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Does fluvastatin favour HCV replication in vivo ? A pilot study on HIV–HCV coinfected patients
Author(s) -
Milazzo L.,
Meroni L.,
Galazzi M.,
Cesari M.,
Caramma I.,
Marchetti G.,
Galli M.,
Antinori S.
Publication year - 2009
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2009.01104.x
Subject(s) - cd36 , fluvastatin , scavenger receptor , hepatitis c virus , interferon , in vivo , immunology , biology , receptor , virology , medicine , pharmacology , lipoprotein , virus , endocrinology , cholesterol , microbiology and biotechnology , simvastatin
Summary. Fluvastatin showed anti‐hepatitis C virus (HCV) activity in vitro , through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)‐α. Nevertheless statins up‐regulate low‐density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T‐cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid‐lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV‐RNA levels, CD36 expression and T‐cell homeostasis in HCV‐RNA positive patients. HCV‐RNA was measured at baseline and after 4 weeks in 42 HCV/HIV‐1 co‐infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T‐cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)‐10, IFN‐γ and IL‐7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group ( P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV‐RNA levels was seen after 4 weeks of fluvastatin ( P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV‐RNA replication in vivo ; conversely we observed a significant increase of HCV‐RNA levels. CD36 expression on monocytes were not up‐regulated by statins as previously reported in vitro . The correlation between HCV infectivity, oxidized‐LDL receptor and statins in HCV infection need further evaluation.