Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients

Abstract

BACKGROUND Reliable biomarkers of cirrhosis, hepatocellular carcinoma (HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73 (GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression. AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression. METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite ® GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece ( n = 366) and Debrecen, Hungary ( n = 266). Aspartate aminotransferase (AST)/Platelets (PLT) ratio index (APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50 (57) mo [median (interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein (AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients. RESULTS Increased serum levels of GP73 (> 20 units) were detected at initial evaluation in 277 out of 632 patients (43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis (96.4% vs 51.5%, P < 0.001), decompensation of cirrhosis (60.3% vs 35.5%, P < 0.001), presence of HCC (18.4% vs 7.9%, P < 0.001) and advanced HCC stage (52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve (AUC) (95%CI): 0.909 (0.885-0.934) vs 0.849 (0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy (AUC: 0.925) compared to GP73 ...

Autoimmune hepatitis in patients aged 70 years or older: Disease characteristics, treatment response and outcome

“…According to our previous publications, 17‐22 patients were divided into two groups according to inflammation: minimal‐mild (score: 0‐8) and moderate‐severe (score: 9‐18) and according to fibrosis: minimal/mild‐moderate (score: 0‐2) and severe fibrosis‐cirrhosis (score: 3‐4). For patients without available biopsy, diagnosis of cirrhosis was based on ultrasonography (coarse echo pattern of the liver parenchyma along with irregular hepatic margins, spleen >12cm, portal vein >16mm), and/or endoscopic findings of portal hypertension, and/or clinical findings of decompensation as we have reported recently 24 …”

Serum Cartilage Oligomeric Matrix Protein and Golgi Protein-73: New Diagnostic and Predictive Tools for Liver Fibrosis and Hepatocellular Cancer?

“…The prototype GP73 ELISA (QUANTA Lite ® GP73, Inova Diagnostics, Inc., San Diego, CA, USA, Research Use Only) was used for the determination of GP73 as we described previously [ 16 ]. Briefly, this assay uses novel anti-GP73 monoclonal and rabbit polyclonal antibodies against the full-length GP73 antigen [ 16 ].…”

“…The prototype GP73 ELISA (QUANTA Lite ® GP73, Inova Diagnostics, Inc., San Diego, CA, USA, Research Use Only) was used for the determination of GP73 as we described previously [ 16 ]. Briefly, this assay uses novel anti-GP73 monoclonal and rabbit polyclonal antibodies against the full-length GP73 antigen [ 16 ]. According to the manufacturer’s instructions, serum samples with more than 20 arbitrary units were considered positive as this cut-off has been established in preliminary experiments in 518 healthy and disease controls [ 16 ].…”

“…Recently, studies from our group and others have shown that serum cartilage oligomeric matrix protein (COMP) and Golgi protein-73 (GP73) levels were positively correlated with indices of progression of chronic liver diseases, such as inflammatory activity, fibrosis/cirrhosis, and HCC [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. COMP is largely found in the extracellular matrix protein of skeletal tissue, but increased COMP expression has been also associated with fibrogenesis in patients with cirrhosis and HCC [ 17 , 23 , 24 , 25 ].…”

GP73 is a glucogenic hormone that contributes to SARS-CoV-2-induced hyperglycemia

“…The fact that hepatocyte GP73 expression is upregulated in patients with viral and nonviral liver disease suggests that this protein is triggered during hepatocyte injury 18 . The liver damage caused by SARS-CoV-2 infection prompted us to investigate whether infection with this virus altered GP73 expression 19 .…”