Author information
1
National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD.
2
NIH Clinical Center, NIH, Bethesda, MD.
3
Massachusetts General Hospital, Boston, MA.
4
National Cancer Institute, NIH, Bethesda, MD.
Abstract
BACKGROUND & AIMS:
Nonalcoholic fatty liver disease is common in HIV, but there are no approved therapies. The aim of this open-label proof-of-concept study was to determine the effect of the mineralocorticoid receptor antagonist eplerenone on hepatic fat in HIV-infected patients with hepatic fat ≥ 5% by magnetic resonance spectroscopy.
METHODS:
Five subjects received eplerenone (25 mg daily x 1 week followed by 50 mg daily x 23 weeks). Laboratory tests were done at each visit, and the primary endpoint, change in hepatic fat content, was determined by MRI spectroscopy at baseline and week 24.
RESULTS:
The study was stopped early after observing unexpected significant increases in hepatic fat at week 24 (mean increase 13.0±7.3%, p=0.02). The increases in steatosis were accompanied by a tendency for transaminase values to decrease (ALT mean change -14 ± 16 IU/L, p=0.14). There were no consistent changes in other metabolic parameters or blood pressure. Repeat assessment of hepatic steatosis 1-2 months after stopping study medication revealed improvements in steatosis towards baseline values.
CONCLUSIONS:
The unexpected observation of increased hepatic steatosis with administration of eplerenone led to early termination of the investigation. While limited due to the small number of participants and the open-label design, the present study provides data to suggest that mineralocorticoid receptor antagonism with eplerenone may not be an effective approach to treat hepatic steatosis in HIV or the general population. Additional research is needed to determine the pathophysiologic mechanism behind these unanticipated observations.