Urinary Vascular Endothelial Growth Factor (VEGF) as a Novel Marker for Early Prediction of Esophageal Varices in Patients with Chronic Liver Disease — Oak Academic Publishing
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Urinary Vascular Endothelial Growth Factor (VEGF) as a Novel Marker for Early Prediction of Esophageal Varices in Patients with Chronic Liver Disease
Department of Medicine, Cairo University, Cairo, Egypt
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Department of Medicine, Cairo University, Cairo, Egypt
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Department of Chemical Pathology, Cairo University, Cairo, Egypt
,
Mataria Hospital, Cairo, Egypt
1 Department of Medicine, Cairo University, Cairo, Egypt
2 Department of Medicine, Cairo University, Cairo, Egypt
3 Department of Chemical Pathology, Cairo University, Cairo, Egypt
Background/Aims : Vascular Endothelial Growth Factor (VEGF) has a crucial role in portal hypertension and collateral vessels formation. This study aims to assess urinary VEGF in cirrhotic patients as a predictor of presence of esophageal varices, and variceal bleeding. Settings and Design: 42 cirrhotic patients were randomly selected and classified into 2 groups according to the presence of variceal bleeding. Methods and Material : Urinary VEGF was measured and corrected against urinary creatinine. Platelet count, liver functions, abdominal ultrasonography and upper endoscopy were done. Statistical Analysis Used : Comparison was done by Mann Whitney and Kruskal Wallis tests. Correlation was done using Spearman rank correlation. Multivariable logistic regression was done to identify predictors of variceal bleeding and presence of large varices. Receiver operator characteristic curve (ROC) analysis was used to determine the optimum cut off value of predictors. Results and Conclusions : Urinary VEGF was lower in cirrhotic patients with esophageal varices than those without. Low VEGF, low platelet count and splenomegaly were found to be independent predictors of both the presence of large esophageal varices, and variceal bleeding. Cut-off values for platelet count ≤ 166.3 × 103/μL, and corrected VEGF ≤ 59.12 pg/mg were predictive of large esophageal varices with 93.1%, 86.2% sensitivity and 74.5%, 58.2% specificity respectively. While variceal bleeding could be predicted at a platelet count ≤ 153 × 103/μL, and corrected VEGF ≤ 45.08 pg/mg with 90.9%, 81.8% sensitivity and 72.6%, 59.7% specificity respectively. The study concludes that urinary VEGF can be used as an alternative to upper endoscopic screening.
De Franchis, R. (2010) Revising Consensus in Portal Hypertension: Report of the Baveno, V. Consensus Workshop on Methodology of Diagnosis and Therapy in Portal Hypertension. Journal of Hepatology, 53, 762-768.
Chan, C.C. (2009) Portal-Systemic Collaterals and Angiogenesis. Journal of the Chinese Medical Association, 72, 223-224.
Garcia-Tsao, G., Sanyal, A.J., Grace, N.D. and Carey, W. (2007) Prevention and Management of Gastro-Oesophageal Varices and Variceal Haemorrhage in Cirrhosis. AASLD Practice Guideline. Hepatology, 46, 922-938. https://doi.org/10.1002/hep.21907
Rye, K., Scott, R., Mortimore, G., Lawson, A., Austin, A. and Freeman, J. (2012) Towards Non-Invasive Detection of Oesophageal Varices. International Journal of Hepatology, 1-9. https://doi.org/10.1155/2012/343591
Colecchia, A., Montrone, L., Scaioli, E., Bacchi-Reggiani, M.L., Colli, A., Casazza, G., Schiumerini, R., Turco, L., Di Biase, A.R., Mazzella, G., Marzi, L., Arena, U., Pinzani, M. and Festi, D. (2012) Measurement of Spleen Stiffness to Evaluate Portal Hypertension and the Presence of Esophageal Varices in Patients with HCV-Related Cirrhosis. Gastroenterology, 143, 646-654. https://doi.org/10.1053/j.gastro.2012.05.035
Yin, Z.H., Liu, X.Y., Huang, R.L. and Ren, S.P. (2005) Expression of TNF-α and VEGF in the Esophagus of Portal Hypertensive Rats. World Journal of Gastroenterology, 11, 1232-1236. https://doi.org/10.3748/wjg.v11.i8.1232
Marques, C., Licks, F., Zattoni, I., Borges, B., de Souza, L.E.R., Marroni, C.A. and Marroni, N.P. (2013) Antioxidant Properties of Glutamine and Its Role in VEGF-Akt Pathways in Portal Hypertension Gastropathy. World Journal of Gastroenterology, 19, 4464-4474. https://doi.org/10.3748/wjg.v19.i28.4464
Statistical Package for the Social Science (2006) Release 15 for Microsoft Windows. SPSS Inc., Chicago.
