucose tolerance test, a liver proton magnetic resonance spectroscopy (1H-MRS) to measure intrahepatic triglyceride content, and a percutaneous liver biopsy to establish the diagnosis of non-alcoholic steatohepatitis (NASH) and to grade and stage the disease in those patients with non-alcoholic fatty liver disease (NAFLD) by 1H-MRS. For determination of the scores, plasma samples were blindly provided to establish the SteatoTest, ActiTest, NashTest-2 and FibroTest scores. A total of 220 patients with T2DM were included in this study. When the ability of the SteatoTest to identify patients with T2DM with NAFLD by 1H-MRS was assessed, the overall performance expressed as the area under the receiver operating characteristic curve was 0.73 (95% CI 0.65 to 0.81). The performance of the ActiTest and NashTest-2 to diagnose definite NASH among patients with T2DM was 0.70 (95% CI 0.63 to 0.77) and 0.69 (95% CI 0.62 to 0.76), respectively. Regarding the FibroTest score, its performance to identify patients with moderate or advanced fibrosis was 0.67 (95% CI 0.58 to 0.76) and 0.72 (95% CI 0.61 to 0.83), respectively. Non-invasive panels for the diagnosis of steatosis, NASH and/or fibrosis, which were developed and validated in non-diabetic cohorts, underperformed when applied to a large cohort of patients with T2DM. Results from non-diabetic populations should not be extrapolated to patients with T2DM.

  • real time shear wave versus transient elastography for predicting fibrosis applicability and impact of inflammation and steatosis a non invasive comparison
    PLOS ONE, 2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Y Ngo, Luminita Bonyhay, Djamel Elaribi, Noemie Seurat, Tam Thanh Pham, E Luckina, Muriel Legroux
    Abstract:

    Background and Aims: Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. Methods: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. Results: A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2–90.8), was significantly higher than that of TE, 85.6%(84.0–87.0; P<0.0001). In patients with non-advanced fibrosis (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI) 0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs 0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar results. Conclusions: Elasticity results including very low minimal signal in the region of interest should be considered not reliable. 2D-SWE had a higher applicability than TE, the reference elastography, with less impact of inflammation and steatosis especially in patients with non-advanced fibrosis, as presumed by blood tests.

  • Subjects Flow chart.
    2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Luminita Bonyhay, Yen Ngo, Tam Pham, Elena Luckina, Djamel Elaribi, Noemie Seurat, Muriel Legroux
    Abstract:

    1 As FibroTest (FT) was taken as the reference, the not-reliable FTs were excluded of the "intention to diagnose population". 2 Several failures or not-reliable results were possible in the same patient explaining why the total failures or not reliable results were greater than the number of patients excluded of the 2D-SWE reliability population and of the concordance population. 3 132 patients had not-reliable SWE, but reliable TE-M and TE-XL and FT.

  • Real-Time Shear Wave versus Transient Elastography for Predicting Fibrosis: Applicability, and Impact of Inflammation and Steatosis. A Non-Invasive Comparison
    PLoS ONE, 2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Luminita Bonyhay, Yen Ngo, Tam Pham, Elena Luckina, Djamel Elaribi, Noemie Seurat, Muriel Legroux
    Abstract:

    Background and Aims: Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. Methods: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. Results: A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2–90.8), was significantly higher than that of TE, 85.6%(84.0–87.0; P

  • Comparison of SWE minimal elasticity value cut-offs according to elasticity concordance with the 3 other reliable tests' results (FibroTest, TE-M, TE-XL), in the "Reliability population" (n = 1,720).
    2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Luminita Bonyhay, Yen Ngo, Tam Pham, Elena Luckina, Djamel Elaribi, Noemie Seurat, Muriel Legroux
    Abstract:

    Comparison of SWE minimal elasticity value cut-offs according to elasticity concordance with the 3 other reliable tests' results (FibroTest, TE-M, TE-XL), in the "Reliability population" (n = 1,720).

Mona Munteanu - One of the best experts on this subject based on the ideXlab platform.

