A long-term experience with biliary atresia. Reassessment of prognostic factors.

Thirty-four infants with biliary atresia were primarily treated at our institution between 1974 and 1987. The mean age at diagnosis was 8.8 weeks. The Kasai portoenterostomy was used in 11 patients (32%) and the Sawaguchi modification in 23 infants (68%). Overall survival was 47% (16/34), with a mean follow-up of 45 months. Fifteen survivors (94%) are jaundice free, with two having undergone liver transplantation. Survival was not influenced by earlier age at operation, size of ductal remnants, or the use of an external biliary vent. Good bile flow was predictive of a favorable outcome. The incidence of cholangitis was increased in the Kasai (87%) versus the Sawaguchi groups (45%) (p less than 0.05), but 1-year survival rates were similar (55% vs 64%). The authors conclude that portoenterostomy offers a reasonable chance for success and should be the initial procedure for biliary atresia.     

Past and future of biliary atresia

BACKGROUND: With the advent of liver transplantation the outcome of children with biliary atresia (BA) has improved. Is Kasai hepatic portoenterostomy (KHPE) still a valuable option for the treatment of these patients? METHODS: From 1974 to 1998, 77 patients with biliary atresia have been treated at our institution: 50 girls and 27 boys. RESULTS: Seventy-four patients had a KHPE, and 3 patients had no KHPE because of delay in diagnosis. A total of 65 of 74 patients (88%) had undergone KHPE type I, 4 patients (5.4%) KHPE type II, 3 patients (4%) had a Suruga modification, and 2 patients (2.6%) had a portocholecystostomy. Among the 74 patients, 11 were lost to follow-up and their cases were considered failures. Seventeen of our patients are alive at long-term follow-up after KHPE. Among the 77 patients, 33 (43%) had an orthotopic liver transplantation (OLT). Successful KHPE patients underwent transplant at a mean age of 9 years, and KHPE failed at a mean age of 11 months. A total of 25 of 77 (32%) of patients are alive thanks to OLT. In the cohort, the overall survival rate for the KHPE plus OLT is 42 of 77 (55%). Mortality and morbidity rates were more frequent among the younger patients who had early OLT after KHPE failure. In our series, overall survival rate was improved when the patient had a successful KHPE (P < .001). CONCLUSIONS: Kasai hepatic portoenterostomy (KHPE) continues to be a valuable procedure in the treatment of infants with biliary atresia (BA). Successful KHPE permits transplantation at an age at which mortality and morbidity are decreased leading to a better outcome.     

Stoma-related variceal bleeding: an under-recognized complication of biliary atresia

The medical records of 52 children with biliary atresia treated by portoenterostomy and evaluated for liver transplantation were reviewed to determine the frequency of stoma variceal bleeding and the optimal strategies for prevention and treatment. Eighteen patients had had prior stoma closure, four by preperitoneal closure without takedown from the abdominal wall. Three of the four developed occult variceal bleeding from the stoma closure site. Twenty-two patients had a stoma present at evaluation. All 22 patients with stomas (100%) had at least one bleeding episode requiring transfusion. Treatment included transfusion and local pressure (9), suture ligation of the bleeding site (5), and stoma closure and/or takedown (11). Local treatment led to recurrences in eight of 14 (57%) of the cases. To reduce the high mortality in patients with biliary atresia awaiting liver transplantation, multiple variceal bleeding episodes should be prevented. To eliminate one source, stoma variceal bleeding, the stoma, whether functioning or nonfunctioning should be taken down and closed. Preperitoneal closure alone does not prevent stoma bleeding.     

Orthotopic liver transplantation for congenital biliary atresia. An 11-year, single-center experience.

