The clinical and biochemical effectiveness and safety of cholic acid treatment for bile acid synthesis defects: a systematic review

Abstract Background Bile acid synthesis defects (BASDs) can be severely disabling involving the liver and nervous system, potentially due to elevated levels of toxic C27-bile acid intermediates. Cholic acid (CA) supplementation is hypothesized to decrease bile acid production, stimulate bile secretion and -flow, and slowing down disease progression. This systematic review assesses the clinical and biochemical effectiveness, and safety of CA in BASDs patients. Methods A systematic review of MEDLINE, Embase and clinical trial registries (ClinicalTrials.gov, ICTRP registry) using controlled MeSH- and Emtree terms. Results From 526 articles 70 publications were deemed eligible for inclusion based on title and abstract. 14 publications were included after full-text assessment comprising case reports and -series with 1–35 patients (162 patients in total) receiving 1 week to 16,5 years of CA treatment. All presented data on effectiveness, 8 studies also presented data on safety. The included population concerned patients with Zellweger spectrum disorders (n = 73), 3β-Hydroxy-Δ5-C27-steroid oxidoreductase deficiency (n = 62), cerebrotendinous xanthomatosis (n = 22), Δ4-3-oxosteroid 5β-reductase deficiency (n = 13), and α-methylacyl-CoA racemase deficiency (n = 3). Main outcomes concerned liver disease (12 studies), general physical examinations, biochemical outcomes, and safety (9 studies), and fat-soluble vitamin absorption (7 studies). The overall risk of bias score was considered to be critical (1 study), serious (4 studies), and moderate (9 studies). Major issues were missing data (10 studies), generalized data (8 studies), and no wash-out between treatments (4 studies). Conclusion More controlled studies are required as the available data is insufficient to draw definite conclusions on the effectiveness and safety of CA treatment in BASD patients. Establishing an independent international disease registry could better utilize existing real-world data.