Published online Sep 14, 2020. doi: 10.3748/wjg.v26.i34.5130
Peer-review started: April 24, 2020
First decision: May 15, 2020
Revised: May 19, 2020
Accepted: August 20, 2020
Article in press: August 20, 2020
Published online: September 14, 2020
Golgi protein-73 (GP73) is a resident Golgi type II transmembrane protein expressed in epithelial cells. Regarding liver, GP73 is expressed mainly in biliary epithelial cells, and to a lesser extent in hepatocytes. Nevertheless, its expression is significantly up-regulated in hepatocytes in patients with liver diseases and particularly in those with hepatocellular carcinoma (HCC).
Although a considerable number of studies with conflicting results have assessed the importance of GP73 in HCC patients, very few have investigated whether serum GP73 levels can be used as reliable diagnostic markers of liver fibrosis and disease progression from chronic hepatitis to cirrhosis, liver decompensation and HCC development.
To specifically evaluate GP73 efficacy as a biomarker for detecting cirrhosis and HCC development, and also to assess its performance in predicting liver disease progression.
Six hundred and thirty-two consecutive patients with chronic viral and non-viral liver diseases who were diagnosed, treated and followed for 50 (57) mo in two Academic centers in Greece (n = 366) and Hungary (n = 266) were retrospectively investigated for GP73 serum levels by a novel GP73 ELISA. APRI score was also determined in all patients. The development of cirrhosis, decompensation of liver disease and/or HCC development during follow-up were evaluated according to well-known international guidelines.
At baseline, 43.8% of patients had high GP73 levels (> 20 units) which were significantly associated with the presence of cirrhosis (P < 0.001), decompensated liver disease (P < 0.001), HCC presence (P < 0.001) and advanced stage of HCC (P = 0.002). Interestingly, GP73 had higher diagnostic accuracy for detecting cirrhosis [AUC, 95%CI: 0.909 (0.885-0.934)] compared to APRI (P = 0.003). Combination of GP73 with APRI improved further the accuracy compared to GP73 or APRI alone. GP73 was significantly higher in HCC patients compared to non-HCC (P < 0.001) and correlated positively with HCC stage (P < 0.001) and tumor dimensions (P = 0.004). However, the discriminative ability for detecting HCC was relatively low. Kaplan-Meier analysis showed that the group of patients with compensated cirrhosis at baseline having GP73 values above the cut-off, had significantly higher rates of decompensation, HCC development, and liver-related deaths compared to those with normal levels.
Although serum GP73 does not seem to be a specific marker for detecting HCC, we showed that its determination by an easy to perform, non-invasive blood test assay which can be performed in any laboratory, is efficient for detecting liver cirrhosis and superior to APRI score. Most importantly however, GP73 proved promising in predicting a worse outcome of patients with both viral and non-viral liver diseases.
As GP73 proved efficient to predict prognosis of patients with chronic liver diseases, GP73 testing by using a simple assay could be used in clinical practice as an additional and very important tool for the initial evaluation and follow-up of these patients. However, future large-scale multicenter studies with prospectively collected serum samples are needed in an attempt to definitely validate our findings.