Liver fibrosis and
steatosis – the role
of radiology
P.Prieditis
P.Stradins Clinical University Hospital
Riga, Latvia
9.X ...
Liver fibrosis
• Alcoholismus
• Virus hepatitis C (VHC)
• Nonalcohol steatohepatitis (NASH)
Morbidity with hr.VHC in Latvia
Reconvalescence 15%
(Hoofnagle JH et al. 1997. Hepatology 1997;26(suppl 1):15S-20S)
Develo...
• Advanced liver fibrosis is reversibl
– Antifibrotic therapy
– Removing of causitive agent
(Bataler R. et al.2005.)
• Liver steatosis
20-30% of world population
(Marchesini G. et al. Minerva Cardioangiol 2006;54:229-239))
• Chr. VHC
50-75...
Liver biopsy – golden standart
• Complications
– “Large complications” 0,4% - 2,8%
– Letality 0% - 0,2% (
(Buscarini E. Co...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• Size of tissue sample
• Number of samples
•...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• Size of tissue sample
15mm sample length – ...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• Number of samples
75 patients, 3 samples fr...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• Punction site
124 laparoscopic biopsy of ri...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• interobsrver and intraobsrver variability
C...
Liver biopsy – golden standart
Morphology - absolut truth?
Chronic hepatitis
• interobsrver and intraobsrver variability
C...
Transient elastography
(Fibroscan )
• Cirrhosis (F-IV) vs no cirrhosis (F0-III)
Sensitivity 84%-90%; specificity 89%-92%)
...
Transient elastography + biochemical tests
complex
• Fibrotest: alfa 2-macroglobulin, apolipoprotein A1, haptoglobin, gamm...
Real time elastography
Elastography integrated in conventional ultrasound scaning
sistem
Correlation of TE, RTE, Fibrotest...
Liver fibrosis
• MR
• CT
• US
Liver fibrosis
MR
• Late accumulation of gadolinium in standart contrast
T1
• Dubble contrast enhanced T2* with gadolinium...
Liver fibrosis
MR
Diffusion-weigted imaging:
Fibrosis F≥2: sensitivity 83,3%, specificity 88,9%
Fibrosis F≥3 ; sensitivity...
Liver fibrosis
CT
cirrhosis
Liver fibrosis
US
Cirrhosis:
Surface nodularity
Parenchimal heterogenety
Caudate lobe hypertrophy
Flattened hepatic vein D...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Maximum portal blood velocity
Mean portal blood velocity
Porta...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Maximum portal blood velocity
Schneider ARJ et al. Liver Inter...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Portal vein pulsitility
Dieterich CF et al. 1998.
Vmax-Vmin ci...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Hepatic arterial velocity
Lim AK et al. AJR 2005
F0-1 73cm/s F...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Resistive index
Lim AK et al. AJR 2005
F0-1 0,69 F2-4 0,56 F5-...
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Hepatic vein Doppler waveform
Liver fibrosis
US
Precirrhotic stage – Doppler measurements
Hepatic vein Doppler waveform
Flatened waveform
control cirrho...
Liver steatosis
MR
MR spectroscopy
Steatosis >5% Steatosis >33%
sensitivity specificity sensitivity specificity
McPherson
...
Liver steatosis
MR
Fatt-sensitive imaging techniqes
• In-phase/opposit-phase
Dixon IP/OP
(SIin-phase - SIop-phase)/ SIin-p...
Liver steatosis
MR
Dixon in-phase/opposit-phase
• Correlation with steatosis grade
In-phase/opposit-phase 0,68-0,69 fat sa...
Liver steatosis
CT
Liver > spleen
10HU
liver – 45HU
spleen - 53HU
liver – 15HU
spleen – 56HU
Liver steatosis
CT
Steatosis > 30%
sensitivity specifity PPV NPV
Lee SS et al
2010
72,7% 91,3% 38,1% 97,9%
Park SH et al.
...
Liver steatosis
US
• Hyperechogenicity of parenhima (bright liver)
• Beem attenuation
• Poor diaphragm visualisation
• Por...
Liver steatosis
US
Disarathy S et al. J of Hepatology 2009;51:1061-1067
Steatosis > 5% Steatosis > 30%
Sensitivity specifi...
Liver steatosis
US
Fatty liver screening
Sensitivity 67% specificity 77%
(Graif M et al. 2000. Invest Radiol 2000;35:319-3...
Liver steatosis
US
• 168 patients 3 radiologists, 4 weeks interval
– Presence of fatt: + / -
– Severity of steatosis: non,...
Liver steatosis
US
Dopplerography
Flattened waveform of hepatic vein
Severe steatosis Mild steatosis
Diterich CF et al
199...
