Z Gastroenterol 2014; 52 - P_5_13
DOI: 10.1055/s-0033-1361022

Endogenous oxidized LDL levels predict treatment response in interferon-based therapy of chronic hepatitis C

P Solbach 1, S Westhaus 2, M Deest 1, T Berg 3, MP Manns 1, C Sarrazin 4, S Ciesek 1, T von Hahn 2
  • 1Medizinische Hochschule Hannover, Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
  • 2Medizinische Hochschule Hannover, Institut für Molekularbiologie, Hannover, Germany
  • 3Universitätsklinikum Leipzig, Sektion Hepatologie, Leipzig, Germany
  • 4Universitätsklinikum Frankfurt, Medizinische Klinik I, Frankfurt am Main, Germany

Background: Oxidized low density lipoprotein (oxLDL) is a naturally occurring chemically altered form of LDL. oxLDL is generated during oxidative processes in the blood vessel wall and oxLDL serum level is not strongly correlated with that of native LDL. Both in vitro generated and endogenous oxLDL potently inhibit entry of hepatitis C virus into liver cells by perturbing the interaction between HCV and scavenger receptor class B type I, one of several essential HCV receptors on the hepatocyte surface. Whether endogenous oxLDL levels have an impact on treatment outcome in chronic hepatitis C is unknown.

Methods: We used a commercial ELISA (Mercodia) to determine oxLDL levels in a subset of n = 120 patients from the INDIV2 study that investigated optimal duration of dual therapy with pegylated interferon (PEG-IFN) and ribavirin and correlated results with treatment outcome and other clinical parameters. In parallel we performed virological assays where the chimeric HCV clone Jc1 (genotype 2a) with an integrated luciferase reporter was used to infect Huh-7.5 cells in vitro.

Results: Baseline serum oxLDL levels were significantly higher in individuals achieving sustained virologic response (SVR) than in those who did not. Moreover, baseline serum oxLDL was predictive of SVR in both univariate and multivariate analysis controlling for other known predictors of SVR. In vitro the 50% inhibitory concentration (IC50) for PEG-IFN mediated inhibition of HCV infection of and replication in hepatoma cells was not different in the presence or absence of oxLDL (4.8 and 6.6 µg/ml, respectively) indicating that oxLDL does not alter cellular interferon responsiveness. Current experiments will determine to what extent serum oxLDL levels may reflect the intensity of systemic inflammation and/or lipid profile.

Conclusion: The endogenous HCV entry inhibitor oxLDL is predictive of SVR in response to PEG/RBV treatment of chronic HCV infection.