1. Protein GP73 (GOLGI PROTEIN 73) A NEW NON-INVASIVE BIOMARKER FOR ASSESSING LIVER FIBROSIS AND RISK OF PROGRESSION TO HEPATOCELLULAR CARCINOMA N.K. Gatselis, G.L.Norman, K.Zachou, Z.Shums, A. Saitis, S.Gampeta, G.N. Dalekos Department of Medicine & Research Laboratory of Internal Medicine, University of Thessaly INOVA Diagnostics, Inc., San Diego, CA, USA

2. Hepatocellular carcinoma HCC is the 5th most common cancer and the 2nd leading cause of cancer death in men worldwide Common causes HBV HCV alcoholic liver disease Common causes HBV HCV alcoholic liver disease Cumulative 5-year incidence of HCC 20% in decompensated HBV cirrhosis 10% in compensated HBV cirrhosis Manesis, Aliment Pharmacol Ther 2009 Papatheodoridis, J Hepatol 2010 Papatheodoridis, Gut 2011 Mazioti, Hepat Mon 2013

3. Diagnosis of hepatocellular carcinoma Prompt diagnosis lack of specific symptoms limited prognostic value of serological and radiological approaches (AFP and US) HCC biomarkers EASL-EORTC, J Hepatol 2012 Lencioni, Dig Liver Dis 2010 Chaiteerakij, Clin Gastroenterol Hepatol 2013

4. Golgi Protein 73 Block, PNAS 2005. Kladney, Hepatology 2002 Golgi membrane glycoprotein 73 (GP73) has been proposed as a serum biomarker for HCC In normal liver, GP73 is expressed in biliary epithelial cells but not in normal hepatocytes GP73 levels are markedly increased in hepatocytes of patients with chronic liver diseases, especially in HCC cells

5. Patients & Methods GP73 was determined by ELISA (Inova Diagnostics) in the sera of: 366 patients 228 male / 138 female age 55±15 years 184 cirrhotic / 182 non- cirrhotic 51 with HCC at baseline 295 patients followed for a median duration of 51 months (range 6-170 months) Aim To evaluate GP73 in patients with chronic liver diseases as a: 1.non-invasive liver fibrosis biomarker 2.predictive marker for HCC 3.diagnostic marker of HCC

6. Results I - Baseline

7. Results II - Baseline p<0.001 for each comparison

8. Results III – during follow up 295 patients were followed for a median duration of 51 months (range 6-170 months) p<0.05p<0.001p=0.07p<0.001 Increased GP73 levels at baseline are associated with higher incidence of development of decompensation, HCC and liver related death during follow up Decompensation HCC HCC in cirrhotic Liver related death N=36 N=64 N=74

9. Results IV – GP73 as a diagnostic marker

10. Conclusions The presence of GP73 in the sera of patients with chronic liver diseases is strongly associated with liver cirrhosis Increased GP73 levels appear to identify a subgroup of patients who are at an increased risk of progressing to HCC and liver-related mortality Serum GP73 is complementary to AFP for the diagnosis of HCC Larger studies of prospectively collected serum samples are needed

11. Thank you for your attention!