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Abstract Background The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. Methods 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. Results The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. Conclusion The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

Background: The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. Methods: 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. Results: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. Conclusion: The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a low survival rate. The identification of mechanisms underlying the development of HCC helps uncover cellular and molecular targets for the diagnosis, prevention, and treatment of HCC. Golgi protein 73 (GP73) level is up-regulated in HCC patients and potentially can be a therapeutic target. Despite many studies devoted to GP73 as a marker for HCC early diagnosis, there is little discussion about the function of GP73 in HCC tumorigenesis. Given the poor response to currently available HCC therapies, a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC. The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis. Its roles in other types of cancer are also discussed.

Background: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to identify and treat EVs have contraindications, complications, and high costs. We sought to identify non-invasive tests (NITs) as alternatives to endoscopic EV screening.Methods: In this case-control study, we retrospectively analyzed 286 cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January to December 2019. We applied ROC curve analysis to assess the accuracy of various NITs in predicting EV hemorrhage.Results: There were significant differences between the hemorrhage and non-hemorrhage groups in median serum albumin (ALB) (p < 0.001), median bilirubin (TBIL) (p < 0.046), prothrombin (PT) time (p < 0.001), Golgi protein 73 (GP73; p = 0.012) and Child-Pugh (C-P) scores (p < 0.001). For ALB (cutoff 14.2 seconds), GP73 (cutoff > 126.4 ng/ml), and C-P scores, the areas under the ROC curves (AUCs) were 73.4% (95% CI: 67.5–79.2), 68.6% (95% CI: 62.4–74.8), 62.2% (95% CI: 52.8–71.5) and 69.8% (95%CI: 63.8–75.8), respectively, with corresponding sensitives of 71.5, 59.8, 69.8, and 92.2% and specificities of 65.6%, 70.1%, 56.5%, and 38.6%. When ALB was combined with GP73, the AUC was 74.3% (95% CI: 66.1–82.5) with a sensitivity of 65.1% and specificity of 76.5%. When ALB, PT, and C-P scores were combined, the AUC was 76.5% (95% CI: 70.9–82.1) with a sensitivity of 79.5% and specificity of 64.3%. When ALB, PT, GP73, and C-P scores were combined, the AUC was 75.2% (95% CI: 67.3–83.1) with a sensitivity of 54.0% and specificity of 86.9%.Conclusion: ALB, TBIL, GP73, and C-P scores, may be used to predict EV hemorrhage in cirrhotic patients. The combination of multiple NITs is better than a single index and can increase diagnostic performance.

Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis‐4(FIB‐4) scores, chitinase‐3‐like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild‐to‐moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB‐4 scores [0.64 (0.39–1.21) vs. 0.35 (0.26–0.52), p<0.001; 2.53 (1.30–3.91) vs. 1.87 (0.89–2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB‐4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real‐world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of hepatocellular carcinoma (HCC) has increased over the past decades in China. Current screening methods of HCC such as detection of a-fetoprotein (AFP) combined with liver ultrasonography remain unsatisfactory. Many HCC patients have already missed the optimal treatment period when diagnosed. Our study aimed to evaluate the value of Glypican 3 (GPC3) and Golgi protein 73 (GP73) in the detection of HCC. Methods: Thirty-nine patients with HCC and 31 patients with liver cirrhosis were enrolled. The level of serum GPC3 and GP73 were determined by ELISA. The expression of GPC3 mRNA and GP73 mRNA in peripheral blood mononuclear cell (PBMC) and liver tissues were also measured with qRT-PCR. Then, receiving operating characteristic (ROC) curves were plotted to detect the sensitivity and specificity of serum GPC3 and GP73 in the diagnosis of HCC. Results: The levels of serum GPC3 and GP73 in the HCC group were significantly higher than in the cirrhosis group (p < 0.0001). Patients with GPC3 > 9.3 µg/L and GP73 > 77.68 ng/mL had a risk of HCC of 92.31%. The HCC diagnosis ROC curve analysis indicated that when setting the GPC3 cutoff value > 9.3 µg/L, AUC = 0.956. The sensitivity and specificity of GPC3 were 89.74% and 96.77%, respectively, with a positive predictive value of 97.2%, negative predictive value of 88.2%, + LR of 27.82 and - LR of 0.11. When setting GP73 cutoff value > 77.68 ng/mL, AUC = 0.937. The sensitivity and specificity of GP73 were 92.31% and 83.87%, respectively, with positive predictive value of 87.8%, negative predictive value of 89.7%, + LR of 5.72 and - LR of 0.092. No significant difference (p > 0.05) was found between GPC3 and GP73 AUC in ROC curves, indicating that these two biomarkers were equivalent in the prediction of HCC. Conclusions: The expression of serum GPC3 and GP73 was significantly higher in the HCC patients compared with the cirrhosis patients. GPC3 and GP73 might be effective non-invasive diagnostic indicators of HCC. [ABSTRACT FROM AUTHOR]

