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!