Predictors of Response to IFN-Based Therapy
Various viral and host factors have been identified as significant determinants of the outcome of IFN-based treatments. Viral genotype and baseline viral load are well-known predictors of response to therapy. Other viral factors include amino acid substitutions at positions 70 and 91 in the HCV core region and in the IFN sensitivity-determining region in NS5A in patients infected with HCV genotype 1. Several host factors related to failure of treatment-induced viral clearance include older age, insulin resistance, advanced fibrosis and hepatic steatosis.[17,18] Ethnicity is also a factor in treatment outcome. The proportion of African American patients achieving SVR on treatment with PEG-IFN/RBV is lower than Caucasian patients,[19–21] indicating that host genetic factors can be an important determinant of treatment outcome.
Analysis of candidate genes has revealed an association between several host genes and spontaneous or treatment-induced clearance of HCV. These include type I IFN receptor-1 (IFNAR1), mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3),[22,23] killer cell immunoglobulin-like receptor (KIR2DL3) and its human leukocyte antigen C group1 (HLA-C1) ligand, and HLA type.[25,26]
J Gastroenterol Hepatol. 2014;29(2):241-249. © 2014 Blackwell Publishing