  • long term prognostic value of the FibroTest in patients with non alcoholic fatty liver disease compared to chronic hepatitis c b and alcoholic liver disease
    Alimentary Pharmacology & Therapeutics, 2018
    Co-Authors: Mona Munteanu, Valentina Peta, Y Ngo, Frederic Charlotte, Pascal Lebray, J Moussalli, Marika Rudler, Raluca Pais, Olivier Deckmyn, Vincent Thibault
    Abstract:

    Background Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non-alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver-related death. Aim To validate the 10-year prognostic value of FibroTest in NAFLD for the prediction of liver-related death. Method Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre-included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan-Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti-viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population. Results 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow-up was 6.0 years (0.1-19.3). Ten year survival (95% CI) without liver-related death in patients with NAFLD was 0.956 (0.940-0.971; 38 events) and 0.832 (0.818-0.847; 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905-0.978)/1638 (342-7839) and even higher than in patients with CHC 0.875 (0.849-0.901; P = 0.01)/2657 (993-6586). Conclusions The FibroTest has a high prognostic value in NAFLD for the prediction of liver-related death. (ClinicalTrials.gov number, NCT01927133).

  • serum apolipoprotein a1 and haptoglobin in patients with suspected drug induced liver injury dili as biomarkers of recovery
    PLOS ONE, 2017
    Co-Authors: Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Y Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu
    Abstract:

    BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN), and BILI <2x ULN. RESULTS: After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending) combining the ActiTest components without BILI and ALT (used as references), apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115) and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500). Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65) versus those that did not (n = 16), at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases. CONCLUSIONS: We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  • Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.
    PloS one, 2017
    Co-Authors: Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Yen Ngo, Vlad Ratziu
    Abstract:

    BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT

  • real time shear wave versus transient elastography for predicting fibrosis applicability and impact of inflammation and steatosis a non invasive comparison
    PLOS ONE, 2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Y Ngo, Luminita Bonyhay, Djamel Elaribi, Noemie Seurat, Tam Thanh Pham, E Luckina, Muriel Legroux
    Abstract:

    Background and Aims: Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. Methods: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. Results: A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2–90.8), was significantly higher than that of TE, 85.6%(84.0–87.0; P<0.0001). In patients with non-advanced fibrosis (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI) 0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs 0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar results. Conclusions: Elasticity results including very low minimal signal in the region of interest should be considered not reliable. 2D-SWE had a higher applicability than TE, the reference elastography, with less impact of inflammation and steatosis especially in patients with non-advanced fibrosis, as presumed by blood tests.

  • Subjects Flow chart.
    2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Luminita Bonyhay, Yen Ngo, Tam Pham, Elena Luckina, Djamel Elaribi, Noemie Seurat, Muriel Legroux
    Abstract:

    1 As FibroTest (FT) was taken as the reference, the not-reliable FTs were excluded of the "intention to diagnose population". 2 Several failures or not-reliable results were possible in the same patient explaining why the total failures or not reliable results were greater than the number of patients excluded of the 2D-SWE reliability population and of the concordance population. 3 132 patients had not-reliable SWE, but reliable TE-M and TE-XL and FT.

Vlad Ratziu - One of the best experts on this subject based on the ideXlab platform.

  • serum apolipoprotein a1 and haptoglobin in patients with suspected drug induced liver injury dili as biomarkers of recovery
    PLOS ONE, 2017
    Co-Authors: Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Y Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu
    Abstract:

    BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN), and BILI <2x ULN. RESULTS: After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending) combining the ActiTest components without BILI and ALT (used as references), apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115) and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500). Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65) versus those that did not (n = 16), at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases. CONCLUSIONS: We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  • Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI) as biomarkers of recovery.
    PloS one, 2017
    Co-Authors: Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Yen Ngo, Vlad Ratziu
    Abstract:

    BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT

  • Comparison between included and non-included patients.
    2015
    Co-Authors: Marika Rudler, Mona Munteanu, Vlad Ratziu, Frederic Charlotte, Dominique Thabut, Pascal Lebray, Sarah Mouri, Philippe Cluzel, Yen Ngo, Thierry Poynard
    Abstract:

    1One FibroTest was not reliable, and all AshTest were reliableComparison between included and non-included patients.

