Angiopoietin-2 Serum Levels Are Elevated in Patients With Liver Cirrhosis and Hepatocellular Carcinoma

Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.

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Serum Zonulin in HBV-Associated Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2019/5945721 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Xin Wang ◽

Ming-ming Li ◽

Ye Niu ◽

Xin Zhang ◽

Ji-bin Yin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Healthy Subjects ◽

Serum Levels ◽

Curve Analysis ◽

Advanced Stage ◽

Roc Curve Analysis

Background. The gut microbiota is involved in the occurrence and development of chronic liver diseases. Zonulin is considered a marker of intestinal permeability. The purpose of this study was to assess zonulin levels in patients with chronic hepatitis B (CHB), HBV-associated liver cirrhosis (LC), and HBV-associated hepatocellular carcinoma (HCC). Materials and Methods. The study population consisted of 90 HBV-associated HCC patients, 90 HBV-associated LC patients, 90 CHB patients, and 90 healthy subjects. Serum levels of zonulin and AFP were determined. The diagnostic accuracy of each marker was evaluated using receiver operating characteristic (ROC) curve analysis (AUC). Results. Serum zonulin levels were significantly higher in patients with HCC than in patients with LC or CHB or healthy subjects (p<0.001). Moreover, the zonulin levels were increased in the advanced stage of LC and HCC. ROC curve analysis revealed that serum zonulin could be used to differentiate CHB from cirrhosis. In addition, the combination of zonulin and AFP exhibited a significantly larger AUC compared with zonulin or AFP alone. Conclusions. Serum zonulin levels were significantly increased both in LC and in HCC and correlated with the advanced stage of LC and HCC. Moreover, the combination of zonulin and AFP confers significant benefit to diagnostic accuracy in differentiating LC from HCC.

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Heat Shock Protein 70 Serum Levels Differ Significantly in Patients with Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2014.00307 ◽

2014 ◽

Vol 5 ◽

Cited By ~ 31

Author(s):

Mathias Gehrmann ◽

Melchiorre Cervello ◽

Giuseppe Montalto ◽

Francesco Cappello ◽

Alessandro Gulino ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Protein 70 ◽

Serum Levels

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Biomarkers of Angiogenesis in Hepatocellular Carcinoma: A Novel Sunshine Road

10.20944/preprints202109.0502.v1 ◽

2021 ◽

Author(s):

Krizia Pocino ◽

Cecilia Napodano ◽

Gabriele Ciasca ◽

Mariapaola Marino ◽

Nicoletta De Matthaeis ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Liver Disease ◽

Chronic Liver Disease ◽

Venous Blood ◽

Serum Levels ◽

Chronic Liver ◽

Number Of Factors ◽

Measurement Results ◽

Before And After

Background: Hepatocellular carcinoma (HCC) is a global health problem associated with chronic liver disease. The pathogenesis of chronic liver disease varies according to the underlying etiological factor, although in most cases it develops from a liver cirrhosis. The worsening progression of liver disease is accompanied by pathological angiogenesis, which is a prerequisite that favors the development of HCC. The aim of this study is to evaluate the clinical utility of circulating angiogenic markers VEGF, Ang-1, Ang-2, the Angiopoietin receptor (Tie1/2), HGF and PECAM-1 to screen early onset patients and to follow the evolution of HCC. Materials and Methods: We enrolled 62 patients; 33 out of 62 subjects were diagnosed for HCC and 29/62 for liver cirrhosis of different etiology without signs of neoplasia. Patients underwent venous blood sampling before and after treatments for VEGF, Ang-1, Ang-2, Tie1, Tie2, HGF and PECAM-1 measurement. Results: Ang-1 and Ang-2 are detectable not only in patients already suffering from HCC but also in cirrhotic patients without signs of cancer. Patients with HCC show higher HGF concentrations than patients with cirrhosis. A significant reduction in serum levels of Ang-2, Ang-2/Ang-1 and Ca 19-9 after DAAs therapy was observed. Moreover, VEGF levels were increased after treatment of HCC. Conclusion: The preliminary study here presented confirms that the mechanism of tumor angiogenesis is very complex and involves a very large number of factors. The integration of different methodologies and multi-marker algorithms is likely to emerge for the early diagnosis of HCC and the monitoring of the risk of relapse.

