Experimental hepatoportoenterostomy: duct mucosal healing with hybrid biliary-intestinal epithelium forming an autoanastomosis

Permanent bile flow following hepatoportoenterostomy for biliary atresia is presumed to follow mucosal healing of the biliary tract to the intestinal epithelium, but the morphology of the anastomosis and the histology of the neo-biliary duct is not known. Experimental portoenterostomies were constructed in five normal 10-kg mini-pigs at approximately 3 months of age to study the healing of the anastomosis. The extrahepatic bile duct was resected in continuity with an en-bloc 1.5 × 0.3-cm segment of liver at the porta hepatis and biliary drainage was achieved with a Roux-en-Y jejunal limb. The bile duct remnant at the porta hepatis measured 3 mm in diameter. HIDA scan performed at 2 months showed prompt excretion of the radioisotope and normal function of the jejunal limb. Animals were killed at 2 weeks, 1 month, and 3 months following operation and the intact hepatobiliary anastomosis examined by routine histology and histochemical staining for acid and neutral mucins. At 2 weeks the biliary epithelial ducts were hyperplastic and showed evidence of cellular regeneration and cholangitis. By 1 month the biliary and intestinal epithelia were in close approximation. At 3 months the biliary-intestinal epithelium was healed, forming a funnel-like autoanastomosis with normal proximal biliary epithelium and distal intestinal epithelium. An intervening zone of hybrid biliary-intestinal epithelium showed basal crypts with characteristics of biliary epithelium, while the superficial glandular epithelium resembled intestinal villi. Mucin histochemistry of the hybrid epithelial lining revealed predominantly neutral mucins in the basal region of the mucosa characteristic of biliary mucosa. The luminal epithelium revealed a high acid mucin content, including goblet cells. A microvillus brush border, rich in neutral mucin, was also present apically on the luminal most cells. We conclude that: (1) hepatoportoenterostomy in normal mini-pigs is a reproducible model to study healing of the anastomosis; (2) a continuous, intact hepatobiliary-intestinal mucosa is present within 3 months following portoenterostomy; and (3) the neo-epithelium has a hybrid biliary-intestinal appearance. This study may have application to understanding the cause of cholangitis following portoenterostomy for biliary atresia.     

Prognosis of extrahepatic bile-duct atresia after hepatoportoenterostomy

 Clinical and histologic findings from 206 patients operated upon for extrahepatic biliary atresia (EHBA) are analyzed in order to define the prognosis of patients with EHBA. The prospective study took into consideration both initial fibrosis of the liver and the morphology of the porta hepatis (PH) at surgery. Kaplan-Meier survival estimates and statistical calculations demonstrated a relationship between long-term survival and histologic findings in the liver and porta hepatis. The efficacy of HPE is significantly influenced by the morphology of the PH and to a lesser extent by the initial liver fibrosis. Surgery should thus achieve pattern 1 morphology of the PH, but this is problematic because of the close relationship of the vascular and biliary structures in its two lateral zones. Accepted: 8 November 1999     

A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000

OBJECTIVE: To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children. STUDY DESIGN: A retrospective study was performed of all children who underwent hepatoportoenterostomy (HPE) for biliary atresia between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months was correlated with demographic and clinical parameters. RESULTS: A total of 104 children underwent HPE; 25% had congenital anomalies, and outcome was worse in those with biliary atresia splenic malformation syndrome. Diagnostic and clinical approaches varied, although specific approaches did not appear to correlate with outcome. The average age at referral was 53 days, and the average age at HPE was 61 days. At age 24 months, 58 children were alive with their native liver, 42 had undergone liver transplantation (37 alive, 5 dead), and 4 had died without undergoing transplantation. Kaplan-Meier analysis of survival without liver transplantation revealed markedly improved survival in children with total bilirubin level<2 mg/dL at 3 months after HPE (84% vs 16%; P<.0001). CONCLUSIONS: Outcome in the study centers was equivalent to that reported in other countries. Total bilirubin in early follow-up after HPE was highly predictive of outcome. Efforts to improve bile flow after HPE may lead to improved outcome in children with biliary atresia.     

Surgical modifications of the Kasai hepatoportoenterostomy minimize invasiveness without compromising short- and medium-term outcomes

Background

Biliary atresia (BA) causes progressive fibrosis and obliteration of the biliary tree, resulting in bile stasis and eventual liver dysfunction. It affects 1 in 10,000–18,000 infants, and if left untreated, universally leads to liver failure. The Kasai hepatoportoenterostomy (KPE) was developed as an effective surgical therapy for BA and can restore bile drainage into the intestine. Traditionally, the KPE procedure extra-corporealizes the liver to expose the portal plate. Here, we describe modifications to the procedure via a smaller incision in which the liver remains within the abdominal cavity and we compare the outcomes of this technique to previous institutional outcomes and to contemporary international series.

Predictors of Need for Liver Transplantation in Children Undergoing Hepatoportoenterostomy for Biliary Atresia

PurposeThe purpose of this study was to determine perioperative risk factors for need of liver transplantation following hepatoportoenterostomy.MethodsA retrospective review of patients undergoing hepatoportoenterostomy for biliary atresia at our institution from 1990 to 2016 was completed.ResultsA total of 81 patients were identified with a median age of 51 days (IQR: 33-68) at hepatoportoenterostomy and a median follow-up time of 5.7 years (IQR: 1-11.6). Ten-year overall survival was 93% (95% CI: 84-97). Thirty-six patients (44%) ultimately required transplantation at a median time from hepatoportoenterostomy of 8.9 months (IQR: 5.2-19). The 10-year transplant-free survival was 36% (95%CI: 24-49). Steroid use (N = 42) was not associated with improved 10-yr transplant-free survival (33% vs. 38%, p = 0.690). Age at hepatoportoenterostomy was not significantly associated with the need for transplantation. Multivariable logistic regression analysis demonstrated that total bilirubin > 2mg/dL (OR: 97, p < 0.001) and albumin < 3.5g/dL (OR: 24, p = 0.027) at 3 months after surgery were independent predictors of the need for transplantation, while adjusting for age, sex, prematurity, and steroid use.ConclusionOverall survival for children with biliary atresia is excellent, although most patients will ultimately require liver transplantation. Total bilirubin and albumin level at 3 months following hepatoportoenterostomy are predictive of the need for transplantation. Steroid use is not associated with improved outcomes.     

Successful revision of portoenterostomy in an infant with biliary atresia

We present a case report of a boy with biliary atresia who, after hepatoportoenterostomy performed on day 21 of life, had immediate resolution of cholestasis and remained anicteric until 3.5 months of age. He then abruptly developed acholic stools. Nuclear medicine imaging study showed no excretion. Broad-spectrum antibiotics and corticosteroids were administered but did not lead to clinical improvement; a surgical revision of the original anastomosis was undertaken at 4 months of age. At 14 months of age, the child is anicteric and growing well. In this case, successful revision of hepatoportoenterostomy averted the need for liver transplantation.