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The following is a summary of “Efficacy and Safety of Obeticholic Acid for Treating Hepatic Steatosis in Patients with Familial Partial Lipodystrophy,” published in the March 2025 issue of Journal of Clinical Endocrinology & Metabolism by Garg et al.

Individuals with familial partial lipodystrophy (FPLD) faced a higher risk of hepatic steatosis and its complications, with no approved treatment available.  

Researchers conducted a retrospective study to evaluate the efficacy and safety of obeticholic acid, a farnesoid X receptor agonist, in reducing hepatic steatosis in individuals with FPLD.  

They carried out a randomized, double-blind, placebo-controlled, cross-over trial at an academic referral center. The study included 10 females aged 19–60 years with Dunnigan variety of familial partial lipodystrophy (FPLD2), all carrying pathogenic heterozygous variants in the lamin A/C gene and presenting with hepatic steatosis (liver fat >5.6% by proton-density fat fraction mapping using magnetic resonance imaging). Participants received obeticholic acid 25 mg daily or a matched placebo for 4 months, separated by a 4-month washout period. The primary outcome was liver fat, while secondary outcomes included serum triglyceride levels and aminotransferase levels.  

The results showed that Obeticholic acid therapy led to a 39.6% reduction in liver fat compared to placebo (median liver fat [minimum – maximum]: 6.4% [2.4% – 18.0%] vs 10.6% [3.4% – 29.3%]; P value for treatment x month interaction = 0.03). No significant differences were observed in serum triglyceride or aminotransferase levels between obeticholic acid and placebo. Obeticholic acid was generally well tolerated, though itching occurred in 4 individuals vs 2 on placebo. Compared to placebo, obeticholic acid increased serum low-density lipoprotein cholesterol by 24% (mean 129 mg/dL vs 104 mg/dL; P = 0.0016).  

Investigators concluded that obeticholic acid safely and effectively reduced hepatic triglyceride levels in patients with FPLD2. 

Source: academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgaf173/8075157