Ezetimibe-Ursodiol Combination Therapy on Biomarkers of Liver Function and Sterol Balance in Subjects With NAFLD

The study will be conducted as a prospective open label trial with pre- and post-treatment
measures for all dependent variables. This trial will enroll subjects with a clinical
diagnosis of nonalcoholic fatty liver disease (NAFLD) by magnetic resonance imaging (MRI),
computed tomography (CT) or ultrasound, including those diagnosed with nonalcoholic
steatohepatitis (NASH). Subjects will be consented, blood collected and a MRI conducted on
the first visit. Patients will be advised on the proper use of the study drug and given the
first three month's supply of the study drug to take home with them. For the remaining three
months, study drug will be delivered by US mail along with return packaging for the prior
three month's study medication in order to monitor compliance. Patients will be called
routinely to encourage compliance, retention, and monitor side effects or adverse events.
After six months of study drug administration, subjects will return for a follow-up visit.
Blood will be drawn, an MRI will be obtained and a post-study questionnaire will be
administered.

Duration of Patient Enrollment: 6 months Duration of Study: 18 months

Inclusion Criteria:

- Steatosis

- ALT >1.5 times normal

- ALT/AST ratio >1.0

- Normal Kidney Function

Exclusion Criteria:

- Normal ALT within last 6 months

- Advanced fibrosis based on 1) biopsy, if available (Stage 3 or 4 NAFLD), 2) imaging,
or 3) lab (platelet count <150,000)

- Daily alcohol use above 20 g/day for women and 30 g/day for men

- Prescription use of ursodiol, ezetimibe, vitamin E, fish oils, thiazolidinediones,
insulin, sulfonylureas, HMG-CoA reductase inhibitors

- Weight loss greater than 15% in past 12 months

- Pregnant or breastfeeding

- Body Mass index greater than 50

- Largest body circumference greater than 160 cm

- Claustrophobia

- Allergy to ezetimibe or ursodiol