A multicenter randomized controlled dose study of ursodeoxycholic acid for chronic hepatitis C.
The effect of ursodeoxycholic acid on liver function tests and on bile acid metabolism was investigated in a multi-center randomized controlled dose study for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600 and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum liver parameters and bile acid composition in the treatment groups were compared with 17 control patients. A similarly significant decrease of serum alanine aminotransferase and serum gamma-glutamyltransferase was observed in patients administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition was determined by high-performance liquid chromatography. At entry, the relative proportions of major bile acids were similar to those observed in normal individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30 mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600 and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic acid increased in a dose-dependent manner, and it was significantly higher than in controls (p < 0.001). The hydrophobicity index of bile acids was calculated by the method of Heuman, and its correlation with serum parameter levels was analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase decreased in the cases in which hydrophobicity index significantly decreased during treatment. The same correlation was observed between the hydrophobicity index and serum gamma = glutamyltransferase in these two groups. There was no correlation between these parameters in the control and 150-mg groups. There was no correlation between reduction rate of serum alanine aminotransferase and initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)
Takano
S
S
Division of Gastroenterology and Hepatology, Kawasaki Chuo Hospital, Japan.
Ito
Y
Y
Yokosuka
O
O
Ohto
M
M
Uchiumi
K
K
Hirota
K
K
Omata
M
M
D000410:Alanine Transaminase / Q000097:blood; D001647:Bile Acids and Salts / Q000097:blood; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012313:RNA / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005723:gamma-Glutamyltransferase / Q000097:blood
D001647:Bile Acids and Salts; D012313:RNA; D014580:Ursodeoxycholic Acid; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase