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

QJM ◽  
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group include 30 pateints with liver cirrhosis,and second group 15 pateints with HCC.In this group of patients DKK1 was withdrawn before TACE & 3 months post intervention, age range 25-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain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

scholarly journals The APAC Score: A Novel and Highly Performant Serological Tool for Early Diagnosis of Hepatocellular Carcinoma in Patients with Liver Cirrhosis

2021 ◽  
Vol 10 (15) ◽  
pp. 3392
Author(s):  
Joeri Lambrecht ◽  
Mustafa Porsch-Özçürümez ◽  
Jan Best ◽  
Fabian Jost-Brinkmann ◽  
Christoph Roderburg ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
At Risk ◽  
Liver Cirrhosis ◽  
Early Stage ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Serum Samples ◽  
Disease Etiology ◽  
Risk Patients ◽  
Scoring Tool

(1) Background: Surveillance of at-risk patients for hepatocellular carcinoma (HCC) is highly necessary, as curative treatment options are only feasible in early disease stages. However, to date, screening of patients with liver cirrhosis for HCC mostly relies on suboptimal ultrasound-mediated evaluation and α-fetoprotein (AFP) measurement. Therefore, we sought to develop a novel and blood-based scoring tool for the identification of early-stage HCC. (2) Methods: Serum samples from 267 patients with liver cirrhosis, including 122 patients with HCC and 145 without, were collected. Expression levels of soluble platelet-derived growth factor receptor beta (sPDGFRβ) and routine clinical parameters were evaluated, and then utilized in logistic regression analysis. (3) Results: We developed a novel serological scoring tool, the APAC score, consisting of the parameters age, sPDGFRβ, AFP, and creatinine, which identified patients with HCC in a cirrhotic population with an AUC of 0.9503, which was significantly better than the GALAD score (AUC: 0.9000, p = 0.0031). Moreover, the diagnostic accuracy of the APAC score was independent of disease etiology, including alcohol (AUC: 0.9317), viral infection (AUC: 0.9561), and NAFLD (AUC: 0.9545). For the detection of patients with (very) early (BCLC 0/A) HCC stage or within Milan criteria, the APAC score achieved an AUC of 0.9317 (sensitivity: 85.2%, specificity: 89.2%) and 0.9488 (sensitivity: 91.1%, specificity 85.3%), respectively. (4) Conclusions: The APAC score is a novel and highly accurate serological tool for the identification of HCC, especially for early stages. It is superior to the currently proposed blood-based algorithms, and has the potential to improve surveillance of the at-risk population.

scholarly journals Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP

2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Young-Sun Lee ◽  
Eunjung Ko ◽  
Eileen L. Yoon ◽  
Young Kul Jung ◽  
Ji Hoon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Hepatoma Cell ◽  
Multiple Reaction Monitoring ◽  
Serum Levels ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Lines ◽  
Proteomic Approach

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.

scholarly journals The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Reham A. Aboelwafa ◽  
Walid Ismail Ellakany ◽  
Marwa A. Gamaleldin ◽  
Marwa A. Saad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C ◽  
Early Stage ◽  
Group Iii ◽  
Real Time Quantitative Pcr ◽  
Early Stages ◽  
Group I ◽  
Egyptian Patients ◽  
Cirrhotic Patients

Abstract Background Hepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR. Results Levels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls. Conclusion Serum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

scholarly journals Talin-1 Gene Expression as a Tumor Marker in Hepatocellular Carcinoma Patients: A Pilot Study

2020 ◽  
Vol 10 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Amal A. Mohamed ◽  
Naglaa El-Toukhy ◽  
Doaa M. Ghaith ◽  
Ingy Badawy ◽  
Sara M. Abdo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Tumor Staging ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Primary Liver Tumor ◽  
Staging Systems ◽  
Diagnostic Role ◽  
Serum Alpha Fetoprotein

