Follow-up studies of long-term survivors after hepatic portoenterostomy for “noncorrectable” biliary atresia

Fourteen patients with “noncorrectable” biliary atresia are living without jaundice for more than 2 yr after hepatic portoenterostomy or its modification. Retardation of physical growth was observed in one of them, and mental retardation in another, both of which seemed irrelevant to biliary atresia. Serial tests for liver function after operation revealed early recovery of serum bilirubin, transaminase, and turbidity, and delayed improvement of alkaline phosphatase. Postoperative needle biopsy of the liver disclosed that changes in hepatic parenchyma and ductular proliferation were rapidly improved after successful operation. Improvement of fibrosis of the liver was delayed, and it was not satis-factory in patients whose preoperative changes in the liver were severe or in whom ascending cholangitis had been a frequent complication. Histologic features of hepatic cirrhosis were observed in the liver in three cases, in two of which there had been frequent episodes of cholangitis. Only one of these showed clinical signs of portal hypertension.Functional and morphologic cure can be achieved in “noncorrectable” biliary atresia by hepatic portoenterostomy or its modifications, although varying degree of hepatic fibrosis may remain according to severity of preoperative changes of the liver and postoperative complication of ascending cholangitis.     

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 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).     

Biliary atresia and the polysplenia syndrome

There is a widely held but unsubstantiated belief that in infants with biliary atresia and coexisting polysplenia syndrome, the Kasai operation fails. An equally poor prognosis has been forecast for patients with this complex treated by liver transplantation. From 1975 to 1989, 16 of 131 infants with biliary atresia (12%) had one or more components of the polysplenia syndrome: polysplenia (8), intestinal malrotation (12), preduodenal portal vein (6), absent inferior vena cava (6), aberrant hepatic artery (4), or abdominal heterotaxia (4). Although technically more demanding, 12 of the 15 polysplenia patients achieved biliary drainage after operation. (One patient had exploration only, because of parental preference). Four children are alive; two are anicteric and well at ages 5 and 8 following Kasai's operation, and two by virtue of liver transplantation done at ages 4 and 7. Three of the five patients who had liver transplantation died. Acturial survival was 44% at 5 years, not significantly different from that of the 115 nonpolysplenia patients (48%). When associated with the constellation of anomalies known as the polysplenia syndrome, biliary atresia is most likely caused by an early (at approximately the fifth week) embryonic insult. The anomalies do not preclude successful biliary reconstruction using the Kasai procedure or successful liver transplantation.     

Long-term follow-up after surgery for patients with biliary atresia

Long-term results after surgery for biliary atresia (BA) in 48 patients, ranging in age from 10 to 33 years, were examined. There were 19 males and 29 females. Twelve had correctable type BA and 36 had the noncorrectable type. Forty-one cases had no jaundice; seven did. Thirty-seven of the 48 cases were leading normal lives. Among them, six cases were enjoying their lives after overcoming sequelae, such as portal hypertension. The main morbidities of the remaining 11 long-term survivors were jaundice and portal hypertension. The growth of most cases were comparable to those of the normal Japanese population. The data of liver function tests were variable and disclosed a moderate degree of abnormality in patients mainly complicated by cholangitis. Eleven cases, including six jaundice cases, required treatment for esophageal varices and/or hypersplenism. In conclusion, the cured states of most cases without jaundice are satisfactory and these former patients have achieved a favorable quality of life. Early operations are essential to obtain good short-term results as well as good long-term results.     

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.     

Encouraging results with a modified Sawaguchi hepatoportoenterostomy for biliary atresia

Since 1974, 25 patients with biliary atresia underwent a modified Sawaguchi hepatoportoenterostomy. Seventeen of 18 patients operated on before the age of 10 weeks became free of jaundice within 2 to 4 months and had biliary intestinal continuity established by 10 months of age. Two of these patients experienced sudden diminution of bile flow with return of jaundice. Both responded to transconduit repeat resection of the portal fibrous tissue with resolution of jaundice, which allowed take-down of the biliostomy. At last follow-up 1 to 13 years postoperatively, all 17 patients were free of jaundice (94 percent of total). One patient in this group never had drainage of bile and eventually died from sepsis. In contrast, five of seven patients operated on after 10 weeks never had drainage of bile. Four of these patients died from hepatic failure and one from bleeding varices. Two patients initially had bile drainage and became anicteric, but thereafter, acute cessation of bile flow and reccurrence of jaundice occurred. Reoperation resulted in a definitive increase in bile flow in both of these patients. The modified Sawaguchi procedure is definitely preferable to liver transplantation as primary treatment in infants with biliary atresia, especially if operation is performed before the age of 10 weeks.     

