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

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.

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A Potential Serum N-glycan Biomarker for Hepatitis C Virus-Related Early-Stage Hepatocellular Carcinoma with Liver Cirrhosis

International Journal of Molecular Sciences ◽

10.3390/ijms21238913 ◽

2020 ◽

Vol 21 (23) ◽

pp. 8913

Author(s):

Mikito Higashi ◽

Takeshi Yoshimura ◽

Noriyoshi Usui ◽

Yuichiro Kano ◽

Akihiro Deguchi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Preparation Method ◽

Patient Survival ◽

Early Stage ◽

Serum Markers ◽

Apparent Correlation ◽

Cirrhotic Patients

Detection of early-stage hepatocellular carcinoma (HCC) is beneficial for prolonging patient survival. However, the serum markers currently used show limited ability to identify early-stage HCC. In this study, we explored human serum N-glycans as sensitive markers to diagnose HCC in patients with cirrhosis. Using a simplified fluorescence-labeled N-glycan preparation method, we examined non-sialylated and sialylated N-glycan profiles from 71 healthy controls and 111 patients with hepatitis and/or liver cirrhosis (LC) with or without HCC. We found that the level of serum N-glycan A2G1(6)FB, a biantennary N-glycan containing core fucose and bisecting GlcNAc residues, was significantly higher in hepatitis C virus (HCV)-infected cirrhotic patients with HCC than in those without HCC. In addition, A2G1(6)FB was detectable in HCV-infected patients with early-stage HCC and could be a more accurate marker than alpha-fetoprotein (AFP) or protein induced by vitamin K absence or antagonists-II (PIVKA-II). Moreover, there was no apparent correlation between the levels of A2G1(6)FB and those of AFP or PIVKA-II. Thus, simultaneous use of A2G1(6)FB and traditional biomarkers could improve the accuracy of HCC diagnosis in HCV-infected patients with LC, suggesting that A2G1(6)FB may be a reliable biomarker for early-stage HCC patients.

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Assessment of Spleen Stiffness for Prediction of Varices in Patients with Hepatitis C Related Cirrhosis Using Transient Elastography

International Journal of TROPICAL DISEASE & Health ◽

10.9734/ijtdh/2020/v41i2430421 ◽

2020 ◽

pp. 9-18

Author(s):

Naglaa El-Toukhy Ramadan El-Toukhy ◽

Sharaf Elsayed Ali Hassanien ◽

Ramy A. Metwaly ◽

Medhat A. Khalil ◽

Badawy A. Abdulaziz

Keyword(s):

Liver Cirrhosis ◽

Hepatitis C ◽

Esophageal Varices ◽

Predictive Value ◽

Transient Elastography ◽

Liver Stiffness ◽

Diagnostic Value ◽

Group I ◽

Spleen Stiffness ◽

Cirrhotic Patients

Background and Study Aims: Portal hypertension is one of the most important complications of liver cirrhosis. The prevalence of varices among cirrhotic patients is variable. Therefore, endoscopic screening of all patients with liver cirrhosis would result in a large number of unnecessary additional burdens to endoscopic units. Our aim was to assess the diagnostic accuracy of spleen stiffness measured by transient elastography (Fibroscan) for prediction of the presence of varices in patients with hepatitis C related cirrhosis. Patients and Methods: The study was carried out on 100 patients with HCV-induced cirrhosis and were divided into 2 groups according to presence or absence of varices by Esophago-gastro-duodenoscopy: Group I: patients with HCV-induced cirrhosis with varices; Group II: patients with HCV-induced cirrhosis without varices. Clinical and laboratory parameters, andominal ultrasonography, Upper gastrointestinal endoscopy and transient elastography to assess the liver and spleen stiffness were carried out to all studied persons. Results: Spleen stiffness had significant diagnostic value to differentiate between cirrhotic patients with varices and cirrhotic patients without varices , it had significant diagnostic value in presence of esophageal varices at cut-off (≥46.4 K Pascal) the sensitivity for detection of esophageal varices was 93%, specificity 100%, positive predictive value (PPV) was 80%, negative predictive value (NPV) was 100%; accuracy was 95% and area under the curve was 0.98 denoting that spleen stiffness is a good predictor of esophageal varices. Conclusion: Spleen stiffness was considered as an excellent predictor of esophageal varices and better than liver stiffness in prediction of esophageal varices presence and had significant diagnostic value to differentiate between the patients with varices and patients without varices at cut off (≥46.4 K Pascal) and it may have a role in variceal grading.

