Non-invasive Diagnosis of liver disease 7/8/88 Hossein Poustchi MD, PhD DDRC/TUMS Shariati Hospital Non-invasive Diagnosis – why bother? • Liver biopsy Not always easy Limitations of Liver Biopsy • Poor patient compliance • Limited usefulness for dynamic follow-up • Risk of complications typical of invasive procedures (Pain, bleeding, mortality) • Sampling errors sampling error is common because only 1/50,000 of the organ is analyzed Sampling error and intra-observer variation (Lancet: 1989;1-253-5) • 3 different samples were obtained: The same result in 3 biopsy were presented in: - 50% of Cirrhosis - 54% of HCC - 55% of Metastatic Cancers - 18.8% of Hepatic Granoloma Sampling Error 2 Scand J Gastroenterol 2003-38 (4) 427 • Two samples: right lobe and single needle biopsy (HAI score): - 34.5% difference≥4 in necroinflamatory score - 38% difference≥1 in fibrosis score - 20% difference≥2 in fibrosis score Mean difference for NI= 2.4 score Mean difference for Fi= 0.6 score Consequence • These limitations may lead to an underestimation of cirrhosis, especially when LB specimens are small or fragmented We need a Test to be more representative of liver And less invasive Non-Invasive Tests • FibroTest: is based on calculating of: (total bilirubin, GGT, haptoglobin, a2-macroglobulin and apoliprotein A1) • The Lok index: (combining PLT count, AST/ALT ratio, and INR) These has been specifically designed for the diagnosis of HCV-cirrhosis influenced by extra-hepatic conditions few have been validated FibroScan •3.5 MHz ultrasound transmitted from the vibrator toward the tissues •pulse-echo ultrasound acquisitions are performed which is directly related to tissue stiffness. •The harder the tissue, the faster the shear wave propagates •The operator, assisted by ultrasound time-motion images •liver portion at least 6 cm thick and free of large vascular structures •The measurement depth is between 25 and 65 mm below the skin surface 100 times larger than liver biopsy Advantages • • • • • • • • Safe Fast screening Acceptability by patients Longitudinal follow-up Efficacy of therapeutic treatments Prognostic evaluation Excellent Intera and inter observation Accurate Fibroscan and liver LTX and PHT LIVER TRANSPLANTATION 12:1791-1798, 2006 Hepatitis C recurrence is the first cause of graft loss in liver transplant programs Frequent liver biopsies= Routine follow-up of HCV-infected patients after LT Relationship between fibrosis stage and liver stiffness Optimal liver stiffness cutoff values (>8.50 kPa for fibrosis >F2, and >12.5 kPa for F4) none of the few cases with liver stiffness below the cutoff value and significant fibrosis in the liver biopsy had bridging fibrosis (F3) or cirrhosis Relationship between fibrosis stage and HVPG significant PHT (>10 mm Hg) PHT cut of (>6 mm Hg) Correlation between liver stiffness measured by TE and HVPG The area under the curve for diagnosis of portal hypertension (HVPG 6 mm Hg) was 0.93. Only a few cases with liver stiffness below 8.74 kPa had portal hypertension and, outstandingly, none of them had significant portal hypertension (HVPG 10 mm Hg) or bridging fibrosis or cirrhosis. Pearson correlation, 0.84; P < 0.001). TE : Fibrosis and PHT Elastography results according to the necroinflammatory activity Accuracy of Fibro Scan 7.9KP for marked fibrosis (F>2 sensitivity 72%, specificity 84%) 10.3KP for severe fibrosis (F>3, sensitivity 76%, specificity 90%) 11.9 for cirrhosis (sensitivity 91% and specificity 89%) Reproducibility of transient elastography Gut 2007;56:968–973 The overall interobserver agreement ICC was 0.98 (95% CI 0.977 to 0.987) The intraobserver agreement The intraobserver agreement ICC was 0.98 for both raters TE and different causes of cirrhosis Hepatology 2006;44,1511:7 0.96 (95% CI: 0.77-0.96) 0.90 (95% CI: 0.77-0.96) 0.96 (95% CI : 0.90-0.98) Corresponding areas under the ROC were 0.95 (95% CI: 0.93-0.97) in the whole population TE and HBV Am J Gastroenterol 2008;103:3071–3081 • 100 Taiwanese with CHB A cutoff of 8.4 kPa : Sensitivity (90%) and NPV (97%) for cirrhosis (Possible cirrhosis) • A cutoff of 13.4 kPa : Specificity (95%) and PPV (79%) for cirrhosis (probable cirrhosis) () Liver stiffness and esophageal varicose Journal of Hepatology 45 (2006) 230–235 Large esophageal varicose Liver stiffness measurement value <19 kPa was highly predictive of the absence of oesophageal varices grade P II (Se: 84%, PPV: 47%, NPV: 93%). Journal of Hepatology 50 (2009) 59–68 TE and other Non-invasive tests Elastography and other Non-invasive tests Journal of Hepatology 50 (2009) 59–68 L. Caste´ra et al. / Overall, the percentage of correctly classified patients in whom LB could have been avoided was as follows: TE (12.5 kPa) 90% and (14.6 kPa) 89%; platelet count 82%; FT 79%; PI 77%; AAR 76%; APRI 70%, Lok index 45%, Gut 2009;58;157-160 Fibroscan in NAFLD subjects EASL 2006 ORAL PRESENTATION • Patients and Methods: • Inclusion ciriteria: Biopsy proven NASH or cryptogenic cirrhosis with risk factors of obesity and diabetes (DM). • Demographics, BMI, presence of diabetes, AST/ALT ratio, AST tocplatelet ratio index (APRI) and FibroScan were performed on all patients. • ROC curves were calculated for prediction of significant fibrosis (> Stage 2). • • • • Results: 129 patients were enrolled Age, DM, AST/ALT ratio and stiffness were predictive of fibrosis stepwise multivariate analysis showed only liver stiffness (OR 1.149; p = 0.0016) and age (OR 1.052; p= 0.031) were predictive. • A cutoff of 10KPa had a sensitivity 88% and a specificity 72% for significant fibrosis. Conclusion: Liver stiffness measurement represents an excellent initial screening test for NASH. Gut published online 30 Apr 2007 (first paper) 67 NAFLD patients confirmed by liver biopsy. The result of this study demonstrate a significant positive correlation between liver stiffness and the stage of fibrosis in NAFLD subjects which is unaffected by the grade of activity or degree of steatosis Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with NAFLD (Digestive and Liver Disease 2008) 97 subjects Relation between degree of Steatosis, Necroinflamatory and fibrosis by liver stiffness P< 0.001 P= 0.19 P= 0.006 Multiple regression analysis of factors predicting liver stiffness ROC=0.99 ROC=0.90 ROC=0.86 ROC=0.92 Limitation • Markedly overweight or obese patients • LS measurement can be influenced by hepatic inflammation (In acute HAV) • Extra Hepatic cholestasis influences liver stiffness score • No Liver biopsy • No Fibrosacn Conclusion • Liver Biopsy is still the gold standard HOWEVER • An accurate and thoughtful use of TE will assist the specialist in discriminating patients to be subjected or not to further invasive investigations (ie, upper gastrointestinal endoscopy, hepatic haemodynamics, biopsy). • TE is a useful tool for initial screening and follow-up of NAFDL subjects THANKS