292 ASSOCIATION OF HBSAG DECLINE WITH INNATE AND ADAPTIVE IMMUNE RESPONSES DURING ACUTE HEPATITIS B VIRUS INFECTION

In contrast, PBMCs from HCV rapid-fibrosers produced less IL-6 in response to TLR3 (p =0.007) and TLR9 stimulation (p =0.02), and less IFNa in response to TLR7/8 stimulation compared with HCV slow-fibrosers (p = 0.02). We confirmed these findings in a prospective cohort of 16 patients who had PBMCs collected and liver biopsy 1 yr post transplant. 8 (50%) had fibrosis progression (F1 or greater). Rapid fibrosers produced less IL-6 in response to TLR3 (p =0.05) and TLR9 stimulation (p =0.06) and less IFNa in response to TLR7/8 stimulation (p =0.01). Additionally, rapid fibrosers produced less TNFa in response to TLR3 stimulation (p =0.009). Conclusion: Rapid fibrosers demonstrate impaired cytokine and IFNa responses to stimulation of antiviral TLRs 3, 7/8 and 9. We postulate that this leads to impaired immune control of HCV and subsequent activation of fibrogenic pathways. These findings suggest impaired antiviral TLR signaling may be an important immune mechanism for aggressive HCV recurrence post transplant.