Host Genetic Variants in the Pathogenesis of Hepatitis C

Abstract

Direct-acting antiviral drugs (DAAs) are currently replacing antiviral therapy for Hepatitis C infection. Treatment related side effects are even worse and the emergence of resistant viruses must be avoided because of the direct-antiviral action. Altogether it remains a challenge to take treatment decisions in a clinical setting with cost restrictions. Genetic host factors are hereby essential to implement an individualized treatment concept. In recent years results on different genetic variants have been published with a strong association with therapy response, fibrosis and treatment-related side effects. Polymorphisms of the IL28B gene were identified as accurate predictors for therapy response and spontaneous clearance of HCV infection and are already used for diagnostic decisions. For RBV-induced side effects, such as hemolytic anemia, associations to genetic variants of inosine triphosphatase (ITPA) were described and different SLC28 transporters for RBV-uptake have been successfully analyzed. Fibrosis progression has been associated with variants of Vitamin D receptor (VDR) and ABCB11 (bile salt export pump). Cirrhotic patients especially have a high treatment risk and low therapy response, so that personalized antiviral treatment is mandatory. This review focuses on different host genetic variants in the pathogenesis of Hepatitis C at the beginning of a new area of treatment.

A new 3p25 locus is associated with liver fibrosis progression in human immunodeficiency virus/hepatitis C virus‐coinfected patients

“…Risk factors such as alcohol consumption, age, and obesity have also been described but account for only a small proportion of the variability in liver fibrosis development . There is growing evidence to suggest that host genetic factors are involved, at least in patients infected with HCV alone; but these factors remain largely unknown …”

CD209 promoter polymorphisms associate with HCV infection and pegylated-interferon plus ribavirin treatment response

“…We analysed promoter polymorphisms within CD209 gene as potential factors involved in the natural course of HCV infection and PEG/IFN + RBV treatment response, traits still partially known at present time (Dustin et al, 2014;Rau et al, 2012). Associations between CD209 genetic variants, HCV infection susceptibility and treatment response were here reported for the first time.…”

Az idült májbetegségek progressziójához vezető folyamatok

“…A D-vitamin-receptor genetikai eltérései a fibrosis előrehaladását befolyásolják. A patatinszerű foszfolipáz-3 (patatin-like phospholipase 3 -PNPLA-3) genetikai polimorfizmusa összefüggést mutatott a nagyobb cirrhosiskockázattal és a rosszabb terápiás válasszal HCV-fertőzésben [39].…”