alexa Sequential Therapy with Tenofovir Plus Peg Interferon Enhances Innate and Adaptive Immunity Compared to Tenofovir Monotherapy in Chronic Hepatitis B Patients
ISSN: 2155-9899

Journal of Clinical & Cellular Immunology
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Research Article

Sequential Therapy with Tenofovir Plus Peg Interferon Enhances Innate and Adaptive Immunity Compared to Tenofovir Monotherapy in Chronic Hepatitis B Patients

Nirupma Trehanpati1*, Arshi Khanam1, Syed Hissar1, Rashi Sehgal1, Ritu Khosla1, Paul David1, Ashish kumar1, Anupama Prashar1, Ankit Bhardwaj2, Shyam Kottilil3 and Shiv Kumar Sarin2*
1Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India
2Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
3Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Corresponding Authors : Dr. Nirupma Trehanpati
Institute of Liver and Biliary Sciences (ILBS) New Delhi – 110070, India
Tel: +91-11-46300000
Fax: +91-11- 26123504
E-mail: [email protected]
  Prof. Shiv Kumar Sarin
Institute of Liver and Biliary Sciences (ILBS) New Delhi – 110070, India
Tel: +91-11-46300000
Fax: +91-11- 26123504
E-mail: [email protected]
Received September 13, 2014; Accepted November 07, 2014; Published November 14, 2014
Citation: Trehanpati N, Khanam A, Hissar S, Sehgal R, Khosla R, et al. (2014) Sequential Therapy with Tenofovir Plus Peg Interferon Enhances Innate and Adaptive Immunity Compared to Tenofovir Monotherapy in Chronic Hepatitis B Patients. J Clin Cell Immunol 5:272. doi: 10.4172/2155-9899.1000272
Copyright: © 2014 Khan N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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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.

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