A pilot study of fenofibrate in hyperlipidemic pts with nonalcoholic fatty liver disease (NAFLD)

Background and aim. Obese pts with metabolic syndrome often have hypertriglyceridemia and NAFLD. Beside of its lipid-lowering effect, fenofibrate may reduce the circulating level of TNF-α, a cytokine incriminated as playing a role in the development of insulin resistance and NAFLD. We therefore conducted a 6-month pilot study to assess the efficacy of fenofibrate among NAFLD pts.

Methods. Ten obese, hyperlipidemic pts (6 men and 4 women) with biopsy-proven NAFLD were enrolled. All had a body mass index (BMI) of >30kg/m2 and displayed a pathologically elevated serum ALT level. Micronized fenofibrate (200mg once daily) was given for 6 months. The pts were asked to keep a low-calory diet and to reduce body weight. BMI, liver enzymes, fasting serum lipids, glucose, insulin, leptin, TNF-α and N-terminal propeptide of procollagen type III (PIIINP) were assessed at baseline and at 1, 3 and 6 months.

Results. At baseline, all pts displayed hyperinsulinemia and insulin resistance (reflected by the insulin resistance index HOMA-RI) and had elevated serum levels of ALT, cholesterol, triglyceride, leptin, TNF-α and PIIINP. During the treatment period, a >10% reduction in BMI was achieved by only 4 pts. As expected, fenofibrate therapy effectively reduced the serum levels of cholesterol and triglyceride, and also diminished the circulating TNF-α level. The changes in other parameters were related to the changes in body wt. A more than 10% reduction in BMI was associated with significant (p<0.05) decreases in serum insulin, HOMA-RI, leptin, ALT, AST and PIIINP, whereas these parameters in those without a significant weight loss showed no improvements.

Conclusion. Weight loss seems to be a major determinant in achieving a clinical improvement in obesity-associated NAFLD. Fenofibrate is effective in reducing pathological serum levels of lipids and TNF-α, but whether it can also exert an beneficial effect adjunctive to body wt loss on the fatty liver disease remains to be elucidated.