Liver fibrosis and steatosis the role of radiology. P.Prieditis P.Stradins Clinical University Hospital Riga, Latvia 9.X 2010.

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1 Liver fibrosis and steatosis the role of radiology P.Prieditis P.Stradins Clinical University Hospital Riga, Latvia 9.X 2010.

2 Liver fibrosis Alcoholismus Virus hepatitis C (VHC) Nonalcohol steatohepatitis (NASH)

3 Morbidity with hr.vhc in Latvia Reconvalescence 15% (Hoofnagle JH et al Hepatology 1997;26(suppl 1):15S-20S) Development of cirrhosis in 2-3 to 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: )

4 Advanced liver fibrosis is reversibl Antifibrotic therapy Removing of causitive agent (Bataler R. et al.2005.)

5 Liver steatosis Chr. VHC NASH 20-30% of world population (Marchesini G. et al. Minerva Cardioangiol 2006;54: )) 50-75% (Fiore G. et al. Eur J Gastroenterol Hepatol 1998;8: ) Cirrhosis 8-26% (Powell EE et al. Hepatology1990;11:74-80)

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 ) Follow up Diagnostic accuracy

7 Liver biopsy golden standart Morphology - absolut truth? Chronic hepatitis Size of tissue sample Number of samples Punction site Morphologist

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: ) 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: )

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): )

10 Liver biopsy golden standart Punction site Morphology - absolut truth? Chronic hepatitis 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: )

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 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 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: )

14 Transient elastography + biochemical tests complex Fibrotest: alfa 2-macroglobulin, apolipoprotein A1, haptoglobin, gammaglutamyl-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 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: ) 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 Liver fibrosis MR CT US

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: )

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 ; ) 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): ) MR elastography: sensitivity 100%, specificity 83%, 98%, 95% and 100% (fibrosis F ) (Huvart L et al. NMR in biomedicine /2; )

19 Liver fibrosis CT cirrhosis

20 Liver fibrosis US Cirrhosis: Surface nodularity Parenchimal heterogenety Caudate lobe hypertrophy Flattened hepatic vein Dopplercurve Portal hypertension signs

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 Liver fibrosis US Precirrhotic stage Doppler measurements Maximum portal blood velocity Schneider ARJ et al. Liver International 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 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 F cm/s F cm/s F cm/s N - 12,6 cm/s; 13,7cm/s; 15,9 cm/s; 19,6 cm/s

23 Liver fibrosis US Precirrhotic stage Doppler measurements Portal vein pulsitility Dieterich CF et al V max -V min cirrhosis 4.0 precirrhosis 4,3 control 6,5 Schneider ARJ et al Undulations 23,5% in F5-6 61,8% in F2-4 63,8% in F0-1 Barkat M control 100% Child-Plugh A 74,1% Child Plugh B 55,6% Child-Plugh C 53,3%

24 Liver fibrosis US Precirrhotic stage Doppler measurements Hepatic arterial velocity Lim AK et al. AJR 2005 F0-1 73cm/s F cm/s F cm/s Bernatic T et al. Eu J Gastroenterol FI -57,8 cm/s FII-50,0 cm/s FII-55,0cm/s FIV-58,0 cm/s

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 FI -0,62 FII- 0,65 FIII- 0,66 FIV- 0,67 Normal RI value Dieterich CF et al ,59 Cioni G et al ,72 O Donahue et al ,64

26 Liver fibrosis US Precirrhotic stage Doppler measurements Hepatic vein Doppler waveform

27 Liver fibrosis US Precirrhotic stage Doppler measurements Hepatic vein Doppler waveform Flatened waveform control cirrhosis Bolondi L et al % 52% Colli A et al % 38,5% (Child-Plugh A) Dietrich CF et al % 53% F 0-1 F 2-3 F 4-5 Schneider AR et al % 38% 52,9% o Donnohue et al ,1% 57% 77% Prieditis P. et al 25,4% 25% 83%

28 Liver steatosis MR MR spectroscopy Steatosis >5% Steatosis >33% sensitivity specificity sensitivity specificity McPherson et al % (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 % 80,2% 72,7% 79%

29 Liver steatosis MR Fatt-sensitive imaging techniqes In-phase/opposit-phase Dixon IP/OP (SI in-phase -SI op-phase )/ SI in-phase X 100 Fatt saturation

30 Liver steatosis MR Dixon in-phase/opposit-phase Steatosis >5% Steatosis >33% sensitivity specificity sensitivity specificity McPherson et al % (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 ,9% 87,1% 90,9% 94% 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: )

31 Liver steatosis CT Liver > spleen 10HU liver 45HU spleen - 53HU liver 15HU spleen 56HU

32 Liver steatosis CT Steatosis > 30% sensitivity specifity PPV NPV Lee SS et al 2010 Park SH et al Shadeh S et al Cho CS et al ,7% 91,3% 38,1% 97,9% 82% 100% 93% 76% 33% 100% 100% 83%

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 Liver steatosis US Disarathy S et al. J of Hepatology 2009;51: 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 Posterior attenuation 32,4% 92,3% 55% 94,3% 41,2% 99,4% 55% 92,5%

35 Liver steatosis US Fatty liver screening Sensitivity 67% specificity 77% (Graif M et al Invest Radiol 2000;35: ) Macrovesicular steatosis Sensitivity 60,9% specifity 100% Microvesicular steatosis Sensitivity 43% specificity 73% (Dasarathy S et al. J of Hepatology 2009;51: )

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 :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 Liver steatosis US Dopplerography Flattened waveform of hepatic vein Severe steatosis Mild steatosis Diterich CF et al Schneider ARJ et al Prieditis P et al % (44/49) 5% (3/57) 90,2% 22,5% 44%(4/9) 24% (17/69) Steatosis >33% sensitivity 88,2% specificity 74,5% (Schneider ARJ et al. Liver international 2005; 25: )

38 Conclusion Radiology can to reduce, but not completely eliminate the need for liver biopsy

39 Thank you for your attention!