Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.

OBJECTIVE: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Epithelial cell adhesion molecule (EpCAM), α-fetoprotein, albumin, and platelets count were assayed in HCC patients (98), liver cirrhosis patients (77). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. RESULTS: A novel score named EpCAM-HCC = AFP (U/L) × 0.11 - Albumin (g/dl) × 1.5 + EpCAM % × 2.9 - Platelets count (×109)/L× 0.75 - 93. EpCAM-HCC score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.7 (i.e., less than 1.7 the case is considered cirrhotic, whereas above 1.7 it is considered HCC. CONCLUSION: EpCAM-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Circulating Tumor Cells in Breast Cancer: A Step Toward Precision Medicine for Real-Time Monitoring of Metastasis.

BACKGROUND/AIMS: Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive score based on degradation of glycosaminoglycans in the extracellular matrix for assessment of metastasis in patients with breast cancer. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of Metastases in patients with breast cancer. MATERIAL & METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19) and CA15.3 were assayed in metastatic breast cancer patients (88), non-metastatic breast cancer patients (129) and healthy control (32). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CTC-MBS = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1. CTC-MBS score produces AUC of 1 for differentiate patients with metastatic breast cancer from those with non-metastatic breast cancer with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered metastatic, whereas above 0 it is considered non-metastatic. CONCLUSION: CTC-MBS score is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer and could replace CA15.3 during screening and follow-up of breast cancer patients.

Diagnostic performance of extrinsic apoptosis pathway in hepatitis C virus patients: apoptosis fibrosis crosstalk.

BACKGROUND/AIM: Liver fibrosis assessment and evaluation of disease severity in hepatitis C virus (HCV) patients provides useful information for therapeutic decisions. Chronic HCV infection is associated with increased levels of peripheral T cell apoptosis. The aim was to study whether peripheral blood T lymphocyte apoptosis markers may contribute to clinical progression, and develop a simple index based on combination of apoptosis and routine biomarkers for accurate evaluation of fibrosis stages in HCV patients. PATIENTS AND METHODS: Peripheral blood T lymphocytes were isolated from 72 patients with hepatitis C virus and 25 healthy control individuals. Serum samples were collected at time of liver biopsy. Liver fibrosis was tested in biopsies using the Metavair score system. Stepwise linear discriminate analysis and area under receiver-operating characteristic curves were utilized to produce a predictive score comprising significant apoptosis biomarkers. RESULTS: A novel score named apoptosis fibrosis index (AFI) was created on the basis of a combination of CD8/Annexin, albumin and platelets. The multivariate discriminate analysis selected a score based on absolute values of the three biochemical markers; score = 5.8 + 0.008×CD8/Annexin-V (%) - 1.4×Albumin (g/dl) - 0.001×Platelet count (10/L), where 5.8 considered numerical constant. AFI produce an area under the curve of one for significant fibrosis, 0.80 for advanced fibrosis, and 0.889 for cirrhosis. CONCLUSION: Apoptosis biomarkers in HCV patients were associated with liver fibrosis. AFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage and may decrease the need for liver biopsy in hepatitis C virus Egyptian patients.

Diagnostic performance of T lymphocyte subpopulations in assessment of liver fibrosis stages in hepatitis C virus patients: simple noninvasive score.

BACKGROUND/AIMS: Evaluation of liver fibrosis in patients infected with hepatitis C virus is highly useful for the diagnosis of the disease as well as therapeutic decision. Our aim was to develop and validate a simple noninvasive score for liver fibrosis staging in chronic hepatitis C (CHC) patients and compare its performance against three published simple noninvasive indexes. MATERIALS AND METHODS: CHC patients were divided into two groups: an estimated group (n=70) and a validated group (n=52). Liver fibrosis was tested in biopsies using the Metavair score system. CD4 and CD8 count/percentage were assayed by fluorescence-activated cell sorting analysis. RESULTS: The multivariate discriminant analysis selects a function on the basis of absolute values of five biochemical markers: immune fibrosis index (IFI); score=3.07+3.06×CD4/CD8+0.02×α-fetoprotein (U/l)-0.07×alanine aminotransferase ratio-0.005×platelet count (10/l)-1.4×albumin (g/dl). The IFI score produced areas under curve of 0.949, 0.947, and 0.806 for differentiation of all patient categories [significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4)]. CONCLUSION: The IFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage in CHC patients. Our score was more efficient than aspartate aminotransferase to platelet ratio index, fibrosis index, and fibroQ and more suitable for use in Egyptian hepatitis C virus patients.