High dose wIFN-α significantly inhibits WHV.

<p>Maximum reductions in (a) serum and (b) intrahepatic viral parameters, and (c) maximum serum ALT and AST levels in response to placebo, low dose (20 μg) wIFN-α and high dose (100 μg) wIFN-α treatment. Changes in viral parameters were calculated relative to week -3 (pre-treatment baseline), with the exception of F1018 (wIFN-α group), for which week 0 was used as the baseline for the intrahepatic cccDNA and RNA analyses. The bar height indicates the mean of each group, and the errors bars represent the standard error of the mean. The lowest WHsAg level for two wIFN-treated animals (M1002 and F1022) was ≤ LLOD (20 ng/mL), and so the LLOD was used to estimate the maximum WHsAg decline. Per the sampling scheme outlined in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005103#ppat.1005103.g001" target="_blank">Fig 1</a>, the following data was included in the analyses: maximum reduction in serum WHV DNA and WHsAg at weeks 0–16 (placebo), 0–7 (20 μg dose) and weeks 8–16 (100 μg dose); maximum reduction in intrahepatic cccDNA and RNA at weeks 0–15 (placebo), weeks 0 and 3 (20 μg dose) and weeks 7, 11 and 15 (100 μg dose); maximum serum ALT and AST levels at weeks 0–16 (placebo), 0–7 (20 μg dose) and weeks 11–16 (100 μg dose). Animals in the wIFN-α group were only included if data from all relevant time-points was available, with the exception of F1020, for which no week 16 sample was available for serum WHV DNA, WHsAg, ALT and AST analysis. Statistical significance was calculated by one-way ANOVA with Tukey's multiple comparison correction.