The outcome of the older (> or =100 days) infant with biliary atresia

Background

There is a detrimental effect of increasing age on the results of the Kasai portoenterostomy for biliary atresia (BA), and some centers routinely advocate primary liver transplantation for the older infant, irrespective of other criteria. This perception that such infants are indeed irretrievable was tested by retrospective analysis.

Methods

All infants who had undergone surgery for BA during the period 1980 through 2000 aged ≥100 days were reviewed. Actuarial survival was calculated using 2 end-points (death and transplantation). A retrospective review of their ultrasonography (n = 12) and preoperative liver histology (n = 22) was also undertaken to ascertain possible predictive criteria.

Results

A total of 422 infants had BA diagnosed during this period, of which 35 (8.2%) were ≥100 days at surgery (median [interquartile range], 133 [range, 108 to 180] days). Surgery included portoenterostomy (n = 26), hepaticojejunostomy (n = 7), and a resection and end-to-end anastomosis (n = 1). A laparotomy only was performed in 1. Five- and 10-year actuarial survival rate with native liver was 45% and 40%, respectively. Currently, 12 (35%) patients are alive with their native liver (8 are anicteric), 9 (28%) have undergone transplantation, and 13 have died. Although there were some survival advantages for types 1 or 2 BA and “noncirrhosis” at time of surgery, neither reached statistical significance. Individual histologic features (eg, degrees of fibrosis, giant cell transformation, bile duct destruction) in the retrospective review of available material were not discriminatory. The finding of a “heterogeneous” parenchyma on ultrasonography was predictive of poor outcome but lacked sensitivity.

Conclusions

The potential for reasonable medium-term survival is present in about one third of infants 100 days or older coming to primary corrective surgery. In the absence of accurate discrimination, the authors continue to favor this option rather than subject all to transplant simply on the basis of age.     

The Kasai portoenterostomy for biliary atresia: A review of a 27-year experience with 81 patients

Purpose

The aim of this study was to utilize clinical outcome methodology through multivariable analysis of perioperative factors to predict a successful Kasai-portoenterostomy (PE).

Methods

Records of 81 patients treated for biliary atresia (BA) were reviewed. Outcome was defined as successful if the patient was alive and had no liver transplant (LT). To predict future successful or failed PE, patients were categorized at 6 months post-PE into 2 groups: Success: direct bilirubin (DB) less than 2.0 mg/dL; Failure: DB greater than 2 mg/dL, or the patient was listed/had undergone LT, or had died. Groups were analyzed for positive or negative predictive values (PPV, NPV) at 2 and 5 years after PE. Cox regression was used to determine risk factors for PE.

Results

PE was successful in 38% and failed in 62%. PPV of future success was 96% at 2 years post-PE and 95% at 5 years post-PE, NPV of failure was 76% and 74%, respectively. Bridging liver fibrosis at the time of PE and postoperative cholangitic episodes were interdependent risk factors for a failed PE (P < .05). Other covariates showed no significant relationship for PE outcome.

Conclusion

Classifying of patients 6 months postoperatively allowed us to determine a successful PE outcome. Bridging liver fibrosis at the time of the Kasai, and the increased number of postoperative cholangitic episodes were predictive of a poor PE outcome.     

Effect of corticosteroid therapy on outcomes in biliary atresia after Kasai portoenterostomy

Purpose

This study tests the hypothesis that steroid administration improves the outcome of biliary atresia (BA) by evaluating the efficacy of postoperative steroid use on surgical outcomes in infants with BA.

Methods

Steroid use and outcomes in patients with BA were retrospectively analyzed at a tertiary pediatric hospital. Institutional review board approval was obtained.

Results

Kasai portoenterostomy (PE) was performed in 43 patients with BA treated from 1992 to 2004 (16 boys and 27 girls). Twenty-one PE patients received steroids and 22 did not. Portoenterostomy was successful in 24 patients (55.8%) with consistent serum bilirubin less than 2 mg/dL. Sixteen (66%) received postoperative steroids. A normal postoperative bilirubin was achieved at 6 months in 16 (76%) of 21 patients with steroids compared with 8 (37%) of 22 in untreated controls (Fisher's Exact test, P = .01). Of the 43 patients, 19 (44%) required liver transplantation, including 7 (37%) of 19 with steroids vs 12 (63%) of 19 without (P = .2). Twenty-eight infants developed cholangitis (fever with and without changes in hepatic function): 25 after PE and 3 after transplant. Of the 25, 12 (48%) received steroids. Seven died (16%) (range, 7 months to 4 years): 2 while awaiting transplantation (received steroids) and 5 after transplantation (1 received steroids and 4 were untreated). Survival was 86% (18/21) in patients with steroids and 82% (18/22) in those without. Transplant survival (74%) was comparable to previously reported historical controls (82%).

