TY  - JOUR
A1  - Solbach, Philipp
A1  - Westhaus, Sandra
A1  - Deest, Maximilian
A1  - Herrmann, Eva
A1  - Berg, Thomas
A1  - Manns, Michael P.
A1  - Ciesek, Sandra
A1  - Sarrazin, Christoph
A1  - Hahn, Thomas von
T1  - Oxidized low-density lipoprotein is a novel predictor of interferon responsiveness in chronic Hepatitis C infection
T2  - Cellular and Molecular Gastroenterology and Hepatology
N2  - Background & Aims: Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C.
Methods: Baseline oxLDL was determined in 379 participants with chronic HCV genotype 1 infection from the INDIV-2 study using a commercial enzyme-linked immunosorbent assay. The mechanistic in vitro studies used full-length and subgenomic HCV genomes replicating in hepatoma cells.
Results: In the multivariate analysis, oxLDL was found to be an independent predictor of SVR. Oxidized LDL did not correlate with markers of inflammation (alanine transaminase, ferritin), nor was serum oxLDL affected by exogenous interferon administration. Also, oxLDL did not alter the sensitivity of HCV replication to interferon. However, oxLDL was found to be a potent inhibitor of cell-to-cell spread of HCV between adjacent cells in vitro. It could thus reduce the rate at which new cells are infected by HCV through either the cell-free or cell-to-cell route. Finally, serum oxLDL was significantly associated with the estimated infected cell loss rate under treatment.
Conclusions: Oxidized LDL is a novel predictor of SVR after interferon-based therapy and may explain the previously observed association of LDL with SVR. Rather than being a marker of activated antiviral defenses it may improve chances of SVR by limiting spread of infection to naive cells through the cell-to-cell route.
KW  - Cell-to-Cell Spread
KW  - oxLDL
KW  - SVR
KW  - SR-BI
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54534
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-545342
SN  - 2352-345X
N1  - © 2015 The Authors. Published by Elsevier Inc. on behalf of the AGA Institute. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
VL  - 1
IS  - 3
SP  - 285
EP  - 294
PB  - Elsevier
CY  - New York, NY
ER  -