Fenofibrate for patients with asymptomatic primary biliary cirrhosis.
OBJECTIVE
Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology, the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation. However, only 20-30% of patients respond fully to UDCA. Recently, lipoprotein-lowering agents have been found to be effective for PBC. The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor alpha, in patients with aPBC.


METHODS
Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA. UDCA was used along with fenofibrate during the study. The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.


RESULTS
The serum levels of alkaline phosphatase (ALP) (285+/-114.8 IU/L) and immunoglobulin M (IgM) (255.8+/-85.9 mg/dl) significantly decreased to 186.9+/-76.2 IU/L and 192.9+/-67.5 mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover, the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.


CONCLUSIONS
Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone. Although the mechanism of fenofibrate on aPBC has not yet been fully clarified, combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its anti-inflammatory effect.
Dohmen
Kazufumi
K
Department of Internal Medicine, Okabe Hospital, 1-2-1 Myojinzaka Umi-machi Kasuya-gun Fukuoka 811-2122 Japan. dohmenk@par.odn.ne.jp
Mizuta
Toshihiko
T
Nakamuta
Makoto
M
Shimohashi
Naoya
N
Ishibashi
Hiromi
H
Yamamoto
Kyosuke
K
D000328:Adult; D000368:Aged; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D017211:Treatment Failure; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
D002756:Cholagogues and Choleretics; D000960:Hypolipidemic Agents; D014580:Ursodeoxycholic Acid; D011345:Fenofibrate