Experimental study of the pathogenesis of infantile obstructive cholangiopathy and its clinical evaluation

1,4-phenylenediisothiocyanate was given to five groups of rats of different developmental stages (97 in all), and the changes in the hepatobiliary system were compared histopathologically. Three groups of rats given the drug after birth showed dilatation of the extrahepatic bile ducts with inflammation. Two groups given the drug during the fetal period or added after birth showed stenotic or atretic extrahepatic bile ducts due to thickening and fibrosis of the wall. This experimental model suggests that differences in the pathologic features of infantile obstructive cholangiopathy (biliary atresia, neonatal hepatitis, and bile duct dilatation) may be the result of various developmental stages in the pathogenic process. After the experiment, 11 cases of correctable type biliary atresia were compared to 24 cases of noncorrectable type in various aspects. It is suggested that the correctable type may have suffered pathogenic process later in the developmental stages than noncorrectable type.     

The portoenterostomy procedure for biliary atresia: a five year experience.

The portoenterostomy (Kasai) procedure in infants with biliary atresia has dramatically altered the outlook for this heretofore fatal disease. When performed on infants under three months of age, bile drainage can be achieved in a majority of the patients. Since 1972, 37 infants have been treated with this operation at our institution. Diagnostic operative cholangiography and liver biopsy are recommended if the cause of conjugated hyperbilirubinemia is presumed to be obstructive. When biliary atresia is encountered, identification of the atretic ducts with transection high in the porta hepatis is carried out. Thirty-two infants have had the portojejunostomy, while five, in whom the proximal hepatic ducts were atretic but the gall bladder and distal ducts were patent, underwent portocholecystostomy. Examination of the resected fibrous duct tissue revealed a statistically significant correlation between ductal histology and postoperative outcome. Extended bile drainage has been achieved in 26 of 37 patients. Seventeen exhibit near normal growth and development four months to five years postoperatively. Seven have died with progressive liver disease despite bile drainage. Two additional patients died, jaundice free, from unrelated causes. Despite bile drainage, progressive hepatic fibrosis has been confirmed by serial biopsies in 14 patients. This finding indicates that biliary obstruction is not the sole component in the development of biliary cirrhosis. These data suggest that extrahepatic biliary atresia is a dynamic obliterative process, which can be favorably modified in approximately 50% of the infants by early surgical treatment.     

Expression of fas ligand on bile ductule epithelium in biliary atresia--a poor prognostic factor

PURPOSE: The aim of this study was to investigate the possible role of Fas and Fas ligand system in biliary atresia. METHODS: Immunohistochemical stains of Fas and Fas ligand (FasL) and in situ hybridization of Fas ligand messenger RNA (mRNA) were performed on paraffin-embedded liver specimens of 36 biliary atresia, 6 choledochal cysts, and 14 nontumorous parts of pediatric liver tumors. Apoptosis was detected by terminal deoxynucleotidyl transferase deoxy-UTP nick end labeling (TUNEL). The grade of liver fibrosis and results of bile drainage on the patients with biliary atresia were compared with the results of FasL expression. RESULTS: Fas protein was positive on the hepatocytes and bile ductule epithelia of all the livers examined and also positive on some monocytes around the portal area in all the biliary atresia patients. FasL protein was positive on bile ductule epithelia in 10 biliary atresia patients and also positive on some monocytes in most of the biliary atresia patients. Positive signals of FasL mRNA were noted on hepatocytes in 4 biliary atresia, bile ductule epithelia in 19 biliary atresia patients, and some monocytes in most of the biliary atresia patients. Apoptotic nuclei were present among monocytes in all the biliary atresia livers but present among bile ductule epithelia only on the BA with positive FasL mRNA signals on ductule epithelium. The fibrosis grade was similar between biliary atresia with positive FasL mRNA signals and negative signals. The bile drainage was better in the biliary atresia without positive FasL mRNA signals. CONCLUSIONS: Fas ligand expression on bile ductule epithelia in biliary atresia may be induced to counterattack the infiltrating lymphocytes. Although the factors for post-Kasai bile drainage are multiple, the authors suggest Fas ligand expression on bile ductule epithelia may be a poor prognostic factor by playing a role in the continuous damage and obliteration of intrahepatic bile ducts after Kasai operation.     

