Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients With Familial Partial Lipodystrophy

Context: Patients with familial partial lipodystrophy (FPLD) have increased risk of hepatic steatosis and its complications, for which there is no approved therapy. Objective This work aimed to investigate the efficacy and safety of obeticholic acid (OCA), a farnesoid X receptor agonist, for reducing hepatic steatosis in patients with FPLD. Methods: A randomized, double-blind, placebo-controlled, crossover trial was conducted at an academic referral center. Ten women (age 19-60 years) with the Dunnigan variety of FPLD (FPLD2), harboring pathogenic heterozygous variants in the lamin A/C gene and hepatic steatosis (liver fat >5.6% by proton-density fat fraction mapping by magnetic resonance imaging), were included. Intervention included OCA 25 mg daily vs matched placebo for 4 months each with a 4-month washout period in between. The primary end point variable was liver fat. Secondary end point variables were serum triglycerides (TGs) and transaminase levels. Results: All patients completed the trial. OCA therapy caused significant (39.6%) reduction in liver fat as compared to placebo (median liver fat [minimum-maximum]; 6.4% [2.4%-18.0%] vs 10.6% [3.4%-29.3%], respectively; P value for treatment x month interaction = .03). There were no significant differences in serum TGs or transaminase levels during OCA and placebo therapy. Overall, OCA was well tolerated except for itching in 4 patients compared to 2 on placebo. OCA, as compared to placebo, caused 24% increase in serum low-density lipoprotein cholesterol (mean 129 mg/dL vs 104 mg/dL, respectively; P = .0016). Conclusion: OCA is safe and effective in lowering hepatic TG levels in patients with FPLD2.