Host pharmacogenetic factors that may affect liver neoplasm incidence upon using direct-acting antivirals for treating hepatitis C infection

Abstract

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.

Keywords

• Pharmacogenomics
• PHARMIP
• HCV direct-Acting antivirals
• Hepatocellular carcinoma
• Personalized medicine
• HCV