Interleukin-17 haplotyping predicts hepatocellular carcinoma in sofosbuvir, pegylated interferon-alpha-2a & ribavirin treated chronic hepatitis C patients

Interleukin-17 haplotyping predicts hepatocellular carcinoma in sofosbuvir, pegylated interferon-alpha-2a & ribavirin treated chronic hepatitis C patients

•G-G haplotype in IL-17A is negatively associated with HCC development in SOF, Peg-IFNα-2a, RBV treated CHC G4 patients.•Serum AFP is only associated with HCC development in Peg-IFNα-2a, RBV treated CHC G4 patients.•SOF might be linked with HCC development in some CHC G4 patients.•Haplotyping of IL-...

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Published in:Virus research Vol. 292; p. 198226
Main Authors: Mostafa, Ahmed M., Saafan, Hesham A., Al-Tawashi, Ahmed S., Kasem, Muhannad H., Alaa, Ahmed M., Eltobgy, Mahmoud M., Moubarak, Ahmed S., Gharib, Manar M., Awwad, Mohamed A., Omar, Hazem M., El-Derany, Marwa O.
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 15-01-2021
Subjects:
Chronic hepatitis C
Haplotype
HCC
IL-17A
Peg-IFNα-2a
Sofosbuvir
NR
ALT
AUROC
TLC
AFP
CIs
G4
SVR
DAAs
ANOVA
RT-PCR
SNPs
Haplotype
AST
OR
Peg-IFNα-2a
IL-17A
RBV
ROC
HCC
SOF
Th-17
Chronic hepatitis C
HCV
Peg-IFN
Sofosbuvir
CHC
ELISA
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Summary:•G-G haplotype in IL-17A is negatively associated with HCC development in SOF, Peg-IFNα-2a, RBV treated CHC G4 patients.•Serum AFP is only associated with HCC development in Peg-IFNα-2a, RBV treated CHC G4 patients.•SOF might be linked with HCC development in some CHC G4 patients.•Haplotyping of IL-17A genes is crucial to personalize the proper treatment protocol for CHC G4 patient. Suspect has been directed towards some direct acting antivirals (DAAs) due to their reported association with hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients. The mechanisms behind HCC development, following CHC treatment, were not well understood and may be linked to genetic variabilities in different patients which affect several cytokine productions involved in angiogenesis and inflammation. Of these variabilities, is the genetic polymorphisms in the interleukin-17 (IL-17) A receptor gene. Being an important pleiotropic cytokine, this study aimed to investigate the association between haplotypes in IL-17A receptor rs2275913 and rs3819024 and development of HCC in CHC patients treated with either triple therapy (sofosbuvir (SOF), pegylated interferon-alpha-2a (Peg-IFNα-2a) & ribavirin(RBV)) or with dual therapy (Peg-IFNα-2a&RBV). A cohort of 100 CHC patients was recruited in this study. Samples were tested for single nucleotide polymorphism (SNPs) in IL-17A receptor (rs2275913 and rs3819024) using TaqMan Genotyping assay. Our results showed that the presence of G-G haplotype in IL-17A (rs2275913& rs3819024) is inversely associated with HCC development in patients receiving triple therapy. While, high serum AFP levels are directly associated with HCC development in patients receiving triple therapy. However, in patients receiving dual therapy, HCC development was only associated with high serum alpha fetoprotein (AFP) levels and was not correlated to any specific allele in our studied SNPs. Such results highlight the importance of IL17A receptor gene haplotyping in the prediction of HCC development in patients receiving triple therapy. These results will aid in performing tailored, personalized strategy for CHC treatment.
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ISSN:0168-1702
1872-7492
DOI:10.1016/j.virusres.2020.198226