CONFOUNDING FACTORS affecting the performance of US elastography

IVICA GRGUREVIC

Ass Prof, MD PhD, FEBGH

Department of Gastroenterology, Hepatology and Clinical Nutrition

University Hospital Dubrava

University of Zagreb School of Medicine, CROATIA

Clinical Ultrasound in Hepatology: Training for Hepatologists UCL Institute for Liver and Digestive Health, Royal Free Hospital, London, UK

June 2018

CONFOUNDING FACTORS affecting the performance of US elastography

• Technical factors

– Different techniques and vendors

– Measurement location

• Operator’s factors

– experience

• Patient’s factors

– Inflammatory activity

– Biliary obstruction

– Hepatic venous congestion

– Liver infiltration

– Liver steatosis

– Deep inspiration

– Food intake

– Body habitus of patients

Kennedy P. Radiology 2018; 286(3): 738-63

Different techniques and vendors

Different techniques and vendors use different shear wave frequencies, the liver stiffness values from different vendors are consequently not exchangeable.

Adjusted SWS estimates obtained by the commercial system used

Hall TJ, In: Ultrasonics Symposium (IUS), 2013. I.E. International. 2013: 397–400

TE Cut-off (kPa) (AUC)

pSWE (ElastPQ) Cut-off (kPa) (AUC)

2DSWE (SSI) Cut-off (kPa) (AUC)

F≥2 7.3-7.7 (0.84-0.87)

7.04-7.06 (0.77-0.88)

7.1 (0.86)

F=4 13-15 (0.93-0.96)

9.11-10.4 (0.88-0.91)

13 (0.93)

Cut-off values for F2 and F4 by different US Elastography methods

Friedrich-Rust, M. Gastroenterology 2008; 134: 960–974 Tsochatzis E. J Hepatol 2011;54:650-659 Ferraioli G. Digestive and Liver Disease 2018; doi.org/10.1016/j.dld.2018.03.033 Fraquelli M. Aliment Pharmacol Ther 2016; 44: 356–365 Herrmann E. Hepatology 2018; 67 (1): 260-72.

Measurement location

• Right liver lobe by intercostal approach – LSM in LL by subcostal approach>LSM RL i.c.

• At least 1 cm below liver capsule – To avoid fibrotic extensions from the Gleason’s capsule

• Decreasing tendency of LSM in the deeper portions of the liver

• The region of interest (ROIs) should be placed in a homogenous area without vessels and artifacts – To ensure good shear wave propagation

Karlas T. Scand J Gastroenterol 2011; Horster S. Clin Hemorheol Microcirc 2010; Shin HJ. Eur Radiol 2016; Ferraioli G. WFUMB guidelines. Ultrasound Med Biol 2015; Barr RG. Radiology 2015; EFSUMB guidelines 2017.

2.5 cm

Adjusted SWS estimates as a function of depth into the the soft phantoms obtained using Siemens S2000 systems

Hall TJ, In: Ultrasonics Symposium (IUS), 2013. I.E. International. 2013: 397–400

Experience

• TE: 100*-500** examinations

• pSWE: 130#

*EASL CPG. J Hepatol 2015; Kettaneh A. J Hepatol 2007;46:628–634. **Castéra L. Hepatology 2010;51:828–835. #Fraquelli M. Aliment Pharmacol Ther 2016; 44: 356–365

Factors that affect liver stifness

Mueller S, Hepatic Medicine: Evidence and Research 2010

Liver under tension

Mueller S, Hepatic Medicine: Evidence and Research 2010

Inflammatory activity

• US elastography is unreliable for detecting liver fibrosis in patients with acute hepatitis

• Not reliable in patients with ALT>5x ULN

Sagir A. Hepatology 2008; Arena U. Hepatology 2008; EASL CPG. J Hepatol 2015 I=Peak ALT; II=50% of peak; III=<2xULN

Biliary obstruction

Millonig G. Hepatology 2008; Attia D. Dig Liver Dis 2014

Attia D et al., Euroson 2013; •42 patients with mechanical biliary obstruction •28 (67%) with cholangitis

Liver steatosis

• Some report have suggested that US elastography was less accurate for detecting severe fibrosis in NAFLD, other studies have reported that liver stiffness was not affected by the presence of hepatic steatosis

Macaluso FS. Journal of Hepatology 2014;61:523–529; ( overestimate) Gaia S. J Hepatol 2011 (underestimate fibrosis) ; Wong VW. Hepatology 2010;51:454-462.