Background & Aims: Hepatocellular Carcinoma (HCC) is the most common primary liver tumor. It is the second most common cancer in men and the sixth in women in Egypt. One of the proteins participating in the trans-endothelial migration is Talin-1. It also has a role in the formation and metastasis of different types of cancer. This study aimed to evaluate the diagnostic impact of Talin-1 gene expression in HCC Egyptian patients. Methods: Our study included forty HCC patients, thirty liver cirrhosis patients without HCC and thirty healthy subjects. For all groups, clinical and biochemical parameters were investigated. Tumor characteristics were assessed and tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. In addition, Serum Alpha-Fetoprotein (AFP) levels were assayed using Enzyme Immunoassay (EIA) and Talin-1 gene expression was assessed in the Peripheral Blood Mononuclear Cells (PBMCs) via quantitative real-time Polymerase Chain Reaction (PCR). Results: Talin-1 gene expression was significantly upregulated in HCC patients in comparison to cirrhotic and control subjects. The Receiver Operating Characteristic (ROC) analysis indicated that Talin-1 gene expression surpasses serum levels of AFP in the diagnosis of HCC. In particular, the cut off value of 9.5 (2-∆∆Ct) recorded an AUC of 85.7% with a sensitivity of 93.3% and specificity of 80%. Conclusion: Our data confirmed an évident diagnostic role of Talin-1 gene expression for HCC detection.

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

2007 ◽  
Vol 102 (11) ◽  
pp. 2471-2481 ◽  
Author(s):  
Arne Scholz ◽  
Vanessa Annina Rehm ◽  
Svenja Rieke ◽  
Katja Derkow ◽  
Petra Schulz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Serum Levels ◽  
Angiopoietin 2

scholarly journals Metabolic Alterations Associated with Early-Stage Hepatocellular Carcinoma and Their Correlation with Aging and Enzymatic Activity in Patients with Viral Hepatitis-Induced Liver Cirrhosis: A Preliminary Study

2020 ◽  
Vol 9 (3) ◽  
pp. 765
Author(s):  
Chung-Man Moon ◽  
Sang Soo Shin ◽  
Suk Hee Heo ◽  
Yong Yeon Jeong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Lactate Dehydrogenase ◽  
Enzymatic Activity ◽  
Viral Hepatitis ◽  
Potential Risk ◽  
Early Stage ◽  
Liver Parenchyma ◽  
Cirrhotic Liver ◽  
1H Mrs

Liver cirrhosis (LC) can develop hepatocellular carcinoma (HCC). However, noninvasive early diagnosis of HCCs in the cirrhotic liver is still challenging. We aimed to quantify the hepatic metabolites in normal control (NC), cirrhotic liver without HCC, cirrhotic liver with HCC (CLH), and early-stage HCC groups using proton magnetic resonance spectroscopy (1H-MRS) with a long echo-time (TE) and to assess the potential association between the levels of hepatic metabolites in these four groups and aging and enzymatic activity. Thirty NCs, 30 viral hepatitis-induced LC patients without HCC, and 30 viral hepatitis-induced LC patients with HCC were included in this study. 1H-MRS measurements were performed on a localized voxel of the normal liver parenchyma (n = 30) from NCs, cirrhotic liver parenchyma (n = 30) from LC patients without HCC, and each of the cirrhotic liver parenchyma (n = 30) and HCC (n = 30) from the same patients in the CLH group. Generalized estimating equations were used to evaluate potential risk factors for changes in metabolite levels. Potential associations between metabolite levels and age and serum enzymatic activities were assessed by correlation analysis. The levels of lactate+triglyceride (Lac+TG) and choline (Cho) in HCC were significantly higher compared to those in LC and CLH. A potential risk factor for changes in the Lac+TG and Cho levels was age, specifically 60–80 years of age. In particular, the Lac+TG level was associated with a high odds ratio of HCC in males aged 60–80 years. The Lac+TG and Cho concentrations were positively correlated with lactate dehydrogenase and alkaline phosphatase activities, respectively. Our findings suggested that 1H-MRS measurement with a long TE was useful in quantifying hepatic Lac+TG and Cho levels, where higher Lac+TG and Cho levels were most likely associated with HCC-related metabolism in the viral hepatitis-induced cirrhotic liver. Further, the level of Lac+TG in HCC was highly correlated with older age and lactate dehydrogenase activity.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
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.

scholarly journals 3-Nitro-Tyrosine as a Biomarker of Minimal Hepatic Encephalopathy in Patients with Liver Cirrhosis

