Quantitation How Accurate

1. Quantitation How Accurate DR. MAMUN-AL-MAHTAB Associate Professor of Hepatology Bangabandhu Sheikh Mujib Medical University Dhaka, Bangladesh

2. Liver Fibrosis: APASL Consensus Recommendations 2009 APASL Working Party on Liver Fibrosis 2nd Consensus Meeting 2014 To review, re-assess and recommend

3. Quantitation of Hepatic Fibrosis • Remains a challenge • Different modalities explored • Some modalities assess liver fibrosis directly (liver biopsy) or indirectly (fibroscan) • Others explore hepatic fibrosis by assessing consequences of hepatic fibrosis (HVPG, etc.) • Quantitation essential to know extent of liver injury and haemodynamic changes Accurate quantitation probably never possible and perhaps also not necessary

4. Liver Biopsy • Most widely accepted and employed • Different scoring systems; Ishak (modefied Knodell-HAI system) most used • Distribution of fibrosis may be heterogeneous • Provides ‘snap-shot in time’ • 1.5 cm and/or 4-6 portal tracts considered representative although approx. 1/5000th of the liver assessed • Reproducibility of hepatic staging irrespective of reporting Histopathologist established Liver biopsy perhaps the ‘best standard’, if not the ‘gold standard’ Ishak et al. J Hepatol 1995 Knodell et al. Hepatol 1981 Bravo et. al. New Eng J Med 2001

5. Hepatic Venous Pressure Gradient (HVPG) • Gradient between free and wedged hepatic venous pressures • Reflects portal pressure accurately • Also correlates with hepatic fibrosis and its progression • Several advantages over liver biopsy (i.e. sample size, sampling error, reproducibility, staging systems and inter and intra-observer variability are not of concern) • Allows assessment of portal pressure and risk of variceal bleeding also • Lack of expertise, lack of access to cath-lab facilities and cost restricts wide-spread acceptability as an alternative to liver biopsy Merkel et al. Hepatol 2000 Samonakiset al. Liver Transpl 2007 Blasco et. al. Hepatol 2006 Wongcharatrawee et. al. Annals of Gastroenterol 2001 HVPG is perhaps superior, but has limitations also

6. Fibroscan • Non-invasive; based on transient elastography • Accuracy excellent in advanced fibrosis • Less accurate in lesser degress Abdominal USG • Reliable in distinguishing cirrhosis from milder fibrosis • Not so in lesser degress • Portal vein peak velocity (PVPV), hepatic artery resistive index (HARI), hepatic artery pulsitivity index (HAPI) not validated Abdominal USG & fibroscan may not be recommended Shaheen et al. J Gastroenterol 2007 Haktaniret al. J Ultrasound Med 2005 Piscaglia et. al. . Ultrasound Med Biol. 2001

7. AST-Platelet Ratio Index (APRI) • Correlates well in HCV related CLD • Not so case of HBV, NASH and ALD • Less accurate in lesser degress Others • Fibrotest has limited acciracy in lesser fibrosis • Acoustic radiation force impulse (ARFI) elastography, Supersonic shear imaging (SSI), magnetic resonance elastrography (MRE) lacks sufficient evidence APRI lacks universal and may not be recommended Schiavonet al. Hepatol 2007 Zhang et al. Abdom Imaging 2014 Guo et al. Abdom Imaging 2014

8. Recommendations 1. Liver biopsy is the best standard for quantification of hepatic fibrosis. Despite some inter and intra-observer variations, the different hepatic grading systems in use are reproducible and can be recommended for quantification of hepatic fibrosis. [A1] 2. HVPG may be recommended instead of liver biopsy to assess hepatic fibrosis in set ups where facilities and expertise are available. [A2]

9. ‘Father of the Nation’ Bangabandhu Sheikh Mujibur Rahman Thank You!