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.     

A long-term follow-up of three patients with biliary atresia

This report reviews the courses of three children who underwent surgery for biliary atresia. They include a patient who is now 25 years of age who underwent correction of an "operable" biliary atresia in the neonatal period. This patient is alive and well without jaundice. The second is a 21-year-old woman who had a Kasai operation, also performed in the neonatal period; she is well and attending school but does have an elevated bilirubin and signs of liver dysfunction. The third patient, who underwent surgery performed by Dr Willis Potts in 1963 for what appeared to be "inoperable" biliary atresia, finally underwent a portal duodenostomy after her third operation. She had satisfactory bile drainage but had numerous bouts of cholangitis early in her life. She survived until she had several major episodes of gastrointestinal hemorrhage from varices and finally died after a portal systemic shunt. These three patients illustrate that prolonged survival is possible after a variety of operations performed for biliary atresia. Furthermore, even though these patients were severely jaundiced early on in life and at least two of them had complicated postoperative courses, they are perfectly normal from an intellectual standpoint and have functioned in a normal fashion.     

Biliary atresia--surgical management. A 10-year review

The surgical results in 39 children operated on for biliary atresia at Red Cross War Memorial Children's Hospital between January 1975 and January 1985 are reported. The mean age at operation was 12.8 weeks (range 6 weeks-6 months). In the first 4 years no patient had sustained bile drainage after operation. Since 1979 16 of 32 patients (50%) have had significant bile drainage. Of these, 8 are alive and have been followed up from 6 months to 6 years after operation. Five are jaundice-free and well. The other 3 are mildly jaundiced, have evidence of ongoing liver damage, and have a poor prognosis. The deaths were due to progressive liver damage with liver failure, portal hypertension, and intercurrent infection. Cholangitis after 'successful' porto-enterostomy was the main cause of poor prognosis and can be related to the age at referral and the presence of cirrhosis of the liver at the time of surgery; thus bile drainage does not necessarily equate with cure. Early referral of infants with conjugated hyperbilirubinaemia to a major centre is of paramount importance if we are to improve the prognosis.     

Kasai's operation for extrahepatic bile duct atresia: a cure or palliative treatment?

The only surgical treatment currently available for patients with extrahepatic biliary atresia is portoenterostomy or portocholecystostomy, the Kasai operation. Seventeen such patients were operated upon at the H?pital Sainte-Justine; 11 had bile excretion. Eight are still alive 12 to 60 months after operation. They have good to fair bile excretion. Twelve of the 17 patients had infectious or hemorrhagic complications and hepatic deficiency is evident in 6 of the 8 living patients. The progressive deterioration of liver function in the majority of the patients still alive raises the question of whether the Kasai procedure should be considered a curative or only a palliative procedure.     

