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Imaging modalities for diagnosis
& staging of hepatic fibrosis
Samir Haffar M.D.
Assistant Professor of Gastroenterology
Imaging modalities in hepatic fibrosis
Techniques Modalities
Ultrasonography Black & white US
Doppler US
Contrast-enhanced...
Structure for a study of diagnostic test
Suspected target
condition
Guyatt G et all. Users’ guides to medical literature: ...
Validity of study design of diagnostic study
 Blind comparison with the gold standard test
 Gold standard test performed...
Limitations of liver biopsy
• Sampling error
Major limitation
Small portion of liver (1/50 000)
• Intra & inter-observer v...
Liver biopsy size
AASLD guidelines1
• Biopsy of at least 2 – 3 cm in length is recommended
Needle of 16-gauge in caliber i...
METAVIR scoring system
Magnification 40; trichrome stains
Faria SC et al. RadioGraphics 2009 ; 29 : 1615 – 1635.
F 0 F 1 F...
Interpretation of different values of kappa
Kappa from Greek letter κ
Value of kappa Strength of agreement
0 – 0.20 Poor
0...
Influence of expertise degree in liver pathology
254 liver specimens – 15 pathologists – Metavir score
1 2 academic senior...
US guided biopsy
AASLD guidelines
Ultrasound guidance with marking of optimal biopsy
site performed immediately preceding ...
Contraindications of liver biopsy
• Uncooperated patients
• Disorders in coagulation profile
• Severe ascites
• Cystic les...
For liver biopsy
The term ‘‘best standard”
more appropriate than ‘‘gold standard”
1 Bedossa P & Carrat F. J Hepatology 200...
Accuracy of test & number of results
• Dichotomous test (only 2 results)
Sensibility (Sn) & Specificity (Sp)
PPV & NPV
Lik...
ROC curve & cut-off point
Peat JK. Health science research: a handbook of quantitative methods.
Allen & Unwin, Australia, ...
Accuracy of diagnostic test using AUROC*
Value of AUROC* Accuracy
0.90 – 1.00 Excellent
* AUROC: Area Under Receiver Opera...
Imaging modalities for hepatic fibrosis
 Acoustic Radiation Force Impulse imaging (ARFI)
 MR elastography
 Transient el...
Acoustic Radiation Force Impulse Imaging
ARFI
Region of interest (ROI) chosen by US guidance
Results expressed in m/sec (r...
Meta-analysis of ARFI
8 studies (518 pts) – All CLD – Metavir – Random effect
Friedrich-Rust M et al. J Viral Hepat 2012 ;...
Elastography
• Assessed by US (FibroScan®) & more recently by MRI
• Evaluates velocity of propagation of a shock wave
with...
MR elastography
Mariappan YK. Clinical Anatomy 2010 ; 23 : 497 – 511.
Conventional MR Wave images at 60 Hz
Shorter wavelen...
MR Elastography for staging of liver fibrosis
Prospective & blind study – 96 patients with CLD
MR elastography, TE, & APRI...
Fibroscan® (Echosens, Paris, France)
Transient elastography
Position of probe & explored volume
Cylinder of 1 cm wide & 4 cm long
From 25 mm to 65 mm below ski...
Results of FibroScan®
Stiffness (kPa)
Median value of 10 shots
 At least 10 shots
 Success Rate: ≥ 60%
 IQR * (kPa)
Int...
Manufacturer’s criteria for LSM interpretation
• First step Number of shots ≥ 10
• Second step Success rate ≥ 60 %
• Third...
LS values in apparently healthy subjects
Prospective study of 429 subjects
Roulot D et al. J Hepatol 2008 ; 48 : 606 – 613...
Liver stiffness cut-offs in chronic liver diseases
F2
Sign
F3
Severe
F4
Cirrhosis
Matavir F0-F1
MildFibrosis
Castéra L et ...
Shear wave propagation velocity according to
severity of hepatic fibrosis (METAVIR score)
Sandrin L et al. Ultrasound Med ...
Reproducibility of TE in assessing hepatic fibrosis.
Bland Altman plot
Fraquelli M et al. Gut 2007 ; 56 : 968 – 973.
