A pilot trial of high-dose ursodeoxycholic acid in nonalcoholic steatohepatitis.
OBJECTIVE
Standard dose (13-15 mg/kg) ursodeoxycholic acid (UCDA) is ineffective in the treatment of nonalcoholic steatohepatitis (NASH), however, its immunomodulatory and hepatoprotective effects are dose related. Therefore, we examined the impact of high-dose (28-32 mg/kg) UCDA on aminotransaminase levels in a pilot study of patients with NASH.


METHODS
Twelve patients with biopsy-proven NASH and elevated aminotransaminases were prescribed high-dose UCDA for 6 months. Liver function tests were monitored during and after treatment with the study endpoint defined as normalization of aminotransaminase levels.


RESULTS
Normalization of aspartate aminotransaminase (AST) levels was observed in two (17%) patients, however, no patient normalized their alanine aminotransaminase (ALT) levels. A trend towards a minor reduction in median (range) ALT values from baseline to end of treatment was noted [124 (66-229) vs. 101 (53-188) IU/l, p = 0.07], whereas AST levels remained unchanged [85 (40-132) vs. 98 (28-147) IU/l, p = 0.83]. One patient discontinued treatment prematurely due to diarrhea. No significant change in fasting glucose, triglyceride or HDL cholesterol was observed with treatment. No significant change in ALT or AST levels was observed in the 6-month period after cessation of treatment.


CONCLUSIONS
High-dose UCDA does not normalize aminotransaminase levels in patients with NASH. Other inexpensive well-tolerated agents for the treatment of NASH need to be investigated.
Leon A
LA
Adams
Paul
P
Angulo
Jan
J
Petz
Jill
J
Keach
Keith D
KD
Lindor