Acoustic Radiation Force Impulse Elastography as Compared to Transient Elastography and Liver Biopsy in Patients with Chronic Hepatopathies

Zusammenfassung

Ziel: Vergleich zweier nicht invasiver Beurteilungsmethoden: transiente Elastografie (TE) und Acoustic Radiation Force Impulse Imaging (ARFI). Patienten und Methoden: In die Studie wurden 114 Patienten eingeschlossen. 38 gesunde Probanden (ohne Fibrose – F0) und 76 Patienten mit chronischen Lebererkrankungen: 53 hiervon hatten eine Leberbiopsie (LB) (7 mit F1, 24 mit F2 und 22 mit F3 Stadium nach Metavir) und 23 zuvor mit Leberzirrhose diagnostizierte Patienten (F4 nach Metavir). Die Leberelastizität wurde bei allen Patienten mittels TE und ARFI untersucht. ARFI (Quantifizierung transversaler Wellengeschwindigkeiten) wurde an 3 Lokalisationen durchgeführt: ausgehend von der Kapsel bei 0 – 1 cm, bei 1 – 2 cm und bei 2 – 3 cm. In jeder Untersuchungstiefe wurden 5 valide Messungen durchgeführt und daraus der Median kalkuliert (in m/s). Ergebnisse: Es zeigte sich eine direkte starke lineare Korrelation zwischen TE und dem Stadium der Fibrose (Spearman rho = 0,848; p < 0,001). Eine signifikante direkte Korrelation zeigte sich auch zwischen den ARFI Messungen bei 1 – 2 cm und 2 – 3 cm unterhalb der Leberkapsel und dem Stadium der Fibrose (rho = 0,675 bzw. 0,714). Die subkapsulär erhobenen ARFI Werte zeigten nur eine schlechte Korrelation mit dem Fibrosegrad (rho = 0,469). Die beste Methode zur Prädiktion einer signifikanten Fibrose (F ≥ 2) war TE; hier ergab sich eine „area under receiver-operating characteristic curve” (AUROC) von 0,908, was signifikant größer war als die mittels ARFI gemessenen AUROCs. Bezüglich der ARFI Messungen hatten die aus einer Untersuchungstiefe von 1 – 2 cm und von 2 – 3 cm unterhalb der Leberkapsel den besten prädiktiven Wert. Hierbei unterschieden sich die AUROCs nicht signifikant voneinander (0,767 bzw. 0,731). Zur Prädiktion einer Fibrose (F > 0) hatte TE den besten prädiktiven Wert: der optimale Cut-off Wert lag bei 5,65 kPa (AUROC – 0,898). Für ARFI lagen die Cut-off Werte bei 1,4 m/s, AUROC - 0,747 (1 – 2 cm), und 1,26 m/s AUROC – 0,721 (2 – 3 cm). Zur Vorhersage einer Zirrhose (F = 4 nach Metavir) waren die optimierten Cut-off Werte: TE –12,9 kPa (AUROC – 0,994); ARFI – 1,78 m/s für die Messung bei 2 – 3 cm subkapsulär, AUROC – 0,951. Schlussfolgerung: Aktuell ist die Messung der Leberelastizität mittels ARFI der Messung mittels TE zur Beurteilung der Leberfibrose nicht überlegen. Mittels ARFI werden die besten Ergebnisse bei Messung 1 – 2 bzw. 2 – 3 cm subkapsulär erzielt. ARFI ist eine akkurate Untersuchungsmethode zur Diagnose einer Zirrhose.

Abstract

Purpose: To compare two methods of noninvasive assessment: transient elastography (TE) and acoustic radiation force impulse elastography (ARFI). Patients and Methods: Our study included 114 subjects: 38 healthy volunteers, (considered to have no fibrosis – F 0) and 76 patients with chronic liver disease: 53 who had undergone liver biopsy (LB) (7 with F 1, 24 with F 2, 22 with F 3 Metavir) and 23 previously diagnosed with cirrhosis (F4 Metavir). In each patient we performed a liver stiffness measurement by means of TE and ARFI. ARFI (shear wave velocity quantification) was performed at 3 points: at 0 – 1 cm, at 1 – 2 cm and at 2 – 3 cm under the capsule. For each depth, 5 valid measurements were made, and a median value was calculated, measured in m/sec. Results: A direct, strong, linear correlation (Spearman rho = 0.848) was found between TE and the stage of fibrosis (p < 0.001). A significant, direct correlation was found between ARFI measurements made 1 – 2 cm and 2 – 3 cm below the liver capsule and the severity of fibrosis (rho = 0.675 and 0.714 respectively). The subcapsularly measured ARFI values showed a poor correlation with fibrosis (rho = 0.469). The best test for predicting significant fibrosis (F ≥ 2) was TE, with the area under receiver-operating characteristic curve (AUROC) 0.908, significantly larger than the AUROCs for ARFI. If only ARFI is considered, measurements made 1 – 2 and 2 – 3 cm below the capsule have the best predictive value, with AUROCs not significantly different from each other (0.767 and 0.731, respectively). For predicting fibrosis (F > 0), TE had the best predictive value: optimized cut-off 5.65 kPa (AUROC –0.898). For ARFI, the cut-offs were: 1.4 m/sec, AUROC –0.747 (1 – 2 cm), and 1.26 m/sec AUROC –0.721 (2 – 3 cm). For predicting cirrhosis (F = 4 Metavir), the optimized cut-offs were: TE –12.9 kPa (AUROC –0.994); ARFI – 1.78 m/sec for measurements made 2 – 3 cm below the capsule, AUROC – 0.951. Conclusion: At present, liver elasticity evaluation by means of ARFI is not superior to TE for the assessment of liver fibrosis. For ARFI, the most reliable results are obtained if measurements are made 1 – 2 and 2 – 3 cm below the liver capsule. ARFI is an accurate test for the diagnosis of cirrhosis.

