Friday, May 16, 2014

questions in liver cirrhosis

A 65 year old African American man came for consultation
he is known to have  Hepatitis C since 1982 when he first  noted jaundice
He met with my predecessor and 2 GI DRs who have advised him current therapy with Interferon and ribaverin, his alpha fetoprotein is 4.  But his Viral load 4 million. His Viral genotype undetermined
and whether such determination matters is a question, since H is "old school" and decline therapy be cause he feels fine! And grant it the Viral load has no defined prognosis value per certain authors.He will only be convinced to treatment if there is evidence of early cirrhosis.  That's where Liver imaging CT sonogram or MRI comes  in.
But is there a way of determining that Cirrhosis is on its way
can genes for fibrosis be detected in time to force the hands of such patients?
literature search brings the importance  of Fibronectin,fibrinogen,laminin Tenascin, TGF-Beta1, Metalloproteiases, TIMP1, Plasminogen-PAI-1, and even CTFRs

Interest in the Quiagen article cited below, is this the way of the future!?
Can we compare this gene abnormality-expression to MRIs of the liver for direction.
what are the biomarkers to use?



From Quiagen (for discussion only)
"Pro-Fibrotic: Acta2 (a-SMA), Agt, Ccl11 (Eotaxin), Ccl12, Ccl3 (MIP-1a), Ctgf, Grem1, Il13, Il13ra2, Snai1
(Snail).

Anti-Fibrotic: Bmp7, Hgf, Ifng, Il10, Il13ra2.
Extracellular Matrix & Cell Adhesion:
ECM Components: COL1A2, COL3A1.
Remodeling Enzymes: Lox, Mmp1a (Collagenase 1), Mmp13, Mmp14, Mmp2 (Gelatinase A), Mmp3, Mmp8, Mmp9
(Gelatinase B), Plat (tPA), Plau (uPA), Plg, Serpina1a (a1-antitrypsin), Serpine1 (PAI-1), Serpinh1, Timp1, Timp2,
Timp3, Timp4.
Cellular Adhesion: Itga1, Itga2, Itga3, Itgav, Itgb1, Itgb3, Itgb5, Itgb6, Itgb8

Inflammatory Cytokines & Chemokines:Ccl11 (Eotaxin), Ccl12, Ccl3 (MIP-1a), Ccr2, Cxcr4, Ifng, Il10, Il13,
Il13ra2, Il1a, Il1b, Tnf.
Growth Factors: Agt, Ctgf, Edn1, Egf, Hgf, Pdgfa, Pdgfb, Vegfa.

Signal Transduction:
TGFß Superfamily: Bmp7, Cav1, Dcn, Eng (EVI-1), Grem1, Inhbe, Ltbp1, Smad2, Smad3, Smad4, Smad6, Smad7,
Tgfb1, Tgfb2, Tgfb3, Tgfbr1 (ALK5), Tgfbr2, Tgif1, Thbs1, Thbs2.
Transcription Factors: Cebpb, Jun, Myc, Nfkb1, Sp1, Stat1, Stat6.

Epithelial-to-Mesenchymal Transition: Akt1, Bmp7, Col1a2, Col3a1, Itgav, Itgb1, Mmp2 (Gelatinase A),
Mmp3, Mmp9, Serpine1 (PAI-1), Smad2, Snai1 (Snail), Tgfb1, Tgfb2, Tgfb3, Timp1.

Others: Bcl2, Fasl (TNFSF6)."
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