200 p...
Meta-analysis of TE for staging liver fibrosis
Severe fibrosis (≥ F3): 0.89
(95% CI: 0.88 – 0.91)
Friedrich-Rust M et al. ...
Improving diagnostic statistical methods
• When there is no perfect gold standard
AUROC >0.90 could not be achieved even f...
Perform LSM
≤ 6 kPa
No significant fibrosis
No biopsy
F0 F1F
Intermediate values
Grey area
Biopsy if results
influence man...
LSM according to different etiologies of CLD
* Gastroentérol Clin Biol 2008 ; 32 :58 – 67.
** J Hepatol 2009 ; 49 : 1062 –...
Place of FibroScan in chronic viral hepatitis
• Two critical end points Significant fibrosis (≥ F2)
Presence of cirrhosis ...
• Liver biopsy still regarded as reference method to assess
grade of inflammation & stage of fibrosis (A2)
• TE can be use...
MA of AUROCt for advanced fibrosis in CHB
Metavir – Random effect – stAUROC – Obuchowski
Poynard T et al. Curr Hepatitis R...
Place of transient elastography in NAFLD
Second most relevant clinical entity in hepatology
• Significant fibrosis does no...
Significance of wide range of LSM in cirrhosis
13 – 75 kPa
Ascites
HCC ?
Variceal bleeding
Foucher J et al. Gut 2006 ; 55 ...
Cumulative incidence of HCC based on LSM
Prospective – 866 CHC – Mean follow-up 3 years
LSM: Liver Stiffness Measurement –...
Cost of FibroScan versus liver biopsy
• Liver biopsy*
Cost of liver biopsy 703 – 1 566 € in a French hospital
with a one d...
LSM in the general population
Social Medical Center
Free medical checkup
1358 healthy subjects over 45 years
Failure, miss...
Limitations of US transient elastography
 Uninterpretable results
 Acute liver injury
 Extrahepatic cholestasis
 Incre...
Uninterpretable results of LSM
5 year prospective study – 13 369 examinations – 5 operators
BMI > 30 kg/m2 (OR 7.5)
Operat...
Feasibility of LSM with FibroScan® using XL probe
New probe for obese patients
de Lédinghen V et al. Liver International 2...
Ascites in liver cirrhosis
Ascites grade 1 according to International Ascites Club
Detectable only by ultrasound
Non-invasive diagnosis of liver fibrosis
Opinions of leaders
“Biopsist”
Biopsy as first-line estimate of liver injury
Biop...
Transient elastography in clinical practice
Examination quality 10 shots at least
Success rate ≥ 60%
IQR ≤ 25% of median v...
Interpretation of results of LSM should
always be done by expert clinicians according
to clinical context
LSM is the only ...
Does it take two to tango?
Castera L & Pinzani M. Gut 2010 ; 59 : 861 – 866.
Liver biopsy & non-invasive tools especially ...
