Value of IFNL3 genetic polymorphism in the prediction of HCV treatment response to direct-acting antiviral drugs versus interferon therapy

ABSTRACT

Background: Despite the outstanding results of direct-acting antiviral therapies (DAAs) of Hepatitis C infection (HCV), non-responders had to be more defined.

Aim: assess the outcome of DAAs in linkage with Interferon lambda 3 (IFNL3) in HCV patients.

Methods: This case-control-study was conducted on 495 chronic-HCV (genotype-4a), previously treated Egyptians by either DAAs (responders 195, 120 relapsers) or interferon/ribavirin (IFN/RBV) (140 responders, 60 relapsers), and 98 healthy controls. IFNL3 distribution, clinical and laboratory data were assessed.

Results: CT was the most predominant genotype in Egyptians (51%). All genotypes were sensitive to DAAs mainly CT genotype (60%), even TT genotype (resistant to IFN/RBV 40%) had 29.2% sensitivity. CT genotype was predominant in sofosbuvir/Daclatasvir responders (67.6%) (OR = 0.66), while non-CT prevailed in relapsers (56.7%). TT genotype may respond to SOF/Ledi better than other regimens (66.7%). In IFN/RBV relapsers; CT genotype was commoner (50%) than others, while CC genotype predominated in responders (54.3%). The c allele was the commonest in responders to IFN/RBV (71.4%), while the T allele was resistant to treatment (65% in relapsers). Addition of RBV to SOF/DCV reported higher resistance with CT genotype (42.2%-50%) and TT genotype (17.8%-27.8%).

Conclusion: This study recommended IFNL3 genotyping to be a prerequisite before stratifying treatment for HCV-4a Egyptians.

KEYWORDS:

• Direct acting antiviral drugs
• HCV
• IFNL3
• single nucleotide polymorphism
• therapy response

Article highlights

• The linkage between HCV treatment by DAAs and IFNL3polymorphisms in genotype-4 had not yet been delineated.

• This study recommended that IFNL3 genotyping might be a prerequisite before stratifying treatment for HCV-4a Egyptian patients.

• Treatment failures with IFN/RBN were the best treated cases with DAAs according to IFNL3genotyping.

• Simeprevir/Sofosbuvir CC genotype is numerically considered the protective gene of relapse in this patient group.

• Sofosbuvir/Ledipasvir regime might be spared for other DAAs regimen relapsers with the utmost expected outcomes.

• However further studies are still needed for better delineation of these results

Acknowledgments

All authors are greatly indebted to Dr Marwa Tahoon for her unlimited help in data analysis.

Author contributions

Samar Ghanem, Nashwa Shebl, Marwa Helal designed the study. Samar Ghanem, Marwa Helal, Fathia I. El‑Bassal, Gamalat a. Elgedawy performed the experiments. Samar Ghanem, and Maha M. Elsabaawy data analysis, writing the manuscript and publication. Nashwa Shebl, Eman Abdelsameea, and Warda Othman helped in clinical data and sample collection. Dalia Elsabaawy was responsible for drug data analysis. All authors read and approved the final manuscript.

Compliance with ethical standards

The study was conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review board of National Liver Institute (NLI IRB 00003415), Menoufia University, Egypt (approval no. 00111/2014). Written informed consents were obtained from both donors and recipients regarding surgery and research

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.