Research Article
Nirupma Trehanpati, Arshi K
Abstract
Viral load reduction followed by immunomodulation is an emerging approach to improve the treatment outcomes in patients with Chronic Hepatitis B (CHB). Persistent functional defects in Dendritic Cells (DC) have been observed in CHB patients, even with effective antiviral therapy. We investigated the effects of Tenofovir plus Peg-IFN Sequential Therapy (SQT) on functional restoration of innate and adaptive immunity in CHB patients. HBeAg+ve CHB patients were randomized to receive 48weeks of either tenofovir monotherapy (TM; Gr.1, n=30) or tenofovir with addition of PEG interferon from week 12 to 36 followed by tenofovir sequential therapy (SQT; Gr. 2, n=28) for 48 weeks. Biochemical parameters improved significantly with treatment at week 24 in both groups, but HBeAg seroconversion at week 48 occurred more frequently after SQT (21%) than TM (13%). At week 24, the expression and function of TLR7 and TLR9 in DCs were significantly increased in SQT compared to TM (p<0.05). Phagocytic activity of DCs, production of IFN-α and TNF-α by mDCs and pDCs and the expression of specific miRNAs for DC proliferation and maturation like miR155 and miR221, were higher in the SQT (p<0.05). After 24 weeks, SQT restored significantly more circulating CD8Tcells (p=0.02), CD8+CD127+ Tcells (p=0.03) and reduced the PD-1 expression on CD8 T-cells (p=0.04) vs. TM. Our results show that in a short period of 24 weeks, SQT significantly improves functionality of DCs. Upregulation of TLR7 and TLR9 and miR155 in DCs by PEG-IFN-α is a novel mechanism that may be quite significant in mounting an effective antiviral response. Influence of longer duration of SQT and immunomodulation needs to be studied.