Biliary atresia with extrahepatic biliary cysts--cholangiographic patterns influencing the prognosis

PURPOSE: Biliary atresia (BA) with extrahepatic biliary cysts (EHBC) has been recognized generally as "correctable" BA, which indicates a good prognosis. The variants of BA with EHBC according to cholangiographic findings and their outcomes were reviewed. METHODS: An EHBC was observed in 8 (20%) of 40 patients with BA who underwent operation at our institute. Intraoperative cholangiographic patterns included visualization of the intrahepatic bile ducts (type I BA with EHBC) in 6 patients and no visualization (type III BA with EHBC) in 2. Intrahepatic biliary cysts (IHBC) and EHBC were observed simultaneously in 2 patients diagnosed at older age. The follow-up periods ranged between 4 months and 20 years. RESULTS: Good bile drainage after a hepaticoenterostomy or portoenterostomy was obtained in all 6 patients with type I BA with EHBC. Two who showed IHBC on intraoperative cholangiography had complications caused by postoperative recurrent cholangitis, which led to a liver transplantation in 1. Revision after the portoenterostomy was required in 2 patients with type III BA with EHBC. One became jaundice free after revision, whereas the other died of hepatic failure without bile drainage. CONCLUSION: Intraoperative cholangiographic findings showing IHBC and type III BA are poor prognostic factors in patients with BA with EHBC.     

腹腔镜肝门肠吻合术治疗胆道闭锁的探讨(12例报告)

目的:探讨经腹腔镜辅助行肝门解剖和肝门肠吻合术治疗先天性胆道闭锁的临床效果。方法:先天性胆道闭锁患儿12例,29~87d11例,5.5个月1例。2例为肝总管闭锁(Ⅱ型),肝门部有直径1.2~2.5cm囊肿与肝内胆管相通;10例为肝门部胆管闭锁(Ⅲ型)。于脐部纵切口置入10mmTrocar,然后分别于右上腹、右中腹和左上腹置入3个5mmTrocar。术中胆道造影,确诊为胆道闭锁,暴露肝门;切除胆囊,游离切除肝门纤维块,空肠行Roux-en-Y吻合术保留肝支30~35cm,然后将肠管送回腹腔,将空肠肝支经结肠后拉至肝门下;用5-0可吸收缝线将空肠与肝门端侧连续吻合。结果:本组12例患儿中1例因肝门渗血中转开腹手术;另11例均在腹腔镜辅助下完成手术,手术时间平均为3.5h(3.1~4.6h),出血量约10ml,没有需在术中和术后输血者,全组患儿无手术后肠粘连梗阻和腹腔感染。结论:经腹腔镜行肝门肠吻合术治疗先天性胆道闭锁安全可靠,具有暴露肝门清晰、肝门纤维块分离和切除准确、对患儿打击小等优点。     

Hepatic portocholecystostomy for biliary atresia.

Four infants with biliary atresia had gross obliteration of the common hepatic duct but residual patency of the gallbladder, cystic duct and common bile duct. The patients were treated by hepatic portocholecystostomy utilizing the extant bile ducts for biliary reconstruction. Bile drainage was achieved in all four infants. There was a conspicuous absence of postoperative cholangitis. Subsequent obstruction of the distal ducts in two patients necessitated reoperation and construction of a standard biliointestinal conduit. The other two children are surviving, jaundice-free, 5 1/2 and 5 years after operation with minimal sequelae of biliary atresia. Hepatic portocholecystostomy is a feasible surgical alternative to intestinal reconstruction in patients with biliary atresia in whom the disease is limited to the proximal extrahepatic bile ducts.     

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.     

A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers.

OBJECTIVE: The authors investigated risk factors for failure after portoenterostomy for biliary atresia using univariate and multivariable methods. SUMMARY BACKGROUND DATA: Kasai's portoenterostomy has gained worldwide acceptance as the initial surgical therapy for infants with biliary atresia. Although extended survival has been achieved for many patients, factors influencing outcome have not been defined clearly. METHODS: The authors analyzed risks for failure in 266 patients treated from 1972 to 1996 by the Kaplan-Meier product limit estimate and Cox proportional hazards model. Failure was defined as death or transplant. RESULTS: Age at surgery, surgical decade, and anatomy of atretic bile ducts were identified as independent risk factors. Five-year survival was 49% and median survival was 15 years when bile drainage was achieved. Sixty-five patients had liver transplants. Mean age at transplant was 5.4 years. CONCLUSIONS: The outcome after portoenterostomy for biliary atresia is determined by age at surgery and anatomy of the atretic extrahepatic bile ducts. Liver transplant will salvage patients with failed Kasai with 10-year posttransplant survival of 71%.     

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.