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Serum Dickkopf-1 as a diagnostic & prognostic marker for Hepatocellular Carcinoma

QJM ◽

10.1093/qjmed/hcab100.092 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Enas Mahmoud Foda ◽

Khaled Amr Mansour ◽

Walaa Mohamed Hashem ◽

Nancy Zakaria Ali

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Prognostic Marker ◽

Early Stage ◽

Serum Levels ◽

University Hospitals ◽

Post Intervention ◽

Curative Therapy ◽

Diagnostic Role ◽

Dickkopf 1

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading reason of cancer-associated deaths around the world.The poor outcome of patients with HCC is attributed to late detection, with more than two-thirds of patients diagnosed at advanced stages of the disease. However, a considerable improvement in survival has been observed (5-year survival up from 40% to 70%) when patients are diagnosed at an early stage and receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation. Objective Evaluate levels of serum Dickkopf-1, & its significance as a diagnostic & prognostic marker for Hepatocellular Carcinoma. Aim of the work assess the possible diagnostic role of serum DKK1 compared to alpha- fetoprotein which is the slandered marker used for diagnosis of HCC.also DKK1 act as prognostic marker for Hepatocellular Carcinoma. Pateints and Methodes This study had been carried out on 45 subjects diveded into 2 groups,first group include 30 pateints with liver cirrhosis,and second group 15 pateints with HCC.In this group of patients DKK1 was withdrawn before TACE & 3 months post intervention, age range 25-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from March 2019 till January 2020.They were distributed as 25 males and 20 females. There were 13 pateints with child A,17 pateints with child B, & 15 pateints (20%) with child C. Results In this study, the serum levels of serum DKK1 were highest in patients with HCC compared to those with liver cirrhosis. Also DKK1 values significally decreased after intervention(TACE). Conclusion Serum DKK1 act as a diagnostic marker for HCC and its level significally decrease after TACE

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Serum levels of Vitamin D3, Zinc, and Parathyroid Hormone in HCV-induced Hepatocellular Carcinoma.

10.21203/rs.3.rs-351301/v1 ◽

2021 ◽

Author(s):

Mahmoud Khattab ◽

Mohammad Omar Abdelaziz ◽

Arwa Mohamad ◽

Ragaa Abd- Elshaheed Matta ◽

Magdy Fouad ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Parathyroid Hormone ◽

Vitamin D3 ◽

Serum Levels ◽

Cross Sectional ◽

Multiple Stepwise Regression Analysis ◽

The Metabolic Syndrome ◽

Calcium And Phosphorus

Abstract Background and AimThe role of the metabolic syndrome in hepatocellular carcinoma (HCC) has been previously reported. This study aims to investigate the possible role of vitamin D3, Zinc, Parathyroid hormone (PTH), calcium and phosphorus serum levels as non-traditional metabolic risk factors in HCV-related HCC.MethodThis cross-sectional observational study recruited HCV infected patients with and without HCC. All patients were subjected to demographic, biochemical, and hematological assessment. Serum levels of vitamin D3, Zinc, PTH, calcium, and phosphorus were determined in all the study participants.ResultsThis study includes 50 patients with HCV-related HCC compared to 40 patients with HCV-related liver cirrhosis and 30 patients with HCV chronic hepatitis C (CHC) without HCC. Our results show significantly higher age, male sex, aspartate transaminase (AST), PTH and corrected serum calcium levels in the HCC patients compared to values in the other two groups, (p < 0.001); while significant lower vitamin D3 and zinc levels were detected among the HCC patients compared to patients with non-HCC liver cirrhosis and CHC, (p < 0.001).Vitamin D3 deficiency was detected in 96% of the HCC patients, while it was detected in only 22.5% of the cirrhotic patients and in none of the CHC patients, (p < 0.001). However, on multiple stepwise regression analysis, only the age, AST, PTH, and corrected calcium levels were the independent predictors for HCC when studied in relation to chronic liver disease.ConclusionThis study indicates the prevalent deficient levels of vitamin D3 and zinc in HCC patients; however, a causal relationship is not established in this study.

