Subscribe to RSS
DOI: 10.1055/s-2007-963008
© Karl Demeter Verlag im Georg Thieme Verlag KG Stuttgart · New York
Nicht invasive Beurteilung des Leberfibrosestadiums mit der transienten Elastografie (FibroScan): Aktueller Stand und Perspektiven
Transient Elastography (FibroScan) for the Non-Invasive Assessment of Liver Fibrosis: Current Status and PerspectivesPublication History
Manuskript eingetroffen: 13.12.2006
Manuskript akzeptiert: 20.2.2007
Publication Date:
15 May 2007 (online)
![](https://www.thieme-connect.de/media/zfg/200705/lookinside/thumbnails/10.1055-s-2007-963008-1.jpg)
Zusammenfassung
Die Kenntnis des Leberfibrosestadiums ist für die Einschätzung von Prognose und Verlauf und zur Beurteilung der Therapieindikation bei Patienten mit chronischen Lebererkrankungen von entscheidender Bedeutung. Die Leberbiopsie gilt immer noch als „Gold”-Standard zur Beurteilung des Leberfibrosestadiums. Allerdings ist die Leberbiopsie eine invasive Methode, deren diagnostische Genauigkeit durch Intra- und Inter-Beobachter-Variabilität und Variabilität der Proben eingeschränkt ist. In den letzten Jahren wurden vermehrt nicht invasive Marker und Verfahren zur Beurteilung des Leberfibrosestadiums evaluiert. Der FibroScan (Echosens, Frankreich) ist ein eigens zur Messung der Lebersteifheit (Liver Stiffness) entwickeltes Gerät, welches sich das Prinzip der transienten Elastografie zunutze macht. Inzwischen (Januar 2007) gibt es 20 Originalpublikationen und 76 Abstracts, in welchen der FibroScan bei verschiedenen Lebererkrankungen evaluiert wurde. Die vorliegende Arbeit gibt eine Übersicht über die bisher publizierten Daten. Die besten Ergebnisse des FibroScans finden sich für die Unterscheidung einer Leberzirrhose versus keiner Leberzirrhose. Durch die Kombination vom FibroScan mit Serumfibrosemarkern kann die diagnostische Genauigkeit auch für die Diagnose einer signifikanten Fibrose (Metavir F ≥ 2) weiter optimiert werden. Ersten Studienergebnissen zufolge scheint der FibroScan auch zur Beurteilung des Therapieansprechens nach einer antiviralen Therapie bei chronischer Hepatitis C Verwendung zu finden. Daneben haben weitere Studien gezeigt, dass die FibroScan-Untersuchung auch zur Einschätzung des Auftretens von Komplikationen einer Leberzirrhose herangezogen werden kann.
Abstract
A precise staging of the degree of liver fibrosis is important for the estimation of prognosis, surveillance and treatment decision in patients with chronic liver diseases. At present, liver biopsy is still the reference standard for the assessment of liver fibrosis. However, it is an invasive method associated with patient discomfort and in rare cases with serious complications. In addition, the accuracy of liver biopsy is limited due to intra- and interobserver variability and sampling errors. Non-invasive markers and methods for the assessment of liver fibrosis have been intensively evaluated in many studies. The FibroScan (Echosens, France) uses the transient elastography principle for the measurement of liver stiffness. At present (January 2007), studies evaluating the FibroScan in a wide range of liver diseases have been published in 20 full papers and 76 abstracts. The present review gives an overview of the current literature. The best results are reported for the differentiation between cirrhosis and no cirrhosis. With the combination of FibroScan and non-invasive serum fibrosis markers, the accuracy for the diagnosis of significant fibrosis (Metavir F ≥ 2) can be further improved. According to recent data the FibroScan can also be useful for the evaluation of treatment response in patients receiving antiviral treatment for chronic hepatitis C. In addition, several studies have shown, that the FibroScan can be applied to estimate the risk of complications associated with liver cirrhosis.
