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Thierry Poynard, Victor de Ledinghen,
Jean-Pierre Zarski,
Carol Stanciu,
Mona Munteanu,
Julien Vergniol,
Julie France,
Anca Trifan,
Gilles Lenaour,
Jean-Christophe Vaillant,
Vlad Ratziu,
Frederic Charlotte
[show abstract]
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ABSTRACT: 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.
Gastroentérologie Clinique et Biologique 09/2012; · 0.80 Impact Factor
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Jérôme Boursier,
Jean-Pierre Zarski, Victor de Ledinghen,
Marie-Christine Rousselet,
Nathalie Sturm,
Brigitte Lebail,
Isabelle Fouchard-Hubert,
Yves Gallois,
Frédéric Oberti,
Sandrine Bertrais,
Paul Calès
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ABSTRACT: BACKGROUND: Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: =10 valid measurements, ≥60% success rate, and IQR/median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. METHODS: 1165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. RESULTS: 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% vs 81.5% well-classified patients for the diagnosis of cirrhosis (p=0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of =10 valid measurements or LSE success rate. These two reliability criteria determined 3 LSE groups: "very reliable" (IQR/M ≤0.10), "reliable" (0.10 <IQR/M ≤0.30, or IQR/M >0.30 with LSE median <7.1 kPa), and "poorly reliable" (IQR/M >0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% (p<10(-3) ). According to these new reliability criteria, 9.1% of LSE were "poorly reliable" (versus 24.3% unreliable LSE with the usual definition, p<10(-3) ), 74.3% were "reliable", and 16.6% were "very reliable". CONCLUSION: The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: "very reliable", "reliable", and "poorly reliable" LSE. (HEPATOLOGY 2012.).
Hepatology 08/2012; · 11.66 Impact Factor
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ABSTRACT: The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis.
Hepatology 09/2011; 55(1):58-67. · 11.66 Impact Factor
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Thierry Poynard, Victor de Ledinghen,
Jean Pierre Zarski,
Carol Stanciu,
Mona Munteanu,
Julien Vergniol,
Julie France,
Anca Trifan,
Gilles Le Naour,
Jean Christophe Vaillant,
Vlad Ratziu,
Frederic Charlotte
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ABSTRACT: 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.
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.
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).
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.
Journal of Hepatology 08/2011; 56(3):541-8. · 9.26 Impact Factor
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Thierry Poynard, Victor de Ledinghen,
Jean-Pierre Zarski,
Carol Stanciu,
Mona Munteanu,
Julien Vergniol,
Julie France,
Anca Trifan,
Joseph Moussalli,
Pascal Lebray,
Dominique Thabut,
Vlad Ratziu
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ABSTRACT: Two widely used biomarkers of fibrosis, FibroTest and liver stiffness measurement (LSM), have been mostly validated in patients with chronic hepatitis C (CHC) using the standard area under the ROC curve (sAUROC) which is not the most appropriate method due to the risk of fibrosis spectrum effect. Furthermore the performance of these biomarkers have not been assessed in "intention to diagnose" which takes into account the failures and non-reliable results.
The aim was to compare the accuracy of FibroTest and LSM for the diagnosis of fibrosis using sAUROC, the pairwise comparison of fibrosis stages by Obuchowski measure (wAUROC), and these AUROCs reassessed after taking into account the applicability rates.
One thousand two hundred and eighty-nine patients with CHC and 604 healthy volunteers were analyzed. The performances of biomarkers assessed were compared in a patients-only group (P1: n=1289), in a population combining both patients and healthy volunteers (P2: n=1893) and in a simulated population (P3: n=1893) with the prevalence of stages observed in a reference population, to demonstrate the impact of spectrum effect. Applicability rates were estimated prospectively in 24,872 consecutive FibroTest and in 13,669 consecutive LSM examinations.
