In individuals receiving odevixibat for progressive familial intrahepatic cholestasis 2 (PFIC2), otherwise known as bile salt export pump (BSEP) deficiency, reductions in serum bile acid (sBA) levels correlated with improvements in key liver function tests (LFTs), according to a post hoc subgroup analysis presented at ESPGHAN 2026.
The median baseline sBA level dropped significantly by week 24 (from 235 to 163 μmol/L; p<0.0001), as did alanine aminotransferase (ALT; from 75 to 46.5 U/L; p=0.0063), aspartate aminotransferase (AST; from 75 to 57 U/L; p<0.0001), and total bilirubin (from 17.4 to 10.7 μmol/L; p=0.0002). [ESPGHAN 2026, abstract EPP234]
Of note, signs of improved liver health are a median ALT level <25 U/L in individuals aged 1 to <14 years, median AST levels <59 U/L (females) and 48 U/L (males) in individuals aged 4 to <7 years, and a median bilirubin level <21 μmol/L.
Furthermore, nearly one-quarter (22.5 percent; p=0.0007) of participants had their ALT levels shift toward the normal range, with similar trends in AST levels (15.8 percent; p=0.0346) and total bilirubin (15.5 percent; p=0.0032), following 24 weeks of odevixibat treatment.
According to the investigators, these results reflect improved biochemical markers of hepatocellular injury and cholestasis in patients with BSEP deficiency. “These changes tended to happen together, suggesting that lower sBA levels may be related to less liver injury and fewer bile flow problems.”
In 40 patients, the median platelet count decreased from baseline to week 24 (from 405 to 300.5 ×109/L) but remained within the normal range of >150 ×10⁹/L. Ninety percent of participants in this subgroup had a normal-to-high platelet count at week 24.
Rare genetic disease
PFIC is a group of rare genetic liver diseases. PFIC2 or BSEP deficiency is caused by ABCB11 mutations, which affect the BSEP protein and, subsequently, bile acid transport, leading to elevations in sBA; severe, debilitating pruritus; liver damage; and reduced native liver survival. [Liver Int 2020;40:1812-1822; Clin Res Hepatol Gastroenterol 2019;43:20-36; J Hepatol 2020;73:84-93]
The phase III PEDFIC 1 and 2 studies have shown that odevixibat conferred sustained sBA reductions and had a favourable safety profile across PFIC types. [Lancet Gastroenterol Hepatol 2022;7:830-842; JHEP Rep 2023;5:100782; AASLD 2024, abstract 5045]
However, the correlation between lower sBA levels and improvements in key LFTs has not been well studied in individuals with BSEP deficiency, the investigators noted.
As such, the researchers evaluated 63 PEDFIC 1 and 2 participants treated with odevixibat 40 or 120 µg/kg/day who had paired sBA and corresponding liver parameter data at baseline and week 24. The mean age of the participants at baseline was 4.7 years, and 49.2 percent were male.
Despite the potential limitation of the observed-data design, the results provide evidence suggesting extended native liver survival with odevixibat in sBA responders. [JPGN Rep 2025;6:S910-S911]
“These exploratory findings suggest that sBA level reductions may lead to improvements in liver biochemistry. [Hence,] sBA should be measured alongside these LFTs when assessing treatment response in patients with BSEP deficiency,” the investigators concluded.
Odevixibat, an ileal bile acid transporter inhibitor, has received FDA approval for the treatment of pruritus in individuals with PFIC aged ≥3 months and EMA approval for the treatment of PFIC in individuals aged ≥6 months. [https://www.drugs.com/newdrugs/fda-approves-bylvay-odevixibat-pruritus-patients-progressive-familial-intrahepatic-cholestasis-pfic-5599.html; https://www.ema.europa.eu/en/medicines/human/EPAR/bylvay; accessed 14 July 2026]