Schlüsselwörter
Leber - Leberfibrose - nicht invasive Fibrosemarker - FibroScan - Elastografie
Key words
liver - liver fibrosis - non-invasive marker of fibrosis - FibroScan - elastography
Literatur
- 1 Zeuzem S. Standard treatment of acute and chronic hepatitis C. Z Gastroenterol. 2004; 42 714-719
- 2 Fleig W E, Krummenerl P, Lesske J. et al . Diagnosis, progression and therapy of hepatitis C virus infection as well as viral infection in children and adolescents - results of an evidenced based consensus conference of the German Society for Alimentary Metabolic Disorders and and in cooperation with the Hepatitis Competence Network. Z Gastroenterol. 2004; 42 703-704
- 3 Fleig W E, Krummener P, Lesske J. Criteria for the definition of acute and chronic hepatitis C. Z Gastroenterol. 2004; 42 707-713
- 4 National Institutes of Health Consensus Development Conference Statement . Management of hepatitis C 2002 (June 10 - 12, 2002). Hepatology. 2002; 36 S3-S20
- 5 Bravo A A, Sheth S G, Chopra S. Liver biopsy. N Engl J Med. 2001; 344 495-500
- 6 Cadranel J F, Rufat P, Degos F. Practices of liver biopsy in France: redults of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the Liver (AFEF). Hepatology. 2000; 32 477-481
- 7 Castera L, Negre I, Samii K. et al . Pain experienced during percutaneous liver biopsy. Hepatology. 1999; 30 1529-1530
- 8 Froehlich F, Lamy O, Fried M. et al . Practice and complications of liver biopsy. Results of a nationwide survey in Switzerland. Dig Dis Sci. 1993; 38 1480-1484
- 9 Lindor K D, Bru C, Jorgensen R A. et al . The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy. Hepatology. 1996; 23 1079-1083
- 10 Perrault J, McGill D B, Ott B J. et al . Liver biopsy: complications in 1000 inpatients and outpatients. Gastroenterology. 1978; 74 103-106
- 11 Bedossa P, Dargere D, Paradise V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003; 38 1449-1457
- 12 Bedossa P, Poynard T, Naveau S. et al . Observer variation in assessment of liver biopsies of alcoholic patients. Alcohol Clin Exp Res. 1988; 12 173-178
- 13 Maharaj B, Maharaj R J, Leary W P. et al . Sampling variability and its influence on the diagnostic yield of percutaneous needle biopsy of the liver. Lancet. 1986; 1 523-525
- 14 Regev A, Berho M, Jeffers L J. et al . Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002; 97 2614-2618
- 15 Pilette C, Rousselet M C, Bedossa P. et al . Histopathological evaluation of liver fibrosis: quantitative image analysis vs semi-quantitative scores. Comparison with serum markers. J Hepatol. 1998; 28 439-446
- 16 Westin J, Lagging L M, Wejstal R. et al . Interobserver study of liver histopathology using the Ishak score in patients with chronic hepatitis C virus infection. Liver. 1999; 19 183-187
- 17 Baunsgaard P, Sanchez G C, Lundborg C J. The variation of pathological changes in the liver evaluated by double biopsies. Acta Pathol Microbiol Scand [A]. 1979; 87 51-57
- 18 Soloway R D, Baggenstoss A H, Schoenfield L J. et al . Observer error and sampling variability tested in evaluation of hepatitis and cirrhosis by liver biopsy. Am J Dig Dis. 1971; 16 1082-1086
- 19 Poynard T, Munteanu M, Imbert-Bismut F. et al . Prospective analysis of discordant results between biochemical markers and biopsy in patients with chronic hepatitis C. Clin Chem. 2004; 50 1344-1355
- 20 Callewaert N, Van Vlierberghe H, Van hecke A. et al . Noninvasive diagnosis of liver cirrhosis using DNA-sequencer-based total serum protein glycomics. Nat Med. 2004; 10 429-434
