JE Heubi et al (JPGN 2017; 65: 321-6) performed a phase 3, open-label, nonrandomized trial on the efficacy and safety of oral cholic acid for patients with Zellweger Spectrum disorders (n=20) and patients with bile acid synthesis disorders (BASD) (n=50). Cholic acid dosing: 10-15 mg/kg/day. Most common BASD were 3β-HSD (n=35), and 5β-reductase (n=10). Based on this work, cholic acid is an FDA-approved agent.
- Urine bile acid metabolite scores improved (P<0.0001) with cholic acid
- Transaminases improved (AST, ALT) (P<0.0001)
- Growth parameters, improved with weight gain reaching statistical significance
- “Liver biopsies showed either stable findings or histologic improvement in all parameters except bridging fibrosis”
- No study drug-related serious adverse events were noted
- With Zellweger spectrum disorders, it is important to note that “there is no evidence that treatment with cholic acid has any impact on the extrahepatic disease.”
My take: Cholic acid helps the liver in these disorders which is particularly important for BASD. It is unclear if this improves outcomes in patients with Zellweger spectrum disorders as it has not been shown to improve extrahepatic disease.
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