OBJECTIVE: The authors analyze a single center's 11-year experience with 190 orthotopic liver transplants for congenital biliary atresia. SUMMARY BACKGROUND DATA: Hepatic portoenterostomy generally is the initial treatment for children with congenital biliary atresia. Despite multiple modifications of the hepatic portoenterostomy, two thirds of treated patients still develop recurrent cholestasis, portal hypertension, cholangitis, and cirrhosis. Therefore, the only hope of long-term survival in the majority of children with congenital biliary atresia is definitive correction with orthotopic liver transplantation. METHODS: The medical records of 190 consecutive patients undergoing orthotopic liver transplantation for congenital biliary atresia from July 1, 1984 to February 29, 1996 were reviewed. Results were analyzed via Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival was determined at 1, 2, and 5 years. The type and incidence of post-transplant complications were determined, as was the quality of long-term graft function. The median follow-up period was 3.21 years. RESULTS: The liver grafts were comprised on 155 whole-organ, 24 reduced-size, and 11 living donor organs. Median pretransplant values for recipient age, weight, and total bilirubin were 1.4 years, 12.3 kg, and 13.8 mg/dL, respectively. One hundred sixty-four patients (86%) had undergone prior hepatic portoenterostomy. Eighty-seven patients (46%) were United Network for Organ Sharing (UNOS) status 1 or 2 at the time of liver transplantation. The majority (15/24, 62%) of reduced-size graft recipients were UNOS status I at the time of transplantation. One hundred fifty-nine patients (84%) received a single graft, whereas 31 patients required 37 retransplants. The 1, 2, and 5 year actuarial patient survival rates were 83%, 80% and 78% respectively, whereas graft survival rates were 81%, 77%, and 76%, respectively. Cox multivariate regression analysis demonstrated that pretransplant total bilirubin, UNOS status, and graft type significantly predicted patient survival, whereas recipient age, weight, and previous hepatic portoenterostomy did not. Current median follow-up values for total bilirubin and aspartate aminotransferase levels in the 154 surviving patients were 0.5 mg/dL and 34 international units/L, respectively. CONCLUSION: Long-term patient survival after orthotopic liver transplantation for congenital biliary atresia is excellent and is independent of recipient age, weight, or previous hepatic portoenterostomy. Optimal results are obtained in this patient population when liver transplantation is performed before marked hyperbilirubinemia, and when possible, using a living-donor graft.     

Orthotopic liver transplantation for biliary atresia. Evolution of management

Forty-five patients with biliary atresia were accepted for orthotopic liver transplantation. Nine patients died awaiting transplantation, and 36 underwent transplantation. A portoenterostomy had been performed in 28 of these 36 patients, and its presence did not significantly affect the intraoperative blood loss (5.6 vs 4.1 blood volumes), the need for retransplantation (21% vs 12%), biliary complications (21% vs 12%), postoperative infections (36% vs 25%), or survival (82% vs 63%). These results indicate that early portoenterostomy is appropriate early therapy for biliary atresia; however, prompt referral to a liver transplant center for evaluation at the first sign of cholestasis is needed to attain optimal results for transplantation. Revisions of the portoenterostomy prior to transplantation did not improve the longevity of the procedure but did substantially increase complications and death after orthotopic liver transplantation.     

The Kasai portoenterostomy: when is it too late?

BACKGROUND/PURPOSE: Kasai portoenterostomy is recommended as the primary initial therapy for extrahepatic biliary atresia if the procedure can be performed within 10 to 12 weeks of life. The optimal management for infants with delayed presentation of biliary atresia remains controversial. The purpose of this study was to determine the success rate and outcome for patients who underwent a "late" Kasai portoenterostomy. METHODS: The authors conducted a retrospective review of the medical records of all patients with biliary atresia who underwent a Kasai portoenterostomy at their institution from 1986 to 1999 (n = 31). The authors analyzed success rates compared with age at the time of the Kasai procedure and the association with patient demographics. Surgical success was defined as achievement of a total serum bilirubin < or = 2 mg/dL. Long-term follow-up assessments included the need for liver transplantation and patient survival rate. RESULTS: The demographics of this study cohort showed a predominance of African-Americans, 19 of 31 (61%), and girls, 23 of 31 (74%). Assessment of success compared with subject age at the time of the initial portoenterostomy showed that 52% (13 of 25) had successful Kasai procedure at 0 to 75 days, compared with 83% success rate (5 of 6) at age 76 days or older (P = .359). Liver transplantation was performed in 16 of 31 patients (45%). Overall survival rate for the entire cohort is 23 of 31 (74%), whereas 12 of 31 (39%) are currently alive without a liver transplant. CONCLUSION: These data suggest that there is no contraindication to performing a Kasai portoenterostomy for biliary atresia in children over 75 days of age.     