Conclusions

The Kasai PE continues to be the procedure of choice in infants with BA younger than 3 months. A significantly improved clearance of postoperative jaundice and lower serum bilirubin levels were observed in patients receiving steroids. However, steroids had no effect on the incidence of cholangitis, need for liver transplantation, and overall survival. A prospective study with standardized dose and length of steroid administration and longer period of follow-up is necessary to more accurately assess the effectiveness of steroids after PE.     

Effect of previous abdominal surgery and gallbladder appearance on biliary atresia outcomes

Background

Biliary atresia (BA) is typically treated by Kasai portoenterostomy (KPE), and there is a relationship between age at surgery and outcome. We hypothesize that previous abdominal surgery (PAS) for associated congenital intestinal conditions could be used to identify BA earlier, perhaps improving prognosis.

Anti-refluxing Roux-en-Y biliary drainage valve for hepatic portoenterostomy: animal experiments and clinical experience

In five dogs, we have created an anti-refluxing Roux en-Y jejunal anastomosis by removing the antimesenteric half of the seromusculature from five cm of the biliary limb proximal to the anastomosis prior to coating the gastric and biliary limbs. In the presence of increasing intraluminal pressure in the gastric and vertical limbs of the Y, the wall of the biliary limb collapses and occludes the lumen, acting as a nonrefluxing one-way valve. All three limbs of the Y were then exteriorized as enterostomies. Saline was instilled into either the gastric or distal limb with the other clamped. There was never reflux from the biliary limb despite intraluminal pressures of 200 mm Hg. We have used the anti-refluxing valve in seven infants. Three are alive at 17, 7, and 2 months postoperatively, one of which had a brief episode of fever without leukocytosis or increasing jaundice. Three have died of unresolved obstruction and one has been lost to follow-up.     

Stimulation of bile output by gastrointestinal hormones following portoenterostomy for biliary atresia

For biliary atresia portoenterostomy with externally draining conduit provides a model for quantitation of hepatic excretory function and for assessment of the physiologic response of the intrahepatic biliary system to gastrointestinal hormones in a human hepatopathologic condition. Four patients with biliary atresia were serially evaluated from 2 weeks to 43 months following total bile diverting portoenterostomy. A fifth patient with no bile flow provided a control for these studies. The pattern of Rose Bengal excretion for three patients with a satisfactory clinical course was different from that of a fourth patient with highly variable flow and persistent cholestasis. Marked volume and bicarbonate concentration increases in bile were noted 30 to 45 minutes after secretin infusion but only in the four patients with bile flow. The volume response to glucagon was more diffuse. Bilirubin and bile acid concentrations decreased in the stimulated bile flow periods and hourly outputs of these cholephils were not increased above basal. During two intervals of low bile output, secretin markedly increased bile flow in the patient with persistent cholestasis establishing the patency of the hepatoenteric anastomosis (functional obstruction) in contrast to the lack of secretin response in the control (structural obstruction).     

Reoperation in patients with biliary atresia

Twenty-seven reoperations were done on 23 patients among 100 infants with biliary atresia who have been treated at Tohoku University Hospital between 1971 and 1981. Nineteen patients had a single reoperation and 4 patients had 2 reoperations. We present the results and the role of reoperation in biliary atresia patients in our institution. Excellent bile drainage after reoperation was obtained in 13 of 15 patients with good bile flow after the initial operation. On the contrary, good bile drainage was not obtained by reoperation in 8 of 12 cases without active bile flow after the initial operation. Cessation of bile flow after successful initial operation is an absolute indication for reoperation. Aggressive reoperations under proper indications improve the surgical results in biliary atresia patients.     

Biliary atresia in England and Wales: results of centralization and new benchmark

Introduction

Biliary atresia (BA) is a rare, potentially life-threatening condition of the newborn presenting with conjugated jaundice. Typically, it is treated by an initial attempt to restore bile flow (the Kasai portoenterostomy [KP]) as soon as possible after diagnosis and, if this fails, liver transplantation. Since 1999, the treatment of BA has been centralized to 3 centers in England and Wales able to offer both treatment options. The aim of this study was to review the outcome of this policy change and provide a national benchmark.

Methods

The management of all infants born within England and Wales during the period January 1999 to December 2009 was assessed using 3 key performance indicators such as median time to KP, percentage clearance of jaundice (≤20 mol/L) post-KP, and 5- and 10-year native liver and true survival estimates. Data are quoted as median (range), and P < .05 was considered significant.