  • performances of elasto FibroTest a combination between FibroTest and liver stiffness measurements for assessing the stage of liver fibrosis in patients with chronic hepatitis c
    Clinics and Research in Hepatology and Gastroenterology, 2012
    Co-Authors: Thierry Poynard, Julien Vergniol, Mona Munteanu, Jeanpierre Zarski, Carol Stanciu, Anca Trifan, Victor De Ledinghen, Gilles Lenaour, Jeanchristophe Vaillant, Vlad Ratziu
    Abstract:

    Summary Background FibroTest ® (FT), and liver stiffness measurement (LSM) are the most validated techniques for the non-invasive assessment of fibrosis in patients with chronic hepatitis C (CHC). The combination between FibroTest ® and LSM has never been assessed using methods assuming that biopsy is not a perfect gold standard. Aim The aim was to assess the performance of a new test the Elasto-FibroTest ® (EFT) combining FibroTest ® and LSM. Methods An integrated data base of 1289 patients with biopsy and 604 healthy volunteers was analyzed. EFT took into account the applicability of both tests, included two algorithms taking one for the diagnosis of advanced fibrosis (EFT-F2) and one for the diagnosis of cirrhosis (EFT-F4). Performances of EFTs were assessed by three methods: area under the ROC curve (AUROC), “Obuchowski method” (OBU) and 1 TAGS the “Latent class with random factor”. Results For the diagnosis of advanced fibrosis EFT-F2 performances (specificity = 0.99 and sensitivity = 0.83) were not greater than the performances of FibroTest ® alone (specificity = 0.93 and sensitivity = 0.99). For the diagnosis of cirrhosis, EFT-F4 performances were greater than those of FibroTest ® alone, particularly for the sensitivity (0.88 vs. 0.74); when compared with LSM, EFT-F4 performances (specificity = 0.99 and sensitivity = 0.99) were also greater than those of LSM alone particularly because of its lower specificity (0.92). Conclusion For the diagnosis of cirrhosis the Elasto-FibroTest ® has higher performances than FibroTest ® or FibroScan ® alone. No improvement in performance has been observed for the diagnosis of advanced fibrosis vs. FibroTest ® alone.

  • relative performances of FibroTest fibroscan and biopsy for the assessment of the stage of liver fibrosis in patients with chronic hepatitis c a step toward the truth in the absence of a gold standard
    Journal of Hepatology, 2012
    Co-Authors: Thierry Poynard, Julien Vergniol, Mona Munteanu, Jeanpierre Zarski, Carol Stanciu, Anca Trifan, Gilles Le Naour, Jean Vaillant, Vlad Ratziu
    Abstract:

    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 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.

Y Ngo - One of the best experts on this subject based on the ideXlab platform.

  • long term prognostic value of the FibroTest in patients with non alcoholic fatty liver disease compared to chronic hepatitis c b and alcoholic liver disease
    Alimentary Pharmacology & Therapeutics, 2018
    Co-Authors: Mona Munteanu, Valentina Peta, Y Ngo, Frederic Charlotte, Pascal Lebray, J Moussalli, Marika Rudler, Raluca Pais, Olivier Deckmyn, Vincent Thibault
    Abstract:

