Unanticipated increases in hepatic steatosis among human immunodeficiency virus patients receiving mineralocorticoid receptor antagonist eplerenone for non-alcoholic fatty liver disease

Abstract

Background & aims: Non-alcoholic fatty liver disease is common in human immunodeficiency virus, 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 human immunodeficiency virus-infected patients with hepatic fat ≥5% by magnetic resonance spectroscopy.

Methods: Five subjects received eplerenone (25 mg daily × 1 week followed by 50 mg daily × 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 = .02). The increases in steatosis were accompanied by a tendency for transaminase values to decrease (alanine aminotransferase mean change -14 ± 16 IU/L, P = .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 the administration of eplerenone led to early termination of the investigation. While limited because of the small number of participants and the open-label design, this study provides data to suggest that mineralocorticoid receptor antagonism with eplerenone may not be an effective approach to treat hepatic steatosis in human immunodeficiency virus or the general population. Additional research is needed to determine the pathophysiological mechanism behind these unanticipated observations.

Trial registration: ClinicalTrials.gov NCT02629094.

Keywords: NAFLD; HIV; MR antagonist; hepatic steatosis.

Conflict of interest statement

Conflicts of Interest: No authors have any conflicts of interest to disclose.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Figure 1.

A.) Representative liver histopathology (H&E stain) for subject 2 at baseline (left, steatosis grade 1) and week 24 on eplerenone (right, steatosis grade 3). B.) Hepatic lipid content changes by MR spectroscopy in each participant at baseline, after 24 weeks on eplerenone (paired t-test between baseline and week 24, p=0.02) and washout (1–2 months after termination of study drug - paired t-test between week 24 and washout, p=0.08).

Figure 1.

A.) Representative liver histopathology (H&E stain) for subject 2 at baseline (left, steatosis grade 1) and week 24 on eplerenone (right, steatosis grade 3). B.) Hepatic lipid content changes by MR spectroscopy in each participant at baseline, after 24 weeks on eplerenone (paired t-test between baseline and week 24, p=0.02) and washout (1–2 months after termination of study drug - paired t-test between week 24 and washout, p=0.08).