Polymorphism in interferon λ3/interleukin‐28B gene and risk to noncirrhotic chronic hepatitis C genotype 3 virus infection and its effect on the response to combined daclatasvir and sofosbuvir therapy

Abstract

Hepatitis C virus (HCV) infection is a considerable public‐health problem and an important cause of liver disease with about 71 million people infected worldwide and more than 399 000 people die every year from hepatitis C‐related liver diseases. The present study was, therefore, initiated to investigate the association of polymorphism in interferon λ3 (IFNL3) also known as interleukin‐28B (IL‐28B) gene with chronic HCV infection and association of these polymorphic variants with the combination daclatasvir and sofosbuvir HCV therapy response. Genotypes were determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) assay in a total of 250 chronic HCV genotype three patients and 500 number of healthy controls. Our data revealed that the TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) exhibited a significant association with chronic HCV genotype 3 infection when compared with controls. The results of treatment response showed that CC (major) genotype of IFNL3 (rs12979860) and TT (major) genotype of IFNL3 (rs8099917) are associated with the likelihood of achieving a higher sustained virological response (SVR), to combined daclatasvir and sofosbuvir therapy, in genotype 3‐infected HCV patients, whereas the individuals with TT (minor) genotype of IFNL3 (rs12979860) and GG (minor) genotype of IFNL3 (rs8099917) are more susceptible to chronic HCV infection and treatment relapse, suggesting a role of IFNL3 (rs12979860) and (rs8099917) in the treatment outcome of combined daclatasvir and sofosbuvir therapy in chronic HCV genotype 3 infection.

Complex analysis of the personalized pharmacotherapy in the management of COVID-19 patients and suggestions for applications of predictive, preventive, and personalized medicine attitude

“…The frequencies of rs12979860 and rs8099917 were 59.95% and 25.88% respectively. All four variations have been reported to impact drug effects in a large number of clinical trials involving antiviral regimens, including ritonavir, daclatasvir, sofosbuvir, ribavirin and interferon alpha 2b [ 38 – 40 ]. Therefore, rs8103142, rs12979860, rs8099917 and rs28416813 may also have a negative impact on the efficacy of these drugs in COVID-19.…”

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients

“…They revealed that the CC genotype of IL-28B (rs12979860) was observed at a significantly higher frequency in patients with SVR (39.5%) compared to relapses (10.5%) and non-responders (17%), demonstrating the correlation of CC genotype with the probability of attaining SVR in contrast to non-CC variants. Moreover, the C allele was more prevalent in patients with SVR (65%), whereas the T allele was more prevalent in non-responders (62%) [14].…”

“…Previous findings of the treatment response demonstrated that the CC (main) genotype of IFN λ 3 (rs12979860) has been correlated with the possibility of attaining a better sustained virological response (SVR) to the combination of daclatasvir (DCV) and SOF treatment in genotype-3-infected HCV [14].…”