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Background and 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 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001).
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.
Arbor Research Collaborative for Health has been awarded a new contract to develop and operate a secure, scalable, and innovative data registry system in support of Michigan’s Obstetrics Initiative (OBI). The initiative, one of several state-wide Collaborative Quality Initiatives (CQI), aims to improve maternal and neonatal outcomes across the state through advanced data-driven insights and
Request for Information: Arbor Research is soliciting information from qualified companies to participate in the PAn-european Registry Addressing Difelikefalin In Goal-oriented Medical treatment for dialysis-related pruritus (PARADIGM) study as the regulatory partner for Ethics Committee submission and coordination in the United Kingdom. Review details here: PARADIGM RFI UK
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December 5, 2024 — Arbor Research Collaborative for Health is proud to announce an innovative collaboration with the Nephrology Associates of Northern Illinois and Indiana (NANI), the largest private nephrology practice in the United States. This partnership marks a significant milestone in advancing chronic kidney disease (CKD) research and management by leveraging NANI’s extensive patient-level