A prospective randomized controlled study of long-term combination therapy using ursodeoxycholic acid and bezafibrate in patients with primary biliary cirrhosis and dyslipidemia.
OBJECTIVE
The aim of this study was to assess the long-term prognosis, efficacy, and safety of combination therapy using ursodeoxycholic acid (UDCA) and bezafibrate (BF) for primary biliary cirrhosis (PBC) patients exhibiting dyslipidemia.


METHODS
We performed a prospective, randomized, controlled, multicenter study to compare the long-term clinical results between combination therapy and UDCA monotherapy for patients refractory to UDCA monotherapy. Twenty-seven consecutive PBC patients were enrolled.


RESULTS
The median treatment period in the UDCA and UDCA+BF groups was 107 and 110 months, respectively. The serum alkaline phosphatase (ALP) levels and the Mayo risk score in the combination therapy group (mean 290 IU/l and 0.91, respectively) were significantly lower than those in the UDCA monotherapy group (mean 461 IU/l and 1.42, respectively) at 8 years after the beginning of the study (P<0.05). The serum creatinine levels in the combination therapy group (mean 0.94 mg/dl) were significantly higher than those in the UDCA monotherapy group (mean 0.56 mg/dl) at 8 years after the beginning of the study (P<0.05). However, the survival rate was not significantly different between the groups. We observed dose reduction or discontinuation of the administration of BF, but not UDCA, due to renal dysfunction or muscle pain.


CONCLUSIONS
Long-term combination therapy significantly improved the serum ALP levels and the Mayo risk score. However, the survival rate was not significantly different between the groups. In addition, long-term combination therapy significantly increased the serum creatinine levels. We should pay close attention to adverse events during this long-term combination therapy.
Department of Gastroenterology, Toho Hospital, Gunma, Japan.
Kenichi
K
Hosonuma
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Ken
K
Sato
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Yuichi
Y
Yamazaki
Department of Gastroenterology, Heisei Hidaka Clinic, Gunma, Japan.
Masatoshi
M
Yanagisawa
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Hiroaki
H
Hashizume
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Norio
N
Horiguchi
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Satoru
S
Kakizaki
Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Gunma, Japan.
Motoyasu
M
Kusano
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Gunma, Japan.
Masanobu
M
Yamada
D000469:Alkaline Phosphatase / Q000097:blood; D001629:Bezafibrate / Q000008:administration & dosage / Q000009:adverse effects; D002756:Cholagogues and Choleretics / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D008105:Liver Cirrhosis, Biliary / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D063806:Myalgia / Q000097:blood / Q000139:chemically induced; D011379:Prognosis; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced; D015996:Survival Rate; D013995:Time; D016896:Treatment Outcome; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000009:adverse effects
D002756:Cholagogues and Choleretics; D000960:Hypolipidemic Agents; D014580:Ursodeoxycholic Acid; D003404:Creatinine; D000469:Alkaline Phosphatase; D001629:Bezafibrate