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Role of Tie2, CD14, Angiopoietin as Angiogenetic Markers in Hepatocellular Carcinoma Complicating Hepatitis C Virus Infection

Journal of Hematology and Oncology Research ◽

10.14302/issn.2372-6601.jhor-19-3084 ◽

2019 ◽

Vol 3 (2) ◽

pp. 23-34

Author(s):

El-Zahraa M. Meghezel ◽

Heba A. Ahmed ◽

Ashraf A Askar ◽

Emad Eldin Nabil ◽

Ashraf Elyamany

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C ◽

High Risk Group ◽

P Value ◽

Group Iii ◽

Group I ◽

Angiopoietin 2 ◽

Chronic Hepatitis C Patients ◽

Potential Use

Background Identifying biomarkers for early detection of hepatocellular carcinoma (HCC) remains quite challenging. In this study we aimed to estimate the number of TIE2-expressing monocytes (TEMs) cells, which display pro-tumoral activities and are defined as CD14+, TIE2+, and angiopoietin-2; and its potential use as a possible diagnostic marker in HCC patients complicating HCV induced cirrhosis. Methods Current study was conducted on 112 patients. They were divided into two groups: Group I (78 patients) with HCC complicating HCV induced cirrhosis; and group II chronic hepatitis C patients (34 patients). Both groups were compared to (age and sex-matched) healthy persons as group III (38 persons). Result The number of the circulating TEMs: CD14+ and TIE2+ monocytes were significantly higher in the peripheral blood of HCC patients than HCV LC patients and healthy controls, sensitivity and specificity for HCC diagnosis were respectively: CD14 (89.7%, 83.3%), TIE 2 (76.9%, 83.3%), and Ang-2 (76.9%, 66.7%). Moreover, analysis of the P-value and the odd’s ratio showed that CD14 has the highest predictive value for HCC. Conclusion Our results suggest that TEMs and Ang-2can be used as diagnostic markers for HCC, especially among the high-risk group of patients.

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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 ◽

10.1093/qjmed/hcaa052.011 ◽

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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Detection of MicroRNA in Hepatic Cirrhosis and Hepatocellular Carcinoma in Hepatitis C Genotype-4 in Egyptian Patients

BioMed Research International ◽

10.1155/2017/1806069 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Hala M. Demerdash ◽

Hend M. Hussien ◽

Ehab Hassouna ◽

Emad A. Arida

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Early Detection ◽

Cell Damage ◽

Diagnostic Value ◽

Genotype 4 ◽

Group Iii ◽

Group I ◽

Potential Biomarker ◽

A Prospective Study

Background. In Egypt, the prevalence of chronic hepatitis C (CHC) infection is 13.8% of whole population and about 80% of the patients with hepatocellular carcinoma have underling hepatitis C. Aim. This study was designed to assess the diagnostic value of plasma miR-122 and miR-21 in patients with CHC, genotype-4, to detect fibrosis progression versus noninvasive indices and their diagnostic value in detection of early stages of hepatocellular carcinoma (HCC). Methodology. A prospective study that included 180 patients, divided into 3 groups: healthy controls (group I), CHC patients (group II), and hepatitis C patients with HCC (group III); all cases were subjected to thorough clinical, radiological, and laboratory investigations. Selected biomarkers were evaluated and correlated with degree of liver damage. Results revealed that miR-122 followed by miR-21 had the highest efficiency in prediction of liver cell damage. Also, miR-21 was strongly correlated with vascular endothelial growth factor (VEGF) and alpha fetoprotein (α-FP) in HCC patients. Conclusions. Plasma miR-122 and miR-21 had strong correlation with degree fibrosis in HCV genotype-4 patients; consequently they can be considered as potential biomarker for early detection of hepatic fibrosis. Moreover, miR-21 can be used as a potential biomarker, for early detection of HCC combined with VEGF and α-FP.

