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Fw: NATAP: Noninvasive liver fibrosis tests-guidelines needed

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  • alleypat
    NATAP http://natap.org/ ... Non-invasive markers of liver fibrosis: How to use them in clinical practice? 2 letters to the editor requesting guidelines on the
    Message 1 of 1 , Feb 20, 2007
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      Non-invasive markers of liver fibrosis: How to use them in clinical practice?

      2 letters to the editor requesting guidelines on the use of non-invasive markers of liver fibrosis.

      Journal of Hepatologt March 2007

      Giada Sebastiani, Alfredo Alberti
      Department of Clinical and Experimental Medicine, University of Padova, and Venetian Institute of Molecular Medicine, Padova, Italy

      To the Editor:

      We fully agree with Castera et al. [1] regarding the need to develop and validate guidelines for the use of non-invasive markers of liver fibrosis in clinical practice. Castera et al. referred to a nationwide survey among French hepatologists, indicating that in France, Fibrotest is the most used marker, followed by Fibroscan and hyaluronan. Liver biopsy was still performed systematically by only 4% of respondants. Liver biopsy was considered still necessary in case of discrepancy between Fibroscan and Fibrotest. Interestingly, guidelines for the use of non-invasive markers in clinical practice were required by 95% of respondants. Similarly, a recent survey assessing the consensus among Italian hepatologists about when and how to take a liver biopsy in chronic hepatitis C showed a great divergence in the management of the same group of patients, indicating the need to better define the role of biopsy and of non-invasive markers [2]. Our studies describing sequential algorithms based on the use of APRI, Fibrotest [3], [4] clearly indicate that liver biopsy cannot be completely avoided when a precise definition of the stage of liver fibrosis is needed in patients chronically infected with HCV or HBV. This may still be essential for treatment decisions in special populations of patients, such as those with high viraemia, or with contraindications, with normal ALT or not highly motivated. In these cases, as well as in many others, the distinction among minimal, intermediate or advanced fibrosis may greatly help in directing management. Available data indicate that non-invasive markers of fibrosis and liver biopsy should be considered as agonists and not antagonists towards the common goal of correctly classifying the stage of liver fibrosis [5]. This is also true for the combined use of Fibrotest and Fibroscan, as reported by Castera et al. [6]. We completely agree with these authors that the most accurate non-invasive markers should be used as first line assessment, limiting liver biopsy to the cases in which they do not agree or have low predictive value. Priority should be given to large scale validation studies of these algorithms in different patient populations inclusive of all major etiologies of chronic liver disease and most frequent cofactors which may affect the diagnostic performance of fibrosis markers.

      References
      [1] [1]Castera L, Denis J, Babany G, Roudot-Thoraval F. Evolving practices of non-invasive markers of liver fibrosis in patients with chronic hepatitis C in France: Time for new guidelines?. J Hepatol. 2007;46:528-529. Full Text | Full-Text PDF (90 KB) | CrossRef
      [2] [2]Almasio PL, Niero M, Angioli D, Ascione A, Gullini S, Minoli G, et al.. Experts' opinions on the role of liver biopsy in HCV infection: a Delphi survey by the Italian Association of Hospital Gastroenterologists (A.I.G.O.). J Hepatol. 2005;43:381-387. Abstract | Full Text | Full-Text PDF (117 KB) | MEDLINE | CrossRef
      [3] [3]Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R, et al.. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol. 2006;44:686-693. Abstract | Full Text | Full-Text PDF (175 KB) | MEDLINE | CrossRef
      [4] [4]Sebastiani G, Vario A, Guido M, Alberti A. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B. World J Gastroenterol, in press.
      [5] [5]Sebastiani G, Alberti A. Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy. World J Gastroenterol. 2006;12:3682-3694. MEDLINE
      [6] [6]Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al.. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-350. Abstract | Full Text | Full-Text PDF (257 KB) | MEDLINE | CrossRef


      Evolving practices of non-invasive markers of liver fibrosis in patients with chronic hepatitis C in France: Time for new guidelines?

