1) Liver fibrosis and steatosis can be assessed through various imaging modalities like ultrasound, CT, MRI and biopsy. However, liver biopsy as the gold standard has limitations related to sample size, number of samples, and inter-observer variability. 2) Non-invasive techniques like transient elastography (FibroScan) and real time elastography have good diagnostic accuracy for staging liver fibrosis compared to biopsy but may overestimate in cases of elevated liver enzymes. 3) Doppler ultrasound of the liver can provide useful information for assessing liver fibrosis through measurements of blood flow in the portal vein, hepatic arteries and hepatic veins. Changes in waveforms indicate advancing fibrosis. 4) MRI and CT can also

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

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. 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. 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;38:1449-1457)
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. 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. 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. 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;6:1027-35)

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. 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. 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;239:425-437)

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. 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 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. 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. 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. 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. 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. 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. 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. Liver steatosis
MR
Fatt-sensitive imaging techniqes
• In-phase/opposit-phase
Dixon IP/OP
(SIin-phase - SIop-phase)/ SIin-phaseX 100
• Fatt saturation

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. 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
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. 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;51:1061-1067
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. 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. 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. 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. Conclusion
Radiology can to reduce, but not completely
eliminate the need for liver biopsy

39. Thank you for your attention !