Thank You
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Imaging modalities & liver fibrosis (elastography) Slide 1 Imaging modalities & liver fibrosis (elastography) Slide 2 Imaging modalities & liver fibrosis (elastography) Slide 3 Imaging modalities & liver fibrosis (elastography) Slide 4 Imaging modalities & liver fibrosis (elastography) Slide 5 Imaging modalities & liver fibrosis (elastography) Slide 6 Imaging modalities & liver fibrosis (elastography) Slide 7 Imaging modalities & liver fibrosis (elastography) Slide 8 Imaging modalities & liver fibrosis (elastography) Slide 9 Imaging modalities & liver fibrosis (elastography) Slide 10 Imaging modalities & liver fibrosis (elastography) Slide 11 Imaging modalities & liver fibrosis (elastography) Slide 12 Imaging modalities & liver fibrosis (elastography) Slide 13 Imaging modalities & liver fibrosis (elastography) Slide 14 Imaging modalities & liver fibrosis (elastography) Slide 15 Imaging modalities & liver fibrosis (elastography) Slide 16 Imaging modalities & liver fibrosis (elastography) Slide 17 Imaging modalities & liver fibrosis (elastography) Slide 18 Imaging modalities & liver fibrosis (elastography) Slide 19 Imaging modalities & liver fibrosis (elastography) Slide 20 Imaging modalities & liver fibrosis (elastography) Slide 21 Imaging modalities & liver fibrosis (elastography) Slide 22 Imaging modalities & liver fibrosis (elastography) Slide 23 Imaging modalities & liver fibrosis (elastography) Slide 24 Imaging modalities & liver fibrosis (elastography) Slide 25 Imaging modalities & liver fibrosis (elastography) Slide 26 Imaging modalities & liver fibrosis (elastography) Slide 27 Imaging modalities & liver fibrosis (elastography) Slide 28 Imaging modalities & liver fibrosis (elastography) Slide 29 Imaging modalities & liver fibrosis (elastography) Slide 30 Imaging modalities & liver fibrosis (elastography) Slide 31 Imaging modalities & liver fibrosis (elastography) Slide 32 Imaging modalities & liver fibrosis (elastography) Slide 33 Imaging modalities & liver fibrosis (elastography) Slide 34 Imaging modalities & liver fibrosis (elastography) Slide 35 Imaging modalities & liver fibrosis (elastography) Slide 36 Imaging modalities & liver fibrosis (elastography) Slide 37 Imaging modalities & liver fibrosis (elastography) Slide 38 Imaging modalities & liver fibrosis (elastography) Slide 39 Imaging modalities & liver fibrosis (elastography) Slide 40 Imaging modalities & liver fibrosis (elastography) Slide 41 Imaging modalities & liver fibrosis (elastography) Slide 42 Imaging modalities & liver fibrosis (elastography) Slide 43 Imaging modalities & liver fibrosis (elastography) Slide 44 Imaging modalities & liver fibrosis (elastography) Slide 45 Imaging modalities & liver fibrosis (elastography) Slide 46 Imaging modalities & liver fibrosis (elastography) Slide 47 Imaging modalities & liver fibrosis (elastography) Slide 48 Imaging modalities & liver fibrosis (elastography) Slide 49 Imaging modalities & liver fibrosis (elastography) Slide 50
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Imaging modalities & liver fibrosis (elastography)

Description of all available modalities for non-invasive diagnosis of liver fibrosis with comparaison to liver biopsy.

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Imaging modalities & liver fibrosis (elastography)

  1. 1. Imaging modalities for diagnosis & staging of hepatic fibrosis Samir Haffar M.D. Assistant Professor of Gastroenterology
  2. 2. Imaging modalities in hepatic fibrosis Techniques Modalities Ultrasonography Black & white US Doppler US Contrast-enhanced US Elasticity measurements Tissue strain imaging Left lobe liver surface (LLS) Real-time elastography Transient elastography Acoustic Radiation Force Imaging (ARFI) Computed Tomography (CT) Positron Emission Tomography (PET) Single Photon Emission CT (SPECT) Magnetic Resonance Imaging Conventional MRI Double contrast-enhanced MR MR elastography Diffusion-weighted MRI MR perfusion imaging MR spectroscopy Bonekamp S et al. J Hepatol 2009 ; 50 : 17 – 35.
  3. 3. Structure for a study of diagnostic test Suspected target condition Guyatt G et all. Users’ guides to medical literature: manual for EBP. McGraw-Hill, New York, USA, 2nd edition, 2008. Gold standard test Positive Negative Diagnostic test Positive Negative
  4. 4. Validity of study design of diagnostic study  Blind comparison with the gold standard test  Gold standard test performed in all patients  Diagnostic test evaluated in appropriate spectrum of pts If no → Stop here
  5. 5. Limitations of liver biopsy • Sampling error Major limitation Small portion of liver (1/50 000) • Intra & inter-observer variation G (κ: 0.2 – 0.6) – S (κ: 0.5 – 0.9) • Invasive procedure Pain 20% Major complications 0.5% Mortality 0.03 % Sufficient length biopsy Scoring system Experienced pathologist US guided biopsy “preferred” AASLD position paper. Hepatology 2009 ; 49 : 107 – 1044.