- 21 Forns X, Ampurdanes S, Llovet J M. et al . Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002; 36 986-992
- 22 Guechot J, Laudat A, Loria A. et al . Diagnostic accuracy of hyaluronan and type III procollagen aminoterminal peptide serum assays as markers of liver fibrosis in chronic viral hepatitis C evaluates by ROC curve analysis. Clin Chem. 1996; 42 558-563
- 23 Hui A Y, Chan H L, Wong V W. et al . Identification of chronic hepatitis B patients without significant liver fibrosis by a simple noninvasive predictive model. Am J Gastroenterol. 2005; 100 616-623
- 24 Imbert-Bismut F, Ratziu V, Pieroni L. et al . Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001; 357 1069-1075
- 25 Murawaki Y, Ikuta Y, Okamoto K. et al . Diagnostic value of serum type IV collagen test in comparison with platelet count for predicting the fibrotic stage in patients with chronic hepatitis C. J Gastroenterol. 2001; 36 399-406
- 26 Patel K, Muir A J, McHutchison J G. Validation of a simple predictive model for the identification of mild hepatic fibrosis in chronic hepatitis C patients. Hepatology. 2003; 37 1222-1223
- 27 Patel K, Lajoie A, Heaton S. et al . Clinical use of hyaluronic acid as a predictor of fibrosis change in hepatitis C. J Gastroenterol Hepatol. 2003; 18 253-257
- 28 Pohl A, Behling C, Oliver D. et al . Serum aminotransferase levels and platelet counts as predictors of degree of fibrosis in chronic hepatitis C virus infection. Am J Gastroenterol. 2001; 96 3142-3146
- 29 Rosenberg W M. Rating fibrosis progresseion in chronic liver disease. J Hepatol. 2003; 38 357-360
- 30 Wai C T, Greenson J K, Fontana R J. et al . A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003; 38 518-526
- 31 Ziol M, Handra-Luca A, Kettaneh A. et al . Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005; 41 48-54
- 32 Castera L, Vergniol J, Foucher J. 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
- 33 Bedossa P. Proteomics and pathology. Ann Pathol. 2003; 1 S25-S26
- 34 Rosenberg W M, Voelker M, Thiel R. et al . Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology. 2004; 127 1704-1713
- 35 Foucher J, Chanteloup E, Vergniol J. et al . Diagnosis of cirrhosis by transient elastography (Fibroscan): a prospective study. Gut. 2005; 55 403-408
- 36 Aube C, Oberti F, Korali N. et al . Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis. J Hepatol. 1999; 30 471-478
- 37 Bernatik T, Strobel D, Hahn E G. et al . Doppler measurements: a surrogate marker of liver fibrosis?. Eur J Gastroenterol Hepatol. 2002; 14 383-387
- 38 Colli A, Fraquelli M, Andreoletti M. et al . Severe liver fibrosis or cirrhosis: accuracy of US for detection - analysis of 300 cases. Radiology. 2003; 227 89-94
- 39 Dietrich C F, Lee J H, Gottschalk R. et al . Hepatic and portal vein flow pattern in correlation with intrahepatic fat deposition and liver histology in patients with chronic hepatitis C. Am J Roentgenol. 1998; 171 437-443
- 40 Lim A KP, Taylor-Robinson S D, Patel N. et al . Hepatic vein transit times using a microbubble agent can predict disease severity non-invasively in patients with hepatitis C. Gut. 2005; 54 128-133
- 41 Lim A KP, Patel N, Eckersley R. et al . Hepatic vein transit time of SonoVue: a comparative study with Levovist. Radiology. 2006; 240 130-135
- 42 Colletta C, Smirne C, Fabris C. et al . Value of two noninvasive methods to detect progression of fibrosis among HCV carriers with normal aminotransferases. Hepatology. 2005; 42 838-845