Key words

transient elastography - acoustic radiation force impulse elastography - liver biopsy - hepatic fibrosis

References

• 1 Gebo K A, Herlong H F, Torbenson M S et al. Role of liver biopsy in management of chronic hepatitis C: A systematic review.  Hepatology. 2002;  36 S161-S172
• 2 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
• 3 Poynard T, Zoulim F, Ratziu V et al. Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during Lamivudine therapy in patients with chronic hepatitis B infection.  Am J Gastroenterol. 2005;  100 1970-1980
• 4 Ratziu V, Massard J, Charlotte F et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.  BMC Gastroenterol. 2006;  6 6
• 5 Lainé F, Bendavid C, Moirand R et al. Prediction of liver fibrosis in patients with features of the metabolic syndrome regardless of alcohol consumption.  Hepatology. 2004;  39 1639-1646
• 6 Rockey C D. Noninvasive Assessment of Liver Fibrosis and Portal Hypertension with Transient Elastography.  Gastroenterology. 2008;  134 8-14
• 7 Talwalkar J A, Kurtz D M, Schoenleber S J et al. Ultrasound-based transient elastography for the detection of hepatic fibrosis: systematic review and meta-analysis.  Clin Gastroenterol Hepatol. 2007;  5 1214-1220
• 8 Friedrich-Rust M, Ong M F, Martens S et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis.  Gastroenterology. 2008;  134 960-974
• 9 Friedrich-Rust M, Ong M F, Herrmann E et al. Real-time elastography for noninvasive assessment of liver fibrosis in chronic viral hepatitis.  Am J Roentgenol. 2007;  188 758-764
• 10 Tatsumi C, Kudo M, Ueshima K et al. Noninvasive evaluation of hepatic fibrosis using serum fibrotic markers, transient elastography (FibroScan) and real-time tissue elastography.  Intervirology. 2008;  51 27-33 . Epub 2008 Jun 10
• 11 Havre R F, Elde E, Gilja O H et al. Freehand real-time elastography: impact of scanning parameters on image quality and in vitro intra-and interobserver validations.  Ultrasound Med Biol. 2008;  34 1638-1650 . Epub 2008 Jun 4
• 12 Fujimoto K, Kato M, Wada S et al. Noninvasive evaluation of Hepatic Fibrosis in patients with Chronic Hepatitis C using Elastography.  Medix. 2007;  Suppl 24-27
• 13 Huwart L, Sempoux C, Vicaut E et al. Magnetic Resonance Elastography for the Noninvasive Staging of Liver Fibrosis.  Gastroenterology. 2008;  135 32-40 . Epub 2008 Apr 4
• 14 Yin M, Talwalkar J A, Glaser K J et al. Assessment of hepatic fibrosis with magnetic resonance elastography.  Clin Gastroenterol Hepatol. 2007;  5 1207.e2-1213.e2
• 15 Nightingale K, Soo M S, Nightingale R et al. Acoustic radiation force impulse imaging: in vivo demonstration of clinical feasibility.  Ultrasound Med Biol. 2002;  28 227-235
• 16 Sporea I, Şirli R, Deleanu A et al. Comparison of the liver stiffness measurement by transient elastography with the liver biopsy.  World J Gastroenterol. 2008;  14 6513-6517
• 17 Ogawa E, Furusyo N, Toyoda K et al. Transient elastography for patients with chronic hepatitis B and C virus infection: Noninvasive, quantitative assessment of liver fibrosis.  Hepatol Res. 2007;  37 1002-1010 . Epub 2007 Jul 1
• 18 Adhoute X, Foucher J, Laharie D et al. Diagnosis of liver fibrosis using FibroScan and other noninvasive methods in patients with haemochromatosis: a prospective study.  Gastroenterol Clin Biol. 2008;  32 180-187
• 19 Yoneda M, Yoneda M, Mawatari H et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD).  Dig Liver Dis. 2008;  40 371-378 . Epub 2007 Dec 20
• 20 Corpechot C, El Naggar A, Poujol-Robert A et al. Assessment of billiary fibrosis by transient elastography in patients with PBC and PSC.  Hepatology. 2006;  43 1118-1124
• 21 Frey H. Real-time elastography: a new ultrasound procedure for reconstruction of tissue elasticity.  Radiologe. 2003;  43 850-855
• 22 Afdhal N. Debate: Are non-invazive tests ready to replace liver biopsy? In favor of the use of non-invazive tests.  Clinical Care Options. 2006;  7-19
• 23 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
• 24 Friedman L S. Controversies in liver biopsy: who, where, when, how and why?.  Curr Gastroenterol Rep. 2004;  6 30-36
• 25 Abdi W, Milan J C, Mezey E. Sampling variability on percutaneous liver biopsy.  Arch Intern Med. 1979;  139 667-669
• 26 Colloredo G, Guido M, Sonzogni A et al. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease.  J Hepatol. 2003;  39 239-244
• 27 Bedossa P, Dargere D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis.  Hepatology. 2003;  38 1449-1457
• 28 Thampanitchawong P, Piratvisuth T. Liver biopsy: complications and risk factors.  World J Gastroenterol. 1999;  5 301-304
• 29 Piccinino F, Sagnelli E, Pasquale G et al. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68,276 biopsies.  J Hepatol. 1986;  2 165-173