MOEXIPRIL IN PBC AND NASH

Primary biliary cirrhosis (PBC) and nonalcoholic steatohepatitis (NASH) are chronic liver diseases of unknown etiology. Disease progression to advanced fibrosis and cirrhosis is known for both conditions. Ursodeoxycholic acid (UDCA), which is associated with increased survival from PBC without liver transplantation, remains ineffective in up to one-third of affected individuals. In contrast, no effective medical therapy for NASH has been identified to date. Both anti-oxidant and anti-fibrotic effects in various organs including the liver have been demonstrated following therapy with angiotensin-converting enzyme (ACE) inhibitors in animal models.

These observations are particularly appealing for individuals affected by NASH. Therefore, the aim of this open-label pilot investigation is to determine the safety and estimated efficacy of moexipril 15 mg daily among 20 PBC subjects with incomplete response to UDCA and 20 subjects with biopsy-proven NASH, respectively. Serum hepatic biochemistries following 12 months of treatment with moexipril will be assessed and compared to baseline values as the primary endpoint. In addition, serum for hepatic fibrosis marker assessment at baseline and following 12 months of therapy will be obtained for secondary endpoint assessment. A positive study will establish the basis for further evaluation of moexipril in the setting of a randomized, placebo-controlled trial.