Abstract
PURPOSE OF REVIEW: Host genetic factors influencing hepatitis C virus (HCV) transmission outcomes are incompletely defined. However, vast differences observed in rates of spontaneous clearance between individuals infected with the same parental HCV strain strongly indicate a role for genetic determinants in the host immune response to HCV. This review discusses genetic association studies, particularly those published in the last year, that show gene linkages with spontaneous and treatment-induced HCV clearance. The valuable role that blood collection centers can play in increasing the sample size of HCV-confirmed seropositive donors with resolved versus persistent infections for large-scale genetic association studies is highlighted. RECENT FINDINGS: Recent groundbreaking genome-wide association study and targeted single-nucleotide polymorphism (SNP) analysis from independent groups have demonstrated immune response gene polymorphisms, and particularly in the interleukin (IL)-28B gene, that are strongly linked to HCV clearance. The IL-28B gene encodes interferon lambda 3, an innate immune response cytokine. SNPs in the promoter region of IL-28B were first shown to be associated with HCV treatment-induced viral clearance and subsequently to be a key determinant of spontaneous HCV resolution in infected individuals. Samples from blood donors with resolved and chronic HCV infections have contributed to these findings. SUMMARY: These genetic studies have provided the strongest evidence so far of a host genetic determinant linked to HCV clearance. Such large-scale genetic association studies will promote better understanding of HCV disease pathogenesis and assist in effective prognosis of HCV in the future. Continued and preferably expanded participation of blood centers in this research is encouraged.