Results

A total of 443 infants had confirmed BA; and of these, most were isolated BA (n = 359), with 84 having other significant anomalies (but predominantly BA splenic malformation syndrome). Four infants died before any biliary intervention. Kasai portoenterostomy was performed in 424 infants (median age, 54 [range 7-209] days), and a primary liver transplant was performed in 15. Clearance of jaundice post-KP was achieved in 232 (55%). There were 41 deaths, including 4 (10%) without any intervention, 24 (58%) post-KP usually because of end-stage liver disease and mostly on a transplant waiting list, and 13 (32%) post-LT usually because of multiorgan failure. Overall, the 5- and 10-year native liver survival estimates were 46% (95% confidence interval [CI], 41-51) and 40% (95% CI, 34-46), respectively. The 5- and 10-year true patient survival estimates were 90% (95% CI, 88-93) and 89% (95% CI, 86-93), respectively. Outcome was worse for those with other anomalies (lower clearance of jaundice post-KP [43% vs 57%; odds ratio, 1.7; 95% CI, 1.04-2.8]; P = .02) and an increased mortality overall (eg, at 5 years, 72 [95% CI, 64-83] vs 94 [95% CI, 91-96]; χ² = 33; P < .0001).

Conclusions

National outcome measures in BA appear better than those from previously published series from comparable countries and may be attributed to centralization of surgical and medical resources.     

Innovative modification of the hepatic portoenterostomy. Our experience of treating biliary atresia

We modified conventional hepatic portoenterostomy by pulling the remnant fibrous mass caudally and placing 5 or 6 numbered and individually clamped absorbable 5-0 double-needle sutures horizontally in the liver surface of the posterior side of the remnant fibrous mass before excision and apposing the posterior and anterior margins of the hepatic portoenterostomy to resemble a flattened isosceles triangle. Our technique was used to treat 14 cases of biliary atresia. Good postoperative biliary excretion (serum total bilirubin, <2 mg/dL) was achieved in 13 (92.9%) of 14 patients.     

Optimum prednisolone usage in patients with biliary atresia postportoenterostomy

Purpose

Prednisolone is used routinely after portoenterostomy (PE) in patients with biliary atresia (BA). The authors reviewed their patients with BA post-PE to assess prednisolone protocols.

Method

Severity of fibrosis at PE (moderate or severe), age at PE (30-70 days), size of bile ductules in the fibrotic biliary remnant at the porta hepatis (>100 μm), and type of BA (uncorrectable type) were used as criteria for selecting 63 subjects from our patients with BA post-PE. Subjects were divided into 5 groups according to prednisolone dosage: group 1, no prednisolone; groups 2 to 4, single courses of intravenous prednisolone commencing on day 7 post-PE administered in decreasing dose for 3 days each as follows: group 2, 6, 4, and 2 mg; group 3, 10, 5, and 2.5 mg; group 4, 20, 15, 10, 5, and 2.5 mg; group 5, same as group 4, but stool color was used to monitor bile excretion and a course was restarted from 20 mg whenever stools began to turn pale. If necessary, single courses were repeated until serum total bilirubin was less than 2.0 mg/dL. Protocol efficacy was assessed by comparing the number of patients who became jaundice free, the period taken to become jaundice free, and the incidence of side effects related to prednisolone.

Results

The number of patients who became jaundice free in the no prednisolone group (group 1, 7/12 or 58.3%) was not significantly different from the number in the single-course groups (group 2, 8/12 or 66.6%; group 3, 10/13 or 76.9%; and group 4, 11/15 or 73.3%). The number in the stool-monitored group (group 5, 10/11 or 90.9%) was significantly greater (P < .05). The mean period taken to become jaundice free in group 1 (82.6 ± 29.1 days) was not significantly different from the single-course groups (group 2, 74.5 ± 29.3 days; group 3, 49.6 ± 19.8 days; and group 4, 48.3 ± 26.0 days). The mean period taken in the stool-monitored group (group 5, 33.3 ± 6.4 days) was significantly shorter (P < .05). The number of subjects who developed cholangitis after becoming jaundice free was not significantly different (group 1, 2/7; group 2, 2/8; group 3, 2/10; group 4, 2/11; group 5, 2/10). There were no prednisolone-related complications identified in any subject.

Conclusions

These results provide strong evidence that large-dose prednisolone therapy with stool color monitoring of bile flow has a positive impact on the time taken for patients with BA post-PE to become jaundice free and the number of patients who remain jaundice free.     