- 43 Corpechot C, El Naggar A, Poujol-Robert A. et al . Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC. Hepatology. 2006; 43 1118-1124
- 44 De Ledinghen V, Trimoulet P, Mannant P R. et al . Outbreak of hepatitis C virus infection during sclerotherapy of varicose veins: Long-term follow-up of 196 patients (4535 patient-years). J Hepatol. 2007; 46 19-25
- 45 De Ledinghen V, Douvin C, Kettaneh A. et al . Diagnosis of hepatic fibrosis and cirrhosis by transient elastography in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr. 2006; 41 175-179
- 46 Foucher J, Castera L, Bernard P H. et al . Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol. 2006; 18 411-412
- 47 Gomez-Dominguez E, Mendoza J, Rubio S. et al . Transient elastography: a valid alternative to biopsy in patients with chronic liver disease. Aliment Pharmacol Ther. 2006; 24 513-518
- 48 Kawamoto M, Mizuguchi T, Katsuramaki T. et al . Assessment of liver fibrosis by a noninvasive method of transient elastography and biochemical markers. World J Gastroenterol. 2006; 12 4325-4330
- 49 Kazemi F, Kettaneh A, N’kontchou G. et al . Liver stiffness measurement selects patients with cirrhosis at risk of bearing large oesophageal varices. J Hepatol. 2006; 45 230-235
- 50 Laharie D, Zerbib F, Adhoute X. et al . Diagnosis of liver fibrosis by transient elastography (FibroScan) and non-invasive methods in Crohn’s disease patients treated with methotrexate. Aliment Pharmacol Ther. 2006; 23 1621-1628
- 51 Maida I, Nunez M, Rios M J. et al . Severe liver disease associated with prolonged exposure to antiviral drugs. J Acquir Immune Defic Syndr. 2006; 42 177-182
- 52 Masaki N, Imamura M, Kikuchi Y. et al . Usefulness of elastometry in evaluating the extents of liver fibrosis in hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus. Hepatol Res. 2006; 35 135-139
- 53 Saito H, Tada S, Nakamoto N. et al . Efficacy of non-invasive elastometry on staging of hepatic fibrosis. Hepatol Res. 2004; 29 97-103
- 54 Sandrin L, Fourquet B, Hasquenoph J M. et al . Transient elastography: a new non-invasive method for assessment of hepatic fibrosis. Ultrasound Med Biol. 2003; 29 1705-1713
- 55 Yeh W C, Li P C, Jeng Y M. et al . Elastic modulus measurements of human liver and correlation with pathology. Ultrasound Med Biol. 2002; 28 467-474
- 56 Carrion J A, Navasa M, Bosch J. et al . Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation. Liver Transpl. 2006; 12 1791-1798
- 57 Erhardt A, Lorke J, Vogt C. et al . Transient elastography for diagnosing liver cirrhosis. Dtsch Med Wochenschr. 2006; 131 2765-2769
- 58 Ganne-Carrie N, Ziol M, L de V. et al . Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology. 2006; 44 1511-1517
- 59 Konate A, Boursier J, Reaud S. et al . Liver stiffness measurement by transient elastography: predictive factors of accuracy, success and reproducibility. Hepatology. 2006; 44 (Supp 1) 452A
- 60 Fraquelli M, Rigamonti C, Conte D. et al . Reproducibility of transient elastography (TE) in assessing hepatic fibrosis. Hepatology. 2006; 44 (Suppl 1) 444A
- 61 Boursier J, Guilluy M, Gorea G. et al . Liver stiffness measurement by transient elastography (FibroScan): is training necessary?. Hepatology. 2006; 44 (Suppl 1) 465A
- 62 Munteanu M, Ngo Y, De Torres M. et al . Three-dimensional and metabolic variability of FibroScan (transient elastography) measures in healthy volunteers. DDW. 2006; Abstract ID 545
- 63 Coco B, Oliveri F, Colombatto B. et al . Liver stiffness measured by transient elastography: the influence of biochemical activity. J Hepatol. 2006; 44 (Suppl 2) S196A
