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Research Pediatrics
University Medical Center Groningen

New key Publication: Genotype correlates with the natural history of severe bile salt export pump deficiency

19 February 2020

BACKGROUND & AIMS: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. The rarity of the disease has prevented determination of associations between genotype and either natural history or the effect of surgical biliary diversion (SBD) on long-term outcome (liver transplantation (LTx), hepatocellular carcinoma (HCC), death). We aimed to determine these associations by assembling the largest genetically defined cohort of severe BSEP deficiency patients to date.

METHODS: This multicentre, retrospective cohort study of patients with homozygous or compound heterozygous pathological ABCB11 mutations included 264 patients. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category.

RESULTS: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4y; BSEP2, 7.0y; BSEP3, 3.5y; P<.001). At age 15y, the proportion of patients with HCC was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (P=0.001). SBD was associated with significantly increased NLS (HR:0.50; 95%CI 0.27-0.94, P=.03) in BSEP1 and BSEP2. A serum bile acid (sBA) concentration below 102 μmol/L and a decrease in sBA by at least 75%, each shortly after SBD, reliably predicted NLS of at least 15 years after SBD (each P<.001).

CONCLUSIONS: The genotype of severe BSEP deficiency strongly predicts the long-term native liver survival, the risk to develop hepatocellular carcinoma, and the chance that surgical biliary diversion increases native liver survival. Serum bile acid parameters shortly after surgical biliary diversion allow the reliable identification of patients with long-term native liver survival.


  • van Wessel DBE
  • Verkade HJ
  • and many other auteurs

Journal of Hepatology :

Last modified:24 February 2020 12.20 p.m.

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