  6. 6. Liver biopsy size AASLD guidelines1 • Biopsy of at least 2 – 3 cm in length is recommended Needle of 16-gauge in caliber is recommended AASLD guidelines. Hepatology 2009 ; 49 : 1017 – 1044. 2 Bedossa P et al. Hepatology 2003 ; 38 : 1449 – 57. • Presence of fewer than 11 complete portal tracts may be incorrect in recognition of grading & staging Even a 25mm long liver biopsy has 25% rate of discordance for fibrosis staging2
  7. 7. METAVIR scoring system Magnification 40; trichrome stains Faria SC et al. RadioGraphics 2009 ; 29 : 1615 – 1635. F 0 F 1 F 2 F 3 F 4
  8. 8. Interpretation of different values of kappa Kappa from Greek letter κ Value of kappa Strength of agreement 0 – 0.20 Poor 0.21– 0.40 Fair 0.41– 0.60 Moderate 0.61– 0.80 Good 0.81–1.00 Very good Perera R, Heneghan C & Badenoch D. Statistics toolkit. Blackwell Publishing & BMJ Books, Oxford, 1st edition, 2008. kappa score of 0.6 indicates good agreement
  9. 9. Influence of expertise degree in liver pathology 254 liver specimens – 15 pathologists – Metavir score 1 2 academic seniors (1 expert – 1 non-expert) 2 2 academic juniors 3 2 academic experts (1 junior – 1 senior) 4 Consensus reading by experts (1 junior – 1 senior) 5 1 academic expert & 3 academic non-experts 6 1 academic expert & 10 non-academic non-experts Rousselet MC et al. Hepatology 2005 ; 41 : 257 – 264.
  10. 10. US guided biopsy AASLD guidelines Ultrasound guidance with marking of optimal biopsy site performed immediately preceding biopsy, by the individual performing the biopsy, is preferred, though not mandatory, because it likely reduces the risk of complications from liver biopsy (Class I, Level B) AASLD guidelines. Hepatology 2009 ; 49 : 1017 – 1044.
  11. 11. Contraindications of liver biopsy • Uncooperated patients • Disorders in coagulation profile • Severe ascites • Cystic lesion • Vascular tumor (hemangioma) • Amiloidosis • Congestive liver disease
  12. 12. For liver biopsy The term ‘‘best standard” more appropriate than ‘‘gold standard” 1 Bedossa P & Carrat F. J Hepatology 2009 ; 50 : 1 – 3.
  13. 13. Accuracy of test & number of results • Dichotomous test (only 2 results) Sensibility (Sn) & Specificity (Sp) PPV & NPV Likelihood Ratios (LRs) Diagnostic Odds Ratio (OR) • Multilevel test (> 2 results) Receiver Operating Characteristic (ROC) CIs
  14. 14. ROC curve & cut-off point Peat JK. Health science research: a handbook of quantitative methods. Allen & Unwin, Australia, 1st edition, 2001. Cut-off point: Point of curve far away from chance diagonal
  15. 15. Accuracy of diagnostic test using AUROC* Value of AUROC* Accuracy 0.90 – 1.00 Excellent * AUROC: Area Under Receiver Operating Characteristics Pines JM & al. Evidence-Based emergency care: diagnostic testing & clinical decision rules. Blackwell’s publishing – West Sussex – UK – 2008. AUROC of a „„good test” should be ≥ 0.80 0.80 – 0.90 Good 0.70 – 0.80 Fair 0.60 – 0.70 Poor
  16. 16. Imaging modalities for hepatic fibrosis  Acoustic Radiation Force Impulse imaging (ARFI)  MR elastography  Transient elastography (TE) or FibroScan® Established Promising but currently under investigation Castera L & Pinzani M. Gut 2010 ; 59 : 861 – 866.