- 64 Coco B, Oliveri F, Colombatto P. et al . Monitoring liver stiffness: a new tool to measure liver fibrosis during therapy. Hepatology. 2005; 42 (Suppl 1) 435 A
- 65 De Ledinghen V, Beaugrand M, Kelleher T B. et al . Prediction of liver fibrosis in non-alcoholic steatohepatitis (NASH): risk factors and diagnostic potential of liver elasticity using FibroScan. J Hepatol. 2006; 44 (Suppl 2) S39 A
- 66 Takeda J, Yasuda T, Kimura M. et al . Noninvasive diagnosis of nonalcoholic steatohepatitis using elastometry. Hepatology. 2006; 44 (Suppl 1) 652A
- 67 Fukuzawa Y, Kizawa S, Ohashi T. et al . Efficacy of non-invasive hepatic fibrosis quantificated-evaluation by liver elasticity measurement in nonalcoholoc steatohepatitis (NASH) - comparison of ultrasonic transient elastography and histopathological diagnosis. Hepatology. 2006; 44 (Suppl 1) 649A
- 68 Fukuzawa Y, Ohashi T, Matsumoto E. et al . Efficacy of non-invasive hepatic fibrosis quantification by liver elasticity measurement in nonalcoholoc steatohepatitis (NASH) - comparison of ultrasonic transient elastography and histopathological diagnosis. DDW. 2006; Abstract ID 539
- 69 Kelleher T B, MacFarlane C, De Ledinghen V. et al . Risk factors and hepatic elastography (Fibroscan) in the prediction of hepatic fibrosis in non alcoholic steatohepatitis. DDW. 2006; Abstract ID 546
- 70 Corpechot C, El Naggar A, Poupon R. Gender and Liver: is the liver stiffness weaker in weaker sex?. Hepatology. 2006; 44 513-514
- 71 Roulot D, Costes J L, Le Clesiau H. et al . Liver stiffness values in subjects without known risk factor for chronic liver diseases. Hepatology. 2006; 44 (Suppl 1) 490A
- 72 Castera L, Le Bail B, Foucher J. et al . Prospective analysis of discordance between FibroScan and FibroTest when used in combination as first-line assessment of liver fibrosis in chronic hepatitis C. Hepatology. 2005; 42 (Suppl 1) 440A
- 73 De Ledinghen V, Le Bail B, Rebouissoux L. et al . FibroScan® is a new non-invasive method for the diagnosis of liver fibrosis in children: a prospective comparison with FibroSure®, and liver biopsy. Hepatology. 2005; 42 (Suppl 1) 472A
- 74 Castera L, Van Hecke A, Trimoulet P. et al . Independent validation and comparison with FibroScan, FibroTest and liver biopsy of clinical glycomics for the non invasive assessment of liver fibrosis in chronic hepatitis C. Hepatology. 2005; 42 (Suppl 1) 436A
- 75 Foucher J, Vergniol J, Castera L. et al . Fibrosis evaluation in chronic liver diseases: comparison of FibroScan® with liver biopsy, FibroTest®, Forns score, APRI, hyaluronan, prothrombin time, and AST/ALT ratio. J Hepatol. 2005; 42 (Suppl 2) 78A
- 76 Le Tallec V, Le Bigot J, Gorea G. et al . Combination of blood scores, doppler ultrasonography, and transient elastography for the diagnosis of liver fibrosis. Hepatology. 2006; 44 (Suppl 1) 453A
- 77 Farnan R, Heitor F, Nasser I. et al . Optimization of the diagnosis of cirrhosis comparing clinical, biochemical and radiological features with liver stiffness by FibroScan. Hepatology. 2006; 44 (Suppl 1) 276A
- 78 Parkes J, Guha I N, Roderick P. et al . Performance of serum marker panels for liver fibrosis in chronic hepatitis C. J Hepatol. 2006; 44 462-474
- 79 Coco B, Oliveri F, Colombatto P. et al . Monitoring liver elasticity: a new tool to measure liver fibrosis during therapy. J Hepatol. 2005; 42 (Suppl 2) 258A
