Analysis of surgical interruption of the enterohepatic circulation as a treatment for pediatric cholestasis

Abstract

To evaluate the efficacy of non-transplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 Alagille syndrome (ALGS), 16 Familial Intrahepatic Cholestasis-1 (FIC1), 18 Bile Salt Export Pump (BSEP) disease, & 4 others with low γ-glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBD), 11 ileal exclusions (IE) and 7 gallbladder-to-colon diversion (GBC). Serum total bilirubin decreased after PEBD in FIC1 (8.1±4.0 vs. 2.9±4.1 mg/dL, preop vs. 12–24 months postop respectively, p=0.02) but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695±465 vs. 457±319 mg/dL; preop vs. 12–24 months postop respectively; p=0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182±70 vs. 260±73 IU/L, preop vs. 24 mos. p=0.03) but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS: 100% vs. 9% severe, FIC1: 64% vs. 10%; BSEP: 50% vs. 20%, preop vs. >24 mos. postop respectively, p<0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%, p=0.03. Overall, there were 15 major complications after surgery. 12 patients (3 ALGS, 3 FIC1, 6 BSEP) subsequently underwent liver transplantation. Conclusion This is the first multi-center analysis of non-transplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally although not uniformly result in improvement of pruritus and cholestasis.

Outcomes of surgical management of familial intrahepatic cholestasis 1 and bile salt export protein deficiencies

“…Several previous case series have presented data on the outcomes of surgical management of PFIC. Unfortunately, those studies have had small numbers or lacked systematic genetic diagnoses . Our data comprise the largest set of outcomes of PEBD or LTX in genetically diagnosed PFIC.…”

Can genetic testing guide the therapy of cholestatic pruritus? A case of benign recurrent intrahepatic cholestasis type 2 with severe nasobiliary drainage‐refractory itch

“…Thus, in contrast to other cholestatic conditions for which NBD was shown to be successful in attenuating refractory cholestatic itch,2 this approach might fail in particular in the subgroup of BRIC patients with severe dysfunction of ABCB11 4, 5. Consistent with our data, a case series demonstrated that pruritus in patients with ABCB11 mutations is less likely to respond completely to partial external biliary diversion compared to carriers of ATP8B1 variants 6. Hence, for patients with BRIC type 2, we recommend extracorporeal blood purification but not NBD as treatment of choice for refractory itch.…”

Bone Density in Children With Chronic Liver Disease Correlates With Growth and Cholestasis

“…In this study, we found no statistically significant differences in height‐adjusted and weight‐adjusted DXA Z scores between participants with and without biliary diversion. Variable clinical response to biliary diversion significantly complicates the interpretation of the results of these analyses . Some patients may respond to biliary diversion with normalization of bilirubin and bile acids, but low intestinal luminal bile acid levels may lead to profound fat‐soluble vitamin deficiencies.…”