Updates on transient elastography Victor de Ldinghen MD PhD CHU - PowerPoint PPT Presentation

Updates on transient elastography Victor de Lédinghen MD PhD CHU Bordeaux France Hong Kong November 5th, 2017

Disclosures AbbVie  Gilead  BMS  MSD  Intercept Pharma  Echosens  Supersonic Imagine  Mayoli 

Guidelines J Hepatol 2015;63:237-64 J Hepatol 2016

Liver stiffness evaluation Quasi-static Shear wave-based elastography Dynamic Mecanical Focused acoustic push beams Transient Real-Time SuperSonic elastography ARFI Elasto-MR Elastography SW Imaging FibroScan

Liver stiffness and Controlled Attenuation Parameter 25 to 65 mm 3 cm 3 Stiffness CAP - fibrosis - steatosis BMI M probe XL probe 30 kg/m² CAP : 100 to 400 dB/m E : 2 to 75 kPa

Many liver lesions are associated with liver stiffness Portal fibrosis Cholestasis Centrolobular fibrosis Liver stiffness Sinusoidal fibrosis Steatosis Portal flow Inflammation 6

Transient elastography in chronic liver diseases HCV  HBV  NAFLD 

Hepatitis C What do we want to know in 2018? Cirrhosis

Cutoff of liver stiffness for the diagnosis of HCV cirrhosis Liver stiffness measurement alone is enough for the diagnosis  of cirrhosis 12 – 14 kPa If fibroscan not available, a biomarker can be used.  EASL guidelines. J Hepatol 2015;63:237-64

Hepatitis B What do we want to know?  Cirrhosis?  Treatment needed? 

HBV infection J Hepatol 2015;63:237-64

HBV infection J Hepatol 2015;63:237-64

NAFLD. What do we want to screen? Steatosis? Advanced fibrosis? NAFL NASH Fibrosis Cirrhosis 10-30% 25-40% 20-30%

Steatosis 25 to 65 mm 3 cm 3 Stiffness CAP - fibrosis - steatosis

Steatosis and Controlled Attenuation Parameter Meta-analysis of individual data on 3,830 patients AUC for Diagnosis of Steatosis 0.82 Best cut-off 248 dB/m The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40 dB/m. Karlas et al, JHEP 2017 Wong VW et al, JHEP 2017

CAP in NAFLD patients N=261 NAFLD patients with Fibroscan + liver biopsy de Lédinghen V et al. J Gastroenterol Hepatol 2016

CAP with XL probe Probe Cutoff Steatosis grade AUROC p Se P Sp p PPV P NPV p type (dB/m) 246  M 0.82 [0.77-0.88] 0.75 0.75 0.74 0.77 1 1 1 1 0.82 ≥ S1 (Pr=48.3 %) 242  0.75 0.75 0.74 0.77 XL 0.83 [0.77-0.88] 0.56 0.32 0.39 0.90 246  0.80 0.74 0.77 0.76 269  M 0.89 [0.84-0.93] 0.80 0.81 0.59 0.92 0.85 0.85 0.97 1 0.63 ≥ S2 (Pr=25.9 %) 267  0.80 0.81 0.60 0.92 XL 0.88 [0.82-0.93] 0.43 0.45 0.89 269  1 0.80 0.83 0.62 0.92 285  M 0.92 [0.89-0.96] 0.81 0.81 0.44 0.96 0.56 0.16 0.13 0.47 0.64 286  S3 (Pr=15.7 %) 0.84 0.84 0.50 0.97 XL 0.93 [0.89-0.97] 0.31 0.16 0.09 0.27 285  0.86 0.84 0.51 0.97 de Lédinghen V et al. Dig Dis Sci 2017

MRI-PDFF is better than CAP for fat quantification Park et al. Gastroenterology 2017 Imajo et al. Gastroenterology 2016

Fibrosis 25 to 65 mm 3 cm 3 Stiffness CAP - fibrosis - steatosis

N=246

Liver Stiffness by Transient Elastography and NAFLD TE has moderate accuracy for diagnosis F2-F4 fibrosis (Sens 79%, Spec 75%) TE has good accuracy for diagnosis F3-F4 fibrosis (Sens 85%, Spec 82%) Kwok et al, APT 2014

Liver Stiffness by Transient Elastography and NAFLD TE has excellent accuracy for diagnosis F4 fibrosis (Sens 92%, Spec 92%) Kwok et al, APT 2014

FibroScan M probe and XL probe PPV advanced fibrosis 9.3 9.6 71 - 72% kPa kPa ? 7.2 7.9 NPV advanced fibrosis 89 - 90% N=193 N=246 Wong V et al. Hepatology 2010; 51:454−62 Wong et al., Am J Gastroenterol 2012; 107:1862–1871