      Laurent Castera
      Jacques Denis
      Gerard Babany
      Françoise Roudot-Thoraval
      Services d'Hépato-Gastroentérologie, Centre Hosiptalier, Universitaire de Bordeaux, Bordeaux, France
      Service d'Hépato-Gastroentérologie, Centre Hospitalier Sud Francilien, Corbeil, France
      Produits Roche, Neuilly sur Seine, France
      Département de Santé Publique, AP-HP, Hôpital Henri Mondor, Créteil, France

      To the Editor:

      We read with interest the article by Sebastiani et al. [1] proposing stepwise algorithms combining non-invasive markers for the diagnosis of significant fibrosis in patients with chronic hepatitis C (CHC). We agree with the authors that combining methods may improve diagnostic accuracy. Indeed, we have also recently proposed an algorithm combining transient elastography (FibroScan®), a new technology allowing measurement of liver stiffness, and FibroTest®[2] as first-line assessment of liver fibrosis in patients with CHC [3]. Based on this algorithm, liver biopsy examination could have been avoided in more than 75% of patients for the diagnosis of significant fibrosis. It can be anticipated that non-invasive markers of fibrosis will become an important tool in clinical practice in the near future [4]. However, no guidelines regarding the use of these markers are currently available and international consensus reports [5], [6] still recommend liver biopsy as mandatory before starting antiviral therapy in CHC patients.

      We conducted a nationwide survey aimed at evaluating, in the absence of guidelines, the current practices of non-invasive markers of fibrosis in naïve patients with CHC and elevated transaminases in France. A questionnaire was sent to all French hepatologists taking care of CHC patients in April 2006. By July, 546 responses (65%) were received (public practice (n=265), academic hospitals (n=147), non-academic hospitals (n=118), private practice (n=153), both (n=128)). FibroTest® was the most widely used marker (81% of respondents for 66% of their patients), then FibroScan® (32% for 60% of their patients), and dosage of hyaluronate (17%). Liver biopsy was still performed systematically by 4% of respondents whereas it was not done anymore by 3%. The respondents estimated that liver biopsy was still necessary for the following: presence of comorbidities such as alcohol abuse or overweight (72%), discrepancy between FibroScan® and FibroTest® or discrepancy between markers and clinical judgement (72%), initiation of antiviral therapy in patients infected by HCV genotype 1 (48%) or 4 (30%), and suspicion of cirrhosis (44%). It was estimated that the use of non-invasive markers resulted in a reduced need for liver biopsy in at least (or more than) 50% of patients by 52% of respondents and in 25-50% of patients by 25% (Fig. 1). In addition, 55% of respondents considered that the use of non-invasive markers increased the number of treated patients (by 35%). Finally, updated guidelines for the use of non-invasive markers in clinical practice were required by 95% of respondents.

      The results of the present study clearly show that non-invasive markers of fibrosis are widely used in routine clinical practice in France, resulting in a significant decrease in the need for liver biopsy. They also emphasize the need for new guidelines, as requested by almost all respondents. We agree, however, with Sebastiani et al. [7] that with an expected rate of misdiagnosis of at least 20%, non-invasive markers will likely reduce but not substitute the need for liver biopsy. Thus, the most rationale way of using them would be that of a compromise in which non-invasive markers would be first used to classify those patients in whom they perform with high accuracy, limiting liver biopsy to the subset in whom precise non-invasive diagnosis is not possible, due to causes of misinterpretation of non-invasive test and/or need for other histological diagnosis.

      References

      [1] [1]Sebastiani G, Vario A, Guido M, Noventa F, Plebani M, Pistis R, et al.. Stepwise combination algorithms of non-invasive markers to diagnose significant fibrosis in chronic hepatitis C. J Hepatol. 2006;44:686-693. Abstract | Full Text | Full-Text PDF (175 KB) | MEDLINE | CrossRef

      [2] [2]Poynard T, Imbert-Bismut F, Munteanu M, Messous D, Myers RP, Thabut D, et al.. Overview of the diagnostic value of biochemical markers of liver fibrosis (FibroTest, HCV FibroSure) and necrosis (ActiTest) in patients with chronic hepatitis C. Comp Hepatol. 2004;3:8.

      [3] [3]Castera L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al.. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343-350. Abstract | Full Text | Full-Text PDF (257 KB) | MEDLINE | CrossRef

      [4] [4]Castera L, Pawlotsky JM. Noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis C. MedGenMed. 2005;7:39.

      [5] [5]EASL International Consensus Conference on hepatitis C. Paris, 26-27 February 1999. Consensus statement. J Hepatol 1999;31:3-8.

      [6] [6]NIH Consensus Statement on Management of Hepatitis C: 2002. Hepatology 2002;36:S3-20.

      [7] [7]Sebastiani G, Alberti A. Non invasive fibrosis biomarkers reduce but not substitute the need for liver biopsy. World J Gastroenterol. 2006;12:3682-3694. MEDLINE



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