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The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.2012.9097 ◽

2012 ◽

Vol 27 (2) ◽

pp. 125-131 ◽

Cited By ~ 8

Author(s):

Hanan H. Soliman ◽

Hala Nagy ◽

Nesreen Kotb ◽

Mohamed A. Alm El-Din

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Predictive Value ◽

Serum Levels ◽

Study Groups ◽

Cross Sectional Study ◽

Cross Sectional ◽

Asymptomatic Patients ◽

Group I

Background and aim To evaluate the role of chemokine CC ligand 20 (CCL20) as a biomarker for hepatocellular carcinoma (HCC). Patients and methods Ninety patients in four groups were enrolled in this prospective cross-sectional study: 30 with HCC (group I), 30 with liver cirrhosis (group II), 15 with hepatitis C virus infection (group III), and 15 healthy blood donors as controls. Alpha fetoprotein (AFP), CCL20 and vascular endothelial growth factor (VEGF) were measured in all groups. Results Serum levels of CCL20 were significantly different among the study groups (F=230.979, p<0.001). The highest level was found in HCC patients (57.305 ± 6.386 pg/mL) followed by patients with cirrhosis (45.999 ± 5.165 pg/mL) compared with 22.781 ± 5.986 pg/mL and 18.585 ± 3.554 pg/mL in asymptomatic patients with HCV infection and controls, respectively. In HCC patients, CCL20 significantly correlated with VEGF (r=0.559, p=0.001), AFP (r=0.814, p<0.001), Child score (r=0.748, p<0.001), and tumor size (r=0.825, p<0.001). The cutoff value of CCL20 for the detection of HCC in HCV-infected patients was 54 pg/mL with 93.1% accuracy, 89.6% negative predictive value, 92.6% positive predictive value, 83.3% sensitivity, and 93.3% specificity. In patients with cirrhosis, CCL20 significantly correlated with VEGF (r=0.455, p=0.011), AFP (r=0.975, p<0.001), and Child score (r=0.977, p<0.001). Conclusion CCL20 may be used for the detection of HCC in HCV-infected patients with comparable specificity and higher sensitivity than AFP.

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IL-6 −174G/C Polymorphism and IL-6 Serum Levels in Patients with Liver Cirrhosis and Hepatocellular Carcinoma

OMICS A Journal of Integrative Biology ◽

10.1089/omi.2010.0093 ◽

2011 ◽

Vol 15 (3) ◽

pp. 183-186 ◽

Cited By ~ 32

Author(s):

Lydia Giannitrapani ◽

Maurizio Soresi ◽

Antonio Giacalone ◽

Maria Elisa Campagna ◽

Marta Marasà ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Serum Levels

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Evaluation of Diagnostic Efficiency of Alpha-Fetoprotein in Patients with Liver Cirrhosis and Hepatocellular Carcinoma: Single-Center Experience

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.344 ◽

2018 ◽

Vol 6 (9) ◽

pp. 1668-1673 ◽

Cited By ~ 4

Author(s):

Lejla Mehinovic ◽

Erna Islamagic ◽

Azra Husic-Selimovic ◽

Amina Kurtovic-Kozaric ◽

Zora Vukobrat-Bijedic ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

High Sensitivity ◽

Serum Levels ◽

Diagnostic Value ◽

Diagnostic Efficiency ◽

Single Center ◽

Single Center Experience ◽

Disease Stages ◽

Tumour Lesion

BACKGROUND: AFP serum levels are considered as diagnostic and specific for hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). AIM: This study aimed to examine the diagnostic value of AFP in the distinguishing of patients with HCC from patients with LC, and to analyse the potential correlation between AFP levels and liver disease stages. MATERIAL AND METHODS: Fifty patients with LC and fifty patients with HCC were included in this study. The majority of the patients were males, while the HBV aetiology was dominant. RESULTS: Significant differences between LC and HCC patients were detected for AST, ALT, GGT, bilirubin, AFP and AP. Patients with HCC had higher AFP values compared to LC. There was no significant correlation between the size of the tumour lesion and serum AFP levels. A positive correlation between AFP concentration and GGT activity was determined, as was the negative correlation between AFP and age of the subjects. The AFP value of 23.34 ng/m showed high sensitivity (84%) and specificity (82%). CONCLUSION: The size of the surface below the ROC curve (AUC) was 0.877 (0.80-0.95), which makes AFP a good biomarker and this diagnostic test is sufficient to separate patients with HCC and LC.

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