Using wAUROC, the conclusions of studies with reliable results in P1 were different than in those of P2 and in P3. There was a lower performance of FibroTest versus LSM in P1 (0.864 [0.855-0.873] vs. 0.883 [0.874-0.892]; P=0.002) which was not found in P2 (0.893 [0.887-0.900] vs. 0.894 [0.887-0.901]; P=0.86) and in P3 (0.899 [0.893-0.905] vs 0.902 [0.895-0.909]; P=0.60). Using the sAUROC, in P1, P2 and P3, there was no significant difference between FibroTest and LSM performance for advanced fibrosis and a lower performance of FibroTest versus LSM for cirrhosis. In intention to diagnose, using wAUROCs performances were higher for FibroTest vs. LSM in P1 (0.857 [0.848-0.866] vs. 0.814 [0.807-0.821]; P<0.0001) and P2 (0.885 [0.879-0.892] vs. 0.743 [0.737-0.749]; P<0.0001), without difference in P3 (0.891 [0.885-0.897] vs. 0.894 [0.887-0.901]; P=0.90). Using sAUROC, the significant differences in favor of FibroTest vs LSM persisted also for the diagnosis of advanced fibrosis, both in P1 and P2 (P<0.0001) and for the diagnosis of cirrhosis in P1 (P<0.001).
When the spectrum effects and applicability rates were taken into account, LSM had lower performance results than FibroTest for the diagnosis of fibrosis stages.
Gastroentérologie Clinique et Biologique 08/2011; 35(11):720-30. · 0.80 Impact Factor
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Jean-Pierre Zarski,
Nathalie Sturm,
Jérôme Guechot,
Adeline Paris,
Elie-Serge Zafrani,
Tarik Asselah,
Renée-Claude Boisson,
Jean-Luc Bosson,
Dominique Guyader,
Jean-Charles Renversez, [......],
Elisabeth Lasnier,
Armelle Poujol-Robert,
Frédéric Ziegler,
Marc Bourliere,
Hélène Voitot,
Dominique Larrey,
Maria Alessandra Rosenthal-Allieri,
Isabelle Fouchard Hubert,
François Bailly,
Michel Vaubourdolle
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ABSTRACT: Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC).
This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method.
Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis.
Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis.
Journal of Hepatology 07/2011; 56(1):55-62. · 9.26 Impact Factor
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Véronique Loustaud-Ratti,
Paul Carrier,
Annick Rousseau,
Marianne Maynard,
Gérard Babany,
Sophie Alain,
Christian Trépo, Victor De Ledinghen,
Marc Bourlière,
Stanislas Pol,
Vincent Di Martino,
Jean-Pierre Zarski,
Alexandrina Pinta,
Denis Sautereau,
Pierre Marquet
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ABSTRACT: Ribavirin remains today a pivotal drug in the treatment of hepatitis C; in standard double therapy, as well as in triple combination with direct antiviral agents, ribavirin reduces relapse and can double the sustained virological response obtained with peginterferon alone or in association with direct antiviral agents. In the complex network of interacting factors determining sustained virological response independently of known predictive factors related to host and virus, two modern tools are emerging: polymorphisms in the IL28B gene and very early exposure to ribavirin. The use of a pharmacokinetic-pharmacodynamic model of early ribavirin exposure to adjust the dose individually would help promote a safer ribavirin use and improve sustained virological response. The variability of the influence of ribavirin exposure on anaemia is probably genetically determined; however, the low prevalence of the implicated protective alleles of the inosine triphosphate pyrophosphatase gene could explain their lack of influence on sustained virological response.
Digestive and Liver Disease 05/2011; 43(11):850-5. · 3.05 Impact Factor
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Jérôme Boursier, Victor de Ledinghen,
Jean-Pierre Zarski,
Marie-Christine Rousselet,
Nathalie Sturm,
Juliette Foucher,
Vincent Leroy,
Isabelle Fouchard-Hubert,
Sandrine Bertrais,
Yves Gallois,
Frédéric Oberti,
Nina Dib,
Paul Calès
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ABSTRACT: Precise evaluation of the level of liver fibrosis is recommended in patients with chronic hepatitis C (CHC). Blood fibrosis tests and Fibroscan are now widely used for the non-invasive diagnosis of liver fibrosis. Detailed fibrosis stage classifications have been developed to provide an estimation of the liver fibrosis stage from the results of these non-invasive tests. Our aim was to develop a new and more accurate fibrosis stage classification by using new scores combining non-invasive fibrosis tests.
In all, 729 patients with CHC (exploratory set: 349; validation set: 380) had liver biopsy for Metavir fibrosis (F) staging, and 6 fibrosis tests: Fibroscan, Fibrotest, FibroMeter, Hepascore, FIB-4, APRI.