  17. 17. Acoustic Radiation Force Impulse Imaging ARFI Region of interest (ROI) chosen by US guidance Results expressed in m/sec (range: 0.5 – 4.4) Friedrich-Rust et al. Radiology 2009 ; 252 : 595 – 604. ROI
  18. 18. Meta-analysis of ARFI 8 studies (518 pts) – All CLD – Metavir – Random effect Friedrich-Rust M et al. J Viral Hepat 2012 ; 19 : e212 – e219. ARFI can be performed with good diagnostic accuracy for noninvasive staging of liver fibrosis Fibrosis Areas under ROC curves Significant fibrosis (F ≥ 2) 0.87 Severe fibrosis (F ≥ 3) 0.91 Cirrhosis 0.93
  19. 19. Elastography • Assessed by US (FibroScan®) & more recently by MRI • Evaluates velocity of propagation of a shock wave within liver tissue (examines a physical parameter of liver tissue which is related to its elasticity) • Rationale Normal liver is viscous Not favorable to wave propagation Fibrosis increases hardness of tissue Favors more rapid propagation Bedossa P. Liver Int 2009 ; 29 (s1): 19 – 22.
  20. 20. MR elastography Mariappan YK. Clinical Anatomy 2010 ; 23 : 497 – 511. Conventional MR Wave images at 60 Hz Shorter wavelength Longer wavelength MR elastography Normal: 1.7 kPa Cirrhosis: 18.83 kPa
  21. 21. MR Elastography for staging of liver fibrosis Prospective & blind study – 96 patients with CLD MR elastography, TE, & APRI versus liver biopsy Huwart L et al. Gastroenterology 2008 ; 135 : 32 – 40. Encouraging results Efforts to standardize equipment & techniques Too expensive & time-consuming for clinical practice
  22. 22. Fibroscan® (Echosens, Paris, France)
  23. 23. Transient elastography Position of probe & explored volume Cylinder of 1 cm wide & 4 cm long From 25 mm to 65 mm below skin surface This volume is at least 100 times bigger than a biopsy sample Jaffer OS et al.Ultrasound 2012 ; 20 : 24 – 32.
  24. 24. Results of FibroScan® Stiffness (kPa) Median value of 10 shots  At least 10 shots  Success Rate: ≥ 60%  IQR * (kPa) Interval around median Contains 50% of valid shots ≤ 30% of median value * IQR: Inter Quantile range
  25. 25. Manufacturer’s criteria for LSM interpretation • First step Number of shots ≥ 10 • Second step Success rate ≥ 60 % • Third step Interquantile range(IQR) ≤ 25% Failure Zero valid shot Unreliable results < 10 valid shots or Success rate ≤ 60% or IQR ≥ 30%
  26. 26. LS values in apparently healthy subjects Prospective study of 429 subjects Roulot D et al. J Hepatol 2008 ; 48 : 606 – 613. 5.2 1.5 kPa 5.8 1.5 kPa p = 0.0002 Normal liver stiffness measurement: 5.49 1.59 kPa
  27. 27. Liver stiffness cut-offs in chronic liver diseases F2 Sign F3 Severe F4 Cirrhosis Matavir F0-F1 MildFibrosis Castéra L et al. J Hepatol 2008 ; 48 : 835 – 847.
  28. 28. Shear wave propagation velocity according to severity of hepatic fibrosis (METAVIR score) Sandrin L et al. Ultrasound Med Biol 2003 ; 29 : 1705 – 1713. E = 3.0 kPa F 0 E = 7.7 kPa F 2 E = 27 kPa F 4
  29. 29. Reproducibility of TE in assessing hepatic fibrosis. Bland Altman plot Fraquelli M et al. Gut 2007 ; 56 : 968 – 973. 200 patients with chronic liver disease 2 different operators within 3 days (800 exams) 8 patients scored outside limits of agreement Upper limit Lower limit Mean 95% limit of agreement
  30. 30. Meta-analysis of TE for staging liver fibrosis Severe fibrosis (≥ F3): 0.89 (95% CI: 0.88 – 0.91) Friedrich-Rust M et al. Gastroenterology 2008 ; 134 : 960 – 974. Cirrhosis (F4): 0.94 (95% CI: 0.93 – 0.95) Cut-off value: 13.0 kPa 50 studies – All type of CLD – Random effect Significant fibrosis (≥ F2): 0.84 (95% CI: 0.82 – 0.86) Cut-off value: 7.7 kPa For significant fibrosis, a high variation of AUROC was found
  31. 31. Improving diagnostic statistical methods • When there is no perfect gold standard AUROC >0.90 could not be achieved even for perfect marker1 Prognostic analysis (morbidity/mortality endpoints) used • Methods for spectrum effect & ordinal scale Standardization of AUROC 2: distribution of fibrosis stages Obuchowski measure3: spectrum effect & ordinal scale 1 Mehta SH et al. J Hepatol 2009 ; 50 : 36 – 41. 2 Poynard T et al. Curr Hepatitis Rep 2011 ; 10 : 87 – 97. 3 Lambert C et al. Clinical Chemistry 2008 ; 54 : 8 : 1372 – 1378.
