title: Interferon alpha induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C.
abstract: The effect of recombinant interferon alpha 2a (rIFN-alpha2a) on serum lipoprotein metabolism was assessed in 39 patients with chronic viral hepatitis C. rIFN-alpha2a was administered intramuscularly at a dose of 9 x 10(6) U/d for 2 weeks and then for 3 times a week over 6 months. The serum cholesterol concentration significantly decreased one week after rIFN-alpha2a administration. Approximately 67% of this decrease was attributed to the reduction of high-density lipoprotein (HDL)-cholesterol; a decrease in HDL2-cholesterol was more evident. By contrast, serum triglyceride levels, largely derived from very-low density lipoprotein (VLDL), significantly increased following rIFN-alpha2a treatment. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin plasma were reduced by 75.7% and by 79.4%, respectively, and decreases in plasma cholesteryl ester transfer protein (CETP) activity and its protein mass were also observed. However, prothrombin time was ameliorated by rIFN-alpha2a, suggesting that the decrease in LPL, HTGL, and CETP activities may not be due to a reduction in protein synthesis by the liver. Simple correlation analysis demonstrated that the changes in LPL activity before and after 2 weeks of treatment with rIFN-alpha2a showed a significant negative correlation with changes in serum triglyceride and VLDL-triglyceride and a positive correlation with changes in HDL-cholesterol and HDL2-cholesterol. These results suggest a major contribution of reduced LPL activity with regard to the lipoprotein disorders. In conclusion, rIFN-alpha2a treatment on patients with chronic hepatitis C causes marked changes in serum lipoprotein metabolism associated with decreases in LPL, HTGL, and CETP activities.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Yamadaoka, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Shinohara
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: T
authors.initials: T
authors.lastname: Arai
authors.forename: S
authors.initials: S
authors.lastname: Nozaki
authors.forename: K
authors.initials: K
authors.lastname: Kameda-Takemura
authors.forename: S
authors.initials: S
authors.lastname: Kawata
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D006023:Glycoproteins; D006493:Heparin; D006526:Hepatitis C / Q000097:blood* / Q000188:drug therapy; D006521:Hepatitis, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008049:Lipase / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D014280:Triglycerides / Q000097:blood*
chemical_list: D000998:Antiviral Agents; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008055:Lipids; D011994:Recombinant Proteins; D014280:Triglycerides; D006493:Heparin; D008049:Lipase