Outcome of surgery for biliary atresia

Forty-seven infants (26 male, 21 female) with biliary atresia under- went hepatic portoenterostomy during the 16-year period 1971-87. Twenty-six patients (55%) are alive 1-17 years after surgery, with 21 (45%) being jaundice-free. For children who became jaundice-free, the mean age at surgery was 78 days (range: 34-125 days), compared with 97 days (range: 48-224 days) for those who did not. Of 39 patients operated on at less than 120 days of age, 24 (60%) are alive. All four patients operated on after 125 days of life died. Of 31 patients operated on more than 5 years ago, 12 (39%) have survived, the oldest being 17 years. Ten (32%) have normal serum bilirubin concentrations, have non-active cirrhosis on liver biopsy, have had normal growth and development, and lead normal lives. The oldest two patients suffered variceal haemorrhage in their teenage years. In our recent experience, 11 of 16 patients (69%) have had complete clearing of jaundice, lead normal lives and do not currently require assessment for liver transplantation. It is believed that early referral of children with biliary atresia to experienced surgical units for portoenterostomy will lead to long-term survival, without the need for liver transplantation in a majority of cases. Liver transplantation should be offered in infancy only after failed portoenterostomy, except for patients presenting after 120 days in whom transplantation may be considered primary therapy.     

Hepatic portoenterostomy: an assessment of its value in the treatment of biliary atresia.

A series of 12 infants undergoing hepatic portoenterostomy for incorrectable-type biliary atresia is reviewed. There has been no evidence of a sustained postoperative increase in bile excretion or improvement in biliary cirrhosis in any patient. Survival statistics for the group as a whole are poor with a mean postop survival time of 11 months and a mean total survival time of 15.3 months. These survival times are worse than that previously reported for infants with untreated biliary atresia. Our disappointing results with hepatic portoenterostomy raise doubts concerning its value in the treatment of biliary atresia.     

Biliary lipid excretion after hepatic portoenterostomy.

Since 1974, 16 consecutive infants with biliary atresia have been treated by hepatic portoenterostomy employing an exteriorized Roux-en-Y intestinal segment (Miluliez). Simultaneous, sequential analyses of bile pigments and lipids in serum and biliary drainage were performed. In the 11 patients with sustained bile drainage, progressive increases in bile volume, bilirubin and biliary lipid concentrations correlated well with their subsequent return toward normal in the serum. Despite relief of biliary obstruction, four patients have had progressive liver cirrhosis. The other 7 have residual liver damage which has been stable, or in two instances, improved, at late biopsy. The clinical and biochemical results suggest that both obstructive and parenchymal factors are operative in infants with biliary atresia.     

Manganese deposition in the globus pallidus in patients with biliary atresia

BACKGROUND: Chronic liver diseases may alter trace element contents in the brain. Among these trace elements, manganese is a ubiquitous transition metal excreted by the liver into the bile. Blood concentrations of manganese are elevated in patients with biliary atresia who have undergone hepatic portoenterostomy. The present study investigated the effects of liver transplantation on manganese deposition in the brain in such patients. METHODS: The signal intensity of the globus pallidus was calculated as an index defined as the percentile ratio of signal intensity in the globus pallidus to the subcortical frontal white-matter in sagittal T1-weighted magnetic resonance imaging planes. RESULTS: Brain magnetic resonance imaging revealed hyperintense signals in the globus pallidus due to manganese deposition in biliary atresia patients. Few neurologic symptoms related to manganese intoxication were observed. However, one 23-year-old female with biliary atresia had depressive symptoms and dyskinesia; she improved after oral administration of the dopamine precursor, L-DOPA. Manganese deposition disappeared in two patients after living-related reduced-size hepatic transplantation. CONCLUSIONS: Manganese accumulates in the brain during cholestasis associated with biliary atresia and disappears after hepatic transplantation. Manganese deposition is likely to be subclinical and reversible but may be associated with some age-related neurologic symptoms.     

