Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease

Xu, Zhengju; Liu, Liguan; Pan, Xingnan; Wei, Kaipeng; Wei, Miaoyan; Liu, Lifei; Yang, Huanwen; Liu, Qian

doi:10.1097/md.0000000000000659

Cited by 49 publications

(56 citation statements)

References 32 publications

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“…Recently, an established hepatocellular carcinoma (HCC) biomarker, serum Golgi protein 73 (GP73), was reported to be correlated with disease severity in chronic hepatitis B (CHB) . The increased serum GP73 in HCC is argued to be attributed to the presence of cirrhosis rather than HCC .…”

Section: Introductionsupporting

confidence: 63%

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Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Wang

Liu

et al. 2017

Journal of Viral Hepatitis

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Transient elastography (TE) is accurate in staging fibrosis noninvasively. However, a reliable serum biomarker with comparable accuracy is also important, especially when TE is unreliable/unavailable. Therefore, we aimed to evaluate the diagnostic performance of serum Golgi protein 73 (GP73) for significant fibrosis in patients with chronic HBV infection. A total of 801 patients with chronic liver disease (CLD; 492 chronic HBV infection and 309 non-HBV liver disease) with liver biopsy performance were enrolled. Healthy controls (n = 180) and hepatocellular carcinoma (HCC) patients (n = 85) were included for comparisons. Liver biopsy was used as the reference method for fibrosis staging. Serum GP73 level was measured in duplicate in double-blind fashion. Serum GP73 was highest in HCC but also significantly higher in chronic hepatitis B than in healthy controls. The elevation of serum GP73 in non-HCC patients was significantly associated with the presence of significant fibrosis independently of ALT level, liver stiffness (LS) value, inflammation grade and other confounding factors. The diagnostic performance of serum GP73 was accurate in antiviral-naïve HBV patients (area under the receiver operating curve [AUROC], 0.76 95% CI: 0.72-0.81) but not in patients with ongoing antiviral treatment (AUROC, 0.60). The utility of serum GP73 was also confirmed in non-HBV CLD (AUROC, 0.80 95% CI: 0.75-0.85). Serum GP73 was comparable to LS (AUROC, 0.78 95% CI: 0.73-0.82) and significantly better than AST to platelet ratio index (APRI) (AUROC, 0.67 95% CI: 0.62-0.72) and FIB-4 (AUROC, 0.68 95% CI: 0.63-0.73). In conclusion, serum GP73 is an accurate serum marker for significant fibrosis in chronic HBV infection, with higher accuracy than APRI and FIB-4. Serum GP73 is potentially a complementary tool for TE when evaluating the necessity of antiviral treatment, particularly in patients without definite antiviral indication.

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Section: Introductionsupporting

confidence: 63%

“…The second strength was the usage of liver biopsy as gold standard for fibrosis staging . Previous reports were limited by small sample sizes and lack of liver biopsy as reference method . Thus, our data provided the strongest evidence to date.…”

Section: Discussionmentioning

confidence: 78%

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Wang

Liu

et al. 2017

Journal of Viral Hepatitis

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“…A similar magnitude of increased GP73 expression was observed in fully established cirrhosis. Consistently, a recent study demonstrated that the levels of sGP73 were low in chronic HBV carriers without liver injury, but they were significantly elevated in patients with prominent hepatic injury and fibrosis, and the sGP73 levels were positively correlated with the severity of liver injury, indicating that the affected hepatocytes released more GP73 into the blood when liver injury was triggered (27). Therefore, the increase of sGP73 is a common feature of liver injury, regardless of the causes.…”

Section: Discussionsupporting

confidence: 60%

Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma

Dong

Chen

et al. 2017

Oncol Lett

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Abstract. Serum Golgi protein 73 (sGP73) is a candidate diagnostic biomarker for hepatocellular carcinoma (HCC). However, current evidence of its diagnostic value is conflicting, primarily due to the small sample sizes of previous studies, and its prognostic role in HCC also remains unclear. In the present study, sGP73 levels in 462 patients with HCC, 186 patients with liver cirrhosis, and 83 healthy controls were evaluated using ELISA, and it was identified that the median sGP73 levels were significantly higher in the HCC (18.7 ng/ml) and liver cirrhosis (18.5 ng/ml) patients than in the healthy controls (0 ng/ml; both P<0.001); however, the levels did not significantly differ between the HCC and liver cirrhosis groups (P=0.632). sGP73 had an inferior sensitivity and specificity for HCC diagnosis (27.79 and 77.96%, respectively) compared with α-fetoprotein (57.36 and 90.96%, respectively; P<0.001). In the HCC group, a high level of sGP73 was associated with aggressive clinicopathological features and independently predicted poor overall survival (OS) time (P<0.001). Additionally, in patients with resectable HCC, a high level of sGP73 was associated with significantly decreased disease-free survival (P<0.001) and OS (P=0.039) times compared with a low level of sGP73. This study demonstrated that sGP73 is unsuitable as a diagnostic marker for the early detection of HCC; however, it is an independent negative prognostic marker, providing a novel risk stratification factor and a potential therapeutic molecular target for HCC.

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“…Non-invasive predictive models of fibrosis are therefore needed. Single markers have been proposed such as platelet count, AST and ALT, gamma-globulins, serum HBsAg levels, CP, red blood cell distribution width, Interleukin-2R, TGF-α, serum Golgi protein 73 (GP73), and miR-122[13,14,16,17,25,28-31]. However, currently, none of these markers are sufficiently liver-specific enough to accurately reflect fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Serum markers of liver fibrosis and non-invasive predictive models of fibrosis can evaluate fibrosis specifically in HBV patients due to high applicability, inter-laboratory reproducibility, wide availability for repeated assays, and limited cost[13-18]. However, in CHB patients with ALT < 2 × ULN, few non-invasive approaches have been developed to evaluate liver fibrosis[14,19-21].…”

Section: Introductionmentioning

confidence: 99%

Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

Zeng

Dong

Jiang

et al. 2016

WJG

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AIMTo develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin (CP) levels and liver fibrosis in chronic hepatitis B (CHB) patients with normal or minimally raised alanine aminotransferase (ALT).METHODSSerum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group (n = 97) and a validation group (n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A non-invasive model was set up through multivariate logistic regression analysis.RESULTSSerum CP levels individualized various fibrosis stages via area under the curve (AUC) values. Multivariate analysis revealed that CP levels were significantly related to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4 (age, ALT, aspartate aminotransferase, platelets) and GP (globulin, platelets) models to predict significant fibrosis (P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4 (P = 0.033) to predict liver cirrhosis.CONCLUSIONThe present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model (CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.

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Serum Golgi Protein 73 (GP73) is a Diagnostic and Prognostic Marker of Chronic HBV Liver Disease

Cited by 49 publications

References 32 publications

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Assessment of serum Golgi protein 73 as a biomarker for the diagnosis of significant fibrosis in patients with chronic HBV infection

Serum Golgi protein 73 is a prognostic rather than diagnostic marker in hepatocellular carcinoma

Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

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