Analysis of patients with biliary atresia coming to liver transplantation

Seventy-two patients with end-stage liver disease underwent liver transplantation between March 1981 and March 1984; 35 (49%) with biliary atresia, the remainder with other disorders. This provided us with a unique opportunity to analyze factors leading to liver failure in patients who had undergone biliary drainage procedures for "uncorrectable" biliary atresia. Four patients in the biliary atresia group were excluded (no corrective procedure done, 3; "correctable" biliary atresia, 1), leaving 31 patients for study. Transplantation survival was 84% for the study group and 73% in children with other primary liver disorders. Most patients were less than 3 months old at the time of initial surgery, had minimal liver disease, and had accepted corrective operations by experienced surgeons. Despite these "favorable" factors, bile drainage was rarely achieved. All patients with continued bile drainage at the time of transplantation had repeated episodes of cholangitis, and cholangitis was associated with cessation of bile drainage in half of those with transient function. Findings at hepatectomy suggested that in four cases where bile drainage was never achieved, reexploration may have been successful. Complications included those associated with hepatic failure and portal hypertension. Of note were a high incidence of bone disease and a 43% incidence of stomal hemorrhage in patients with stomas. The short-term survival after transplantation was comparable in the biliary atresia group and the children with other disorders. This suggests that while the presence of a previous biliary drainage procedure may increase the technical difficulty of transplantation, it does not decrease survival.     

The surgical management of the unusual forms of biliary atresia

Of 50 infants undergoing laparotomy for biliary atresia during the last 9 yr at the Kobe Children's Hospital, 9 had variant forms, including (A) a gallbladder with a demonstrable connection with the intrahepatic biliary system, (B) a gallbladder with a connection with the extrahepatic biliary system and duodenum, and (C) a grossly visible subhepatic cyst. Three patients with form A underwent cholecystoduodenostomy. All these patients died of cholangitis and hepatic failure within 2 mo after operation. Two patients with form B were successfully treated by hepatic portocholecystostomy without any episodes of cholangitis. Two of the patients with form C, occurring in 1970, underwent an anastomosis between the subhepatic cyst and the duodenum. There was no bile excretion in these patients. The other two patients were treated subsequently by hepatic portoenterostomy with complete excision of the subhepatic cyst and excellent bile excretion was obtained. Infants with forms A and C should be treated by hepatic portoenterostomy instead of a direct anastomosis between the dilated portion of the extrahepatic biliary system and the alimentary tract. For patients with form B, hepatic portocholecystostomy seems to be the most suitable procedure relative to the prevention of postoperative cholangitis, which is the most serious complications in infants obtaining successful bile excretion.     

Intrahepatic cystic lesions in children with biliary atresia after Kasai procedure

BackgroundIntrahepatic cystic lesion (ICL) is a common complication for biliary atresia post-Kasai portoenterostomy. The purpose of this study was to review the cases in our hospital and assess the correlation between characteristics of ICL and clinical outcomes.MethodsWe retrospectively analyzed 787 cases of biliary atresia from 2012 to 2016. Demographics, clinical details, and postoperative outcomes were reviewed.ResultsA total of 76 patients were diagnosed with ICLs using ultrasound post-Kasai procedure, and the incidence was 9.7%. Preoperative characteristics showed no significant differences between ICL (+) and ICL (?) groups. Nearly 70% (53/76) of the patients with ICLs had a history of cholangitis. The 2-year native liver survival rate was 60.4% for those with a history of cholangitis and 87% for those without (P = 0.017). Further analysis showed that the 2-year native liver survival rate was 42.9% for those diagnosed within 3 months post-Kasai procedure, 54.2% for those diagnosed between 3 and 6 months, and 80.0% for those diagnosed beyond 6 months (P = 0.002), while no significance was observed for type (P = 0.094) or site (P = 0.406) of ICL.ConclusionPatients with ICLs had a high incidence of cholangitis. The prognosis was closely related with the history of cholangitis and the onset time of ICLs.Level of evidenceLevel II.     

Kasai portoenterostomy: 12-year experience with a novel adjuvant therapy regimen

Aim

The role of adjuvant therapy with corticosteroids and choleretics after Kasai portoenterostomy for biliary atresia (BA) remains uncertain. Experience with a novel postoperative adjuvant therapy regimen is reported.