Golgi protein 73 (GP73) has been recognized as a biomarker for evaluating liver diseases, although the serum profile of patients with HIV remains unclear. This study was designed to investigate the diagnostic values of serum GP73 in patients with HIV. A total of 92 patients with HIV and 60 healthy participants were selected, and serum samples were collected; 51 of 92 patients were followed up and all indicators were re-tested after 1 year. Patients with HIV had significantly lower GP73 concentration, lower viral load, and higher CD4+ T cell counts after antiretroviral treatment. A significant correlation between the changes of GP73 level and CD4+ T cell count was observed. The CD4+ T cell count was significantly correlated with the glycosylated GP73 level. The area under the ROC curve (AUC) of GP73 to predict negative viral load-negative conversion alone was 0.705. When the cut-off value was set at 146.7 ng/mL, the sensitivity and specificity were 73% and 70% respectively. These results indicate that serum GP73 may have predictive ability for negative viral load-negative conversion. [ABSTRACT FROM AUTHOR]

Objective To compare the levels of Golgi glycoprotein 73 (GP73), alpha - fetoprotein heterogeneity 3 (AFP - L3), alpha - fetoprotein (AFP), and a - L - fucosidase (AFU) between patients with different liver diseases and the diagnostic value of any or a combination of these makers for liver cancer. Methods The 272 patients with liver cancer, 203 patients with liver cinhosis, and 248 patients with chronic hepatitis admitted to our hospital from January to December, 2013, as well as 210 healthy individuals, were included in the study. Serum levels of GP73, AFP - L3, AFP, and AFU were determined. Comparison of non - normally distributed data was made by Kruskal - Wallis H test, and multiple comparisons were made by Mann - Whitney U test. Comparison of rates was made by chi - square test. P <0.05 was considered significantly diferent. Receiver operating characteristic (ROC) curves were drawn with healthy individuals and patients with chronic hepatitis or liver ciirhosis as controls, and Logistic fiiting and ROC analysis were used to evaluate the diagnostic values of these markers. Results The GP73 level of liver cirrhosis group (177.0 (116.0, 247.0) ng/ml) was significantly higher than those of liver cancer group (141.0 (83.3,218.8) ng/ml) and chronic hepatitis group (151.0 (83.0, 235.3) ng/ml) (U = 22 116.5 and 21 052.0, P <0.05 for both). The AFP - L3 ad AFP levels of liver cancer group (11.3 (4.3,21.2)% ad 78.4 (7.1,2455.8) ng ml) were signiicantly higher than those of liver ciirhosis group (6.0 (4.0,8.0)% and 10.0 (3.8,49.5) ng/ml) and chronic hepatitis group (7.0 (5.0,9.0)% and 18.8 (4.4, 7 9.6) ng/ml) (U = 16009.0/16083.5 and 22456.5/22346.5, P <0.05 for all) . According to the ROC curves drawn rising healthy individuals as a control, the areas under the ROC curve (AUCs) for GP73, AFP - L3, AFP, and AFU were 0.827, 0.817, 0.901, and 0.680, respectively ; GP73, AFP - L3, and AFP had a higher diagnostic accuracy for liver cancer than AFU. According to the ROC curves drawn using non - liver cancer patients as a control, the AUCs for the four markers were 0.573, 0.734, 0.753, and 0.552, respectively; AFP - L3 and AFP had some diagnostic accuracy for liver cancer, and their cut - off values were 8.55% (56.6%, 84.9%) and 49.88 ng/ml (57.7%, 8 0.9 %), respectively, when the sensitivity and specificity reached the peak values. Conclusion Increased GP73 is related to hepatic impairment and chronic fibrosis, and it has a better sensitivity for the diagnosis of liver diseases. AFP - L3 and AFP have good specificity for the diagnosis of liver cancer, and a combination of the two markers can increase the diagnostic sensitivity for liver cancer to 62.1%. [ABSTRACT FROM AUTHOR]

Background and Aims: As a hepatocellular carcinoma biomarker, serum Golgi protein 73 (GP73) is reportedly related to inflammation. Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation. In this study, we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF (ALD-ACLF)., Methods: This retrospective cohort study involved 126 Chinese adults with ALD-ACLF. Baseline serum GP73 level was measured using enzyme-linked immunosorbent assay. Patients were followed-up for 90 d and outcomes were assessed. Data were analyzed using multivariate Cox regression and piecewise linear regression analyses. The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves., Results: The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF. Compared with the lowest tertile, the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model [at 28 days: hazard ratio (HR): 4.29 (0.99-18.54), p =0.0511; at 90 days: HR: 3.52 (1.15-10.79), p =0.0276]. Further analysis revealed a positive linear association. GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-sodium score in predicting short-time prognosis of patients with ALD-ACLF., Conclusions: The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF. GP73 improved the predictive value of classic prognostic scores., Competing Interests: FL has been an editorial board member of Journal of Clinical and Translational Hepatology since 2013. Other authors have no conflict of interests related to this publication., (© 2022 Authors.)