  32. 32. Perform LSM ≤ 6 kPa No significant fibrosis No biopsy F0 F1F Intermediate values Grey area Biopsy if results influence management F2 Implementation of other NI tests ≥ 12.5 kPa Advanced fibrosis No biopsy F4 Treatment or Follow-up F3 Vizzutti et al. Gut 2009;58:156-60.
  33. 33. LSM according to different etiologies of CLD * Gastroentérol Clin Biol 2008 ; 32 :58 – 67. ** J Hepatol 2009 ; 49 : 1062 – 68. Aliment Pharmacol Ther 2008 ; 28 : 1188 – 98. *** Hepatology 2010 ; 51 : 454 – 62. Gastroentérol Clin Biol 2008 ; 32 : 58 – 67.
  34. 34. Place of FibroScan in chronic viral hepatitis • Two critical end points Significant fibrosis (≥ F2) Presence of cirrhosis (F4) • Chronic hepatitis C ≥ F2: TE + serum markers F4: TE • Chronic hepatitis B Immunotolerant phase: TE ≥ F2: more studies needed F4: TE Castera L & Pinzani M. Gut 2010 ; 59 : 861 – 866.
  35. 35. • Liver biopsy still regarded as reference method to assess grade of inflammation & stage of fibrosis (A2) • TE can be used to assess liver fibrosis in CHC (A2) • Non-invasive serum makers can be recommended for detection of significant fibrosis (METAVIR F2 – F4) (A2) • Combination of blood tests or TE & blood test Improve accuracy & reduce necessity of liver biopsy (C2) EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. J Hepatol 2011 ; 55 : 245 – 264. Chronic hepatitis C EASL Clinical Practice Guidelines
  36. 36. MA of AUROCt for advanced fibrosis in CHB Metavir – Random effect – stAUROC – Obuchowski Poynard T et al. Curr Hepatitis Rep 2011 ; 10 : 87 – 97. All significantly higher than random 0.50 value No significant heterogeneity (Cochran’s Q = 6.3) AUROC: 0.89 (0.83 – 0.96) AUROC: 0.84 (0.79 – 0.86)
  37. 37. Place of transient elastography in NAFLD Second most relevant clinical entity in hepatology • Significant fibrosis does not represent critical end point in absence of standardized treatment regimens • TE could be useful to select those requiring liver biopsy for more accurate staging of disease (cut-off value 7.9 kPa) Castera L & Pinzani M. Gut 2010 ; 59 : 861 – 866. Wong VW et al. Hepatology 2010 ; 51 : 454 – 462.
