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

• Published in: World journal of gastroenterology : WJG 2020-09, Vol.26 (34), p.5130-5145
• Main Authors: Gatselis, Nikolaos K, Tornai, Tamás, Shums, Zakera, Zachou, Kalliopi, Saitis, Asterios, Gabeta, Stella, Albesa, Roger, Norman, Gary L, Papp, Mária, Dalekos, George N
• Format: Article
• Language: English
• Subjects: Biomarkers; Carcinoma, Hepatocellular; Greece; Humans; Hungary; Liver Cirrhosis - diagnosis; Liver Neoplasms; Membrane Proteins; Prognosis; Retrospective Studies; Retrospective Study
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v26.i34.5130

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. To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression. 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 ( = 366) and Debrecen, Hungary ( = 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. 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% 51.5%, < 0.001), decompensation of cirrhosis (60.3% 35.5%, < 0.001), presence of HCC (18.4% 7.9%, < 0.001) and advanced HCC stage (52.9% 14.8%, = 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) 0.849 (0.813-0.886), = 0.003]. Combination of GP73 with APRI improved f