Hayward, R.M., Kirk, M.J., Sproull, M., Scott, T., Smith, S., Cooley Zgela, T., Crouse, N.S., Citrin, D.E. and Camphausen, K. (2008) Post-Collection, Pre-Measurement Variables Affecting VEGF Levels in Urine Biospecimens. Journal of Cellular and Molecular Medicine, 12, 343-350. https://doi.org/10.1111/j.1582-4934.2007.00135.x
Assy, N., Paizi, M., Gaitini, D., Baruch, Y. and Spira, G. (1999) Clinical Implication of VEGF Serum Levels in Cirrhotic Patients with or without Portal Hypertension. World Journal of Gastroenterology, 5, 296-300.
Kraft, A., Weindel, K., Ochs, A., Marth, C., Zmija, J., Schumacher, P., Unger, C., Marme, D. and Gastl, G. (1999) Vascular Endothelial Growth Factor in the Sera and Effusions of Patients with Malignant and Nonmalignant Disease. Cancer, 85, 178-187. https://doi.org/10.1002/(SICI)1097-0142(19990101)85:1 3.0.CO;2-7
Chow, N.H., Hsu, P.I., Lin, X.Z., Yang, H.B., Chan, S.H., Cheng, K.S., Huang, S.M. and Su, I.J. (1997) Expression of Vascular Endothelial Growth Factor in Normal Liver and Hepatocellular Carcinoma: An Immunohistochemical Study. Human Pathology, 28, 698-703.
Akiyoshi, F., Sata, M., Suzuki, H., Uchimura, Y., Mitsuyama, K., Matsuo, K. and Tanikawa, K. (1998) Serum Vascular Endothelial Growth Factor Levels in Various Liver Diseases. Digestive Diseases and Sciences, 43, 41-45. https://doi.org/10.1023/A:1018863718430
Nasr, F.M., Metwaly, A., Abd el Khalik, A, Sabry, A.I., Hassan, M. and Desouky, A.M. (2013) VEGF and PDGF in Liver Cirrhosis and Their Relation to Echocardiographic Parameters and Carotid Intima-Media Thickness. Life Science Journal, 10, 1102-1110.
Abdelmoaty, M.A., Bogdady, A.M., Attia, M.M. and Zaky, N.A. (2009) Circulating Vascular Endothelial Growth Factor and Nitric Oxide in Patients with Liver Cirrhosis: A Possible Association with Liver Function Impairment. Indian Journal of Clinical Biochemistry, 24, 398-403. https://doi.org/10.1007/s12291-009-0071-5
Enjoji, M., Nakamuta, M., Yamaguchi, K., Ohta, S., Kotoh, K., Fukushima, M., et al. (2005) Clinical Significance of Serum Levels of Vascular Endothelial Growth Factor and Its Receptor in Biliary Disease and Carcinoma. World Journal of Gastroenterology, 11, 1167-1171. https://doi.org/10.3748/wjg.v11.i8.1167
Li, C.P., Lee, F.Y., Hwang, S.J., Lu, R.H., Lee, W.P., Chao, Y., et al. (2003) Spider Angiomas in Patients with Liver Cirrhosis: Role of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor. World Journal of Gastroenterology, 9, 2832-2835. https://doi.org/10.3748/wjg.v9.i12.2832
Yang, Y.Y., Hou, M.C., Lin, M.W., Chen, P.H., Liao, W.C., Chu, C.J. and Lin, H.C. (2013) Combined Platelet Count with sCD163 and Genetic Variants Optimizes Esophageal Varices Prediction in Cirrhotic Patients. Journal of Gastroenterology and Hepatology, 28, 112-121. https://doi.org/10.1111/j.1440-1746.2012.07245.x
Bosch, J., Abraldes, J.G., Fernández, M. and García-Pagán, J.C. (2010) Hepatic Endothelial Dysfunction and Abnormal Angiogenesis: New Targets in the Treatment of Portal Hypertension. Journal of Hepatology, 53, 558-567.