Steatosis increases LSM

N=324 NAFLD pts, all LB

Petta S. Hepatology 2017

Hepatic venous congestion

Millonig G. J Hepatol 2010;52:206-210. Frulio N. Hepatology 2009;50:1674-1675

Before After recomp. 10 pts

Liver infiltration

• Diffuse infiltrative liver disease, such as amyloidosis, can also increase the liver stiffness.

• LS with tumours is best measured at >2 cm away from the tumour edge.

• The AUCs of LSM at 1 cm, 2 cm and >2 cm from the tumour edge for diagnosing cirrhosis were 0.760, 0.833 and 0.940.

Loustaud-Ratti VR. Amyloid 2011;18:19-24.

Deep inspiration

• Deep inspiration has been shown to increase stiffness measurements compared with a resting expiratory position.

Karlas T. Scand J Gastroenterol 2011;46:1458-1467; Dietrich CF. EFSUMB guidelines. Ultraschall Med 2017

Food intake

• Food intake significantly increase LSM

• associated with an increase in splanchnic and hepatic blood circulation.

• Fasting at least 2-3h prior to LSM

Mederacke I. Liver Int 2009; Popescu A. Ultrasound Med Biol 2013;39:579-584. Gersak MM. Ultrasound Med Biol 2016;42:1295-1302.

Alcohol intake

• LSM cut-off 22.7 kPa suggests cirrhosis if actively drinking (AUROC 0.87)

• LSM cut-off 12.5 kPa suggests cirrhosis if abstinent (AUROC 0.91)

Nahon P. J Hepatol 2008;49:1062–1068. Mueller S. World J Gastroenterol 2010;16:966–972.

Body habitus

• narrow intercostal space and severe obesity, can affect all US elastography methods

Sandrin L. Ultrasound Med Biol 2003;29:1705-1713. Foucher J. Gut 2006;55:403-408. Castéra L. Hepatology 2010;51:828-835.

Failure to measure liver stiffness -impact of body weight-

Castera L. Hepatology 2010; 51(3): 828

N=13 369 examinations N= 7 261 pts

Failure to measure liver stiffness

• LSM not interpretable in 18.9% of cases

• LSM failure in 3.1%..... independently associated with:

– BMI > 30 kg/m2 – operator experience < 500 examinations – age > 52 years – type 2 diabetes

• Unreliable results in 15.8%....independently associated with:

– BMI >30 kg/m2 – operator experience < 500 examinations – age > 52 years – female sex – hypertension – type 2 diabetes

• N=7 261 pts • Different etiologies Castera L. Hepatology 2010

Sporea I. Eur J Radiol 83 (2014) e118– e122 N=383

No LB; TE as a reference

Čimbenici povezani s neuspješnim LSM

pomoću TE i 2D-SWE

Reliable LSM were similar for TE and 2D-SWE (73.9% vs 79.9%)

M vs XL probe

The manufacturer recommends that the XL probe be used in patients with a skin-capsular distance 25 mm.

M XL

Ultrasound frequency 3.5 MHz 2.5 MHz

Vibration amplitude 2 mm 3 mm

Tip diameter 9 mm 12 mm

Measurement depth 25-65 mm 35-75 mm

M vs XL probe

*p<0.05

Myers RP. Hepatology 2012

M vs XL probe

Myers RP. Hepatology 2012

M=XL+(1-2kPa)

Tapper EB. Clinical Gastroenterology and Hepatology 2015 13, 27-36DOI: (10.1016/j.cgh.2014.04.039)

Summary/Conclusion

Journal of Hepatology 2015 Chairmen: Laurent Castera & Henry Lik Yuen Chan (EASL), Marco Arrese (ALEH). Clinical Practice Guidelines Panel members: Nezam Afdhal, Pierre Bedossa, Mireen Friedrich-Rust, Kwang-Hyub Han, Massimo Pinzani

Ultraschall in Med/Eur J Ultrasound 2017