Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

Abstract

Summary HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.

Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate

“…Several papers have reported an increase in the incidence of HCC occurrence and/or recurrence after DAA administration. Tumorigenesis after DAAs can be attributed to an imbalance between cell apoptosis and pro-survival[ 2 , 23 ]. The direct and rapid viral eradication caused by DAAs without immune system involvement can disrupt the natural surveillance by the immune system with subsequent dormant tumor cells progression[ 23 , 24 ].…”

“…Tumorigenesis after DAAs can be attributed to an imbalance between cell apoptosis and pro-survival[ 2 , 23 ]. The direct and rapid viral eradication caused by DAAs without immune system involvement can disrupt the natural surveillance by the immune system with subsequent dormant tumor cells progression[ 23 , 24 ]. This fast viral eradication induces disruption of the innate immunity and reduction of in IFN receptors II and III that regulate tumor angiogenesis and tumor anti-proliferative effects[ 24 , 25 ].…”

From cirrhosis to hepatocellular carcinomaAn investigation into hepatitis C viral oncogenesis

“…Nowadays, genes alterations in HCC following DAA treatment and pathological pathways from cirrhosis to HCC in HCV are being investigated. [ 15 ] In this study, we aimed to characterize better the pathways involved in the oncogenesis of chronic HCV infection, and demonstrate the utility of crowd-sourced data and our STARGEO platform in the investigation of HCV-related HCC. [ 16 ]…”

“…Nowadays, genes alterations in HCC following DAA treatment and pathological pathways from cirrhosis to HCC in HCV are being investigated. [15] In this study, we aimed to characterize better the pathways involved in the oncogenesis of chronic HCV infection, and demonstrate the utility of crowd-sourced data and our STARGEO platform in the investigation of HCV-related HCC. [16] Introduction Hepatitis C virus (HCV) is a leading cause of liver disease with chronic infection, potentially leading to cirrhosis in approximately 20-30% of the infective patients.…”