Acidul Hialuronic si HEPASCORE

diagnostic inovativ al fibrozei hepatice

Proton Impex 2000

Topics

Ce este Acidul Hialuronic (AH)?• Structura chimica

• Caracteristici medicale

De ce e utila masurarea AH?

• Semnificatia clinica a AH ca si marker unic

Ce este HEPASCORE ?

Structura chimica a AH

• Izolat in 1934 din ochiul de vaca , „Hyalos“ = sticlos

• Polizaharid linear compus din unitati repetitive dizaharidice (N-

acetylglucosamine si D-glucuronic acid)

• Masa moleculara variabila

O

O

H

H

HO

H

H

OHH

COOH

OHO

O

H

H

H

H

NHAcH

O

OH

O

H

H

HO

H

H

OHH

COOH

OHO

O

H

H

H

H

NHAcH

O

OH

O

H

H

HO

H

H

OHH

COOH

OHO

O

H

H

H

H

NHAcH

O

OH

O

H

H

HO

H

H

OHH

COOH

OHO

O

H

H

H

H

NHAcH

O

OH

Mw = 2-6 × 106

O

H

H

HO

H

H

OHH

COOH

OHO

O

H

H

H

H

NHA cH

HO

O

O

-D-glucuronic acid-β-1,3-D-N-acetylglucosamine-β-1,4

Caracteristici

• Este distribuit ubicuitar in organism, in special in tesut conjunctiv

articulatii , matrice extracelulara , cartilaj , piele , ochi

• Capacitate crescuta de a lega moleculele de apa (1:1000); buffer

osmotic si „lubrifiant“ pentru articulatii

• Concentratie scazuta in ser, timp de injumatatire 2-5 minute , este

degradat de celulele endoteliale sinusoidale hepatice

• Concentratia serica crescuta in artrite , sepsis, mesotheliom , fibroza

/ciroza hepatica

• Celuele endoteliale sinusoidale hepatice sunt afectate in caz de

expunere la etanol sau patogeni (HBV/HCV)

Se coreleaza foarte bine cu modificarile histopatologice hepatice

(fibroza)

Semnificatie clinica AH

• Semnificatie clinica dovedita pentru multe etiologii

Etiologie Performanta Diagnostica Reference

Hepatita Virus C

(HCV)

100% NPV pentru ciroza (cutoff 50 ng/ml) Halfon P et al.

Hepatita Virus B

(HBV)

90,9% sensibilitate, 98,1% specificitate pentru

fibroza extensiva (cutoff 126,4 ng/ml)

Montazeri G et al.

Alcoholic Liver

Diseases (ALD)

82,8% sensibilitate 69% specificitate ptr.

Fibroza hepatica , > Ludwig stadiul 2 (cutoff

55,5 ng/ml); concentratia serica a AH creste pe

masura ce distructia hepatica avanseaza

Stickel F et al.

Non-Alcoholic Fatty

Liver Disease

(NAFLD)

85% sensibilitate , 80% specificitate ptr. fibroza

severa (cutoff 46,1 ng/ml)

Suzuki A et al.

C282Y

Hemochromatosis

(HH)

100% sensitivitate and specificitate ptr. Ciroza

(cutoff 46,5 ng/ml) la pacientii cu feritina >1000

ng/ml

Crawford DHG et al.

Semnificatie Clinica a AH

• AH este cunoscut ca si marker de fibroza hepatica de ~20 ani

• AH cel mai bun marker „utilizat singur“ in detectia stadiilor F3/F4

• Test produs de firma WAKO CHEMICALS – JAPONIA

Accuracy of HA for

predicting fibrosis

stages in HCV,

Halfon et al. 2005

Com. Hepatol.

100% NPV ptr

ciroza ; cut-off

50 ng/ml AH

Algorithmi de stadializare

• Acidul Hialuronic poate fi utilizat singur sau in combinatie cu alti

parametrii

Name Single tests Comments

Forns Index platelets, GGT, Chol, age Chol is influenced by HCV genotype, low specificity for

signifcant fibrosis

APRI AST, platelets Low sensitivity for significant fibrosis, but acceptable,

easy and cheap

Fibrotest GGT, haptoglobulin, tBil, alpha-2-

macroglobulin, ApoA, age, sex

Commercialised by Biopredictive (France) and by far most

used score, massive investigated with HCV patients

Fibrospect HA, TIMP-1, alpha-2-macroglobulin Good differentiation between F2 and F4

ELF HA, PIINP, TIMP-1, age Good staging published, commercialised by Siemens and

IQUR (UK)

Fibrometer platelets, HA, alpha-2-macroglobulin, AST,

Urea, prothrombin index

Good staging published, commercialised by Biolivescale

(France)

Hepascore tBil, GGT, HA, alpha-2-macroglobulin, age,

sex

Good staging published, mostly evaluated with HCV

patients

SHASTA HA, Alb, AST Only evaluated for HIV/HCV coinfected patients

Protocol evaluare fibroza

HEPASCORE

• Dezvoltat de un grup de cercetatori Australieni in 2005 – Adams et al.