Exploratory set: Fibroscan and FibroMeter were the independent predictors of different diagnostic targets of liver fibrosis. New fibrosis indexes combining FibroMeter and Fibroscan were thus developed for the diagnosis of clinically significant fibrosis (CSF-index) or severe fibrosis (SF-index). The association of CSF- and SF-indexes provided a new fibrosis stage classification (CSF/SF classification): F0/1, F1/2, F2 ± 1, F2/3, F3 ± 1, F4. Validation set: CSF/SF classification had a high diagnostic accuracy (85.8% well-classified patients), significantly higher than the diagnostic accuracies of FibroMeter (69.7%, P<0.001), Fibroscan (63.3%, P<0.001), or Fibrotest (43.9%, P<0.001) classifications.
The association of new fibrosis indexes combining FibroMeter and Fibroscan provides a new fibrosis stage classification. This classification is significantly more accurate than Fibrotest, FibroMeter, or Fibroscan classifications, and improves the accuracy of the non-invasive diagnosis of liver fibrosis stages to 86% without any liver biopsy.
The American Journal of Gastroenterology 04/2011; 106(7):1255-63. · 7.28 Impact Factor
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Journal of Hepatology 11/2010; 54(5):1079-80. · 9.26 Impact Factor
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ABSTRACT: There is a need for noninvasive methods to detect liver steatosis, which can be a factor of liver fibrosis progression. This work aims to evaluate a novel ultrasonic controlled attenuation parameter (CAP) devised to target, specifically, liver steatosis using a sophisticated process based on vibration control transient elastography (VCTE™). CAP was first validated as an estimate of ultrasonic attenuation at 3.5 MHz using Field II simulations and tissue-mimicking phantoms. Performance of the CAP was then appraised on 115 patients, taking the histological grade of steatosis as reference. CAP was significantly correlated to steatosis (Spearman ρ = 0.81, p < 10(-16)). Area under receiver operative characteristic (ROC) curve (AUC) was equal to 0.91 and 0.95 for the detection of more than 10% and 33% of steatosis, respectively. Furthermore, results show that CAP can efficiently separate several steatosis grades. These promising results suggest that CAP is a noninvasive, immediate, objective and efficient method to detect and quantify steatosis.
Ultrasound in medicine & biology 11/2010; 36(11):1825-35. · 2.02 Impact Factor
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Vlad Ratziu, Victor de Ledinghen,
Fréderic Oberti,
Philippe Mathurin,
Claire Wartelle-Bladou,
Christophe Renou,
Philippe Sogni,
Marianne Maynard,
Dominique Larrey,
Lawrence Serfaty,
Dominique Bonnefont-Rousselot,
Jean-Philippe Bastard,
Marc Rivière,
Jean Spénard
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ABSTRACT: Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease associated with increased morbidity and mortality. Ursodeoxycholic acid (UDCA) may have antioxidant, anti-inflammatory, and antifibrotic properties and may reduce liver injury in NASH. To date, no studies have assessed the efficacy and safety of high-dose UDCA (HD-UDCA) in patients with NASH.
We conducted a 12-month, randomized, double-blind, placebo-controlled multicenter trial to evaluate the efficacy and safety of HD-UDCA (28-35 mg/kg per day) in 126 patients with biopsy-proven NASH and elevated alanine aminotransferase (ALT) levels. The primary study end point was reduction in ALT levels from baseline in patients treated with HD-UDCA compared with placebo. Secondary study end points were the proportion of patients with ALT normalization, relative reduction in the scores of serum markers of fibrosis and hepatic inflammation, and safety and tolerability.
HD-UDCA significantly reduced mean ALT levels -28.3% from baseline after 12 months compared with -1.6% with placebo (p<0.001). At the end of the trial, ALT levels normalized (≤35 IU/L) in 24.5% of patients treated with HD-UDCA and in 4.8% of patients who received placebo (p=0.003). Both results were not accounted for by changes in weight during the trial. HD-UDCA significantly reduced the FibroTest® serum fibrosis marker (p<0.001) compared with placebo. HD-UDCA also significantly improved markers of glycemic control and insulin resistance. There were no safety issues in this population.
Treatment with HD-UDCA was safe, improved aminotransferase levels, serum fibrosis markers, and selected metabolic parameters. Studies with histologic end points are warranted.
