A New Two-Dimensional Shear Wave Elastography for Noninvasive Assessment of Liver Fibrosis in Healthy Subjects and in Patients with Chronic Liver Disease

Carla Serra; Valentina Grasso; Fabio Conti; Cristina Felicani; Elena Mazzotta; Marco Lenzi; Gabriella Verucchi; Antonietta D'errico; Pietro Andreone

doi:10.1055/s-0043-119356

Ultraschall in der Medizin - European Journal of Ultrasound, Inhaltsverzeichnis

Ultraschall Med 2018; 39(04): 432-439
DOI: 10.1055/s-0043-119356

Original Article

A New Two-Dimensional Shear Wave Elastography for Noninvasive Assessment of Liver Fibrosis in Healthy Subjects and in Patients with Chronic Liver Disease

Eine neue zweidimensionale Shear-Wave-Elastografie zur nicht-invasiven Beurteilung der Leberfibrose bei Gesunden und bei Patienten mit chronischer Lebererkrankung

Carla Serra

¹Department of Organ Insufficiency and Transplantation, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Valentina Grasso

¹Department of Organ Insufficiency and Transplantation, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Fabio Conti

²Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Cristina Felicani

¹Department of Organ Insufficiency and Transplantation, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Elena Mazzotta

¹Department of Organ Insufficiency and Transplantation, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Marco Lenzi

²Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Gabriella Verucchi

²Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Antonietta D'errico

³Department of Specialty, Diagnostic and Experimental Medicine, S.Orsola-Malpighi Hospital, University of Bologna, Italy

,

Pietro Andreone

²Research Centre for the Study of Hepatitis, Department of Medical and Surgical Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Italy

› Institutsangaben

Abstract

Purpose To assess the performance of two-dimensional shear wave elastography (2D-SWE) on the GE LOGIQ E9 ultrasound system in a cohort of healthy subjects and to investigate its accuracy in the staging of liver fibrosis in patients with chronic liver disease (CLD) using liver biopsy as a reference standard.

Materials and Methods From October 2014 to June 2016, 54 healthy subjects and 174 patients with CLD were consecutively enrolled. Liver fibrosis stage was assessed by the METAVIR scoring system. 18 (10.3 %) and 17 (9.8 %) patients had advanced fibrosis and cirrhosis, respectively. The correlation of liver stiffness measurement (LSM) and continuous variable was assessed using the Spearman rank correlation. The accuracy of 2D-SWE was evaluated with areas under the receiver operating characteristics curves (AUROC).

Results Reliable LSMs were obtained in all subjects. The interobserver agreement ICC was excellent: 0.847. In healthy subjects, gender, but not anthropometric and biochemical data, were correlated with LSM. In patients with CLD, LSM had a strong positive correlation with fibrosis stage (rho = 0.628; p > 0.001). The AUROC was 0.724 for mild fibrosis (F≥ 1), 0.857 for moderate fibrosis (F≥ 2), 0.946 for severe fibrosis (F≥ 3), and 0.935 for cirrhosis (F4). Likewise, good accuracy was observed in the HCV subgroup. The optimal cut-off value in differentiating healthy subjects from CLD patients with any fibrosis was 5.47 kPa with an AUROC of 0.875.

Conclusion 2D-SWE is a reliable and reproducible method to assess LSM with good diagnostic accuracy to assess liver fibrosis in patients with CLD.

Zusammenfassung

Ziel Beurteilung der Leistungsfähigkeit der zweidimensionalen, auf dem GE LOGIQ E9 Ultraschallsystem durchgeführten Shear-Wave-Elastografie (2D-SWE) in einer Kohorte gesunder Probanden (HS) und die Untersuchung der Genauigkeit beim Staging der Leberfibrose bei Patienten mit chronischer Lebererkrankung (CLD) mittels Leberbiopsie als Referenzstandard.

Material und Methoden Von Oktober 2014 bis Juni 2016 wurden 54 HS und 174 CLD-Patienten nacheinander aufgenommen. Das Stadium der Leberfibrose wurde durch das METAVIR-Scoring-System beurteilt. Es zeigten 18 Patienten (10,3 %) eine fortgeschrittene Fibrose und 17 Patienten (9,8 %) eine Zirrhose. Die Korrelation der Lebersteifigkeitsmessung (LSM) und der stetigen Variablen wurde mittels Spearman-Rangkorrelation beurteilt. Die Genauigkeit der 2D-SWE wurde durch „Areas Under the Receiver Operating characteristics Curves“ (AUROC) ausgewertet.

Ergebnisse Eine verlässliche LSM wurden bei allen Probanden erzielt. Die Inter-Observer-Übereinstimmung (ICC) war mit 0,847 hervorragend. In HS waren geschlechtsspezifische, nicht aber anthropometrische und biochemische Daten, mit der LSM korreliert. Bei CLD-Patienten zeigte die LSM eine signifikante positive Korrelation mit dem Fibrose-Stadium (rho = 0,628; p > 0,001). Die AUROC betrug 0,724 bei milder Fibrose (F≥ 1), 0,857 bei moderater Fibrose (F≥ 2), 0,946 bei schwerer Fibrose (F≥ 3) und 0,935 bei Zirrhose (F4). Ebenso wurde in der HCV-Untergruppe eine hohe Genauigkeit beobachtet. Der optimale Grenzwert für die Differenzierung der HS von den CLD-Patienten mit jeglicher Fibrose betrug 5,47 kPa bei einer AUROC von 0,875.