- 80 De Ledinghen V, Castera L, Foucher J. et al . Evaluation of fibrosis regression using FibroScan in HCV responder patients. A prospective controlled study. J Hepatol. 2006; 44 (Suppl 2) S210A
- 81 Grando-Lemaire V, De Ledinghen V, Bourcier V. et al . Liver stiffness measurement (LMS) as a tool to measure liver fibrosis in treated patients with chronic hepatitis C (CHC). J Hepatol. 2006; 44 (Suppl 2) S214A
- 82 De Ledinghen V, Castera L, Foucher J. et al . Evaluation of fibrosis evolution using non-invasive methods according to sustained virological response in HCV patients. A pilot prospective controlled study. Hepatology. 2006; 44 (Suppl 1) 337A
- 83 Serejo F, Marinho R, Costa A. et al . Transient elastography (FibroScan®) in chronic hepatitis C. Will it modify the assessment and the follow-up of treated patients?. Hepatology. 2006; 44 (Suppl 1) 322A-323A
- 84 De Ledinghen V, Foucher J, Castera L. et al . Evaluation of fibrosis regression using non-invasive methods in very long-term follow-up of HCV responder patients. Hepatology. 2006; 44 (Suppl 1) 317A
- 85 Foucher J, Castera L, Bernard P H. et al . Assessment of cirrhosis and its severity by FibroScan and biochemical markers in alcoholic patients. J Hepatol. 2006; 44 (Suppl 2) S39A
- 86 Morente A, Romero M, Barreiro P. et al . Clinical manifestation of end-stage liver disease (ESLD) in patients with chronic viral hepatitis and advanced liver fibrosis assessed by elastography. Hepatology. 2005; 42 (Suppl 1) 338A-339A
- 87 Kim J K, Kim H S, Park Y N. et al . Transient elastography: a new and useful non-invasive method in determination of endoscopic surveillence for esophageal varices in hepatitis B related compensated cirrhosis. Hepatology. 2006; 44 (Suppl 1) 447A-448A
- 88 Nahon P, Kettaneh A, Lemoine M. et al . Liver stiffness measurement (LSM) by FibroScan in cirrhotic patients with small hepatocellular carcinoma (HCC): retrospective study comparing 50 cases with 197 compensated Child-Pugh A cirrhotic patients without HCC. Hepatology. 2006; 44 (Suppl 1) 513A
- 89 Bureau C, Metivier S, Peron J M. et al . Prospective assessment of liver stiffness for the non-invasive diagnosis of portal hypertension. Hepatology. 2006; 44 (Suppl 1) 467A-468A
- 90 Foucher J, Castera L, Adhoute X. et al . Assessment of the severity of cirrhosis according to different values of FibroScan: a prospective study. Hepatology. 2006; 44 (Suppl 1) 450A
- 91 Lemoine M, Katsahian S, Nahon P. et al . Liver stiffness measurement is correlated with hepatic venous pressure gradient in patients with uncomplicated alcoholic and/or HCV related-cirrhosis. Hepatology. 2006; 44 (Suppl 1) 204A
- 92 Khohkar A, Farnan R, MacFarlane C. et al . Liver stiffness and biomarkers: correlation with cirrhosis, portal hypertension and hepatic synthetic function. Hepatology. 2005; 42 (Suppl 1) 433A
- 93 Friedrich-Rust M, Ong M F, Herrmann E. et al . Realtime-Elastography for non-invasive assessment of liver firbrosis in chronic viral hepatitis. Am J Roentgenol. 2007; 188 758-764
- 94 Rouviere O, Yin M, Dresner M A. et al . MR elastography of the liver: preliminary results. Radiology. 2006; 240 440-448
- 95 Lewin M, Poujol-Robert A, Boelle P Y. et al . Diffusion-weighted MR imaging for the diagnosis of liver fibrosis in patients with chronic hepatitis C. Hepatology. 2006; 44 (Suppl 1) 280A-281A
Dr. Mireen Friedrich-Rust
Medizinische Klinik I, Klinikum der Johann Wolfgang Goethe-Universität
Theodor-Stern-Kai 7
60590 Frankfurt am Main
Phone: ++49/69/63 01 52 12
Fax: ++49/69/63 01 47 80
Email: Mireen.Friedrich-Rust@kgu.de