Conclusion
Radiology can to reduce, but not completely
eliminate the need for liver biopsy
Thank you for your attention !
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Prieditis steatosis bcr10

  1. 1. Liver fibrosis and steatosis – the role of radiology P.Prieditis P.Stradins Clinical University Hospital Riga, Latvia 9.X 2010.
  2. 2. Liver fibrosis • Alcoholismus • Virus hepatitis C (VHC) • Nonalcohol steatohepatitis (NASH)
  3. 3. Morbidity with hr.VHC in Latvia Reconvalescence 15% (Hoofnagle JH et al. 1997. Hepatology 1997;26(suppl 1):15S-20S) Development of cirrhosis in 2-3 to 30-40 years after infection Cirrhosis in 20 y after infection 9% Cirrhosis in 40 y after infection 44% (Poynard T et al. J Hepatol 2001;34:730-739)
  4. 4. • Advanced liver fibrosis is reversibl – Antifibrotic therapy – Removing of causitive agent (Bataler R. et al.2005.)
  5. 5. • Liver steatosis 20-30% of world population (Marchesini G. et al. Minerva Cardioangiol 2006;54:229-239)) • Chr. VHC 50-75% (Fiore G. et al. Eur J Gastroenterol Hepatol 1998;8:125-129 ) • NASH Cirrhosis 8-26% (Powell EE et al. Hepatology1990;11:74-80)
  6. 6. Liver biopsy – golden standart • Complications – “Large complications” 0,4% - 2,8% – Letality 0% - 0,2% ( (Buscarini E. Complications of abdominal interventional ultrasound. Poleto edizioni 1996.34-47) • Follow up • Diagnostic accuracy
  7. 7. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • Size of tissue sample • Number of samples • Punction site • Morphologist
  8. 8. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • Size of tissue sample 15mm sample length – corect estimation 65% 25 mm – 75% Longer – diagnostic accuracy do not improve (Bedosa P. Hepatology 2003;38:1449-1457) 30 mm/1,4mm 15 mm/1mm 10mm/1mm Slight inflamation 49,7% 62,2% 86,6% Slight fibrosis 59% 63,3% 80,1% (Colloredo G. J Hepatol 2003;39:239-244)
  9. 9. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • Number of samples 75 patients, 3 samples from diferent places through one site – Equal estimation in all 3 samples 36% gadījumu – Cirrrhosis 50% – HCC 54,5% – Mts 50% – Liver granuloma 18,8% (Maharaj B et al. Lancet 1986;1(8480):523-525)
  10. 10. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • Punction site 124 laparoscopic biopsy of right and left lobe – One level difference: grade 30(24,2%), stage 41 (33,1%), – Fibrosis-3 in one lobe, cirrhosis in another 18 (14,5%) – Two level difference 2,4% un 1,6% (Regev A et al. Am J Gastroenterol 2004;97:2614-2618)
  11. 11. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • interobsrver and intraobsrver variability Chron. hepatitis C: 10 patologists 22 patomorphological signs interobserver agreement – almost perfect (0,8 – 1): 2 signs (cirrhosis, portal fibrosis) – good (0,6-0,8): 3 signs (fibrosis level., steatosis, portal limfoid agregation) – moderate (0,4-0,6): 5 signs, incl. Knodel index – weak (<0,4): 12 signs (The French METAVIR cooperative study group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;20:15-20)
  12. 12. Liver biopsy – golden standart Morphology - absolut truth? Chronic hepatitis • interobsrver and intraobsrver variability Chron. hepatitis C: 4 patologists 22 patomorphological signs, 1 month interval intraobserver agreement – Almost perfect (0,8 – 1): 2 signs (cirrhosis, fibrosis level.) – Good (0,6-0,8): 1 sign (centrilobular fibrosis ) – Moderate (0,4-0,6): 9 signs, incl. Knodel index, steatosis – Weak (<0,4): 10 signs (The French METAVIR cooperative study group. Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994;20:15-20)