Journal of Hepatology 10/2010; 54(5):1011-9. · 9.26 Impact Factor
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ABSTRACT: A 73-year-old woman was admitted after the first upper gastric tract haemorrhage due to gastric variceal bleeding. A CREST syndrome associated with Hashimoto's thyroiditis, Gougerot-Sjögren syndrome, cryoglobulinaemia and complicated with severe pulmonary hypertension was diagnosed. Liver histology found precirrhotic lesions of primary biliary cirrhosis (PBC) and nodular regenerative hyperplasia (NRH). Collagen diseases are often associated with liver test abnormalities and liver disease usually associated with CREST syndrome is PBC. NRH has been found in association with collagen diseases but also with haematological diseases or drugs or with autoimmune diseases, such as PBC. This case shows the association of PBC and NRH with porto pulmonary hypertension in CREST syndrome.
European journal of gastroenterology & hepatology 09/2010; 22(9):1145-8. · 1.66 Impact Factor
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Julien Villeneuve,
Sébastien Lepreux,
Audrey Mulot,
Annie M Bérard,
Arisa Higa-Nishiyama,
Pierre Costet, Victor De Ledinghen,
Paulette Bioulac-Sage,
Charles Balabaud,
Alan T Nurden,
Jean Rosenbaum,
Eric Chevet,
Jean Ripoche
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ABSTRACT: Inflammation and lipid metabolism pathways are linked, and deregulation of this interface may be critical in hepatic steatosis. The importance of the dialog between inflammatory signaling pathways and the unfolded protein response (UPR) in metabolism has been underlined. Herein, we studied the role of CD154, a key mediator of inflammation, in hepatic steatosis. To this end, Balb/c mice, wild-type or deficient in CD154 (CD154KO), were fed a diet rich in olive oil. In vitro, the effect of CD154 was studied on primary hepatocyte cultures and hepatocyte-derived cell lines. Results showed that CD154KO mice fed a diet rich in olive oil developed hepatic steatosis associated with reduced apolipoprotein B100 (apoB100) expression and decreased secretion of very low-density lipoproteins. This phenotype correlated with an altered UPR as assessed by reduced X-Box binding protein-1 (XBP1) messenger RNA (mRNA) splicing and reduced phosphorylation of eukaryotic initiation factor 2α. Altered UPR signaling in livers of CD154KO mice was confirmed in tunicamycin (TM) challenge experiments. Treatment of primary hepatocyte cultures and hepatocyte-derived cell lines with soluble CD154 increased XBP1 mRNA splicing in cells subjected to either oleic acid (OA) or TM treatment. Moreover, CD154 reduced the inhibition of apoB100 secretion by HepG2 cells grown in the presence of high concentrations of OA, an effect suppressed by XBP1 mRNA silencing and in HepG2 cells expressing a dominant negative form of inositol requiring ER-to-nucleus signaling protein-1. The control of the UPR by CD154 may represent one of the mechanisms involved in the pathophysiology of hepatic steatosis. Conclusion: Our study identifies CD154 as a new mediator of hepatic steatosis.
Hepatology 08/2010; 52(6):1968-79. · 11.66 Impact Factor
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Jérôme Boursier,
Julien Vergniol,
Apollinaire Sawadogo,
Taoufiq Dakka,
Sophie Michalak,
Yves Gallois,
Véronique Le Tallec,
Frédéric Oberti,
Isabelle Fouchard-Hubert,
Nina Dib,
Marie Christine Rousselet,
Anselme Konaté,
Naïma Amrani, Victor de Ledinghen,
Paul Calès
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ABSTRACT: Blood tests and liver stiffness evaluation (LSE) by ultrasonographic elastometry are accurate tools for diagnosing liver fibrosis. We evaluated whether their synchronous combination in new scores could improve the diagnostic accuracy and reduce liver biopsy requirement in algorithm.
Three hundred and ninety patients with chronic liver disease of miscellaneous causes were included. Five blood fibrosis tests were evaluated: APRI, FIB-4, Hepascore, Fibrotest and FibroMeter. The reference was fibrosis Metavir staging.
Diagnosis of significant fibrosis (Metavir F>or=2). The most accurate synchronous combination was FibroMeter+LSE, which provided a significantly higher area under the receiver operating characteristic curve (0.892) than LSE alone (0.867, P=0.011) or Fibrometer (0.834, P<10(-3)). An algorithm using the FibroMeter+LSE combination and then a liver biopsy in indeterminate cases had 91.9% diagnostic accuracy and required significantly fewer biopsies (20.2%) than previously published Bordeaux algorithm (28.6%, P=0.02) or sequential algorithm for fibrosis evaluation (SAFE) (55.7%, P<10(-3)). The Angers algorithm performance was not significantly different between viral hepatitis and other causes. Diagnosis of cirrhosis. The most accurate synchronous combination was LSE+FibroMeter, which provided >or=90% predictive values for cirrhosis in 90.6% of patients vs 87.4% for LSE (P=0.02) and 57.9% for FibroMeter (P<10(-3)). An algorithm including the LSE+FibroMeter combination, and then a liver biopsy in indeterminate cases, had a significantly higher diagnostic accuracy than the SAFE algorithm (91.0 vs 79.8%, P<10(-3)), and required significantly fewer biopsies than the Bordeaux algorithm (9.3 vs 25.3%, P<10(-3)).
