INTERFERON-ALPHA INDUCES DISORDER OF LIPID-METABOLISM BY LOWERING POSTHEPARIN LIPASES AND CHOLESTERYL ESTER TRANSFER PROTEIN ACTIVITIES IN PATIENTS WITH CHRONIC HEPATITIS-C

The effect of recombinant interferon alpha 2a (rIFN-alpha(2a)) on seru m lipoprotein metabolism was assessed in 39 patients with chronic vira l hepatitis C. rIFN-alpha(2a) was administered intramuscularly at a do se of 9 x 10(6) U/d for 2 weeks and then for 3 times a week over 6 mon ths. The serum cholesterol concentration significantly decreased one m eek after rIFN-alpha(2a) administration. Approximately 67% of this dec rease was attributed to the reduction of high-density lipoprotein (HDL )-cholesterol; a decrease in HD2-cholesterol was more evident. By cont rast, serum triglyceride levels, largely derived from very-low density Lipoprotein (VLDL), significantly increased following rIFN-alpha(2a), treatment. Lipoprotein Lipase (LPL) and hepatic triglyceride lipase ( HTGL) activities in the postheparin plasma were reduced by 75.7% and b y 79.4%, respectively, and decreases in plasma cholesteryl ester trans fer protein (CETP) activity and its protein mass were also observed. H owever, prothrombin time was ameliorated by rIFN-alpha(2a), 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 ana lysis demonstrated that the changes in LPL activity before and after 2 weeks of treatment with rIFN-alpha(2a) showed a significant negative correlation with changes in serum triglyceride and VLDL-triglyceride a nd a positive correlation with changes in HDL-cholesterol and HDL2-cho lesterol. These results suggest a major contribution of reduced LPL ac tivity with regard to the lipoprotein disorders. In conclusion, rIFN-a lpha(2a) treatment on patients with chronic hepatitis C causes marked changes in serum lipoprotein metabolism associated with decreases in L PL, HTGL, and CETP activities.