1. Evaluating the Patient With Abnormal Liver Tests-2 פרופ ' צבי אקרמן מבית חולים הדסה הר הצופים

2. Imaging studies Abdominal Ultrasound with Doppler of hepatic and portal veins Abdominal MRCP Upper endoscopy (EGD) Liver biopsy Non Invasive Tests for Fibrosis

3. Imaging studies-1 Abdominal Ultrasound with Doppler of hepatic and portal veins-1 Abdominal ultrasound is helpful in the evaluation of patients with cirrhosis. It may reveal a shrunken, nodular liver suggestive of cirrhosis.

4. 1a Imaging studies- 1a The liver may appear echogenic if excessive fat has infiltrated the liver as in NAFLD (nonalcoholic fatty liver disease). It is sensitive for the detection of small to moderate amounts of ascites. It can be used to screen for liver masses which may suggest the presence of hepatocellular carcinoma.

6. Imaging studies- 2 Abdominal Ultrasound with Doppler of hepatic and portal veins-2 The use of Doppler ultrasonography can provide information about the hepatic and portal veins such as portal vein thrombosis. Because it is relatively inexpensive, and widely available, ultrasonography is the preferred initial imaging modality in patients with cirrhosis.

7. Imaging studies- 3 Abdominal MRCP MRI is not indicated in every evaluation of liver disease, only in cases where specific bile duct pathology is suspected. It is expensive and ‘simple”information can be obtained with ultrasonography.

8. Imaging studies- 4 Upper endoscopy (EGD) Upper endoscopy is useful in the diagnosis of esophageal varices, a finding seen with portal hypertension. In cirrhotic patients, it is useful to document the presence of varices so prophylactic measures can be instituted to decrease the risk of bleeding.

9. Imaging studies-3

12. Imaging studies Abdominal Ultrasound with Doppler of hepatic and portal veins Abdominal MRCP Upper endoscopy (EGD) Liver fibrosis Assessment : Liver biopsy Liver fibrosis Assessment : Non Invasive Tests for Fibrosis

14. Liver Biopsy  Hepatic Injury : necrotico-inflammatory activity, necrotico-inflammatory activity, fibrosis, fibrosis, steatosis, steatosis, biliary lesions, vascular lesions biliary lesions, vascular lesions  Fibrosis scores ( METAVIR, Knodell, Ishak,…) ( METAVIR, Knodell, Ishak,…)  Invasive procedure  Invasive procedure morbidity : 0.3 to 0.6% morbidity : 0.3 to 0.6% mortality : 0 to 0.05% mortality : 0 to 0.05%  Cost : approximately 4000 NIS ( without complications)

17. F1 F4 F2

18. F1 F4

19. Imaging studies

22. BioMarkers of liver injury Markers of Fibrosis Scores of Fibrosis

24. How must be an ideal marker of liver Fibrosis? Specific to the Liver Independant to metabolic dysfunction Easy to perform Sensitivity to detect the different stages of liver fibrosis Can reliably assess the efficacy of antifibrotic treatment Can be used whatever the etiology of chonic liver fibrosis Non influenced by extra-hepatic factors

25. Haptoglobin Alpha2Macroglobulin Apolipoprotein A1 Total Bilirubin Gamma GT In Situ In Serum: FibroTest Liver Injury Activated Stellate Cells Fibrotic Matrix ALT

27. 0.00 0.10 0.20 0.30 0.40 0.50 0.60 0.70 0.80 0.90 1.00 01234 FibroTest METAVIR Fibrosis Stage Multicenter Independant Validation Halfon, Am J Gastroenterol 2006 n=519

28. Myers et al 2003 Poynard et al 2004 Myers et al 2003 Ratziu et al 2004 Naveau et al 2005 FibroTest: fibrosis marker in other chronic liver diseases (n=2,706)

29. LONGITUDINAL STUDIES The Fibrotest was found to predict the evolution of HCV patients towards cirrhosis better than liver biopsy after 5 years of follow-up Ngo Clin Chem 2006

30. Progression of liver fibrosis F METAVIR Duration in years Rapid Intermediate Slow fibroser Poynard et al

31. Abnormal Liver Test Results: Points for Clinical Practice Abnormal liver test results will be identified in 8%-20% of patients during clinical care. Most patients with abnormal liver test results should have additional evaluation. A referral to the gastroenterologist may be needed. A careful history and physical examination frequently provide the diagnosis, obviating the need for invasive testing. If there are signs or symptoms of chronic liver disease, considering the patient's age may assist in the diagnosis. Isolated elevation of GGT occurs and a cause may not be identified.

32. CON -Abnormal Liver Test Results: Points for Clinical Practice The presence of multiple abnormal test results makes significant liver disease more likely. Aminotransferase, alkaline phosphatase, and GGT levels can be elevated from causes other than liver disease. Persisting abnormalities of aminotransferases or enzymes of cholestasis should be further evaluated because up to two thirds will have a diagnosis requiring follow-up or intervention. Supplemental testing with additional laboratory tests, ultrasonography, or magnetic resonance cholangiography should be considered when the diagnosis is unclear or confirmation of liver disease diagnosis is required.

33. תודה רבה על ההקשבה