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“Interpreting Your Test Results”. Jim Boyer Ensign Professor of Medicine Yale University School of Medicine. Your Liver Tests. Routine Liver function tests Liver Imaging ( Hepatic Ultrasound, MRCP, ERCP) Liver Biopsy Enhanced Liver Fibrosis Score (ELF)
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“Interpreting Your Test Results” Jim Boyer Ensign Professor of Medicine Yale University School of Medicine
Your Liver Tests • Routine Liver function tests • Liver Imaging ( Hepatic Ultrasound, MRCP, ERCP) • Liver Biopsy • Enhanced Liver Fibrosis Score (ELF) • Fibroscan (Transient Elastography) • Magnetic resonance elastography (MRE); • Antibodies • CA-19-9
Liver Function Tests HepatitisCirrhosisCholestasisInfiltrates SGOT: 2-4+ 1+ 0-1+ 0 SGPT: 2-4+ 1+ 0-1+ 0 Alk.Ph. 0-1+ 0-1+ 2-4+ 2-4+ Bilirubin 0-4+ 0-4+ 0-4+ 0-2+ Albumin 0-4+ 2-4+ 0-1+ 0-1+ Pro-time 0-4+ 0-2+ 0-2+ 0-1+
Use of the Alkaline Phosphatase as a marker of Prognosis and therapeutic response • #605 Long term follow-up of a multicenter , randomized controlled trial of ursodeoxycholic acid in primary sclerosing cholangitis • # 623 Alkaline phosphatase as biomarker in primary sclerosing cholangitis: Better prognostic value one year after diagnosis UDCA improves LT-free survival in patients with PSC who experience normal ALP with its use (13-15 mg/Kg)
Radiologic Imaging Studies:Comparison of ERCP with MRCP ERCP MRCP
Stages of Fibrosis as Classified by Liver Biopsy • Stage 1 - Periportal fibrosis • Stage 2 - Fibrosis extending from portal triads into the surrounding liver tissue • Stage 3 - Fibrosis spans or “bridges” between adjacent portal triads • Stage 4 - Fibrosis surrounds the portal triads producing nodules
Metavir fibrosis scoring system(Bedossa et al. Groupe Metavir, Elsevier.p.32’00)
Non-invasive tests of fibrosis 1) Enhanced Liver Fibrosis Score (ELF Score) 2) Transient Elastography (Fibroscan)
ELF Score • The Enhanced Liver Fibrosis (ELF) score is an extracellular matrix marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease
Transient Elastography The Fibroscan
Box Plot of Liver Stiffness Measurement depending on histological fibrosis state
Liver stiffness (TE) predicts fibrosis in PSC in randomized trial of Simtuzumab (Bowlus et al J.Hep.64:S434’16)
Non-invasive markers Liver stiffness (TE) and ELF Correlate with rho = 0.706,p=0.001in PSC ( Eddowes et al. J Hep 64:S640’16) The Enhanced Liver Fibrosis (ELF) score is an ECM marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA) showing good correlations with fibrosis stages in chronic liver disease
Serum Antibodies • Anti-neutrophil cytoplasmic antibodies -~80% • Anti-nuclear antibodies and smoosth muscle antibodies ~ 20-50%
CA-19-9 • Serum tumor marker for pancreatic and cholangiocarcinoma(CCA) • 31% of PSC patients without CCA had elevated CA-19-9 followed for 4 years (More likely to have higher risk scores and dominant strictures) • 33% of group had no etiology identified • 62% underwent transplant. • Median OLT-free survival with elevated CA-19-9 9 yrs from Dx compared to 14 yrs without (Dig Dis Sci 58:850,2013)
Clinical Significance of CA-19-9 • 73 Mayo Clinic patients with PSC and serum levesl of CA 19-9 > 129 U/ml • 37 % had no evidence of CCA after median follow up of 30 months. • Those with CCA had higher levels (895 vs 286 U/ml) • Many patients with elevated CA 19-9 do not develop CCA. (ClinGastroenterolHepato 9:434’2011)
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