Objective: The aim of the present study was to further evaluate the clinical value of single or joint of golgi protein 73 (GP73) and alphafetoprotein (AFP) in diagnosis of hepatocellular (HCC). Methods: One hundred and eighteen, 94 and 47 serum samples from the patients with HCC, chronic liver disease (CLD) and liver cirrhosis (LC) were collected, respectively. Serum levels of AFP and GP73 were assayed with commercial kit according to the manufacturer's instructions. Results: Patients with HCC had higher serum concentration of AFP than that of the patients with CLD ( P < 0.01), but was similar to that of the patients with LC. Serum GP73 levels in the patients with CLD or LC were significantly lower than that in the patients from HCC group ( P < 0.01). Among 118 HCC patients, the positive rate of GP73 and AFP was 80.5% and 48.3%, respectively ( P < 0.001). The ROC curve analysis showed that the AUC value of GP73 was higher than that of serum AFP. Moreover, the sensitivity and the accuracy of GP73 were 77.1% and 82.6%, respectively, which were greater more than that of AFP at 90% specificity (28.8% and 59.8%, respectively). The AUC, the sensitivity and the accuracy of GP73 in combination of AFP (AFP/GP73) were 0.855, 78.0% and 83.0%, respectively, which were similar to that of GP73 alone but were much higher than that of the single marker AFP. Conclusion: For HCC diagnosing, GP73 was more sensitive and specific than AFP. The diagnostic value of AFP/GP73 was similar to GP73 but was much higher than AFP. [ABSTRACT FROM AUTHOR]

Background: This study was performed to quantify the expression of Golgi protein-73 (GP73) in healthy controls and in patients with liver disease, and to evaluate the correlations between GP73 and other serum markers in different liver diseases. Methods: Serum GP73 was measured in 478 healthy controls and 296 patients with different types of liver disease. Quantitative hepatitis B virus (HBV) DNA was determined in two chronic hepatitis B (CHB) groups. Other serum liver fibrosis markers were measured in the liver fibrosis group and α-fetoprotein (AFP) was measured in hepatocellular carcinoma (HCC) group. The correlations between GP73 and these markers were evaluated. Results: The GP73 value in hepatitis B e antigen (HBeAg)-positive CHB group, HBeAg-negative CHB group, liver fibrosis group and HCC group was significantly higher (p<0.001) than that in healthy controls. GP73 showed significant correlation with other markers in the liver fibrosis group and with AFP in the HCC group. Conclusions: Compared with healthy controls, GP73 in patients with liver disease was significantly increased. With the progression of liver disease, GP73 showed a significantly increasing trend. These results suggest that GP73 might be used as a serum marker for the diagnosis of liver diseases and for monitoring disease progression. [ABSTRACT FROM AUTHOR]

Background: The hepatocellular carcinoma is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains intricate.Methods: A literature search identified potential markers for hepatocellular carcinoma. These markers were analysed and justification was provided for these factors' inclusion to (or exclusion from) the markers of hepatocellular carcinoma (HCC). A search of the literature was made using cancer literature and the PubMed database for the following keywords: "markers and HCC," "Lens culinaris agglutinin reactive AFP (AFP-L3) and HCC," "Des-γ-carboxy prothrombin (DCP) and HCC," "Glypican-3 and HCC," "Chromogranin A and HCC," "Transforming growth factor β1(TGF) and HCC," "α-l-fucosidase (AFU) and HCC," "Golgi protein-73 (GP73) and HCC," "Hepatocyte growth factor (HGF) and HCC," "Nervous growth factor (NGF) and HCC."Conclusions: Despite the large number of studies devoted to the immunohistochemistry of HCC, at the present time, the absolute positive and negative markers for HCC are still lacking, and even those characterized by very high sensitivity and specificity do not have an universal diagnostic usefulness. Given the poor response to current therapies, a better understanding of the molecular pathways active in this disease could potentially provide new targets for therapy. However, AFP shows a low sensitivity, therefore other biomarkers have been developed to make an early diagnosis and improve patients' prognosis. [ABSTRACT FROM AUTHOR]

