Hypoxia Inducible Factor 1α as a Diagnostic and Predictor Test of Liver Fibrosis

Abstract

Introduction: Regulation of the the metabolic activities of the liver is done by oxygen, which is considered as a critical signaling molecule in that issue. Oxygen delivery dysregulation provoke hepatic steatosis and inflammation. Hypoxia inducible factors (HIF1α) control the expression of gene essential for adaptation to low level of oxygen. In the state of cell hypoxia, (HIF 1α) protein level increase. Aim of the Work: Study the role of hypoxia inducible factor (HIF1α) as non-invasive marker and predictor of cirrhosis. Patients and Methods: The study was conducted on 80 patients selected from chronic hepatitis c patients at National Liver Institute, Menofia university. Subjects were randomized into 2 main groups according to the degree of liver disease: Non-Cirrhotic group; included 40 cases with early fibrosis; while Cirrhotic group included 40 cases with liver cirrhosis; and finally, Control group:  included 20 apparently healthy with no definite fibrosis by liver biopsy(historical control). Excusion criteria included, Hepatic tumors, or hepatic focal lesion, Vascular liver diseases or, portal, superior mesenteric, thrombosis, and unfit for US guided liver biopsy, all subjects had liver function tests, virology screen, complete blood counts, serum creatinine, fasting and two hours postprandial blood sugar, abdominal ultrasound, recent liver biopsy and hypoxia inducible factor (HIF1α) assay. Results: Non-Cirrhotic group showed moderate significant positive correlation between grade of fibrosis and HIF1α level, while there was inverse, moderate, significant correlation between albumin and HIF1α. Cirrhotic group, showed significant positive correlation between HIF1α, and total bilirubin, direct bilirubin, PT and INR while there was significant negative correlation with albumin. HIF1α was significantly increased with increased fibrosis grade. HIF1α level significant increased in Cirrhotic group compared to Non-Cirrhotic (2.16±0.65 vs 1.02±0.41 respectively), and in decompensated cases compared to compensated cases (2.50±0.46 vs 1.72±0.60 respectively).  Finally, HIF1α had a predictor values for diagnosis of early fibrosis as area under the curve (AUC) was 0.97. The best cut off value was 0.68, with 92.5% sensitivity and 90.0% specificity. Conclusion: HIF1α can be a useful sensitive, diagnostic, and predictor marker of hepatic fibrosis.