    Background Although the FibroTest has been validated as a biomarker to determine the stage of fibrosis in non-alcoholic fatty liver disease (NAFLD) with results similar to those in chronic hepatitis C (CHC), B (CHB), and alcoholic liver disease (ALD), it has not yet been confirmed for the prediction of liver-related death. Aim To validate the 10-year prognostic value of FibroTest in NAFLD for the prediction of liver-related death. Method Patients in the prospective FibroFrance cohort who underwent a FibroTest between 1997 and 2012 were pre-included. Mortality status was obtained from physicians, hospitals or the national register. Survival analyses were based on univariate (Kaplan-Meier, log rank, AUROC) and multivariate Cox risk ratio taking into account age, sex and response to anti-viral treatment as covariates. The comparator was the performance of the FibroTest in CHC, the most validated population. Results 7082 patients were included; 1079, 3449, 2051, and 503 with NAFLD, CHC, CHB, and ALD, respectively. Median (range) follow-up was 6.0 years (0.1-19.3). Ten year survival (95% CI) without liver-related death in patients with NAFLD was 0.956 (0.940-0.971; 38 events) and 0.832 (0.818-0.847; 226 events; P = 0.004) in CHC. The prognostic value (AUROC / Cox risk ratio) of FibroTest in patients with NAFLD was 0.941 (0.905-0.978)/1638 (342-7839) and even higher than in patients with CHC 0.875 (0.849-0.901; P = 0.01)/2657 (993-6586). Conclusions The FibroTest has a high prognostic value in NAFLD for the prediction of liver-related death. (ClinicalTrials.gov number, NCT01927133).

  • serum apolipoprotein a1 and haptoglobin in patients with suspected drug induced liver injury dili as biomarkers of recovery
    PLOS ONE, 2017
    Co-Authors: Valentina Peta, Chantal Tse, Hugo Perazzo, Mona Munteanu, Y Ngo, An Ngo, Nittia Ramanujam, Lea Verglas, Maxime Mallet, Vlad Ratziu
    Abstract:

    BACKGROUND: There is a clear need for better biomarkers of drug-induced-liver-injury (DILI). AIMS: We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI. METHODS: We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC) of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN), and BILI <2x ULN. RESULTS: After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending) combining the ActiTest components without BILI and ALT (used as references), apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115) and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500). Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65) versus those that did not (n = 16), at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases. CONCLUSIONS: We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  • real time shear wave versus transient elastography for predicting fibrosis applicability and impact of inflammation and steatosis a non invasive comparison
    PLOS ONE, 2016
    Co-Authors: Thierry Poynard, Hugo Perazzo, Mona Munteanu, Y Ngo, Luminita Bonyhay, Djamel Elaribi, Noemie Seurat, Tam Thanh Pham, E Luckina, Muriel Legroux
    Abstract:

    Background and Aims: Real-time shear wave elastography (2D-SWE) is a two-dimensional transient elastography and a competitor as a biomarker of liver fibrosis in comparison with the standard reference transient elastography by M probe (TE-M). The aims were to compare several criteria of applicability, and to assess inflammation and steatosis impact on elasticity values, two unmet needs. Methods: We took FibroTest as the fibrosis reference and ActiTest and SteatoTest as quantitative estimates of inflammation and steatosis. After standardization of estimates, analyses used curve fitting, quantitative Lin concordance coefficient [LCC], and multivariate logistic regression. Results: A total of 2,251 consecutive patients were included. We validated the predetermined 0.2 kPa cut-off as a too low minimal elasticity value identifying not-reliable 2D-SWE results (LCC with FibroTest = 0.0281[-0.119;0.175]. Other criteria, elasticity CV, body mass index and depth of measures were not sufficiently discriminant. The applicability of 2D-SWE (95%CI) 89.6%(88.2–90.8), was significantly higher than that of TE, 85.6%(84.0–87.0; P<0.0001). In patients with non-advanced fibrosis (METAVIR F0F1F2), elasticity values estimated by 2D-SWE was less impacted by inflammation and steatosis than elasticity value estimated by TE-M: LCC (95%CI) 0.039 (0.021;0.058) vs 0.090 (0.068;0.112;P<0.01) and 0.105 (0.068;0.141) vs 0.192 (0.153;0.230; P<0.01) respectively. The three analyses methods gave similar results. Conclusions: Elasticity results including very low minimal signal in the region of interest should be considered not reliable. 2D-SWE had a higher applicability than TE, the reference elastography, with less impact of inflammation and steatosis especially in patients with non-advanced fibrosis, as presumed by blood tests.