The synchronous combination of a blood test plus LSE improves the accuracy of the non-invasive diagnosis of liver fibrosis and, consequently, markedly decreases the biopsy requirement in the diagnostic algorithm, notably to <10% in cirrhosis diagnosis.
Liver international: official journal of the International Association for the Study of the Liver 09/2009; 29(10):1507-15. · 3.82 Impact Factor
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Journal of Hepatology 05/2009; · 9.26 Impact Factor
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ABSTRACT: The brief intervention lasts from 5 to 20 minutes and uses motivational interview techniques. This brief intervention is addressed not at alcohol-dependent patients (approximately 1.5 million people in France) but at those whose consumption is harmful or at risk (estimated at approximately 4 million people in France), especially men. The efficacy of the brief intervention is demonstrated by numerous randomized studies and meta-analyses. A mean reduction of one glass of an alcoholic beverage a day results, with consumption returning to a moderate rather than at-risk level for approximately 30%. This efficacy has been demonstrated for a duration of at least 4 years. Given that evidence also supports the behavioral changes, these findings should be taken into account by healthcare providers.
La Presse Médicale 03/2009; 38(7-8):1126-33. · 0.67 Impact Factor
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Eugenia Vispo,
Pablo Barreiro,
José Del Valle,
Ivana Maida, Victor de Ledinghen,
Carmen Quereda,
Alberto Moreno,
Juan Macías,
Laurent Castera,
Juan Antonio Pineda,
Vincent Soriano
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ABSTRACT: Transient elastography (TE) is a non-invasive method that allows liver fibrosis staging on the basis of hepatic stiffness measurements. Little is known about the influence of chronic liver inflammation on the stiffness of hepatic tissue.
A total of 112 patients with chronic hepatitis C underwent a liver biopsy and TE.
Mean values of liver stiffness (in kPa) by inflammation strata were 4.8, 6.4, 9.4 and 12.6 for A0, A1, A2 and A3, respectively, in hepatitis C virus (HCV)-monoinfected individuals (P=0.018). These figures were 8.0, 10.4, 12.9 and 12.6 for A0, A1, A2 and A3, respectively, in HIV-HCV-coinfected patients (P=0.35). In HCV-monoinfected patients with fibrosis staging F3-F4, mean liver stiffness was greater if inflammation was > or =A2 versus A0-A1 (14.6 versus 6.2 kPa; P=0.04). By contrast, no differences in liver stiffness according to inflammation were seen in HCV-monoinfected patients with <F3 or in HIV-HCV-coinfected patients regardless of liver fibrosis staging. Among HCV-monoinfected patients, mean liver stiffness was greater for alanine aminotransferase >100 versus <100 IU/l (10.5 versus 8.5 kPa; P=0.04).
The extent of liver inflammation might affect the accuracy of TE for staging liver fibrosis, particularly in HCV-monoinfected patients with advanced fibrosis on liver biopsy and/or increased alanine aminotransferase levels.
Antiviral therapy 01/2009; 14(2):187-93. · 3.16 Impact Factor
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Jérôme Boursier,
Yannick Bacq,
Philippe Halfon,
Vincent Leroy, Victor de Ledinghen,
Anne de Muret,
Marc Bourlière,
Nathalie Sturm,
Juliette Foucher,
Frédéric Oberti,
Marie Christine Rousselet,
Paul Calès
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ABSTRACT: Objective: Blood tests are usually designed to identify significant fibrosis. We evaluated their diagnostic accuracy, and how to increase it, for the clinically important targets of severe fibrosis and cirrhosis.
Methods: The accuracy for severe fibrosis or cirrhosis of four blood tests was evaluated based on Metavir staging in 1056 patients with chronic hepatitis C recruited in five independent hospitals.
