Follow-up in children with progressive familial intrahepatic cholestasis after partial external biliary diversion
Henrik Arnell1, Nikos Papadogiannakis, Helen Zemack
1Department of Pediatrics, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden. henrik.arnell@karolinska.se
Insights
Partial external biliary diversion (PEBD) can reverse liver fibrosis in children with progressive familial intrahepatic cholestasis (PFIC). Longer cholestasis duration post-PEBD correlates with fibrosis, but specific genetic mutations predict good outcomes.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Medical Genetics
Background:
- Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic liver diseases.
- Histological fibrosis is a key indicator of disease progression and liver damage in PFIC.
- Partial external biliary diversion (PEBD) is a surgical option for managing PFIC.
Purpose of the Study:
- To evaluate fibrosis reversion after PEBD in PFIC patients.
- To determine if cholestasis duration post-PEBD affects fibrosis.
- To assess the utility of genetic testing in predicting PEBD outcomes.
Main Methods:
- Retrospective analysis of children with PFIC who underwent PEBD.
- Serial histological assessment of liver specimens.
- Correlation of histological findings with cholestasis duration and genetic mutations.
Main Results:
- Significant reductions in histological cholestasis and fibrosis were observed post-PEBD.
- Longer duration of cholestatic episodes after PEBD correlated with increased fibrosis severity.
- Patients homozygous for the ABCB11 c.890A>G missense mutation showed a positive response to PEBD.
Conclusions:
- PEBD is a promising surgical treatment for noncirrhotic PFIC patients with severe ABCB11 mutations.
- PEBD may also be effective for other forms of PFIC.
- Genetic profiling aids in predicting treatment response to PEBD.
Objectives:
The aim of this study was to examine whether reversion of histological fibrosis followed partial external biliary diversion (PEBD) in patients with progressive familial intrahepatic cholestasis (PFIC); whether the duration of cholestatic episodes after PEBD influenced the evolution of fibrosis; and whether genotyping was helpful in predicting outcome of PEBD.
Patients And Methods:
Children with PFIC who underwent PEBD were investigated with genetic, biochemical, and anthropometric standard methods. Serial liver specimens were assessed histologically without knowledge of genotype and outcome. Findings were evaluated in the contexts of the total duration of cholestasis and the clinical outcome after PEBD.
Results:
From a total of 18 children with PFIC, 13 underwent PEBD, and 12 of these (among them 10 with identified ABCB11 mutations) were amenable for clinical and histological follow-up. When compared with baseline at PEBD, statistically significant reductions were found in histological cholestasis 1 and 3 years after PEBD, and in fibrosis 5 and >10 years after PEBD. The relative duration of cholestatic episodes after PEBD was positively correlated with the severity of fibrosis. Children homozygous for the missense mutation c.890A>G in ABCB11 responded well to PEBD.
Conclusions:
Biliary diversion should be regarded as the first choice of surgical treatment in noncirrhotic patients with severe ABCB11 disease and may also be efficacious in other forms of PFIC.
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