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

To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 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 (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, 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, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; 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%, preoperatively vs. >24 months postoperatively, 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. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation. CONCLUSION: This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).

Newborn screening for biliary atresia in the United States.

Despite advances in our understanding of the pathogenesis of biliary atresia (BA), BA remains the most common cause of end-stage liver disease in children and the leading indication for pediatric liver transplantation. Age at time of Kasai portoenterostomy (KPE), performed to provide bile drainage, strongly correlates with transplant-free survival, mostly due to progression of intrahepatic fibrosis to cirrhosis. Unfortunately, challenges remain in recognizing that a jaundiced infant may have BA. To better diagnose infants with BA at an earlier age, population-based screening programs in countries such as Taiwan, Japan, and China have utilized stool color cards. Early results have been promising demonstrating earlier diagnosis, earlier KPE, and, hence, improved outcomes. Cost-effectiveness studies focused on stool color card screening in North America where the incidence of BA is much lower also project improved transplant-free survival rate with a savings in terms of healthcare expenditure. There is also evidence that postnatal serum bilirubin levels may also be effective as a screening tool given that all infants with BA exhibit hyperbilirubinemia at birth. The American Academy of Pediatrics (AAP) recently advocated studying the implementation of newborn screening for BA in the United States. Further efforts and analyses within the United States are ongoing, but current evidence is supportive of screening for BA even in low incidence countries.