Lwakiri, Y., Shah, V. and Rockey, D.C. (2014) Vascular Pathobiology in Chronic Liver Disease and Cirrhosis—Current Status and Future Directions. Journal of Hepatology, 61, 912-924.
Ayub, A. (2013) Esophageal Varices, Non Endoscopic Prediction of the Presence. The Professional Medical Journal, 20, 653-660.
Eslam, M., Ampuero, J., Jover, M., Abd-Elhalim, H., Rincon, D., Shatat, M., Camacho, I., Kamal, A., Lo Iacono, O., Nasr, Z., Grande, L., Banares, R., Khattab, M.A. and Romero-Gomez, M. (2013) Predicting Portal Hypertension and Variceal Bleeding Using Noninvasive Measurements of Metabolic Variables. Annals of Hepatology, 12, 420-430.
Tapper, E.B., Robson, S.C. and Malik, R. (2013) Coagulopathy in Cirrhosis: The Role of the Plat1elet in Hemostasis. Journal of Hepatology, 59, 889-890.
Bai, C.Z. (2008) Study of Expression of VEGF, bFGF and TNF-α in Esophagus of Portal Hypertensive Patient and Mechanism of Disruption of Esophageal Varices in Portal Hypertensive Patient. Master’s Thesis, General Surgery, Guangxi Medical University.
Mathonnet, M., Descottes, B., Valleix, D., Labrousse, F. and Denizot, Y. (2006) VEGF in Hepatocellular Carcinoma and Surrounding Cirrhotic Liver Tissues. World Journal of Gastroenterology, 12, 830-831. https://doi.org/10.3748/wjg.v12.i5.830
Jaroszewicz, J., Januszkiewicz, M., Flisiak, R., et al. (2008) Circulating Vascular Endothelial Growth Factor and Its Soluble Receptors in Patients with Liver Cirrhosis: Possible Association with Hepatic Function Impairment. Cytokine, 44, 14-17.
Mukozu, T., Nagai, H., Matsui, D., Kanekawa, T. and Sumino, Y. (2013) Serum VEGF as a Tumor Marker in Patients with HCV-Related Liver Cirrhosis and Hepatocellular Carcinoma. Anticancer Research, 33, 1013-1021.
Poon, R.T.P., Ng, I.O.L., Lau, C., Zhu, L.X., Yu, W.C., Lo, C.M., Fan, S.T. and Wong, J. (2001) Serum Vascular Endothelial Growth Factor Predicts Venous Invasion in Hepatocellular Carcinoma: A Prospective Study. Annals of Surgery, 233, 227-235. https://doi.org/10.1097/00000658-200102000-00012
Imanishi, T., Tsujioka, H. and Akasaka, T. (2008) Endothelial Progenitor Cells Dysfunction and Senescence: Contribution to Oxidative Stress. Current Cardiology Reviews, 4, 275-286. https://doi.org/10.2174/157340308786349435
Miller-Kasprzak, E. and Jagodzinski, P.P (2007) Endothelial Progenitor Cells as a New Agent Contributing to Vascular Repair. Archivum Immunologiae et Therapia Experimentalis, 55, 247-259. https://doi.org/10.1007/s00005-007-0027-5
Robinson, C.J. and Stringer, S.E. (2001) The Splice Variants of Vascular Endothelial Growth Factor (VEGF) and Their Receptors. Journal of Cell Science, 114, 853-865.