1. HCV-related liver and lymphoproliferative diseases: association with polymorphisms of IL28B and TLR2
- Author
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De Re, V, De Zorzi, M, Caggiari, L, Lauletta, G, Tornesello, ML, Fognani, E, Miorin, M, Racanelli, V, Quartuccio, L, Gragnani, L, Russi, S, Pavone, F, Ghersetti, M, Costa, EG, Casarin, P, Bomben, R, Mazzaro, C, Basaglia, G, Berretta, M, Vaccher, E, Izzo, F, Buonaguro, FM, De Vita, S, Zignego, AL, De Paoli, P, Dolcetti, R, De Re, V, De Zorzi, M, Caggiari, L, Lauletta, G, Tornesello, ML, Fognani, E, Miorin, M, Racanelli, V, Quartuccio, L, Gragnani, L, Russi, S, Pavone, F, Ghersetti, M, Costa, EG, Casarin, P, Bomben, R, Mazzaro, C, Basaglia, G, Berretta, M, Vaccher, E, Izzo, F, Buonaguro, FM, De Vita, S, Zignego, AL, De Paoli, P, and Dolcetti, R
- Abstract
To explore the relationship between innate immunity and hepatitis C Virus (HCV) in determining the risk of cirrhosis (CIR), hepatocellular carcinoma (HCC), mixed cryoglobulinemia syndrome (MCS) and non-Hodgkin lymphoma (NHL), we investigated the impact of the toll-like receptor-2 (TLR2) and interleukin-28B (IL28B) genetic variants. TLR2 -174 del variant was associated with TLR2 expression and with specific downstream molecules that drive the expression of different interleukins; rs12979860 Il28B was important in response to interferon-treatment and in spontaneous clearance of HCV. The risk for liver and lymphoproliferative diseases in HCV progression was clarified by stratifying 862 HCV-positive patients into groups based on liver (CIR, HCC) and lymphoproliferative HCV-related diseases (MCS, NHL) and compared with chronic HCV (CHC) infection. Analysis of TLR2-IL28B haplotypes showed an association of wild type haplotype with the lymphoproliferative diseases (OR 1.77, p = 0.029) and a slight increase in HCV viral load (HR 1.38, p = 0.054). Wild type haplotype (TLR2 ins/ins- IL28B C/C) was also found associated with older age in patients with an hepatic diseases (in CIR and in HCC p = 0.038 and p = 0.020, respectively) supporting an effect of innate immunity in the liver disease progression. TLR2 and IL28B polymorphisms in combination showed a role in the control of HCV viral load and different HCV disease progression.
- Published
- 2016