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
E A Awad ◽  
M N Mohammed ◽  
M M Sayyed ◽  
A E Elkhayal ◽  
M A S Ahmed
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Encephalopathy ◽  
Motor Coordination ◽  
Serum Levels ◽  
Minimal Hepatic Encephalopathy ◽  
Neurological Status ◽  
Trail Making Test ◽  
University Hospitals ◽  
Predictive Values ◽  
Trail Making

Abstract Background hepatic encephalopathy (HE) is a common complication in patient with liver cirrhosis. It comprises of a broad spectrum of neuropsychiatric abnormalities of varying severity, and affected patients usually suffer from psychomotor, cognitive, emotional, behavioural, and motor coordination dysfunctions. Patients with minimal HE (MHE), a subclinical form of HE, usually have a normal mental and neurological status upon routine clinical examination. The subtle deficits in patients with MHE can only be elicited by specialized neuropsychological tests. Aim of the Work the aim of this study was to evaluate the role of 3-Nitro-Tyrosine as a biomarker of Minimal Hepatic Encephalopathy in patients with liver cirrhosis. Patients and Methods our conducted study was a prospective case control study carried on 60 adult patients and 30 age matched controls. All were recruited from Internal Medicine and Hepatology and Gastroenterology Department at Ain Shams University Hospitals in the period between September 2016 and June 2018. All patients enrolled in the study were subjected to detailed history taking, full physical examination, laboratory investigations, psychometric tests for detection of MHE using specially digit symbol test (DST), Trail making test A (TMT A), Trail making test B (TMT B), serial dotting test (SDT) and 3-Nitro-Tyrosine level (3NT). Results our study found that the serum levels of 3-nitro-tyrosine are a good predictor of the presence of MHE in patients with liver cirrhosis, with good sensitivity (90%) and specificity (93.33%) and positive and negative predictive values were 93.1% and 90.3% respectively at a cutoff of 14.8 ng. Conclusion determination of 3-nitro-tyrosine in serum is easy and is not time consuming. It only requires taking a serum sample from the patient and determining 3-nitro-tyrosine concentration. This procedure can be therefore easily added to the routine clinical determinations in patients with liver cirrhosis. This would also allow extending the diagnosis of MHE to most clinical settings, helping to identify patients with MHE.

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

2014 ◽  
Vol 5 ◽  
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

scholarly journals A Comparative Study of the Diagnostic and Prognostic Value of Macrophage Activation Marker Soluble CD163 and Alpha Fetoprotein in Cirrhotic Patients with Hepatitis C Virus-related Hepatocellular Carcinoma treated by Loco-Regional Therapy

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
K A Mohamed ◽  
E S Mohamed ◽  
A M Hussein ◽  
M H A Fouad ◽  
A S Allam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Prognostic Marker ◽  
Prognostic Value ◽  
Macrophage Activation ◽  
Activation Marker ◽  
Soluble Cd163 ◽  
Cirrhotic Patients

Abstract Background hepatocellular carcinoma (HCC) shows an increasing incidence and represents the third most common cause of cancer-related death. Aim of the Work is to evaluate the diagnostic value of serum level of Macrophage activation marker soluble CD163 as a tumor marker for HCC and its prognostic value after transarterial chemo-embolization (TACE) or radiofrequency ablation (RFA), in comparison to alpha-feto protein (AFP). Patients and Methods this study was performed on 60 subjects from the outpatient Hepatology clinic and inpatient Gastroenterology and Hepatology Department at Ain Shams University Hospital. Group I includes 40 randomly selected cirrhotic patients with hepatitis C virus-related hepatocellular carcinoma (excluding BCLC class D) who underwent either RFA or TACE. Group II includes 20 patients with liver cirrhosis without hepatocellular carcinoma considered as control. Results soluble CD163 expression did not differ significantly between HCC group and liver cirrhosis group. This proves that soluble CD163 is not suitable for diagnostic use. On the other hand, soluble CD163 was associated with the severity of liver disease. Baseline soluble CD163 was significantly associated with disease progression independent of other risk factors known to be associated with an unfavorable course in HCC. Also the marked significant reduction of serum soluble CD163 levels in HCC patients subjected to either RF ablation or TACE proved that soluble CD163 may play a prognostic marker in HCC monitoring. Conclusion soluble CD163 is not suitable as a diagnostic marker for HCC but can be used as a prognostic marker for HCC.

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