Methods

Between 1994 and 2006, 71 infants with BA were referred. Four died from uncorrectable congenital heart disease/cardiorespiratory failure without undergoing portoenterostomy, 7 underwent primary liver transplantation (3 referred ≥19 weeks of age), and 60 underwent portoenterostomy at a median of 51 (10-104) days. Of these, 55 (92%) had type 3 BA and 6 had the BA splenic malformation syndrome. Fifty (83%) received the following adjuvant therapy beginning on postoperative day 5: oral dexamethasone 0.3 mg/kg bd for 5 days, 0.2 mg/kg bd for 5 days, and 0.1 mg/kg bd for 5 days together with oral ursodeoxycholic acid 5 mg/kg bd and phenobarbitone 5 mg/kg nocte, both of which were continued for 1 year. All infants received routine perioperative prophylactic antibiotics.

Results

Overall, 42 of 60 (70%) infants cleared their jaundice (bilirubin <20 μmol/L): 38 of 50 (76%) with the dexamethasone/ursodeoxycholic acid regimen compared with 4 of 10 (40%) not receiving this adjuvant treatment. There were 4 late deaths after portoenterostomy: 2 from associated congenital disorders and 2 after liver transplantation. Of the remaining 56 children, 39 (70%) are currently alive with their native liver at a median follow-up of 3.3 years and 17 are alive after liver transplantation. Surgical complications occurred in 3 after portoenterostomy: adhesive bowel obstruction (2) and an anastomotic leak. One infant had gastrointestinal bleeding that may have been related to dexamethasone, but this resolved with ranitidine. There were no perioperative septic complications.

Conclusion

In this series, adjuvant postoperative treatment with a short course of oral dexamethasone and longer-term ursodeoxycholic acid significantly improved the outcome after Kasai portoenterostomy.     

The intussusception antireflux valve is ineffective for preventing cholangitis in biliary atresia: a prospective study

Purpose: Cholangitis after Kasai portoenterostomy for biliary atresia (BA) strongly influences outcome, and an intussusception antireflux valve (IAV) in the Roux-en-Y limb has been advocated for the prevention of cholangitis without definitive evidence. The authors report a prospective study to evaluate the effectiveness of IAV in BA.Methods: Twenty-one consecutive patients with uncorrectable-type BA were the subjects for this study. IAV was included based on informed parental request to give 2 groups: IAV− (n = 11) and IAV+ (n = 10). The incidence/duration of episodes of cholangitis (temperature > 38°C, elevated serum bilirubin level, and leukocytosis) during the first 6 months after Kasai were statistically compared between the 2 groups (P > .05 was regarded as not significant).Results: Technical variations in surgical technique were minimized because the same surgeon supervised all procedures. There were no significant differences between the 2 groups for age and weight at the time of Kasai, mean size of bile ductules at the porta hepatis, and degree of liver cirrhosis present. Protocols for antibiotic and steroid therapy were the same for both groups. The total number of patients who had cholangitis in the IAV− group was 6 of 11 and 5 of 10 in the IAV+ group (P = NS). The total number of episodes of cholangitis was 16 in the IAV− group versus 17 in the IAV+ group (P value, not significant). The mean duration of an episode of cholangitis (number of days per number of episodes) was 12 ± 6 days in the IAV− group versus 11 ± 7 days in the IAV+ group (P value, not significant).Conclusions: IAV does not make any significant impact on the incidence or duration of cholangitis in the early post-Kasai period.     

Evidence for segmental bile drainage by hepatic portoenterostomy for biliary atresia: Cholangiographic, hepatic venographic, and histologic evaluation of the liver taken at liver transplantation

Background

The result of hepatic portoenterostomy for biliary atresia (BA) has improved, but there are some patients who experience worsened liver function in the long term after one decrease in jaundice owing to portoenterostomy. However, the cause of the liver dysfunction in the long term has not been clearly ascertained.

Methods

Five patients (5 to 28 years of age) with BA underwent liver transplantation (LT) because of liver dysfunction after successful portoenterostomy. To clarify the cause of liver dysfunction occurring in the long term, the authors performed a cholangiogram, hepatic venogram, and macroscopic/microscopic examination of the liver just after LT.

Results

(1) Macroscopically, the liver could be divided into 3 areas, the hypertrophic, atrophic, and intermediate, with findings between those of the hypertrophic and atrophic areas. (2) The divided areas clearly corresponded to the liver segments. Segment IV was the hypertrophic area in all patients, but segments VI and VII were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic and microscopic findings, the hypertrophic area had near-normal structure with bile ducts. The atrophic area had severe fibrosis and contained only a few bile ducts in the intralobular spaces of liver.

Conclusions

It seems that segmental bile drainage must have been established by hepatic portoenterostomy in some patients and that some postoperative patients might have worsened liver function in the long-term follow-up period accompanied with progression of fibrosis and impaired bile drainage. These pathologic changes occur in each liver segment.