Interferon α induces disorder of lipid metabolism by lowering postheparin lipases and cholesteryl ester transfer protein activities in patients with chronic hepatitis C

✍ Scribed by E Shinohara; S Yamashita; S Kihara; K Hirano; M Ishigami; T Arai; S Nozaki; K Kameda-Takemura; S Kawata; Y Matsuzawa

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 205 KB
• Volume: 25
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510250632

✦ Synopsis

KAWATA, AND YUJI MATSUZAWA lipid compositions in patients treated with IFN-a. [3][4][5] Recently, The effect of recombinant interferon alpha 2a (rIFNchronic viral hepatitis C has been accepted as an appropriate a 2a ) on serum lipoprotein metabolism was assessed in indication for IFN-a 2a 6 ; however, changes in lipid metabolism 39 patients with chronic viral hepatitis C. rIFN-a 2a was in such subjects have not been fully investigated. In the presadministered intramuscularly at a dose of 9 1 10 6 U/d ent study, we characterized the effects of rIFN-a 2a adminisfor 2 weeks and then for 3 times a week over 6 months.

tration on serum lipoprotein metabolism in patients with The serum cholesterol concentration significantly dechronic viral hepatitis C. Furthermore, to clarify the mechacreased one week after rIFN-a 2a administration. Approxnism by which rIFN-a 2a induces alterations of serum lipids imately 67% of this decrease was attributed to the reducand lipoproteins, we determined the activities of lipoprotein tion of high-density lipoprotein (HDL)-cholesterol; a lipase (LPL), hepatic triglyceride lipase (HTGL), and cholesdecrease in HDL 2 -cholesterol was more evident. By conteryl ester transfer protein (CETP). We demonstrate that trast, serum triglyceride levels, largely derived from rIFN-a 2a treatment causes marked changes in serum lipoprovery-low density lipoprotein (VLDL), significantly intein metabolism in association with decreases in LPL, HTGL, creased following rIFN-a 2a treatment. Lipoprotein lipase and CETP activities. (LPL) and hepatic triglyceride lipase (HTGL) activities in the postheparin plasma were reduced by 75.7% and by PATIENTS AND METHODS

79. 4%, respectively, and decreases in plasma cholesteryl

Patients. The current study included 29 patients (18 men and 11 ester transfer protein (CETP) activity and its protein women) who were seropositive for hepatitis C and who were diagmass were also observed. However, prothrombin time nosed by liver biopsy to have chronic active hepatitis. The average was ameliorated by rIFN-a 2a , suggesting that the deage of the subjects was 47 { 11 years (mean { SD). Patients histologi- crease in LPL, HTGL, and CETP activities may not be cally classified with liver cirrhosis were excluded from this study. due to a reduction in protein synthesis by the liver. Sim-Patients took neither triglyceride-and cholesterol-lowering drugs ple correlation analysis demonstrated that the changes nor drugs affecting lipid metabolism. rIFN-a 2a (Takeda Chemical in LPL activity before and after 2 weeks of treatment Industries Ltd., Osaka, Japan) was administered intramuscularly at a dose of 9 1 10 6 U/d for 2 weeks and then for 3 times a week over with rIFN-a 2a showed a significant negative correlation 6 months with informed consent. Patients were instructed to follow mL; and HDL 3 , d Å 1.125-1.210 g/mL.

Activities of LPL and HTGL in Postheparin Plasma. Plasma samples were obtained 15 minutes after the intravenous injection of heparin at a dose of 50 IU/kg of body weight.