Table 3.
A Summary of Studies Evaluating Bile Acids in Pediatric Cholestatic Disorders.
| Author | Sample size and therapy | Inclusion criteria, stage of fibrosis | Type of study, drug dose | Duration of therapy | Outcome |
|---|---|---|---|---|---|
| Baumann et al, Clinics and research in hepatology and gastroenterology, 2021129 | N = 24; 10–200 μg/kg oral odevixibat daily | PFIC (n = 13), Alagille syndrome (n = 6), biliary atresia (n = 3), other causes of intrahepatic cholestasis (n = 2) | Open-label, multicenter Phase 2 study | 4 weeks | ↓ serum BA compared with baseline levels (reductions up to 98%). Improved pruritus (three scales) and sleep. No serious ADEs |
| van Wessel et al. Hepatology, 2021130 | N = 130, surgical biliary diversion | Compound heterozygous- or homozygous-predicted pathogenic ATP8B1 variants (PFIC) | Multicenter, combined retrospective, and prospective study | – | Postsurgical diversion serum BA concentrations <65 μmol/L show a trend of association (P = 0.05) with improved NLS |
| Deneau et al. The Journal of pediatrics 2019131 | N = 263; GGT normalization after 12 months (n = 122); non-norm (n = 141) | PSC with baseline serum GGT levels >50 IU/L | Retrospectively reviewed patient records | 12 months | ↓ in AST, ALT, ALP; 5-year survival with native liver better in the GGT normalization group |
| Black et al. Hepatology communications 2019132 | N = 22; Null (n = 7), ALT, and GGT persistently ≤29 IU/L; Flare (n = 8), ALT, and/or GGT >100 IU/L; indeterminant (n = 7), ALT, and/or GGT >29 IU/L and <100 IU/L; during UDCA dose reduction and withdrawal |
PSC | Treatment withdrawal and reintroduction study | 24 weeks; multiple phases | All flares responded to UDCA reinstitution |
| Shneider et al. Hepatology communications, 2018133 | N = 37; Maralixibat 70, 140, or 280 μg/kg/day (n = 25) or placebo (n = 12) once daily | Children with Alagille syndrome | Randomized double-blind, placebo-controlled Phase 2b trial | 13 weeks | Significant ↓ in ItchRO with 70 and 140 μg/kg/day but not 280 μg/kg/day (Maralixibat). A 1-point ↓ in pruritus in the drug-treated group. No serious ADEs |
| Dinler et al. The Turkish journal of pediatrics 1999134 | N = 24; Follow-up biopsy N = 17; UDCA 15–20 mg/kg/day |
Intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) | Uncontrolled trial | 12 months | Complete resolution of pruritus in 16.7% with some improvement in all. Significant ↓ in AST, ALT, ALP, bilirubin, GGT |
| Dinler et al. Pediatrics international 1999135 | Nine children aged between 1.5- and 9-years UDCA orally at doses of 15–20 mg/kg per day | PFIC1 (Byler disease) | Uncontrolled trial | 12 months | Pruritus resolved completely in 22.2%, ↓ in 22.2% and unchanged in 55.6%. Significant ↓ AST. ↔ GGT, cholesterol, and serum TBAs. Cholestatic changes on histology resolved in 22.2%, ↓ in 33.3%, and ↔ in 22.2%. No ADEs |
| Narkewicz et al. Journal of pediatric gastroenterology and nutrition 199877 | N = 13; CF (n = 6), Alagille syndrome (n = 4), PFIC (n = 2), and nonsyndromic intrahepatic bile duct paucity (n = 1). UDCA 15–20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months |
Intrahepatic cholestatic liver disease for at least 6 months in a child >5 years old not previously on UDCA therapy | Open-label, crossover study | 2.5 years | Majority (75%) had biochemical or symptomatic relapse on UDCA discontinuation, requiring retreatment with UDCA. No sustained improvements in the biochemical indices at 24 months |
| Jacquemin et al. Hepatology, 199772 | N = 39; UDCA orally (20–30 mg/kg/day), Group 1 (n = 26) normal GGT, and group 2 (n = 13) high GGT. The dose of UDCA corresponded to a total daily dose of 28 ± 7 mg/kg of body weight in group 1 and 26 ± 7 mg/kg of body weight |
Children with PFIC | Uncontrolled trial | Group 1: 26 ± 16 months Group 2: 49 ± 11 months | ↓ in AST, ALT, serum TBAs in both groups and GGT only in group 2 Hepatomegaly and pruritus significantly ↓ in both groups. After therapy cessation: ↑ transaminases. No serious ADEs |
| Kardorff et al. Klinische Padiatrie, 199673 | N = 20; (biliary atresia n = 10, Alagille's syndrome n = 4, intrahepatic biliary hypoplasia n = 3, Byler disease/PFIC1 n = 3). UDCA 13 (7–26) mg/kg/d in two divided doses |
Inherited disorders of cholestasis treated for at least 6 months | Retrospective analysis | – | Significant ↓ GGT and GLDH, AST, and ALT ↔ Bilirubin and albumin. First 12 months: pruritus improved (20% only) |
BA, bile acid; ADE, adverse drug event; ItchRO, itch reported outcome; UDCA, ursodeoxycholic acid; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, γ-glutamyltransferase; GLDH, glutamate dehydrogenase; PFIC, progressive familial intrahepatic cholestasis; NLS, native liver survival; TBA, total bile acids.