US EPA

3169796 

Journal Article 

Effectiveness of fenofibrate in comparison to bezafibrate for patients with asymptomatic primary biliary cirrhosis 

Dohmen, K; Tanaka, H; Haruno, M 

2013 

1 

Fukuoka Igaku Zasshi
ISSN: 0016-254X 

104 

10 

350-361 

English 

24511666 

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) is currently the only available pharmacological treatment for asymptomatic primary biliary cirrhosis (aPBC). Fibrates may be useful for treating aPBC patients who exhibit incomplete responses to UDCA. The mechanism of action of such fibrates involves the regulation of the expression of various kinds of lipids and proteins through the activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha ), which increases the phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids. Among these fibrates, the binding activity of fenofibrate to PPAR-alpha is stronger than that of bezafibrate. Because the majority of PBC patients exhibit a slow progression of their disease, and since the administration of UDCA plus fibrate may further delay the liver deterioration, cardiovascular risk factors, such as dyslipidemia may thus have a bigger impact on the long-term survival of PBC patients. The aim of this study was to evaluate the effects of fenofibrate in patients with aPBC who are refractory to UDCA and to simultaneously compare the effectiveness of fenofibrate with that of bezafibrate.

METHODS: This study included 14 patients with aPBC treated with fenofibrate (80 mg/day) plus UDCA (fenofibrate group) for 48 weeks and seven patients with aPBC treated with bezafibrate (400 mg/day) plus UDCA (bezafibrate group) for 48 weeks. The data for the aPBC patients in both groups were analyzed to compare the effects of fenofibrate and bezafibrate.

RESULTS: In the patients in the fenofibrate group, the serum alkaline phosphatase (ALP), gamma-glutamyl transpeptitase (gamma GTP) and serum IgM levels decreased from 522.5 +/- 181.4 to 236.8 +/- 47.8 IU/l, 197.1 +/- 98.4 to 47.2 +/- 37.5 IU/l and 337.6 +/- 160.6 to 174.5 +/- 101.1 mg/dl (p < 0.0001), respectively. In the patients in the bezafibrate group, the serum levels of ALP, gamma GTP and IgM decreased from 595.9 +/- 247.8 to 238.0 +/- 80.4 IU/l, 188.3 +/- 85.6 to 46.3 +/- 31.9 IU/l and 304.7 +/- 165.2 to 155.1 +/- 45.4 mg/dl (p < 0.0001), respectively. The serum levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL) significantly decreased in both groups and the LDL levels significantly decreased in the patients in the fenofibrate group compared to those in the bezafibrate group (p = 0.0357). In addition, the serum uric acid levels of the patients in the fenofibrate group decreased significantly (from 4.7 +/- 1.4 to 3.6 +/- 0.9 mg/dl, p < 0.0001), while those in the patients in the bezafibrate group did not change from 4.1 +/- 0.6 to 4.1 +/- 0.4 mg/dl.

CONCLUSION: Combination therapies with fenofibrate plus UDCA and bezafibrate plus UDCA induce significant biochemical improvements in patients with aPBC. However, the ability of fenofibrate to reduce the LDL and uric acid levels in aPBC patients is superior to that of bezafibrate. As a result, the use of fenofibrate might translate into a decreased risk of developing cardiovascular events and renal failure in patients with aPBC.