Association of ITPA Gene Expression and Hematological Abnormalities Induced by Dual therapy in HCV-infected Patients | ||||
Scientific Journal for Damietta Faculty of Science | ||||
Volume 11, Issue 1, September 2021, Page 56-66 PDF (645.99 K) | ||||
Document Type: Original articles | ||||
DOI: 10.21608/sjdfs.2021.195591 | ||||
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Authors | ||||
Naglaa ELarabany 1; Nahed A. Omar1; Mostafa M. Elshaer2; Ahmed Abdelkhalek3; Mai Alaa Eldin Ali Rashed1 | ||||
1Department of Zoology, Faculty of Science, Damietta University, Damietta, Egypt. | ||||
2Department of Microbiology at specialized medical Hospital, Mansoura University, Egypt. | ||||
3Plant Protection and Bimolecular Diagnosis Department, ALCRI, City of Scientific. Research and Technological Applications, New Borg El Arab city, Alexandria 21934, Egypt | ||||
Abstract | ||||
The combination therapy has been the standard treatment for chronic hepatitis C virus (HCV) infection, but many patients have side effects due to this therapy. Recently, new direct-acting antivirals (DAAs) have enhanced the response rate, especially in difficult-to-treat patients infected with HCV genotypes (GT) 1 or 4, and have made adverse effects less common. RBV plays continually an important role in HCV therapy even with the introduction of DAAs. Hemolytic anemia is a common side effect in HCV-infected patients on combination therapy, affecting up to 30 % of patients, which needs to followup hemoglobin and dose modification in up to 15 % of patients. RBV-induced anemia primarily results in the reduction of adenosine triphosphate (ATP) levels in erythrocytes, affecting ATP-dependent oxidative metabolism. Genetic variations in the inosine triphosphatase (ITPA) gene, which encodes an inosine triphosphate pyrophosphohydrolase (ITPase), protect from hemolytic anemia during dual therapy. These ITPA variants affect ITPase functionality, causing a drop in its activity, resulting in an accumulation of inosine triphosphate (ITP) in erythrocytes and the prevention of oxidative stress. The functional variants in ITPA gene leads to ITPase deficiency and a strong accumulation of ITP in erythrocytes, which is associated with lower RBV-toxicity. These genetic variants have been associated with protection from anemia. | ||||
Keywords | ||||
ITPA; Hemolytic anemia; Ribavirin; Chronic hepatitis C; HCV therapy | ||||
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