  13. 13. Transient elastography (Fibroscan ) • Cirrhosis (F-IV) vs no cirrhosis (F0-III) Sensitivity 84%-90%; specificity 89%-92%) F II-IV vs F 0-I Sensitivity 67%-73%; specificity 80%-88%) (University of Biringham, National Institute for Health Reserch, 2008) • Disconcordance between TE and biopsy 97/300 cases (34,2%) 76 underestimation F≥2 21 overestimation F≤2 (J Viral Hepatol 2009,25) • Overestimation of fibrosis in patients with elevated ALAT (Clin Gastroenterol Hepatol 2008;6:1027-35)
  14. 14. Transient elastography + biochemical tests complex • Fibrotest: alfa 2-macroglobulin, apolipoprotein A1, haptoglobin, gamma- glutamyl-transpeptidase, total bilirubin • Fibrometer: platlets, prothrombin index, aspatrat transaminase, alfa 2- macroglobulin, hyaluronate, urea, patient age • Fibrospect, ELFG, APRI, Forns index etc. FibroScan + Fibrotest Metaanalisis of 30 studies with 6378 patients • Ability to diferenciate F0 vs F3-4 and F0-1 vs F2-3 • Decrise biopsy reqirement to 50% Poynard T et al. Meta-analysis of Fibrotest diagnostic value in chronic liver disease. BMC Gastroenterology 2007; 7:40
  15. 15. Real time elastography Elastography integrated in conventional ultrasound scaning sistem Correlation of TE, RTE, Fibrotest and biopsy 134 patients with chronic liver disease (Friedrich-Rust M et al. Real time-elastography versus FibroScan for non-invasive assessement of liver fibrosis in chronic liver diseases. Ultrashall Med 2009;30:478-484.) Spearmen correlation coef. Diagnostic accurasy Fibrosis F≥2 Cirrhosis TE 0,78 0,84 0,97 RTE 0,34 0,69 0,65 Fibrotest 0,67 0,85 0,83
  16. 16. Liver fibrosis • MR • CT • US
  17. 17. Liver fibrosis MR • Late accumulation of gadolinium in standart contrast T1 • Dubble contrast enhanced T2* with gadolinium and supraparamagnetic iron oxide (SPIO) Sensitivity, specifity and accuracy >90% to differentiate F2-F3 fibrosis (Aguirre DA et al. Radiology 2006;239:425-437)
  18. 18. Liver fibrosis MR Diffusion-weigted imaging: Fibrosis F≥2: sensitivity 83,3%, specificity 88,9% Fibrosis F≥3 ; sensitivity 83,3%, specificity 80,0% Diffusion-weighted MR can be usefull for prediction of moderate and severe fibrosis (Taouli B et al.AJR 2007 189;799-806.) MR spectroscopy: F0-2 vs F3-4 sensitivity 81%, specificity 69% or 93% and 54% (Norden B et al. Eur J Radiol 2008;66(2):313-320.) MR elastography: sensitivity 100%, specificity 83%, 98%, 95% and 100% (fibrosis F 1-2-3-4) (Huvart L et al. NMR in biomedicine 2008. 19/2;173-179)
  19. 19. Liver fibrosis CT cirrhosis
  20. 20. Liver fibrosis US Cirrhosis: Surface nodularity Parenchimal heterogenety Caudate lobe hypertrophy Flattened hepatic vein Dopplercurve Portal hypertension signs
  21. 21. Liver fibrosis US Precirrhotic stage – Doppler measurements Maximum portal blood velocity Mean portal blood velocity Portal vein pulsitility Hepatic arterial velocity Resistive index Hepatic vein Doppler waveform
  22. 22. Liver fibrosis US Precirrhotic stage – Doppler measurements Maximum portal blood velocity Schneider ARJ et al. Liver International 2005. F0-1 15,9cm/s F2-4 14,8cm/s F5-6 13,8cm/s F5-6 specificity 53% sensitivity 74,5% Bernatic T et al. Eu J Gastroenterol 2002. FI -20,3 cm/s FII-20,3 cm/s FII-17,7cm/s FIV-18,2 cm/s Lim AK et al. AJR 2005 F0-1 22 cm/s F2-4 23 cm/s F5-6 22 cm/s N - 12,6 cm/s; 13,7cm/s; 15,9 cm/s; 19,6 cm/s
  23. 23. Liver fibrosis US Precirrhotic stage – Doppler measurements Portal vein pulsitility Dieterich CF et al. 1998. Vmax-Vmin cirrhosis 4.0 precirrhosis 4,3 control 6,5 Schneider ARJ et al. 2005. Undulations 23,5% in F5-6 61,8% in F2-4 63,8% in F0-1 Barkat M 2005. control 100% Child-Plugh A 74,1% Child –Plugh B 55,6% Child-Plugh C 53,3%
  24. 24. Liver fibrosis US Precirrhotic stage – Doppler measurements Hepatic arterial velocity Lim AK et al. AJR 2005 F0-1 73cm/s F2-4 62 cm/s F5-6 60 cm/s Bernatic T et al. Eu J Gastroenterol 2002. FI -57,8 cm/s FII-50,0 cm/s FII-55,0cm/s FIV-58,0 cm/s
