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Institute of Liver & Biliary Sciences

APASL Cairo 2014. Institute of Liver & Biliary Sciences. Can WHVP be recommended as a routine surrogate marker of fibrosis !. Dr S K Sarin Institute of Liver and Biliary Sciences (ILBS), New Delhi shivsarin@gmail.com. D-1, Vasant Kunj, Delhi, India www.ilbs.in. Outline.

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Institute of Liver & Biliary Sciences

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  1. APASL Cairo 2014 Institute of Liver & Biliary Sciences Can WHVP be recommended as a routine surrogate marker of fibrosis ! Dr S K Sarin Institute of Liver and Biliary Sciences (ILBS), New Delhi shivsarin@gmail.com D-1, Vasant Kunj, Delhi, India www.ilbs.in

  2. Outline • Assessment of Fibrosis • Non-invasive • Elastography • Biochemical • Doppler – Hepatic Venous Transit time (HVTT) • Microbubble Technique • CEUS • Endoscopic Variceal Monitor • Invasive • Liver Biopsy • HVPG • HVPG and Stage of Fibrosis • Recommendations

  3. Variceal Pressure Monitor

  4. Kong Dr PLOSone 2013

  5. Portal Hypertension: Dynamic relation with fibrosis Cirrhotic Liver ↑ Portal Inflow to Overcome Resistance ↑ Hepatic Resistance ↑ Portal Pressure > 5 mm ↑ Cardiac Output Varices at Diagnosis - 40% Yearly - 10% Formation of By-Pass Channels =Varices Physiological Stresses ↑ Portal Pressure Meals, exercise, Abdominal pressure Alcohol Dilation of varices Small to large varices: 5-30% yr Portal Pressure > 12 mmHg Variceal rupture Bleeding: 15% yr

  6. HVPG HPS (mmHg) HRS HE Clinical SBP PHG ASCITES BLEEDING 12 Varices 10 Subclinical portal hypertension 5 0 Syndrome of Portal Hypertension: Complications and HVPG Cirrhosis + CSPH Cirrhosis + Cirrhosis

  7. HVPG in pre-cirrhotic and cirrhotic liver(van Leuveen et al., Scand J Gastroenterol, 1989) Group HVPG (mmHg) • Normal 3.4 • Chronic hepatitis 6.0 • Chronic hepatitis going to cirrhosis 10.3 • Established cirrhosis 15.4

  8. Nodule size vs. HVPG (Nagula S, J Hepatol 2006)

  9. Septal thickness vs. HVPG (Nagula S, J Hepatol 2006)

  10. Correlation with Fibrosis: HVPG predicts Fibrosis Score ≥ 3 in HBV (Kumar and SarinLiv. Int. 2008) Area under ROC curve = 0.906.

  11. 30.00 25.00 HVPG (mm Hg) 20.00 15.00 10.00 Large Mixed Small NODULE SIZE HVPG : Alternative to Liver Biopsy Kumar and SarinAlimPharmaTherap 2008 P<0.001 P<0.001 HVPG increases with decreasing nodule size & increasing septal thickness

  12. Sub-classification of cirrhosis Category A: Composite Score 1 to 3 Category B: Composite Score 4 to 6 Kumar and Sarin Alim Pharmacol Therap 2008

  13. HVPG in Sub-categories of cirrhosis HVPG significantly more in subcategory B. HVPG correlates with Liver Stiffness, Pinzani 2007 Kumar and Sarin Alim Pharmacol Therap 2008

  14. Correlation of HVPG and METAVIR score (n=68) Tai SK et al. European J of Gastro & Hepatology 2013, ;25(10), p 1170–1176

  15. AUROCs of each test. *P<0.05 compared with HVPG. wP<0.05 compared with logit models.

  16. Histological Classification and HVPGKim et al J Hepatology 2011

  17. HVPG and Histological Gr of Cirrhosis

  18. Difficult to Assess Nodule size and fibrosis

  19. Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146–1153. Quantitative Histological Hemodynamic Correlations

  20. Correlation between histological parameters and HVPG Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146

  21. Histological parameters and presence or absence of clinically significant portal hypertension Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146

  22. Correlation between HVPG and total fibrosis area in biopsies

  23. Correlation of LSM and HVPG(Hong et al Clin Mol Hepatology 2013) N=59

  24. HVPG correlates with Post Transplant HCV Recurrence and Fibrosis

  25. ILBS Data • Study period: 5.2011 to 5.2012 • Study population: 1717 patients • Inclusion criteria: All patients

  26. HVPG Correlates with Liver Stiffness Chandan et al 2012

  27. Correlation of HVPG with Esophageal varices HVPG cut off predictive of large varices was 15.3 mmHg, sensitivity 61% ,specificity 55.1% (AUROC 0.62) 14.8mmHg predicted PHG with sensitivity 65%, specificity 54% (AUROC 0.61)

  28. Correlation of LSM with CSPH LSM cut off predictive of CSPH was 20.9kPa, sensitivity 72.1% and specificity 71.4% (AUROC 0.77, CI 0.731- 0.804)

  29. Does Antiviral Rx Decrease Portal Pressure?

  30. Interferon treatment vs.HVPG (García-Tsao G, Gastroenterology 1996)

  31. Anti-viral therapy vs. HVPG (Rincon D, Am J Gastroenterol 2006)

  32. Anti-viral therapy vs. HVPG... (Rincon D, Am J Gastroenterol 2006)

  33. End of treatment response vs. HVPG (Rincon D, Am J Gastroenterol 2006)

  34. Recommendations: Hepatic fibrosis and PP HVPG: • Correlates with histological stage of fibrosis and CPA (1A), but not beyond >F4 • Correlates with Liver stiffness. (2,A) add complications and more details • Could be considered as a dynamic marker of fibrosis progression, specially pre-cirrhotic stage (2,B) regression !

  35. Recommendations: Hepatic fibrosis and PP HVPG: 4. Correlates with post-transplant hepatic fibrosis (2B) • negatively correlates with platelet counts, probably due to hypersplenism(3,B) • may suggest an end-point in antiviral therapy, irrespective of antiviral response (3,B)

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