  • staging chronic hepatitis b into seven categories defining inactive carriers and assessing treatment impact using a fibrosis biomarker FibroTest and elastography fibroscan
    Journal of Hepatology, 2014
    Co-Authors: Julien Vergniol, Mona Munteanu, Y Ngo, Thierry Poynard, Pascal Lebray, Vincent Thibault, J Foucher, Wassil Merrouche, Marika Rudler
    Abstract:

    Background & Aims The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. Methods The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. Results Of the 1312 patients without a history of complications, varices had occurred after 10years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6–2.8]), and severe complications in 25 (F4.3 3.7% [1.8–5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5–5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71–0.90]; p p Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p =0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p =0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2–9.1]) including 19 HCC (5.8% [2.6–9.0]) and 10 with varices (2.6% [0.8–4.4]). Of the 138 responders with advanced fibrosis, only 31% (15–47%) had fibrosis regression. Conclusions FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.

  • biopsy as well as FibroTest fibrosure is suboptimal for discriminating intermediate fibrosis stages in patients with chronic hepatitis b
    The American Journal of Gastroenterology, 2014
    Co-Authors: Mona Munteanu, Y Ngo, Marion Houot, Thierry Poynard
    Abstract:

    Biopsy as well as FibroTest/Fibrosure Is Suboptimal for Discriminating Intermediate Fibrosis Stages in Patients With Chronic Hepatitis B

Francoise Imbertbismut - One of the best experts on this subject based on the ideXlab platform.

  • validation of liver fibrosis biomarker FibroTest for assessing liver fibrosis progression proof of concept and first application in a large population
    Journal of Hepatology, 2012
    Co-Authors: Thierry Poynard, Mona Munteanu, Y Ngo, V Ratziu, Olivier Deckmyn, F Drane, J M Castille, Chantal Housset, Francoise Imbertbismut
    Abstract:

    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 30years. The cumulative fibrosis progression rate to minimal fibrosis in women crossed the "man curve" around the age of 80years. The following factors were associated with LFP to F4 (all p Conclusions Validated biomarkers such as FibroTest should allow powerful analysis of fibrosis progression in chronic liver diseases and better identification of risk factors.

  • applicability and precautions of use of liver injury biomarker FibroTest a reappraisal at 7 years of age
    BMC Gastroenterology, 2011
    Co-Authors: Thierry Poynard, Mona Munteanu, Y Ngo, Vlad Ratziu, Djamila Messous, Olivier Deckmyn, F Drane, J M Castille, Chantal Housset, Francoise Imbertbismut
    Abstract:

    FibroTest (FT) is a validated biomarker of fibrosis. To assess the applicability rate and to reduce the risk of false positives/negatives (RFPN), security algorithms were developed. The aims were to estimate the prevalence of RFPN and of proven failures, and to identify factors associated with their occurrences. Four populations were studied: 954 blood donors (P1), 7,494 healthy volunteers (P2), 345,695 consecutive worldwide sera (P3), including 24,872 sera analyzed in a tertiary care centre (GHPS) (P4). Analytical procedures of laboratories with RFPN > 5% and charts of P4 patients in with RFPN were reviewed. The prevalence of RFPN was 0.52% (5/954; 95%CI 0.17-1.22) in P1, 0.51% (38/7494; 0.36-0.70) in P2, and 0.97% (3349/345695; 0.94-1.00) in P3. Three a priori high-risk populations were confirmed: 1.97% in P4, 1.77% in HIV centre and 2.61% in Sub-Saharan origin subjects. RFPN was mostly associated with low haptoglobin (0.46%), and high apolipoproteinA1 (0.21%). A traceability study of a P3 laboratory with RFPFN > 5% permitted to correct analytical procedures. The mean applicability rate of FibroTest was 99.03%. Independent factors associated with the high risk of false positives/negatives were HIV center, subSaharan origin, and a tertiary care reference centre, although the applicability rate remained above 97%.

