title: Additive improvement induced by bezafibrate in patients with primary biliary cirrhosis showing refractory response to ursodeoxycholic acid.
abstract: OBJECTIVE
  Ursodeoxycholic acid (UDCA) has been widely used in the treatment of patients with primary biliary cirrhosis (PBC). However, some patients are refractory to UDCA. The aim of this study is to clarify the additive improvement induced by bezafibrate in patients refractory to UDCA.
  
  
  METHODS
  This study was a prospective analysis of 37 consecutive PBC patients. All patients were treated first for 6 months with UDCA, and then with bezafibrate, if their alkaline phosphatase (ALP) levels did not decrease more than 40% or within the normal range after 6 months' treatment with UDCA. Clinical parameters were monitored for the subsequent 24 months.
  
  
  RESULTS
  Twenty-two patients (59%) achieved improvement of ALP levels after the treatment with UDCA. Those patients (Group A) had significantly lower levels of ALP at diagnosis than those with abnormal ALP levels after 6 months' treatment with UDCA (Group B; P = 0.020). They continued UDCA monotherapy, and maintained normal ALP levels at subsequent follow ups. However, immunoglobulin M (IgM) levels remained abnormal in eight patients, whose IgM levels at the time of diagnosis were significantly higher than those whose IgM were normalized after 6 months' treatment with UDCA (P = 0.026). Those in Group B were treated additionally with bezafibrate, and 12 patients (80%) achieved normal ALP and IgM levels within 12 months of commencement of therapy.
  
  
  CONCLUSIONS
  Higher ALP level at diagnosis is one of the predictors for UDCA failure. Combination treatment of bezafibrate in addition to UDCA may be an effective treatment for PBC patients refractory to UDCA.
authors: Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan.
authors: Yasuto
authors: Y
authors: Takeuchi
authors: Fusao
authors: F
authors: Ikeda
authors: Shin-Ichi
authors: S
authors: Fujioka
authors: Toshiyuki
authors: T
authors: Takaki
authors: Toshiya
authors: T
authors: Osawa
authors: Tetsuya
authors: T
authors: Yasunaka
authors: Yasuhiro
authors: Y
authors: Miyake
authors: Akinobu
authors: A
authors: Takaki
authors: Yoshiaki
authors: Y
authors: Iwasaki
authors: Haruhiko
authors: H
authors: Kobashi
authors: Kazuhide
authors: K
authors: Yamamoto
authors: Tatsuya
authors: T
authors: Itoshima
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D001629:Bezafibrate / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007564:Japan; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D007075:Immunoglobulin M; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase; D001629:Bezafibrate