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Vitamin D Receptor Gene Polymorphisms and the Risk of Chronic Hepatitis C Related Hepatocellular Carcinoma in Egyptian Population

The Open Biomarkers Journal ◽

10.2174/1875318302111010079 ◽

2021 ◽

Vol 11 (1) ◽

pp. 79-85

Author(s):

Amal A. Mohamed ◽

Sherief Abd-Elsalam ◽

Hanan M. Mostafa ◽

Asmaa Abdalla ◽

Ahmed Farouk ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Vitamin D ◽

Liver Cirrhosis ◽

Hepatitis C ◽

Vitamin D Receptor ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Stepwise Logistic Regression ◽

Vitamin D Receptor Gene ◽

Egyptian Patients

Background: Small percentage of hepatitis C (HCV) patients develop hepatocellular carcinoma (HCC) during their lifetime, suggesting that genetic factors might modulate HCC development. Numerous variations on the vitamin D receptor gene (VDR) have been recognized in human cancers. The majority of them cause VDR to be unable to bind to 1, 25-OH-D. The aim of the present work was to investigate the relation of VDR FokI (rs2228570), BsmI (rs3782905) and ApaI (rs7975232) gene polymorphisms and the risk of HCC development in chronic HCV Egyptian patients. Methods: A total of 311 Egyptian patients were enrolled for this study. They were divided into 3 groups: 103 patients with liver Cirrhosis, 107 patients with HCC and 101 normal healthy subjects as the control group. Human genomic DNA Extraction was carried out using QIAamp® DNA Blood Mini Kit (QIAGEN) Genotyping of VDR ApaI (rs7975232) single nucleotide polymorphism (SNP) was carried out using real-time PCR TaqMan allelic discrimination assay with allele-specific designed fluorescent MGB probes. Results: Patients with HCC had a higher frequency of ApaI CC genotype (P=0.035) CI (0.031-0.038). Patients with HCC carried a higher ratio of ApaI CC genotype compared to those with liver cirrhosis (x2=5.4 and P = 0.03) or controls (x2=6.8 and P = 0.01). Univariate analysis revealed that age, lower platelet count (<150×103/μL), higher AFP (>100 ng/ml), and ApaI CC genotype were the factors significantly associated with the development of HCC. Stepwise logistic regression analysis showed that all were independent predictors. Conclusion: ApaI CC VDR gene mutation is an independent risk factor for HCC development in Egyptian Cirrhotic HCV patients.

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APPLICATION OF ALPHA-FETOPROTEIN AND OSTEOPONTIN COMBINATION FOR EARLY DIAGNOSIS OF HEPATOCELLULAR CARCINOMA ASSOCIATED WITH HEPATITIS C

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-10-607-612 ◽

2019 ◽

Vol 64 (10) ◽

pp. 607-612

Author(s):

Sergey Igorevich Malov ◽

I. V. Malov ◽

V. V. Dvornichenko ◽

R. I. Rasulov ◽

A. G. Kuvshinov ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C ◽

Early Diagnosis ◽

Early Stage ◽

Alpha Fetoprotein ◽

Diagnostic Efficacy ◽

Imaging Methods ◽

Stage Of Development ◽

Advanced Phase

Liver cirrhosis in the outcome of hepatitis C is the leading cause of hepatocellular carcinoma (HCC) in the world. Early diagnosis and timely treatment of HCC are important for reducing mortality and increasing life expectancy of patients with hepatocellular carcinoma. To assess the risk of HCC, the definition of alpha-fetoprotein (AFP) in the blood is most widely used, but low sensitivity limits its diagnostic value. In 2012, a new HCC biomarker - osteopontin (OPN), which is a secreted phosphoprotein that has a high affinity for integrins was proposed. The level of acute renal failure begins to rise in the early stages of malignancy, before the period of HCC detection by imaging methods, and has significantly better sensitivity than AFP. The purpose of this study is to evaluate the diagnostic efficacy of the combined determination of alpha-fetoprotein and osteopontin in prospective monitoring of patients with chronic hepatitis C in the advanced phase of liver fibrosis. Monitoring of 588 patients with hepatitis C was carried out from February 2013 to February 2019. HCC was detected in 55 of them (2.6% per year). The combination of 2 biomarkers showed better diagnostic efficacy than alpha-fetoprotein and osteopontin separately: AUC 0.85 (95% CI 0.80-0.90) versus AUC 0.63 (95% CI 0.57-0, 70) and AUC 0.82 (95% CI 0.77-0.88), respectively. This combination showed a sensitivity of 85.5% and made it possible to diagnose HCC with a prognostic level of a positive result of 72.3% at 19,4±0,8 weeks before the diagnosis was confirmed by instrumental imaging methods (ultrasound, MRI, CT). In the combined variant, ARF made the greatest contribution to the increase in diagnostic efficacy (AUC). At an early and very early stage of HCC development, isolated HCC elevations were found in only 5.4% of patients. Conclusion: the combined use of alpha-fetoprotein and osteopontin as a diagnostic panel can be recommended for monitoring patients with liver cirrhosis in the outcome of hepatitis C and predicting HCC at an early stage of development.

