Published online Jan 14, 2020. doi: 10.3748/wjg.v26.i2.168
Peer-review started: October 8, 2019
First decision: December 5, 2019
Revised: December 11, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: January 14, 2020
Hepatitis C virus (HCV) infection is a complex multifactorial process that involves multiple viral and host interactions. Besides, the high mutation rate of HCV that enables the virus to generate escape mutants resistant to treatment, emphasizing the need for a proper understanding of the pathogenesis of HCV infection, and various research efforts should be oriented to develop novel diagnostic and prognostic molecular tools.
lncRNAs are transcripts greater than 200 nucleotides with poor coding potential, that play important roles in regulating gene expression. Emerging evidence suggests that lncRNAs play relevant roles in viral infection and in antiviral responses. To date, the expression profiles of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and its mRNA BST2 in HCV GT4 patients and their clinical relevance as biomarkers for HCV infection have not been studied yet.
To assess the serum levels of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 in naïve, treated and relapsed Egyptian HCV patients to examine their relation to HCV infection and their potential usefulness as new diagnostic and prognostic biomarkers for HCV GT4.
Serum lncRNAs and mRNABST2 were measured using quantitative real-time polymerase chain reaction. The study included six groups; group I healthy controls and group II naïve HCV patients without treatment. Groups from III to V comprised HCV patients treated daily with three different 12-wk oral treatment regimens as follows: Group III received combination of sofosbuvir and simeprevir. Group IV received combination of sofosbuvir and daclatasvir. Group V received sofosbuvir and daclatasvir with ribavirin. Group VI included HCV patients who relapsed after 12-week treatment with sofosbuvir and simeprevir.
We found that serum levels of lncRNAGAS5 and LncRNABISPR were upregulated, whereas mRNA BST2 and LncRNA HEIH levels were downregulated in naïve patients compared to healthy controls. In contrast, HCV patients treated with sofosbuvir and simeprevir; with sofosbuvir and daclatasvir; or with sofosbuvir, daclatasvir and ribavirin exhibited lower levels of lncRNAGAS5 and lncRNABISPR with higher mRNABST2 compared to naïve patients. Notably, patients relapsed from sofosbuvir and simeprevir showed higher levels of these lncRNAs with lower mRNABST2 compared to treated patients. Moreover, lncRNA GAS5, lncRNA BISPR and mRNA BST2 could differentiate naïve patients from controls and treated patients, whereas lncRNA HEIH best differentiated relapsed from treated patients.
Differential expression of lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 in naïve, treated and relapsed HCV Egyptian patients suggests their involvement in HCV-pathogenesis or antiviral response. In addition, lncRNA GAS5, lncRNA HEIH, lncRNA BISPR and mRNA BST2 could serve as potential diagnostic biomarkers in HCV GT4 Egyptian patients while, lncRNA GAS5, lncRNA BISPR and mRNA BST2 could also be considered novel prognostic biomarkers for treatment in HCV patients. Importantly, lncRNA HEIH might represent a powerful prognostic marker for differentiating relapsed patients from sofosbuvir and simeprevir treatment.
Further multicentre studies with large number of participants infected with either HCV or other infectious agents unlike HCV should be conducted to justify the specificity of these markers. Moreover, a prospective longitudinal study is needed to follow the same group of patients before and after treatment to confirm the potential of these biomarkers as prognostic tools for HCV and occurrence of relapse after therapy.