We thank Grebely et al. for their recent InC study confirming that the IL28B genotype and female sex are associated with the spontaneous clearance of hepatitis C virus (HCV). However, we and others showed that spontaneous HCV resolution is associated with another genetic factor more than 10 years ago. This factor is the DQB1*0301 allele of the major histocompatibility complex class II. The IL28B genotype was shown to be the most important factor associated with a sustained virologic response to pegylated-interferon ribavirin therapy and also with the spontaneous outcome of HCV infection. However, the study showing that genetic variations in IL28B is associated with spontaneous clearance of HCV focused on a single nucleotide polymorphism and was not a genome-wide association study (GWAS). A new multicenter collaborative study on 919 North American and European subjects whose HCV was resolved spontaneously was conducted to explain the conflicting results.[2, 4] It was shown that IL28B rs12979860 and DQB1*0301 rs4272729 alleles were independently associated with the spontaneous resolution of HCV. Surprisingly, these results are not discussed by Grebely et al.
The InC study is important because the authors confirmed prospectively the well-known IL28B polymorphism and reported that being a female is also associated with the clearance of an acute HCV infection. Our previous cohort studies[2, 6] also found this statistically significant association with female sex (P < 0.004), but it was not an independent factor in multivariate analysis. We also reported that viral genotype plays no role in spontaneous resolution of HCV infection.[2, 6] We are disappointed that the InC study did not test the DQB1*0301 allele in each subject. It is technically easy to do so and not costly. We believe that they would have found that this host factor is also associated with spontaneous HCV resolution. We suggest that female sex will not be an independent predictor of spontaneous HCV clearance when both these genetic factors are included in a multivariate analysis.
Laurent Alric, Ph.D., M.D.1
Delphine Bonnet, M.D.1
Marylise Fort, M.D.2
1Internal Medicine Digestive Department Purpan Hospital
UMR152, IRD Toulouse III University, Toulouse, France
2Immunology Unit Rangueil Hospital, Toulouse, France