ArticleJHEP reports : innovation in hepatology2023
Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.
Article in JHEP reports : innovation in hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NAtural Course and Prognosis of PFIC and Effect of Biliary Diversion (NAPPED Study), Meta-analysis of Individual Patient Data of PFIC Before and After Surgery (Bile Diversion or Liver Transplantation)
Prospective Analysis of the Treatment of Progressive Familial Intrahepatic Cholestasis (TreatFIC)
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Pooled it
- Pooled it
- Pretreatment serum bile acid composition and predictability of subsequent response to odevixibat in patients with bile salt export pump (BSEP) deficiency.Hepatology (Baltimore, Md.) · 2026Trial
- Genetic and clinical spectrum of progressive familial intrahepatic cholestasis type 1: novel ATP8B1 variants and genotype-phenotype correlations.European journal of pediatrics · 2026Article
- Liver-directed gene therapy results in amelioration of progressive familial intrahepatic cholestasis type 2 in mice.Hepatology communications · 2026Article
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Beyond the Pump: The Evolving Molecular Landscape of Intrahepatic Cholestasis.Diagnostics (Basel, Switzerland) · 2026Review
- Pediatric Cholestatic Diseases in the Era of Ileal Bile Acid Transporter (IBAT) Inhibitors.Pediatric reports · 2026Review
- Challenges in the diagnosis and treatment of genetic cholestasis in adults.JHEP reports : innovation in hepatology · 2026Review
- Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease.Hepatology (Baltimore, Md.) · 2025Review
- Case Report: Sustained biochemical remission following early initiation of odevixibat in an infant with monoallelic ABCB11 mutation and histologically confirmed PFIC2.Frontiers in pediatrics · 2025Article
- Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis.JHEP reports : innovation in hepatology · 2024Article
- Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring.Frontiers in oncology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
73 authors at 20 institutions in 20 countries.
Funding
Abstract
Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.