• 4 teste biochimice , varsta si sexul pacient :

• GGT ,

• Bilirubina ,

• alpha 2 Macroglobulina ,

• Acid Hialuronic

• Testele se pot efectua automat pe un singur analizor

• Algorithm de calcul gratuit – poate fi folosit de orice laborator**

• Validat de Autoritatea Nationala pentru Sanatate in Franta si utilizat

de Quest Diagnostics in SUA

• Performante foarte bune , comparabile cu alti algoritmi

Alegerea testelor

Bilirubina – creste pe masura ce fibroza avanseaza ca rezultat al

excretiei hepatice reduse

GGT – este corelata cu fibroza hepatica la pacientii infectati cu hepatita

B si C.

AH – fibroza mareste productia de AH de catre celulele stelate hepatice

si diminueaza clerance-ul in celulele endoteliale sinusoidale

Alpha 2-Macroglobulina – este un inhibitor de proteaza a carui

concentratie creste in momentul activarii celulelor stelate si a evolutiei

fibrozei

Algoritm HEPASCORE

HEPASCORE = y / ( 1 + y )

* Un program informatic pentru calcul automat al scorului va fi pus la

dispozitia laboratoarelor care vor utiliza acest algoritm.

Interpretare

• HS ≥ 0,5 - Fibroza semnificativa (≥ F2 )– ( 92% specificitate si 67% sensitivitate , PPV 87% )

• HS < 0,5 - Absenta fibroza avansata (≥ F3 )– ( 81% specificitate si 95% sensitivitate )

• HS < 0,84- Exclude Ciroza Hepatica– ( 84% specificitate si 71% sensitivitate , NPV 94% )

HEPASCORE vs Fibroza

Hepascore : An accurate Validated Predictor of liver Fibrosis in Chronic Hepatitis C Infection – Adams

et Al. – 2005

cut-off 0,5

cut-off 0,84

Valoare diagnostica

• HS ≥ 0,5 – pacientul poate fi candidat ptr.terapie antivirala fara

a se efectua o biopsie ;

• HS < 0,5 – excluderea fibrozei avansate poate fi utila ca si

prognostic pentru pacientii care nu doresc biopsie sau pentru

pacientii in varsta la care e improbabil sa apara o morbiditate /

mortalitate corelata afectarii hepatice in absenta fibrozei avansate.

• HS > 0.84 – specific 84-89% pentru prezenta cirozei , poate

elimina necesitatea biopsiei hepatice la pacientii la care se

suspecteaza o ciroza oculta sau sa ghideze managementul

deciziilor privind screening-ul variceal sau de carcinom , precum si

monitorizarea pacientului

Hepascore

„Automation of the Hepascore and

validation as a biochemical index“

… Guéchot et al. Clin Chim Acta

2010

Valoare diagnostica si cost

“ Contribution of the ELFG Test in

Algorithms of Noninvasive Markers towards

the Diagnosis of Significant Fibrosis in

Chronic Hepatitis C “

*Jean Pierre Zarski et al. , March 21, 2013

*** Test ELFG utilizat cand unul din testele de prima intentie nu ofera rezultate

concludente

Numar de biopsii evitate

Valoare diagnostica validata

“Retrospective and recent independent prospective studies

have shown that the four most validated non-invasive

methods, Fibrotest, Fibrometer, Hepascore and Fibroscan

have similar performances for the diagnosis of

significant fibrosis (METAVIR F>2) in CHC …….

These methods have been recently approved after an

independent systematic review by the French National

Authority for Health for the first line assessment of

fibrosis in naıve patients with CHC …...”

Cost redus

Corelatia cu alte metode

• Conclusions: ……. interpretable Fibroscan™, Fibrometer, and Hepascore

perform best and similarly for diagnosis of significant fibrosis and cirrhosis.

(1)

(1) “ Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C:

The ANRS HCEP-23 study “ Jean-Pierre Zarski et al. 2011

(2) Evaluation des méthodes non invasives de mesure de la fibrose hépatique au cours de l’hépatite B

Chronique – Haute Authorite de Sante France 2013

• Les méthodes non invasives les plus utilisées en France seraient

FIBROSCAN et FIBROTEST et de façon moindre Hepascore,

FIBROMETRE et l’ARFI. (2)

Concluzii

• Acidul Hialuronic determinat singur poate

discrimina intre ciroza si fibroza avansata

• Hepascore este utilizat cu succes in ghidare

deciziilor terapeutice avand aceeasi valoare

diagnostica ca si testele recunoscute in acest

moment in Romania

Acest produs va este oferit de :

PROTON IMPEX 2000 SRL

no. 9, Mugur Mugurel str. ,sector 3

Bucuresti , 031227

www.proton.com.ro

Va multumesc pentru atentie !