Bile duct size does not predict success of portoenterostomy for biliary atresia

BACKGROUND/PURPOSE: Presence of large bile ducts (>200 microm) at the portal end-plate has been suggested to predict success after portoenterostomy. The authors reviewed their patients with biliary atresia to test the hypothesis that bile duct size in patients with successful portoenterostomy was no different than in the patients with unsuccessful portoenterostomy. METHODS: The authors reviewed the patients at their institution from 1989 to 1998 who had the diagnosis of biliary atresia (n = 38). A pathologist blinded to the results of the operation confirmed the measurements of the bile duct remnants. RESULTS: Five of the 38 patients did not have a portoenterostomy. They underwent cholangiogram and liver biopsy and were evaluated for liver transplantation. All patients who underwent surgery (n = 33) had a Roux-en-y hepaticojejunostomy. Twenty-one patients had successful surgery (64%) and 12 patients (36%) had unsuccessful surgery. The average age at operation in the successful group was 50.9 +/- 3 days and in failures, 57.9 +/- 4 days (P = .16). Duct size at the portal end-plate was not different between the successes and failures. Two of the patients in the success group had no evidence of bile ducts grossly or histologically. CONCLUSION: Children presenting early in infancy (<3 months) with biliary atresia should undergo a portoenterostomy regardless of the size of the bile ducts at the time of exploration.     

Surgical experience in children with biliary atresia treated with portoenterostomy

OBJECTIVE: Biliary atresia is the result of a fibrosing destructive inflammatory process affecting intrahepatic and extrahepatic bile ducts, which lead to cirrhosis and portal hypertension. Without surgical intervention, mortality reaches 100%. The 5-year survival rate after portoenterostomy ranges from 13% to 60%, with approximately 60% of patients requiring liver transplantation at a later stage because of insufficient bile flow. METHODS: This retrospective analysis includes 30 consecutive patients undergoing portoenterostomy for biliary atresia at our hospital. RESULTS: The 5-year actuarial survival of the 30 patients was 68%. Thirteen patients (43.3%) died 3 days to 7 years after portoenterostomy. Four patients (13.3%) underwent liver transplantation 3 to 24 months after the Kasai procedure with a 100% survival. In 65% of patients without presence of cirrhosis, the portoenterostomy was successful, compared with 35% of cases with liver cirrhosis (p = 0.0148). Liver cirrhosis with extrahepatic biliary atresia alone was present in 5 of 17 patients (29%) as compared with 8 of 12 patients (66%) with intrahepatic biliary hypoplasia in addition to extrahepatic biliary atresia and cirrhosis. CONCLUSIONS: Portoenterostomy remains the treatment of choice for patients with extrahepatic biliary atresia. However, the presence of cirrhosis portends a poorer prognosis and may be an indication for early transplantation. Cirrhosis is more commonly present in the setting of intrahepatic biliary hypoplasia and may account for the lower success rates of portoenterostomy in this group of patients. Five-year survival of the female patients was 88% as compared with 55% of the male patients.     

The therapy of biliary atresia combining the Kasai portoenterostomy with liver transplantation: a single center experience

Survival has improved dramatically for children with extrahepatic biliary atresia (EHBA), but optimal surgical management remains controversial. We have studied 28 infants born between June 1981, and April 1988, who underwent Kasai's portoenterostomy as primary surgical treatment. Those with evidence of subsequent hepatic decompensation were evaluated for liver transplantation (LT). All were cared for by surgeons who perform both the Kasai portoenterostomy and LT. Following the Kasai operation, 16 of 28 patients (57.1%) have achieved total biliary drainage, while 5 of 28 (17.9%) achieved partial drainage, and 7 of 28 (25%) achieved no drainage. Nine of 28 (32.1%) have undergone LT, 4 of whom were transplanted at greater than 2 years of age. To date, 25 of 28 (89.3%) are alive. Twenty three of 25 (92%) living are jaundice-free, 65% of whom have undergone the Kasai operation only. We project that 5 of 28 (17.8%) will come to transplantation, and 12 of 28 (43%) have no current indication that they are likely to come to transplantation. We conclude that combining Kasai's portoenterostomy with LT as needed is an effective therapy for children with EHBA, that the Kasai operation offers significant benefit by delaying LT in many, and that the long-term results of management remain to be determined.     

Comparison of drainage techniques for biliary atresia

Purpose

Traditional Kasai portoenterostomy and porto-appendiceal duodenostomy have been utilized for biliary atresia. Differences in outcome between patients who underwent either Kasai portoenterostomy or porto-appendiceal duodenostomy were compared.