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Expression of a Disintegrin and Metalloprotease 10 Gene Polymorphisms in a Cohort of Egyptian Patients with Hepatocellular Carcinoma

Current Cancer Therapy Reviews ◽

10.2174/1573394717666210427122703 ◽

2021 ◽

Vol 17 ◽

Author(s):

Amal Ahmed Mohamed ◽

Dina M. Abo-Elmatty ◽

Omnia I ezzat ◽

Ahmed A. Youssef ◽

Eman T. Mehanna ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Nucleotide Polymorphisms ◽

Abdominal Ultrasonography ◽

Therapeutic Goals ◽

Group Iii ◽

Group I ◽

Significant Difference ◽

Egyptian Patients ◽

Adams Family ◽

And Control

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality. There is a need for a marker associated with HCC progression. A disintegrin and metalloprotease (ADAMs) family proteins have a lot of functions in cell adhesion, migration, proteolysis and signaling. Aim: The aim of the study was to investigate the relation between ADAM 10 gene single nucleotide polymorphisms (SNPs) and HCC progression. Methods: This study involved 201 cases divided: Group I (67 HCC patients), Group II (67 cirrhotic patients), Group III (67 control). Each group was subjected to laboratory investigations: (CBC, blood sugar, kidney and liver function, viral markers, alpha fetoprotein), imaging: (abdominal ultrasonography, and triphasic C.T) and ADAM 10 gene polymorphism (rs 653765, rs 383902) detection by real – time PCR. Results: There was a statistically significant difference in the frequency and genotyping of ADAM10 SNPs in HCC patients in comparison to cirrhotic and control groups [the frequency of rs 653765 genotypes (p=0.015) and model (p=0.013)]; likewise, the frequency of rs 383902 genotypes (p<0.001) and model (p=0.001)). Also, there was a statistically significant association between different SNP rs 383902 genotype with CLIP stages (p=0.02), and with VISUM stages (p=0.035). Conclusion: ADAM-10 are overexpressed in HCC patients and involved in HCC progress. These findings highlight that ADAM inhibitor may be used as therapeutic goals in treatment of HCC.

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Annexin A5 as a marker for hepatocellular carcinoma in cirrhotic hepatitis C virus patients

Egyptian Liver Journal ◽

10.1186/s43066-021-00101-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Waleed Mohamed Serag ◽

Basem Eysa Elsayed

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Longitudinal Study ◽

Hepatitis C ◽

Serum Levels ◽

Control Group ◽

Annexin A5 ◽

Medicine Research ◽

Cirrhotic Patients

Abstract Background The tumorigenesis and development in a variety of cancers is reportedly encouraged via Annexin A5. The levels of Annexin A5 were tested in patients with or without HCC who were affected by liver cirrhosis. The objective of our study was to detect Annexin A5 levels in such patients in order to assess their function as an HCC marker. The longitudinal study comprised 91 cirrhotic HCV patients with and without HCC, and 20 healthy volunteers in the control group approved by the National Hepatology and Tropical Medicine Research Institute (NHTMRI) between March 2017 and August 2018.The serum levels Annexin A5 were found in all groups with ELISA. ANOVA, Mann-Whitney, and χ2 tests had been applied. Results High scales of Annexin A5 (3.89 + 0.85) were recorded for cirrhosis with HCC, either than cirrhotic patients without HCC (3.06 ± 0.88) (P = 0.041), and either than the control group (0.54 ± 0.11) (P < 0.001). Conclusion In HCV cirrhotic patients with and without HCC, AnxA5 can be used as HCC marker.

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

Journal of Clinical Medicine ◽

10.3390/jcm10153392 ◽

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.

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