Presence of interferon-λ 4, male gender, absent/mild steatosis and low viral load augment antibody levels to hepatitis C virus.

OBJECTIVES: Despite recombinant interferon-λ 4 (IFN-λ4) demonstrating anti-viral activity in vitro and the ancestral functional gene ( IFNL4 ) being conserved in all other primates, there has been speculation that IFN-λ4 may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4 , on antibody levels to hepatitis C virus (HCV).

MATERIALS AND METHODS: Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay.

RESULTS: Patients producing IFN-λ4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-λ4 ( IFNL4 rs12979860 CT/TT versus CC, p <.0001, Mann-Whitney U -test). Additionally, in univariate analyses S/CO was significantly higher in men than women ( p <.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0-2 versus 3-4, p  = .009), and absent/mild steatosis (grade 0-1 versus 2-3, p  = .0005). Also, an inverse correlation with HCV RNA level ( rs = -0.14, p  = .02) was noted. In multivariate analysis IFN-λ4, gender, steatosis and viral load remained independently associated.

CONCLUSIONS: To our knowledge, this is the first report that demonstrates that the ability to produce IFN-λ4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-λ4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection. ClinicalTrials.gov Identifier: NCT00143000.