Background: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to identify and treat EVs have contraindications, complications, and high costs. We sought to identify non-invasive tests (NITs) as alternatives to endoscopic EV screening. Methods: In this case-control study, we retrospectively analyzed 286 cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January to December 2019. We applied ROC curve analysis to assess the accuracy of various NITs in predicting EV hemorrhage. Results: There were significant differences between the hemorrhage and non-hemorrhage groups in median serum albumin (ALB) ( p < 0.001), median bilirubin (TBIL) ( p < 0.046), prothrombin (PT) time ( p < 0.001), Golgi protein 73 (GP73; p = 0.012) and Child-Pugh (C-P) scores ( p < 0.001). For ALB (cutoff <33.2g/L), PT time (cutoff > 14.2 seconds), GP73 (cutoff > 126.4 ng/ml), and C-P scores, the areas under the ROC curves (AUCs) were 73.4% (95% CI: 67.5-79.2), 68.6% (95% CI: 62.4-74.8), 62.2% (95% CI: 52.8-71.5) and 69.8% (95%CI: 63.8-75.8), respectively, with corresponding sensitives of 71.5, 59.8, 69.8, and 92.2% and specificities of 65.6%, 70.1%, 56.5%, and 38.6%. When ALB was combined with GP73, the AUC was 74.3% (95% CI: 66.1-82.5) with a sensitivity of 65.1% and specificity of 76.5%. When ALB, PT, and C-P scores were combined, the AUC was 76.5% (95% CI: 70.9-82.1) with a sensitivity of 79.5% and specificity of 64.3%. When ALB, PT, GP73, and C-P scores were combined, the AUC was 75.2% (95% CI: 67.3-83.1) with a sensitivity of 54.0% and specificity of 86.9%. Conclusion: ALB, TBIL, GP73, and C-P scores, may be used to predict EV hemorrhage in cirrhotic patients. The combination of multiple NITs is better than a single index and can increase diagnostic performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Huang, Jeyarajan, Ma, Zhu, Zhu, Jiang, Li, Shao, Han, Tan and Lin.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a low survival rate. The identification of mechanisms underlying the development of HCC helps uncover cellular and molecular targets for the diagnosis, prevention, and treatment of HCC. Golgi protein 73 (GP73) level is upregulated in HCC patients and potentially can be a therapeutic target. Despite many studies devoted to GP73 as a marker for HCC early diagnosis, there is little discussion about the function of GP73 in HCC tumorigenesis. Given the poor response to currently available HCC therapies, a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC. The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis. Its roles in other types of cancer are also discussed., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

Background: Alpha-fetoprotein (AFP) has been extensively applied in clinical practice to detect and predict postoperative outcomes of patients with hepatocellular carcinoma (HCC). However, due to its low sensitivity and specificity, its efficacy has been questioned. Recently, novel serum biomarkers including Golgi protein 73 (GP73) and glypican-3 (GPC-3) have shown a better discriminatory ability than AFP in detecting early HCC. The results of the combined use of GP73, GPC-3 and AFP in the diagnosis of HCC remain inconclusive. This investigation aimed to evaluate the discriminatory ability of GP73, GPC-3 and AFP to jointly identify HCC using the statistical methods of meta-analysis., Methods: Comprehensive database searches of, Web of Science, the Cochrane Library, Embase, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure were performed for literature dated up to 1 November, 2019. Studies relating to the diagnostic accuracy of the combination of GP73, GPC-3 and AFP in the identification of HCC were included. A random-effects model was used to pool sensitivity, specificity, the positive and negative likelihood ratios [positive likelihood ratio (PLR) and negative likelihood ratio (NLR), respectively], and the diagnostic odds ratio (DOR). We applied the Fagan nomogram to assess the clinical utility of joint detection. The overall detection accuracy was determined using summary receiver operating characteristic curve (SROC) analysis. Meta-regression analysis of heterogeneity publication bias was analyzed with Stata (version 12.0)., Results: Our meta-analysis focused on 12 studies involving 919 patients with HCC and 1,549 non-HCC patients. Sensitivity, specificity, PLR, NLR and DOR for joint detection, were 0.91 (95% CI: 0.87-0.94), 0.84 (95% CI: 0.77-0.89), 5.83 (95% CI: 4.05-8.40), 0.10 (95% CI: 0.07-0.15), 57.51 (95% CI: 35.92-92.08), respectively, when pooled, and the area under the SROC curve was 0.95., Conclusions: Current evidence indicates that GP73, GPC-3 and AFP exhibit much better accuracy for the diagnosis of HCC when used in combination rather than alone or in pairs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.02.89). LL serves as the unpaid editorial board member of Annals of Translational Medicine from Apr 2020 to Mar 2022. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)