  25. 25. Liver fibrosis US Precirrhotic stage – Doppler measurements Resistive index Lim AK et al. AJR 2005 F0-1 0,69 F2-4 0,56 F5-6 0,68 Bernatic T et al. Eu J Gastroenterol 2002. FI -0,62 FII- 0,65 FIII- 0,66 FIV- 0,67 Normal RI value Dieterich CF et al. 1998 0,59 Cioni G et al. 1993 0,72 O’Donahue et al. 2004. 0,64
  26. 26. Liver fibrosis US Precirrhotic stage – Doppler measurements Hepatic vein Doppler waveform
  27. 27. Liver fibrosis US Precirrhotic stage – Doppler measurements Hepatic vein Doppler waveform Flatened waveform control cirrhosis Bolondi L et al. 1991. 0 % 52% Colli A et al. 1994. 0 % 38,5% (Child-Plugh A) Dietrich CF et al. 1998. 25% 53% F 0-1 F 2-3 F 4-5 Schneider AR et al. 2005 23% 38% 52,9% o’Donnohue et al. 2004. 2,1% 57% 77% Prieditis P. et al 25,4% 25% 83%
  28. 28. Liver steatosis MR MR spectroscopy Steatosis >5% Steatosis >33% sensitivity specificity sensitivity specificity McPherson et al. 2009. 90% (F0-1) 96% (F2-4) 100% (F0-1) 87% (F2-4) 100% (F0-1) 92% (F2-4) 97% (F0-1) 92% (F2-4) Lee SS et al 2010 80% 80,2% 72,7% 79%
  29. 29. Liver steatosis MR Fatt-sensitive imaging techniqes • In-phase/opposit-phase Dixon IP/OP (SIin-phase - SIop-phase)/ SIin-phaseX 100 • Fatt saturation
  30. 30. Liver steatosis MR Dixon in-phase/opposit-phase • Correlation with steatosis grade In-phase/opposit-phase 0,68-0,69 fat saturated T2 0,61-0,54 (Qayyum A et al. Clinical imaging 2009;33:110-115) Steatosis >5% Steatosis >33% sensitivity specificity sensitivity specificity McPherson et al. 2009. 88% (F0-1) 87% (F2-4) 100% (F0-1) 83% (F2-4) 93% (F0-1) 85% (F2-4) 97% (F0-1) 97% (F2-4) Lee SS et al. 2010 90,9% 87,1% 90,9% 94%
  31. 31. Liver steatosis CT Liver > spleen 10HU liver – 45HU spleen - 53HU liver – 15HU spleen – 56HU
  32. 32. Liver steatosis CT Steatosis > 30% sensitivity specifity PPV NPV Lee SS et al 2010 72,7% 91,3% 38,1% 97,9% Park SH et al. 2006 82% 100% Shadeh S et al. 2002 93% 76% Cho CS et al 2008 33% 100% 100% 83%
  33. 33. Liver steatosis US • Hyperechogenicity of parenhima (bright liver) • Beem attenuation • Poor diaphragm visualisation • Portal and hepatic vein blurring (Rumac CM et al. Diagnostic ultrasound 1998)
  34. 34. Liver steatosis US Disarathy S et al. J of Hepatology 2009;51:1061-1067 Steatosis > 5% Steatosis > 30% Sensitivity specifity sensitivity specifity Presence of fatt 82,4% 100% 100% 84,9% Bright liver 82,4% 100% 100% 84,9% HV blurred 79,4% 97,4% 100% 84,9% Poor diaphragm visualisation 32,4% 92,3% 55% 94,3% Posterior attenuation 41,2% 99,4% 55% 92,5%
  35. 35. Liver steatosis US Fatty liver screening Sensitivity 67% specificity 77% (Graif M et al. 2000. Invest Radiol 2000;35:319-324) Macrovesicular steatosis Sensitivity 60,9% specifity 100% Microvesicular steatosis Sensitivity 43% specificity 73% (Dasarathy S et al. J of Hepatology 2009;51:1061-1067)
  36. 36. Liver steatosis US • 168 patients 3 radiologists, 4 weeks interval – Presence of fatt: + / - – Severity of steatosis: non, mild, moderate, severe (Straus S et al. AJR 2007189:w320-w323) Intraobsrtever agreement Interobserver agreement Presence of fatt k=0,54 76% k=0,43 72% Severity of steatosis k=0,51-0,63 45%-63% k= 0,4-0,51 47%-63,7%
  37. 37. Liver steatosis US Dopplerography Flattened waveform of hepatic vein Severe steatosis Mild steatosis Diterich CF et al 1998. 90% (44/49) 5% (3/57) Schneider ARJ et al. 2005. 90,2% 22,5% Prieditis P et al 2007. 44%(4/9) 24% (17/69) Steatosis >33% sensitivity 88,2% specificity 74,5% (Schneider ARJ et al. Liver international 2005; 25:1150-1155 )
  38. 38. Conclusion Radiology can to reduce, but not completely eliminate the need for liver biopsy
  39. 39. Thank you for your attention !
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