Results: Using original scores, an original diagnostic target (significant fibrosis) and best diagnostic cutoff, the correct classification rates in severe fibrosis and cirrhosis stages were, respectively: FibroMeter: 90.1, 100%, Fibrotest: 78.2, 95.1%, Hepascore: 73.8, 94.9%, aspartate aminotransferase to platelet ratio index (APRI): 71.4, 88.0% (P<0.003, P=0.004, respectively, between tests). The corresponding area under the receiver operating characteristics were FibroMeter: 0.885, 0.907, Fibrotest: 0.837, 0.882, Hepascore: 0.834, 0.896, APRI: 0.822, 0.841 (P<0.003, respectively). Observed 100% negative predictive values for severe fibrosis and cirrhosis were, respectively, FibroMeter: 15.4, 47.5%, Fibrotest: 3.6, 31.9%, Hepascore: 0.3, 24.6%, APRI: 1.4, 5.3% of patients (P<0.003, respectively, between tests). By calculating a specific test for cirrhosis, including the FibroMeter markers, the correct classification (93.0%) was significantly higher for the cirrhosis diagnosis compared with the original FibroMeter (90.9%, P=0.005). This specific test provided a 100% positive predictive value for cirrhosis diagnosis versus 88% for original FibroMeter.
Conclusion: Using the most accurate original test, cirrhosis can be excluded in 47.5% of patients and is correctly diagnosed, as significant fibrosis, in 100% of patients. A specific test for cirrhosis provides a significant gain in diagnostic accuracy to 93% and in positive predictive value to 100% compared with the original test.
European Journal of Gastroenterology & Hepatology 12/2008; 21(1):28-38. · 1.76 Impact Factor
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ABSTRACT: Although an increasing number of noninvasive fibrosis markers are available in HCV-monoinfected patients, data on the performance of these tests in HIV-HCV-coinfected patients are lacking.
To assess the diagnostic performance for predicting hepatic fibrosis stage of four simple and inexpensive noninvasive indexes (FIB-4, APRI, Forns, and platelet count) in HIV-HCV-coinfected patients.
Two hundred consecutive HIV-HCV-coinfected patients from the ANRS-CO3 Aquitaine cohort who underwent liver biopsy were studied. Fibrosis stage was assessed according to Metavir scoring system by a single pathologist unaware of the data of the patients. Diagnostic performances were assessed by measuring the areas under the receiver operating characteristic curves (AUROC) and the percentage of patients correctly identified (PCI).
For predicting significant fibrosis (F > or = 2), APRI, Forns index, and FIB-4 had AUROCS of 0.77, 0.75, and 0.79, with 39%, 25%, and 70% of PCI, respectively. For predicting severe fibrosis (F > or = 3), FIB-4 had AUROC of 0.77 with 56% of PCI. For predicting cirrhosis (F4), FIB-4, APRI, and platelet count had AUROCs of 0.80, 0.79, and 0.78, with 59%, 60%, and 76% of PCI, respectively. Overall, diagnostic performances of the different indexes did not differ significantly for both significant fibrosis and cirrhosis.
The use of these noninvasive indexes could save liver biopsies in up to 56-76% of cases for the prediction of severe fibrosis-cirrhosis. However, given the high percentage of misclassified cases for significant fibrosis, such indexes do not appear currently suitable for use in clinical practice in HIV-HCV-coinfected patients.
The American Journal of Gastroenterology 09/2008; 103(8):1973-80. · 7.28 Impact Factor
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ABSTRACT: Approximately 20% of patients infected with the hepatitis B or C virus (HBV and HCV) develop cirrhosis of the liver. It is essential, especially for preventive purposes, to test for related etiological factors, especially excess alcohol consumption, metabolic syndrome, and obesity. The frequency of these health problems and their hepatic tropism explain these frequent associations. In patients with chronic HBV and HCV, alcohol consumption and metabolic syndrome increase the risk of fibrosis; in those with HCV, they also reduce the likelihood of treatment response. In patients with alcoholic hepatitis, overweight increases cirrhotic risk. If cytolysis persists after the identified factor is controlled, another etiologic factor must be sought and treated. For patients with excess alcohol consumption and similarly those with metabolic syndrome, it is essential to differentiate between dependency, which is more difficult to treat, and other risk situations, for which the efficacy of a brief intervention by the physician has been demonstrated. In this more holistic approach, the physician treats a person with liver disease, rather than just a diseased liver.
La Presse Médicale 05/2008; 37(9):1274-80. · 0.67 Impact Factor
