protein gp73 (golgi protein 73) a new non-invasive biomarker for assessing liver fibrosis and risk...
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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
Hepatocellular carcinoma
HCC is the 5th most common cancer and the 2nd leading cause of
cancer death in men worldwide
Common causesHBVHCV
alcoholic liver disease
Cumulative 5-year incidence of HCC
• 20% in decompensated HBV cirrhosis
• 10% in compensated HBV cirrhosis
Manesis, Aliment Pharmacol Ther 2009Papatheodoridis, J Hepatol 2010
Papatheodoridis, Gut 2011Mazioti, Hepat Mon 2013
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 2012Lencioni, Dig Liver Dis 2010
Chaiteerakij, Clin Gastroenterol Hepatol 2013
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
Patients & Methods
HCV
HBV
ALD
AIH
PBC cirrhosisno cirrhosis
124
189
25
8
23
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)
AimTo 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
Results I - Baseline
GP73 pos26%
GP73 neg74%
GP73 positivity
cirrhotic non cirrhotic
84 (89%)
10 (11%)
GP73 pos GP73 neg
34%
7%
66% 93%
Presence of HCC ac-cording to GP73 pos-
itivity
HCC non-HCC
Results II - Baseline
GP73 pos GP73 neg
89%
37%
11% 63%
Presence of cirrhosis according to GP73
positivity
cirrhotic non-cirrhotic
GP73 pos GP73 neg
45%
20%
55% 80%
Presence of de-compensation ac-cording to GP73
positivity
decompensatedcompensated
p<0.001 for each comparison
Results III – during follow up295 patients were followed for a median duration of 51 months (range 6-170 months)
p<0.05 p<0.001 p=0.07 p<0.001
Increased GP73 levels at baseline are associated with higher incidence of development of decompensation, HCC and liver related death during follow up
Decompensa-tion
HCC HCC in cirrhoticLiver related
deathN=36 N=64 N=64
N=74
Results IV – GP73 as a diagnostic marker
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
Thank you for your attention!