  • meta analyses of FibroTest diagnostic value in chronic liver disease
    BMC Gastroenterology, 2007
    Co-Authors: Thierry Poynard, Laurent Castera, Philippe Halfon, V Ratziu, R Morra, Francoise Imbertbismut, Dominique Thabut, Didier Lebrec, S Naveau, Fabien Zoulim
    Abstract:

    Background FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC). The aim was to test two hypotheses, one, that the FT diagnostic value was similar in the three other frequent fibrotic diseases: chronic hepatitis B (CHB), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD); and the other, that the FT diagnostic value was similar for intermediate and extreme fibrosis stages.

  • optimal correlation between different instruments for FibroTest actitest protein measurement in patients with chronic hepatitis c
    Gastroenterologie Clinique Et Biologique, 2007
    Co-Authors: Maria Alessandra Rosenthalallieri, Philippe Halfon, Mona Munteanu, Thierry Poynard, Djamila Messous, Francoise Imbertbismut, Albert Tran, Marieline Peritore, Alain Bernard
    Abstract:

    Summary Objectives Combination of alpha 2-macroglobulin, haptoglobin, apolipoprotein-A1, γ-glutamyl transpeptidase, total bilirubin and alanine aminotransferase measurements allows to determine the FibroTest-Actitest score, an alternative to liver biopsy in hepatitis C virus infection. The aims of this study were to evaluate the analytical variability of the FibroTest-Actitest proteins alpha 2-macroglobulin, haptoglobin and apolipoprotein-A1, and to assess their impact on the FibroTest-Actitest scores. Methods We compared 129 sera from hepatitis C virus infected patients for alpha 2-macroglobulin, haptoglobin and apolipoprotein-A1 levels obtained with the Immage ® (Beckman-Coulter) and the BNProspec ® (Dade-Berhing) automates. We evaluated FibroTest-Actitest results obtained with the two nephelemeters. Results Optimal correlation was found for alpha 2-macroglobulin (Y=1.05X + 0.01, correlation coefficient: 0.98) and haptoglobin (Y=1.05X - 0.07, correlation coefficient: 0.98). Apolipoprotein-A1 levels, as determined by Immage ® , were sligtly lower than those obtained by BNProspec ® (Y=0.86X - 0.02, CC=0.95). When FibroTest-Actitest scores obtained with the two protein measurements were compared adjusting for apolipoprotein-A1 from Immage ® , the concordance rate was 0.903±0.096, with only 2/107 patients showing minimal discordance >0.10 for FibroTest, and 1.00±0.06 for Actitest, with no discordance >0.10. Conclusions Measurement of apolipoprotein-A1, included in the FibroTest-Actitest score, depends on the equipment used. Such discordance is of little clinical consequence for liver fibrosis evaluation in hepatitis C virus patients.

  • relationship between the FibroTest and portal hypertension in patients with liver disease
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: Dominique Thabut, Thierry Poynard, Djamila Messous, Francoise Imbertbismut, Mona Muntenau, Dominique Cazalshatem, Dominique Valla, Richard Moreau, Didier Lebrec
    Abstract:

    SUMMARY Background The best technique to estimate portal hypertension (PHT) is to measure the hepatic venous pressure gradient (HVPG), which is an invasive method. Aim To assess the relationship between the FibroTest (Biopredictive, Paris, France) and the presence and degree of PHT in patients with liver disease, and to determine if the FibroTest can diagnose severe PHT, defined by HVPG ‡ 12 mmHg, in cirrhotic patients. Methods Patients who underwent a transjugular liver biopsy were prospectively included. HVPG was measured, and classification of histological lesions assessed. The same day, blood samples for FibroTest were performed. Results A total of 130 patients were included (no or minimal fibrosis: 12%, moderate fibrosis 17%, cirrhosis 71%). There was a significant correlation between FibroTest and HVPG (Pearson correlation coefficient = 0.58, P < 0.0001), also weaker in cirrhotic patients (Pearson correlation coefficient = 0.24, P = 0.02). In cirrhotic patients, FibroTest was significantly higher when there was a severe PHT (0.87 0.15 vs. 0.73 0.14, respectively, P = 0.02). The areas under the receiver operating characteristic curves for the diagnosis of severe PHT was 0.79 0.07, not different from that of platelets and Child-Pugh score.