MRE is better than TE for stage of fibrosis in NAFLD Three single center studies have shown that MRE is better than transient elastography. Park et al. Gastroenterology Imajo et al. Gastroenterology 2016 Chen et al. Radiology 2016

NAFLD: Fibroscan, SWE or MRE? AUROCs for the diagnosis of advanced fibrosis 1 P<0.01 0.95 0.96 0.9 0.88 0.85 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 M probe XL probe SWE MRE 13,046 NAFLD subjects Xiao G et al. Hepatology 2017;66:1486-1501

Transient elastography in NAFLD CAP is more a « metabolic » parameter than a method to  quantify steatosis Transient elastography is a good method to exclude advanced  fibrosis and an excellent method to diagnose cirrhosis It is enough for clinical practice at bedside

Transient elastography as screening test?

EASL Guidelines Patients with insulino-resistance and/or metabolic factors  (obesity, diabetes, hypertension, dyslipidemia) should undergo diagnostic procedures for the diagnosis of NAFLD (A1) J Hepatol 2016

EASL guidelines - Diabetes In patients with T2DM, the presence of NAFLD should be  looked for irrespective of liver enzymes, since T2DM patients are at high risk of disease progression (A2)

Screening diabetic patients for NAFLD N = 1800 CAP 222 dB/m TE 9.6 kPa (M) 9.3 kPa (XL) Kwok R et al. Gut 2016;65:1359-68

Screening diabetic patients for NAFLD Factors associated with increased LSM Longer duration of diabetes  High BMI  Increased ALT  Low HDL cholesterol  Spot urine albumin/creatinine ratio  N = 1800 CAP 222 dB/m TE 9.6 kPa (M) 9.3 kPa (XL) Kwok R et al. Gut 2016;65:1359-68

Transient elastography and cirrhosis

Liver stiffness and cirrhosis Garcia-Tsao G et al. Hepatology 2010;51:1-5

Liver stiffness is associated with the severity of cirrhosis 63 54 37.5 49 15 27.5 75 kPa Liver ver stiff iffness No OV grade 2/3 No Child-Pugh B or C No ascites No HCC No OV bleeding Foucher J et al. Gut 2006; 55: 403-8

Liver stiffness and advanced chronic liver disease 15 kPa 10 kPa No cACLD ? cACLD de Franchis R et al. J Hepatol 2015;63:743-52 (Baveno VI).

Stiffness and portal hypertension Berzigotti A. J Hepatol 2017;67:399-411

Spleen stiffness for oesophageal varices? Roccarina D et al. Expert Rev Gastro Hepatol 2017

Non-invasive diagnosis of oesophageal varices de Franchis R et al. J Hepatol 2015;63:743-52 (Baveno VI).

Pragmatic use of liver stiffness Berzigotti A. J Hepatol 2017;67:399-411

Liver stiffness is associated with the risk of hepatocellular carcinoma  866 patients with HCV infection, 3-year follow up  Hepatocellular carcinoma during follow-up: 77 1.0 0.9 Cumulative Incidence 0.8 P < 0.001 0.7 0.6 0.5 LSM > 25 kPa 0.4 0.3 20 < LSM < 25 kPa 15 < LSM < 20 kPa 0.2 10 < LSM < 15 kPa 0.1 0.0 LSM < 10 kPa 0 1 2 3 Years After Enrollment No. At risk < 10 kPa 511 501 476 427 10.1 – 15 kPa 142 130 111 94 15.1 – 20 kPa 79 76 63 51 20.1 – 25 kPa 47 41 36 29 > 25 kPa 87 75 54 41 Masuzaki R et al, Hepatology 2009;49:1954-61

Liver stiffness is associated with overall survival 1457 HCV patients; Follow-up: 5 years Overall survival: 91.7% Vergniol J, et al. Gastroenterology 2011;140:1970-9

Conclusion

Transient elastography in clinical practice 9 kPa 12 kPa 15 kPa HBV HBV ACLD nALT ALT <6 kPa 8-10kPa 20 kPa < 10 kPa 12-14 kPa HBV NAFLD Varices No ACLD HCV

Transient elastography : the future Screening general population or specific populations  Follow-up of patients  Treated HBV or SVR HCV patients  NASH with specific treatments  Prediction of NAFLD patients at risk of cirrhosis or HCC  Prediction of CV risks in NAFLD patients  Spleen stiffness? 

Thanks victor.deledinghen@chu-bordeaux.fr