Methods

A review of all children who underwent a drainage procedure for biliary atresia from 1986 to 2000 (n = 30) was performed. Age at drainage procedure, subsequent liver transplantation, and outcomes were evaluated. Outcome variables included success rates (total bilirubin < 2.0 mg/dL) and survival rate. Statistical analysis was done with χ² and Student’s t test.

Results

Long-term follow-up was available on 28 of 30 patients. Age at biliary drainage was insignificant. Success rates between porto-appendiceal duodenostomy (31%) and Kasai portoenterostomy (82%) were statistically significant. Survival rate for patients who underwent a Kasai portoenterostomy was 10 of 11 patients. Survival rate for patients who underwent porto-appendiceal duodenostomy was 14 of 16 patients. Overall survival rate was comparable between porto-appendiceal duodenostomy (88%) and Kasai portoenterostomy (91%).

Conclusions

Although overall survival rate was comparable, patients who underwent porto-appendiceal duodenostomy were less successful in alleviating hyperbilirubinemia compared with Kasai portoenterostomy. This is shown further by the greater incidence of subsequent liver transplantation in infants with prior porto-appendiceal duodenostomy. Although the appendix may serve as an alternative biliary conduit, traditional Kasai portoenterostomy appears to achieve better biliary drainage.     

Orthotopic transplantation of the liver in children with biliary atresia and polysplenia syndrome: report of two cases

Biliary atresia is the most common indication for liver transplantation in infants and children, despite the advent of the Kasai operation. Coexisting anomalies, which have been noted in up to 27% of patients with biliary atresia, may form an association known as the "polysplenia syndrome," which includes (1) polysplenia, (2) midgut malrotation, (3) preduodenal portal vein, (4) absent prerenal inferior vena cava with azygos continuation, (5) situs inversus, (6) symmetric liver, (7) hepatic arterial anomalies, and (8) bilobed right lung with hyparterial bronchus. Two of 31 patients undergoing orthotopic liver transplantation for biliary atresia following failed portoenterostomy over the past 11 years manifested the polysplenia syndrome with absent prerenal inferior vena cava. The clinical course of these patients, constellation of anomalies, and technical adjustments required to perform liver transplantation are described. We do not believe that these complex congenital anomalies preclude liver transplantation.     

Liver transplantation for biliary atresia

Biliary atresia is the most common indication for liver transplantation (OLT) in children. We present our experience with OLT as a treatment for end-stage liver disease in children with biliary atresia. We performed a retrospective review of 20 biliary atresia patients (11 male, 9 female patients; mean age, 21.4 months; range, 6 to 84 months) who had undergone OLT. Mean preoperative weight and height were 10.1 +/- 5.8 kg and 72.5 cm, respectively. Thirteen recipients were younger than 1 year of age, and 15 weighed less than 10 kg at the time of OLT. Fourteen recipients had undergone a Kasai operation prior to the OLT. The mean serum total bilirubin level was 22.56 mg/dL before OLT. Eighteen left lateral segment grafts and two whole grafts were transplanted. The mean recipient operative time was 9.25 hours. The mean recipient intraoperative blood loss was 1.81 U. Two hepatic arterial thromboses and one biliary leak occurred soon after surgery. Portal vein stenoses developed in two recipients at 10 and 12 months after OLT; both were treated with balloon dilatation. Two biliary stenoses, which occurred at 10 months and 3.5 years after surgery, were treated with balloon dilatation. Two recipients died at 2 and 12 days after OLT because of respiratory distress syndrome and sepsis, respectively. The remaining 18 (90%) recipients are alive with good graft function. The overall rejection rate was 31.25%. OLT is an effective treatment for children with biliary atresia and a failed Kasai procedure. Living related liver grafts represented an excellent organ supply for these patients.     

The future role of hepatic portoenterostomy as treatment of biliary atresia.

