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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 [email protected] D-1, Vasant Kunj, Delhi, India www.ilbs.in. Outline.

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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

[email protected]

D-1, Vasant Kunj, Delhi, India

www.ilbs.in


Outline
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


Variceal pressure monitor
Variceal Pressure Monitor


Kong Dr PLOSone 2013


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


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


Hvpg in pre cirrhotic and cirrhotic liver van leuveen et al scand j gastroenterol 1989
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


Nodule size vs hvpg
Nodule size vs. HVPG

(Nagula S, J Hepatol 2006)


Septal thickness vs hvpg
Septal thickness vs. HVPG

(Nagula S, J Hepatol 2006)


Correlation with Fibrosis:

HVPG predicts Fibrosis Score ≥ 3 in HBV

(Kumar and SarinLiv. Int. 2008)

Area under ROC curve = 0.906.


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


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


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


Correlation of HVPG and METAVIR score (n=68)

Tai SK et al. European J of Gastro & Hepatology 2013, ;25(10), p 1170–1176


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


Histological classification and hvpg kim et al j hepatology 2011
Histological Classification and HVPGKim et al J Hepatology 2011


Hvpg and histological gr of cirrhosis
HVPG and Histological Gr of Cirrhosis



Sethasine s et al hepatology apr 2012 55 4 1146 1153
Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146–1153.

Quantitative Histological Hemodynamic Correlations


Correlation between histological parameters and hvpg
Correlation between histological parameters and HVPG

Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146


Histological parameters and presence or absence of clinically significant portal hypertension

Sethasine S et al. Hepatology. Apr 2012; 55(4): 1146


Correlation between HVPG and total fibrosis area in biopsies


Correlation of lsm and hvpg hong et al clin mol hepatology 2013
Correlation of LSM and HVPG(Hong et al Clin Mol Hepatology 2013)

N=59



Ilbs data
ILBS Data Fibrosis

  • Study period: 5.2011 to 5.2012

  • Study population: 1717 patients

  • Inclusion criteria: All patients


HVPG Correlates with Liver Stiffness Fibrosis

Chandan et al 2012


Correlation of hvpg with esophageal varices
Correlation of HVPG with Esophageal varices Fibrosis

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)


Correlation of lsm with csph
Correlation of LSM with CSPH Fibrosis

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


Does antiviral rx decrease portal pressure
Does Antiviral Fibrosis Rx Decrease Portal Pressure?


Interferon treatment vs hvpg
Interferon treatment Fibrosis vs.HVPG

(García-Tsao G, Gastroenterology 1996)


Anti viral therapy vs hvpg
Anti-viral therapy vs. HVPG Fibrosis

(Rincon D, Am J Gastroenterol 2006)


Anti viral therapy vs hvpg1
Anti-viral therapy vs. HVPG... Fibrosis

(Rincon D, Am J Gastroenterol 2006)


End of treatment response vs hvpg
End of treatment response vs. HVPG Fibrosis

(Rincon D, Am J Gastroenterol 2006)


Recommendations hepatic fibrosis and pp
Recommendations: Fibrosis 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 !


Recommendations hepatic fibrosis and pp1
Recommendations: Fibrosis 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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