Evaluating the Value of the Genetic Risk Variants of Haem-Oxygenase-1, Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 in Prediction of the Presence of Esophageal Varices in Patients with Liver Cirrhosis | ||||
| The Medical Journal of Cairo University | ||||
| Article 70, Volume 89, June, June 2021, Page 1009-1016 PDF (344.2 K) | ||||
| DOI: 10.21608/mjcu.2021.184538 | ||||
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| Authors | ||||
| AHMED MOUSTAFA, M.D.; SHERIF HAMDY, M.D.; AYMAN RASHAD, M.D.; WALAA AHMED, M.D.; AHMED NASHAAT, M.Sc.; SAEED M. EL-NAHAAS, M.D. | ||||
| The Departments of Endemic Medicine & Hepatology* and Clinical Pathology**, Faculty of Medicine, Cairo University and The Department of Hepatology and Gastroenterology, Ahmed Maher Teaching Hospital***, Cairo, Egypt | ||||
| Abstract | ||||
| Abstract Background: Current guidelines recommend screening for Esophageal Varices (EV) by Esophagogastroduodenoscopy (EGD) for all cirrhotic patients. The cost and invasive nature of endoscopic screening mean that there is an interest in developing noninvasive predictors for EV that would decrease the number of EGDs performed. The genetic factors that are involved in the development and maintenance of porto-systemic collateral circulation have been rarely investigated. Variation at the genes that encode proteins involved in the systemic and splanchnic vasodilation, which include angi-otensin-converting enzyme and endothelial/constitutive nitric oxide synthase, have been found to be involved in the EV risk among patients withcirrhosis. In cirrhosis, Vascular Endothelial Growth Factor (VEGF) receptor 2/VEGF and carbon monoxide (CO) activity are significantly increased and are closely correlated with porto-systemic collateral vasodilations. Haem-Oxygenase-1 (HO-1) is the main rate-limiting enzyme involved in CO production. Aim of Study: This study aimed at investigating the value of the genetic risk variants of HO-1, VEGF and VEGF Re-ceptor-2 (VEGFR-2) in prediction of the presence of EV in patients with liver cirrhosis. Patients and Methods: Our study included 300 Egyptian patients with liver cirrhosis, aged 18 years or older, with no history of gastrointestinal bleeding, hepatic schistosomiasis, hepatocellular carcinoma, injection sclerotherapy or band ligation for EV, surgery for portal hypertension or portal or splenic vein thrombosis by ultrasonography. Patients underwent EGD to evaluate the presence and degree of EV, fibroscan for detection of liver stiffness and genetic investigation of HO-1, VEGF and VEGFR-2. Demographic, biochemical and endoscopic data were collected. Patients were divided into Group I (no varices), Group II A (small varices), Group IIB (large varices) and Group III (100 healthy control subjects). Results: All groups were age & BMI matched, platelet count and serum albumin were significantly lower in group II B compared to groups I & II A (p-value <0.001), while serum bilirubin level was significantly higher in group II B compared to groups I & II A (p-value <0.001). TT genotype SNP of HO-1 was associated with the presence of EV, while low grade varices were more detected in patients who carry AT genotype. Other genetic risk variants of VEGF and VEGFR-2 were not helpful in the prediction of EV or in the differen-tiation between small and large varices. Conclusion: Genetic risk variants of HO-1 genotype are helpful in prediction of EV as well as in differentiation between small and large varices. Combining these genetic variants to other noninvasive parameters will be a more sensitive and specific tool to predict EV in cirrhotic patients; it may help to select patients for endoscopic screening and decrease the number of EGDs. However, further studies will be needed from the economic point of view to determine the applicability of using these noninvasive tools as predictors of varices instead of EGD. | ||||
| Keywords | ||||
| Genetic variants; Esophageal varices | ||||
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