According to our recent study, 38 of 93 patients (40.9%) who underwent portoenterostomy at Juntendo University Hospital between 1977 and 1986 survived for more than 5 years. In order to learn the future improvement of the prognosis of biliary atresia patients who undergo portoenterostomy, we investigated the relationship between the prognosis of biliary atresia patients and the age and the histological changes of liver at the time of surgery. Twenty-seven of 30 patients (90%) who survived for more than 5 years with no jaundice and no findings of liver cirrhosis had a mild degree of liver fibrosis (F1 or F2) and a mild degree of degeneration of intrahepatic bile ducts (B1 or B2) at the time of surgery, in spite of the difference of size of intrahepatic bile ducts at the porta hepatis. On the other hand, all 8 patients who showed severe liver fibrosis (F3) and severe degeneration of intrahepatic bile ducts (B3) did not survive for more than 5 years. Accordingly, we can expect promising prognoses in patients who undergo refined portoenterostomy procedures and receive proper postoperative treatment before they have severe histological changes of liver. The portoenterostomy will still play an important role as treatment of biliary atresia in the future.     

First orthotopic liver transplantation in patient with biliary atresia and situs inversus in spain

Biliary atresia is the most common indication for liver transplantation in the pediatric age group. The Kasai portoenterostomy has become established as the primary treatment for biliary atresia. If portoenterostomy fails, death before 2 years of age is likely without liver transplantation. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, which forms a constellation of defects of body symmetry, splenic development and vascular anomalies, including situs inversus, polysplenia and others. The situs inversus was formerly considered an absolute contraindication for liver transplantation. Recently however, several case reports have been published suggesting that neither situs inversus nor this particular subset of vascular abnormalities should be considered contraindications to liver transplantation. We present one case of liver transplantation performed in patient with biliary atresia, situs inversus and polysplenia. This is the first report described in Spain for a liver transplant in a child with biliary atresia plus situs inversus.     

The surgery of biliary atresia

One hundred thirty-one consecutive infants with biliary atresia were operated on during the 15-year period between 1973 and 1988. Six patients did not have biliary reconstruction because of advanced cirrhosis or transplant preference. The other 125 infants had excision of all nonpatent extrahepatic bile ducts; biliary drainage was provided by a gallbladder-common bile duct conduit in 14 patients and by a Roux-en-Y portoenterostomy in 111 infants (including the seven patients with correctable biliary atresia). The bilioenteric conduit was temporarily exteriorized and, for the past 2 years, a conduit intussusception valve was incorporated. Immediate postsurgical bile drainage was achieved in 103 infants (82%). Reoperation during the first 6 postoperative weeks restored bile flow in 14 of 18 infants who had shut down. Seventy-two patients (57%) had sustained (more than 1 year) relief of biliary obstruction. Postoperative morbidity was substantial. The six children not having corrective surgery died within 19 months. Three patients were lost to follow-up. Sixty-eight patients having Kasai's operation died, 55 from complications of liver disease, 1 from a coexisting malformation, and 12 after liver transplantation. Fifty-seven patients are alive, 13 by virtue of liver replacement, 9 with mild-to-moderate hepatic sequelae, and 35 (28%) with normal to near-normal liver function. Although none is considered "cured," the 35 children are anicteric, have normal growth and development, and participate in full school activities (including contact sports). Average follow-up is 85.8 months (range 1 to 15 years).     

Histologic oddities at the porta hepatis in biliary atresia

Purpose

Highly unusual histologic findings at the porta hepatis in 3 infants who underwent Kasai portoenterostomy for biliary atresia are reported.

Methods

Portoenterostomy was performed using a standard operative technique. Serial transverse sections of the excised portal plate were examined by light microscopy along with sections from the distal extrahepatic biliary remnants, gallbladder, and liver biopsy.

Results

Of 61 consecutive infants who underwent Kasai portoenterostomy for biliary atresia, 3 were found to have highly unusual histologic features at the porta hepatis. All had type 3 biliary atresia. Two had hilar biliary ductules lined in part by squamous epithelium, and the third had a focus of mature hyaline cartilage surrounded by perichondrium adjacent to biliary ductules. In each case, these unusual histologic features were localized to the porta hepatis in the region of the transected portal plate.

Conclusions

The presence of hyaline cartilage at the portal plate is likely to be an expression of defective morphogenesis, thus supporting the concept of disordered embryogenesis in the etiology of biliary atresia. Squamous epithelium within biliary ductules might also reflect a similar mechanism but could alternatively be an unusual metaplastic response to inflammation at this site.