Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection
Introduction: Direct-acting antivirals (DAAs) represent a breakthrough in hepatitis C virus (HCV) treatment as they directly inhibit HCV nonstructural (NS) proteins (NS3/4A, NS5A, and NS5B). However, ongoing debates exist regarding their relationship with hepatocellular carcinoma (HCC) whose inciden...
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doaj-6a3a6763d3de4ab2ae0daddb1c1f4ae52021-06-03T14:44:56ZengElsevierHeliyon2405-84402021-05-0175e06908Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infectionAhmad M. Zidan0Eman A. Saad1Nasser E. Ibrahim2Medhat H. Hashem3Amal Mahmoud4Alaa A. Hemeida5Department of Bioinformatics, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, Egypt; Clinical Research Department, Monof Chest Hospital, Menoufia directorate, Ministry of health & population (MOHP), Egypt; Corresponding author.Department of Bioinformatics, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, EgyptDepartment of Bioinformatics, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, EgyptDepartment of Animal Biotechnology, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, EgyptDepartment of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, 31441, Dammam, Saudi ArabiaDepartment of Bioinformatics, Genetic Engineering & Biotechnology Research Institute, University of Sadat City, EgyptIntroduction: Direct-acting antivirals (DAAs) represent a breakthrough in hepatitis C virus (HCV) treatment as they directly inhibit HCV nonstructural (NS) proteins (NS3/4A, NS5A, and NS5B). However, ongoing debates exist regarding their relationship with hepatocellular carcinoma (HCC) whose incidence is widely debated among investigators. This study was conducted to identify host pharmacogenetic factors that may influence HCC incidence upon using HCV DAAs. Materials and methods: Details regarding 16 HCV DAAs were collected from literature and DrugBank database. Digital structures of these drugs were fed into the pharmacogenomics/pharmacovigilance in-silico pipeline (PHARMIP) to predict the genetic factors that may underpin HCC development. Results: We identified 184 unique genes and 40 unique variants that may have key answers for the DAA/HCC paradox. These findings could be used in different methods to aid in the precise application of HCV DAAs and minimize the proposed risk for HCC. All results could be accessed at: https://doi.org/10.17632/8ws8258hn3.2. Discussion: All the identified factors are evidence related to HCC and significantly predicted by PHARMIP as DAA targets. We discuss some examples of the methods of using these results to address the DAA/HCC controversy based on the following three primary levels: 1 - individual DAA drug, 2 - DAA subclass, and 3 - the entire DAA class. Further wet laboratory investigation is required to evaluate these results.http://www.sciencedirect.com/science/article/pii/S2405844021010112PharmacogenomicsPHARMIPHCV direct-Acting antiviralsHepatocellular carcinomaPersonalized medicineHCV |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ahmad M. Zidan Eman A. Saad Nasser E. Ibrahim Medhat H. Hashem Amal Mahmoud Alaa A. Hemeida |
spellingShingle |
Ahmad M. Zidan Eman A. Saad Nasser E. Ibrahim Medhat H. Hashem Amal Mahmoud Alaa A. Hemeida Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection Heliyon Pharmacogenomics PHARMIP HCV direct-Acting antivirals Hepatocellular carcinoma Personalized medicine HCV |
author_facet |
Ahmad M. Zidan Eman A. Saad Nasser E. Ibrahim Medhat H. Hashem Amal Mahmoud Alaa A. Hemeida |
author_sort |
Ahmad M. Zidan |
title |
Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection |
title_short |
Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection |
title_full |
Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection |
title_fullStr |
Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection |
title_full_unstemmed |
Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection |
title_sort |
host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis c infection |
publisher |
Elsevier |
series |
Heliyon |
issn |
2405-8440 |
publishDate |
2021-05-01 |
description |
Introduction: Direct-acting antivirals (DAAs) represent a breakthrough in hepatitis C virus (HCV) treatment as they directly inhibit HCV nonstructural (NS) proteins (NS3/4A, NS5A, and NS5B). However, ongoing debates exist regarding their relationship with hepatocellular carcinoma (HCC) whose incidence is widely debated among investigators. This study was conducted to identify host pharmacogenetic factors that may influence HCC incidence upon using HCV DAAs. Materials and methods: Details regarding 16 HCV DAAs were collected from literature and DrugBank database. Digital structures of these drugs were fed into the pharmacogenomics/pharmacovigilance in-silico pipeline (PHARMIP) to predict the genetic factors that may underpin HCC development. Results: We identified 184 unique genes and 40 unique variants that may have key answers for the DAA/HCC paradox. These findings could be used in different methods to aid in the precise application of HCV DAAs and minimize the proposed risk for HCC. All results could be accessed at: https://doi.org/10.17632/8ws8258hn3.2. Discussion: All the identified factors are evidence related to HCC and significantly predicted by PHARMIP as DAA targets. We discuss some examples of the methods of using these results to address the DAA/HCC controversy based on the following three primary levels: 1 - individual DAA drug, 2 - DAA subclass, and 3 - the entire DAA class. Further wet laboratory investigation is required to evaluate these results. |
topic |
Pharmacogenomics PHARMIP HCV direct-Acting antivirals Hepatocellular carcinoma Personalized medicine HCV |
url |
http://www.sciencedirect.com/science/article/pii/S2405844021010112 |
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