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. 2023 Mar 30;7(4):e0092.
doi: 10.1097/HC9.0000000000000092. eCollection 2023 Apr 1.

Native liver survival in bile salt export pump deficiency: results of a retrospective cohort study

Eva-Doreen Pfister  1 , Veronika K Jaeger  2 , André Karch  2 , Denys Shay  2   3 , Nagoud Schukfeh  4 , Johanna Ohlendorf  1 , Norman Junge  1 , Imeke Goldschmidt  1 , Amelie Stalke  1   5 , Verena Keitel-Anselmino  6   7 , Ulrich Baumann  1   8
Affiliations

Native liver survival in bile salt export pump deficiency: results of a retrospective cohort study

Eva-Doreen Pfister et al. Hepatol Commun. .

Abstract

Background: Bile salt export pump (ABCB11) deficiency [Progressive familial intrahepatic cholestasis (PFIC2)] is the most common genetic cause of PFIC and is associated with pruritus and progressive liver disease. Surgical biliary diversion or pharmacological [ileal bile acid transporter inhibitor (IBATi)] approaches can be used to block the recirculation of bile acids to the liver. There is a paucity of detailed data on the natural history and, in particular, the longitudinal evolution of bile acid levels to predict treatment response. Cross-sectional data from large international consortia suggested a maximum cutoff value of bile acids after the intervention to predict a successful outcome.

Methods: This retrospective, single-center, cohort study included all patients with confirmed biallelic pathogenic ABCB11 genotype PFIC2 treated at our institution with ≥2 years follow-up. The outcomes of interventions and predictors of long-term health were analyzed.

Results: Forty-eight cases were identified with PFIC2. Eighteen received partial external biliary diversion (PEBD) surgery, and 22 patients underwent liver transplantation. Two patients developed HCC and 2 died. Improved survival with native liver was closely associated with genotype, complete normalization of serum bile acids following PEBD, and alleviation of pruritus. Persistence of mild-to-moderate elevation of bile acids or a secondary rise following normalization was associated with liver disease progression and led to transplantation, suggesting that any prolonged elevation of bile acids worsens the chance of native liver survival. Higher-grade fibrosis at the time of PEBD was not associated with reduced long-term native liver survival. Patients with PFIC2 benefit from PEBD even at a stage of advanced fibrosis.

Conclusion: Serum bile acid levels are an early predictor of treatment response and might serve as the gold standard in the evaluation of novel therapies including IBATi.

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Conflict of interest statement

Ulrich Baumann is a consultant for, advises for, is on the speakers’ bureau, and received grants from Mirum Pharmaceuticals and Albireo Pharmaceuticals. He consults for, advises, and received grants from Alexion. He consults for and advises Vivet Pharma and Nestle. Eva-Doreen Pfister is on the speakers’ bureau and received grants from Mirum Pharma. She advises, is on the speakers’ bureau, and received grants from Albireo and Alexion Pharma. She advises Univar Pharma. Amelie Stalke received grants from BMBF. Verena Keitel-Anselmino advises Astra Zeneca; she is on the speakers’ bureau of Albireo, Falk, Abbvie, Gilead, CSL Behring, and Sanofi. The remaining authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Kaplan-Meier plot of native liver survival of patients and Ishak score at the time of PEBD. Abbreviations: PEBD, partial external biliary diversion.
FIGURE 2
FIGURE 2
Kaplan-Meier plot of the native liver survival of patients with missense versus nonfunctional variants in ABCB11.
FIGURE 3
FIGURE 3
Individual longitudinal bile acid levels (µmol/l) in PEBD patients without LTx (n = 9). *n = 2 Relapse due to stoma-associated complication, resolved after stoma revision surgery. Patient ID = number in the top left of each panel. Dotted line = PEBD. Abbreviations: LTx, liver transplantation; PEBD, partial external biliary diversion.
FIGURE 4
FIGURE 4
Individual longitudinal bile acid levels (µmol/l) in PEBD patients with LTx (n = 9). *n = 2 long-term responders with decompensation due to noncompliance 14 respectively 21 years after PEBD. Dotted line = PEBD. Patient ID = number in the top left of each panel. Abbreviations: LTx, liver transplantation; PEBD, partial external biliary diversion.
FIGURE 5
FIGURE 5
Cohort overview. Abbreviations: BSEP, bile salt export pump deficiency; LTx, liver transplantation; PEBD, partial external biliary diversion.
See this image and copyright information in PMC

References

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