  38. 38. Significance of wide range of LSM in cirrhosis 13 – 75 kPa Ascites HCC ? Variceal bleeding Foucher J et al. Gut 2006 ; 55 : 403 – 408. EV stage 2 or 3 27 Child-Pugh B or C 37 49 53 622.5 7513
  39. 39. Cumulative incidence of HCC based on LSM Prospective – 866 CHC – Mean follow-up 3 years LSM: Liver Stiffness Measurement – HR: Hazard Ratio Masuzaki R et al. Hepatology 2009 ; 49 : 1954 – 1961. LSM > 25 kPa HR 45.5 (p< 0.001) LSM ≤ 10 kPa HR 0 10 < LSM ≤ 15 kPa HR 16.7 (p< 0.001) 15 < LSM ≤ 20 kPa HR 20.9 (p< 0.001) 20 < LSM ≤ 25 kPa HR 25.6 (p< 0.001)
  40. 40. Cost of FibroScan versus liver biopsy • Liver biopsy* Cost of liver biopsy 703 – 1 566 € in a French hospital with a one day observation period * Blanc J et al. Hepatol Res 2005 ; 32 : 1 – 8. ** Canadian Agency for Drugs and Technologies in Health (CADTH). Transient Elastography (FibroScan) for Non-invasive Assessment of Liver Fibrosis; 2006. • Fibroscan® ** FibroScan equipment 70 000 € Low running cost except probe calibration twice/year Cost per FibroScan® exam 100 € with 150 exams annually
  41. 41. LSM in the general population Social Medical Center Free medical checkup 1358 healthy subjects over 45 years Failure, missing data N = 238 28 subjects underwent liver biopsy Roulot et al. 2009 EASL meeting Copenhagen. D. Roulot et al. J Hepatol 2009 ; 50 : S 89. LS < 8 kPa N = 1040 8 kPa ≤ LS < 14.6 kPa N = 72 LS ≥ 14.6 kPa N = 8 Prevalence of cirrhosis was at least 0.7%
  42. 42. Limitations of US transient elastography  Uninterpretable results  Acute liver injury  Extrahepatic cholestasis  Increased CVP  Ascites  Narrow intercostal spaces
  43. 43. Uninterpretable results of LSM 5 year prospective study – 13 369 examinations – 5 operators BMI > 30 kg/m2 (OR 7.5) Operator experience (OR 2.5) Age > 52 years (OR 2.3) Type 2 diabetes (OR 1.6) Failure (3%) BMI > 30 kg/m2 (OR 3.3) Operator experience (OR 3.1) Age > 52 years (OR 1.8) Female sex (OR 1.4) Hypertension (OR 1.3) Type 2 diabetes (OR 1.1) Unreliable results (16%) Castéra L et al. Hepatology 2010 ; 51 : 828 – 835. LSM uninterpretable in one of five cases Main raisons: Obesity ( WC) – Operator experience
  44. 44. Feasibility of LSM with FibroScan® using XL probe New probe for obese patients de Lédinghen V et al. Liver International 2010 ; : 1043 – 1048. 60% not measured by M probe successfully measured by XL probe
  45. 45. Ascites in liver cirrhosis Ascites grade 1 according to International Ascites Club Detectable only by ultrasound
  46. 46. Non-invasive diagnosis of liver fibrosis Opinions of leaders “Biopsist” Biopsy as first-line estimate of liver injury Biopsy not perfect gold standard but best estimate Rarely admits biopsy as false-positive/false negative Typically head of pathology unit “Biomarkerist’’ Biomarker as first-line estimate of liver injury Biomarker not perfect test but as accurate as biopsy Discordance with biopsy: failure due to either (50%) In case of non-interpretability: another biomarker If still not interpretable: biopsy as 3rd line assessment “BioCocktailist” Biomarker first then biopsy if result not convincing Colleague of Biopsist & close friend of Biomarkerist Usually also has a statistician friend Poynard T. J Hepatol 2011 ; 54 ; 586 – 587.
  47. 47. Transient elastography in clinical practice Examination quality 10 shots at least Success rate ≥ 60% IQR ≤ 25% of median value Liver disease Not used in acute hepatitis Not used in acute exacerbation Not used in ascites & EH cholestasis Choice of cutoff point Cutoffs different for each CLD Range of value rather than cutoff De Lédinghen V et al. Gastroentérol Clin Biol 2008 ; 32 : 58 – 67.
  48. 48. Interpretation of results of LSM should always be done by expert clinicians according to clinical context LSM is the only established imaging modality for non-invasive diagnosis of liver fibrosis at the present time
  49. 49. Does it take two to tango? Castera L & Pinzani M. Gut 2010 ; 59 : 861 – 866. Liver biopsy & non-invasive tools especially TE should be employed as integrated system to maximize their potential Acting like two tango dancers
  50. 50. Thank You
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Description of all available modalities for non-invasive diagnosis of liver fibrosis with comparaison to liver biopsy.

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