Schlussfolgerung Die 2D-SWE ist eine verlässige und reproduzierbare Methode zur LSM, um mit hoher diagnostischer Treffsicherheit die Leberfibrose bei CLD-Patienten zu beurteilen.

Key Words

liver stiffness - GE LOGIQ E9 - liver fibrosis - noninvasive assessment - real-time shear wave

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References
1 Altekruse SF, Henley SJ, Cucinelli JE. et al. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol 2014; 109: 542-553
2 Vergniol J, Foucher J, Terrebonne E. et al. Noninvasive tests for fibrosis and liver stiffness predict 5-year outcomes of patients with chronic hepatitis C. Gastroenterology 2011; 140: 1970-1979
3 Younossi ZM, Stepanova M, Rafiq N. et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 2011; 53: 1874-1882
4 Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344: 495-500
5 Regev A, Berho M, Jeffers LJ. et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 2002; 97: 2614-2618
6 Barr RG, Ferraioli G, Palmeri ML. et al. Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology 2015; 276: 845-861
7 European Association for Study of Liver. Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015; 63: 237-264
8 Rockey DC, Caldwell SH, Goodman ZD. et al. Liver biopsy. Hepatology 2009; 49: 1017-1044
9 The METAVIR cooperative group. Inter- and intra-observer variation in the assessment of liver biopsy of chronic hepatitis C. Hepatology 1994; 20: 15-20
10 Nightingale K, McAleavey S, Trahey G. Shear-wave generation using acoustic radiation force: in vivo and ex vivo results. Ultrasound Med Biol 2003; 29: 1715-1723
11 Sarvazyan AP, Rudenko OV, Swanson SD. et al. Shear wave elasticity imaging: a new ultrasonic technology of medical diagnostics. Ultrasound Med Biol 1998; 24: 1419-1435
12 Song P, Zhao H, Manduca A. et al. Comb-push ultrasound shear elastography (CUSE): a novel method for two-dimensional shear elasticity imaging of soft tissues. IEEE Trans Med Imaging 2012; 31: 1821-1832
13 Song P, Macdonald M, Behler R. et al. Two-dimensional shear-wave elastography on conventional ultrasound scanners with time-aligned sequential tracking (TAST) and comb-push ultrasound shear elastography (CUSE). IEEE Trans Ultrason Ferroelectr Freq Control 2015; 62: 290-302
14 Zheng J, Guo H, Zeng J. et al. Two-dimensional shear-wave elastography and conventional US: the optimal evaluation of liver fibrosis and cirrhosis. Radiology 2015; 275: 290-300
15 Thiele M, Madsen BS, Procopet B. et al. Reliability Criteria for Liver Stiffness Measurements with Real-Time 2D Shear Wave Elastography in Different Clinical Scenarios of Chronic Liver Disease. Ultraschall in Med 2016 [Epub ahead of print]
16 Ferraioli G, Tinelli C, Dal Bello B. et al. Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study. Hepatology 2012; 56: 2125-2123
17 Tada T, Kumada T, Toyoda HH. et al. Utility of real-time shear wave elastography for assessing liver fibrosis in patients with chronic hepatitis C infection without cirrhosis: Comparison of liver fibrosis indices. Hepatol Res 2015; 45: E122-129
18 Bota S, Paternostro R, Etschmaier A. et al. Performance of 2-D shear wave elastography in liver fibrosis assessment compared with serologic tests and transient elastography in clinical routine. Ultrasound Med Biol 2015; 41: 2340-2349
19 Piscaglia F, Salvatore V, Mulazzani L. et al. Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage. Ultraschall in Med 2016; 37: 1-5
20 Das K, Sarkar R, Ahmed SM. et al. "Normal" liver stiffness measure (LSM) values are higher in both lean and obese individuals: a population-based study from a developing country. Hepatology 2012; 55: 584-593
21 Koehler EM, Plompen EP, Schouten JN. et al. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study. Hepatology 2016; 63: 138-147
22 Conti F, Vukotic R, Foschi FG. et al. Transient elastography in healthy subjects and factors influencing liver stiffness in non-alcoholic fatty liver disease: An Italian community-based population study. Dig Liver Dis 2016 [Epub ahead of print]
23 Roulot D, Czernichow S, Le Clésiau H. et al. Liver stiffness values in apparently healthy subjects: influence of gender and metabolic syndrome. J Hepatol 2008; 48: 606-613
24 Yasuda M, Shimizu I, Shiba M. et al. Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats. Hepatology 1999; 29: 719-727
25 Jiang T, Tian G, Zhao Q. et al. Diagnostic Accuracy of 2D-Shear Wave Elastography for Liver Fibrosis Severity: A Meta-Analysis. PLoS One 2016; 11: e0157219
26 Talwalkar JA, Kurtz DM, Schoenleber SJ. et al. Ultrasoundbased transient elastography for the detection of hepatic Fibrosis: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2007; 5: 1214-1220
27 Tsochatzis EA, Gurusamy KS, Ntaoula S. et al. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol 2011; 54: 650-659
28 European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol 2016 [Epub ahead of print].
29 Castera L, Sebastiani G, Le Bail B. et al. Prospective comparison of two algorithms combining non-invasive methods for staging liver fibrosis in chronic hepatitis C. J Hepatol 2010; 52: 191-198
30 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