liver fibrosis and steatosis - the role of radiology

Liver fibrosis and steatosis – the role

of radiology

P.PrieditisP.Stradins Clinical University Hospital

Riga, Latvia9.X 2010.

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)

Development of cirrhosis in 2-3 to 30-40 years after infectionCirrhosis in 20 y after infection 9%Cirrhosis in 40 y after infection 44%

(Poynard T et al. J Hepatol 2001;34:730-739)

• 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%

(Fiore G. et al. Eur J Gastroenterol Hepatol 1998;8:125-129 )

• NASH Cirrhosis 8-26%

(Powell EE et al. Hepatology1990;11:74-80)

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


Morphology - absolut truth?Chronic hepatitis

• Size of tissue sample• Number of samples• Punction site• Morphologist



• Size of tissue sample15mm 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/1mmSlight inflamation 49,7% 62,2% 86,6%Slight fibrosis 59% 63,3% 80,1%

(Colloredo G. J Hepatol 2003;39:239-244)



• 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)



• 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)

Liver biopsy – golden standartMorphology - absolut truth?

Chronic hepatitis• interobsrver and intraobsrver variabilityChron. 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)

Liver biopsy – golden standartMorphology - absolut truth?

Chronic hepatitis• interobsrver and intraobsrver variabilityChron. 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)

Transient elastography(Fibroscan )

• Cirrhosis (F-IV) vs no cirrhosis (F0-III)Sensitivity 84%-90%; specificity 89%-92%)

F II-IV vs F 0-ISensitivity 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≥221 overestimation F≤2

(J Viral Hepatol 2009,25)

• Overestimation of fibrosis in patients with elevated ALAT

(Clin Gastroenterol Hepatol 2008;6:1027-35)

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

Real time elastographyElastography integrated in conventional ultrasound scaning

sistem

Correlation of TE, RTE, Fibrotest and biopsy134 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

Liver fibrosis

• MR• CT• US

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)

Liver fibrosis

MRDiffusion-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)

Liver fibrosis

CTcirrhosis

Liver fibrosis

USCirrhosis:

Surface nodularityParenchimal heterogenety Caudate lobe hypertrophyFlattened hepatic vein DopplercurvePortal hypertension signs

Liver fibrosis

USPrecirrhotic stage – Doppler measurements

Maximum portal blood velocityMean portal blood velocityPortal vein pulsitilityHepatic arterial velocityResistive indexHepatic vein Doppler waveform

Liver fibrosis


Maximum portal blood velocitySchneider ARJ et al. Liver International 2005.

F0-1 15,9cm/s F2-4 14,8cm/s F5-6 13,8cm/sF5-6 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

Liver fibrosis


Portal vein pulsitilityDieterich 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 F0-1Barkat M 2005.

control 100% Child-Plugh A 74,1% Child –Plugh B 55,6% Child-Plugh C 53,3%

Liver fibrosis


Hepatic arterial velocityLim AK et al. AJR 2005

F0-1 73cm/s F2-4 62 cm/s F5-6 60 cm/sBernatic 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

Liver fibrosis


Resistive indexLim AK et al. AJR 2005

F0-1 0,69 F2-4 0,56 F5-6 0,68Bernatic T et al. Eu J Gastroenterol 2002.

FI -0,62 FII- 0,65 FIII- 0,66 FIV- 0,67

Normal RI valueDieterich CF et al. 1998 0,59Cioni G et al. 1993 0,72O’Donahue et al. 2004. 0,64

Liver fibrosis


Hepatic vein Doppler waveform

Liver fibrosisUS

Precirrhotic stage – Doppler measurementsHepatic 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%

Liver steatosis

MRMR spectroscopy

Steatosis >5% Steatosis >33%

sensitivity specificity sensitivity specificityMcPherson 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%

Liver steatosis

MRFatt-sensitive imaging techniqes

• In-phase/opposit-phaseDixon IP/OP

(SIin-phase - SIop-phase)/ SIin-phaseX 100• Fatt saturation

Liver steatosis

MRDixon in-phase/opposit-phase

• Correlation with steatosis gradeIn-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 specificityMcPherson 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%

Liver steatosisCT

Liver > spleen10HU

liver – 45HUspleen - 53HU

liver – 15HUspleen – 56HU

Liver steatosisCT

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%

Liver steatosisUS

• Hyperechogenicity of parenhima (bright liver)• Beem attenuation• Poor diaphragm visualisation• Portal and hepatic vein blurring(Rumac CM et al. Diagnostic ultrasound 1998)

Liver steatosisUS

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%

Liver steatosisUS

Fatty liver screeningSensitivity 67% specificity 77%

(Graif M et al. 2000. Invest Radiol 2000;35:319-324)

Macrovesicular steatosisSensitivity 60,9% specifity 100%

Microvesicular steatosisSensitivity 43% specificity 73%

(Dasarathy S et al. J of Hepatology 2009;51:1061-1067)

Liver steatosisUS

• 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%

Liver steatosisUS

DopplerographyFlattened 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 )

Conclusion

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

Thank you for your attention !

liver fibrosis and steatosis - the role of radiology

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