Acidul ialuronic si EPASCRE diagnostic inovativ al fibrozei hepatice Proton Impex 2000
Topics Ce este Acidul ialuronic (A)? Structura chimica Caracteristici medicale De ce e utila masurarea A? Semnificatia clinica a A ca si marker unic Ce este EPASCRE?
Structura chimica a A Izolat in 1934 din ochiul de vaca, yalos = sticlos Polizaharid linear compus din unitati repetitive dizaharidice (Nacetylglucosamine si D-glucuronic acid) Masa moleculara variabila C NAc C NAc C NAc C NAc C NA c Mw = 2-6 10 6 -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 (BV/CV) Se coreleaza foarte bine cu modificarile histopatologice hepatice (fibroza)
Semnificatie clinica A Semnificatie clinica dovedita pentru multe etiologii Etiologie Performanta Diagnostica Reference epatita Virus C (CV) epatita Virus B (BV) Alcoholic Liver Diseases (ALD) 100% NPV pentru ciroza (cutoff 50 ng/ml) alfon P et al. 90,9% sensibilitate, 98,1% specificitate pentru fibroza extensiva (cutoff 126,4 ng/ml) 82,8% sensibilitate 69% specificitate ptr. Fibroza hepatica, > Ludwig stadiul 2 (cutoff 55,5 ng/ml); concentratia serica a A creste pe masura ce distructia hepatica avanseaza Montazeri G et al. Stickel F et al. Non-Alcoholic Fatty Liver Disease (NAFLD) C282Y emochromatosis () 85% sensibilitate, 80% specificitate ptr. fibroza severa (cutoff 46,1 ng/ml) 100% sensitivitate and specificitate ptr. Ciroza (cutoff 46,5 ng/ml) la pacientii cu feritina >1000 ng/ml Suzuki A et al. Crawford DG et al.
Semnificatie Clinica a A A este cunoscut ca si marker de fibroza hepatica de ~20 ani A cel mai bun marker utilizat singur in detectia stadiilor F3/F4 Test produs de firma WAK CEMICALS JAPNIA Accuracy of A for predicting fibrosis stages in CV, alfon et al. 2005 Com. epatol. 100% NPV ptr ciroza ; cut-off 50 ng/ml A
Algorithmi de stadializare Acidul ialuronic poate fi utilizat singur sau in combinatie cu alti parametrii Name Single tests Comments Forns Index platelets, GGT, Chol, age Chol is influenced by CV 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 CV patients Fibrospect A, TIMP-1, alpha-2-macroglobulin Good differentiation between F2 and F4 ELF A, PIINP, TIMP-1, age Good staging published, commercialised by Siemens and IQUR (UK) Fibrometer platelets, A, alpha-2-macroglobulin, AST, Urea, prothrombin index Good staging published, commercialised by Biolivescale (France) epascore tbil, GGT, A, alpha-2-macroglobulin, age, sex Good staging published, mostly evaluated with CV patients SASTA A, Alb, AST nly evaluated for IV/CV coinfected patients
Protocol evaluare fibroza
EPASCRE 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 ialuronic 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. A fibroza mareste productia de A 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 EPASCRE EPASCRE = y / ( 1 + y ) * Un program informatic pentru calcul automat al scorului va fi pus la dispozitia laboratoarelor care vor utiliza acest algoritm.
Interpretare S 0,5 - Fibroza semnificativa ( F2 ) ( 92% specificitate si 67% sensitivitate, PPV 87% ) S < 0,5 - Absenta fibroza avansata ( F3 ) ( 81% specificitate si 95% sensitivitate ) S < 0,84- Exclude Ciroza epatica ( 84% specificitate si 71% sensitivitate, NPV 94% )
EPASCRE vs Fibroza cut-off 0,84 cut-off 0,5 epascore : An accurate Validated Predictor of liver Fibrosis in Chronic epatitis C Infection Adams et Al. 2005
Valoare diagnostica S 0,5 pacientul poate fi candidat ptr.terapie antivirala fara a se efectua o biopsie ; S < 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. S > 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
epascore Automation of the epascore 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 epatitis 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, epascore and Fibroscan have similar performances for the diagnosis of significant fibrosis (METAVIR F>2) in CC. These methods have been recently approved after an independent systematic review by the French National Authority for ealth for the first line assessment of fibrosis in naıve patients with CC...
Cost redus
Corelatia cu alte metode Conclusions:. interpretable Fibroscan, Fibrometer, and epascore perform best and similarly for diagnosis of significant fibrosis and cirrhosis. (1) Les méthodes non invasives les plus utilisées en France seraient FIBRSCAN et FIBRTEST et de façon moindre epascore, FIBRMETRE et l ARFI. (2) (1) Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: The ANRS CEP-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 aute Authorite de Sante France 2013
Concluzii Acidul ialuronic determinat singur poate discrimina intre ciroza si fibroza avansata epascore este utilizat cu succes in ghidare deciziilor terapeutice avand aceeasi valoare diagnostica ca si testele recunoscute in acest moment in Romania
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