Treatment Of Biliary Atresia Research Articles

Atrésie des voies biliaires : une urgence diagnostique et thérapeutique

Every neonatal jaundice lasting more than 2 weeks needs urgent investigations, beginning with examination of stools colour, and blood tests with total and conjugated serum bilirubin. If neonatal cholestasis (NC) is confirmed, vitamin K should be immediately injected, and the child should be referred to a specialised centre for investigations and treatment. Biliary atresia (BA) is the first cause of NC. Its diagnosis is urgent, since the chance of success of the conservative surgical treatment (Kasai operation or variants) decreases rapidly as the age at surgery increases. Normal ultrasound scans cannot rule out BA. After prompt work-up looking for the main other causes of NC, BA can often be strongly suspected before surgery, and is confirmed by operative findings and cholangiogram if needed. In case of failure to restore the biliary drainage, biliary cirrhosis progresses and leads to liver transplantation, generally in the first years of life. Currently, more than 90 % of children with BA can live, with a close to normal quality of life for most of them. Early diagnosis and treatment of BA contribute to decrease the needs for liver transplantation in infancy and childhood.

Hepatic Portocholecystostomy (HPC) is Ineffective in the Treatment of Biliary Atresia with Patent Distal Extrahepatic Bile Ducts

ABSTRACTObjective: To compare the effects of hepatic portocholecystostomy (HPC) and the Kasai procedure for the treatment of biliary atresia with patent distal extrahepatic bile ducts (BA with PDEBD) and to determine the reasons for the differences between the two procedures. Methods: The case files of 29 patients with BA with PDEBD were reviewed retrospectively. Twenty patients were treated with the Kasai procedure, and 9 patients were treated with HPC. We compared the rate of jaundice clearance, the incidence of cholangitis, survival rates of the native liver, and clinical outcomes between the two groups. Healthy gallbladders were collected for comparison with the pathologic specimens. Van-Gieson stains were used to detect the severity of fibrosis, and immunohistochemical methods were used to investigate the expression of CD68. Image analysis technology was used to quantitatively analyze the results. Results: Six months after surgery, the rate of jaundice clearance was 85% in the Kasai group and 33.3% in the HPC group (p = .01). The three-year survival rates of the two groups were 73.68% and 33.3%, respectively (p = .009). According to the criteria that define a cured state, there was an obvious difference between the two groups (p = .0056). The fibrosis and CD68+ cell infiltration were more severe in the gallbladders of patients with BA than in controls (p < .05). Conclusion: HPC was inferior to the Kasai procedure in the treatment of BA with PDEBD. This result may be due to the progressive inflammation and fibrosis of the extrahepatic bile duct.

Posterior reversible encephalopathy syndrome after liver transplantation in children: A rare complication related to calcineurin inhibitor effects

PRES is a neuroclinical and radiological syndrome that results from treatment with calcineurin inhibitor immunosuppressives. Severe hypertension is commonly present, but some patients may be normotensive. We report herein two children who received liver transplants, as treatment for biliary atresia in the first case and for Alagille's syndrome in the second one. In the early postoperative, both patients presented hypertension and seizures. In both cases, the image findings suggested the diagnosis of PRES. The CT scan showed alterations in the posterior area of the brain, and brain MRI demonstrated parietal and occipital areas of high signal intensity. Both children were treated by switching the immunosuppressive regimen and controlling arterial blood pressure. They displayed full recuperation without any neurologic sequelae. Probably, the pathophysiology of PRES results from sparse sympathetic innervation of the vertebrobasilar circulation, which is responsible for supplying blood to the posterior areas of the brain. In conclusion, all liver-transplanted children who present with neurological symptoms PRES should be considered in the differential diagnosis, although this is a rare complication. As treatment, we recommend rigorous control of arterial blood pressure and switching the immunosuppressive regimen.

Biliary Atresia in Canada: The Effect of Centre Caseload Experience on Outcome

: Biliary atresia (BA) is a leading cause of end-stage paediatric liver disease. Standard BA treatment is sequential surgery with an initial Kasai procedure (KP) followed by liver transplant (LT) for patients who progress to liver failure. A key determinant for the post-KP patient survival with their native liver is patient age at KP (older age, poorer outcome). Recently, European studies have reported that caseload experience influences prognosis with centres managing <5 cases per year (UK) or <2 cases per year (France) having worse survival. Our study investigates the effect of caseload experience on outcomes of Canadian patients with BA. : A national database of cases with BA, born from 1992 to 2002, was examined. Patients were grouped according to treatment centre size (A: on average <1 case per year; B: 1 to 3 cases per year; and C: >3 cases per year). Overall patient, post-KP native liver, and LT survivals were compared between centres. Outcome parameters were reevaluated for patients grouped by the largest Canadian centre (>5 cases per year) and all other centres (<5 cases per year). : Two-hundred thirty patients were identified among 6 group A, 4 group B, and 2 group C centres. The overall median age at KP was 64 days. There were no significant differences in patient, post-KP native liver, or LT survivals between the sized centres and even the largest centre, with the overall 4-year post-KP native liver survival being 39%. : Caseload experience does not importantly affect the outcomes for Canadian children with BA. Although outcomes in Canada are comparable to those elsewhere, national policies directed towards timely referral and earlier age at KP rather than centralisation of care are needed.

Long‐term Outcome of Children With Biliary Atresia Who Were Not Transplanted After the Kasai Operation: &gt;20‐year Experience at a Children's Hospital

Sequential strategies combining the Kasai operation as a first-line treatment and liver transplantation as a second-line option, if necessary, have been accepted for patients with biliary atresia (BA). To understand the role of the Kasai operation in the treatment of BA, it is necessary to analyze the long-term outcome of the operation alone and to evaluate the present status of survivors retaining their native livers. A retrospective chart review was carried out for a group of 80 patients who had undergone the Kasai operation between 1970 and 1986 at the Kanagawa Children's Medical Center. The 5-, 10-, and 20-year survival rates of patients with their native livers were 63%, 54%, and 44%, respectively. The survival rates varied significantly depending on the type of BA, age at initial Kasai operation, era of surgery, and surgical method. By age 20, nearly half of the adult survivors had already developed liver cirrhosis and its sequelae. Episodes of cholangitis and gastrointestinal bleeding occurred after 20 years of age in 37% and 17% of the adult patients, respectively, and 20% of the adult patients died of liver failure or underwent living-related partial liver transplantation in their 20s. Five female patients gave birth to a total of 9 children, and 1 male patient fathered a child. Although increasing numbers of patients with BA survive 20 years or more after the Kasai operation, meticulous lifelong postoperative care should be continued for the survivors because of the possibility of hepatic deterioration.

Liver Transplantation for Biliary Atresia in Taiwan: A National Study

A national database for orthotopic liver transplantation (OLT) among biliary atresia (BA) cases in Taiwan has not been reported. Using the National Health Insurance (NHI) database to investigate the prognostic features of patients with BA receiving OLT, we studied the prognosis of this procedure for BA. The NHI in Taiwan covers most of the population (>99%). From 1996–2004, 106 BA patients underwent transplantation. A linear time trend analysis was performed to estimate the annual slope for BA patients to receive OLT. The rate of increase per year of 2.6 cases was significant ( R 2 = .649; P = .029). The 5-year overall survival after OLT was 97.1% ± 1.6%, which was not different between those who had or had not previously undergone portoenterostomy (94.9% vs 97.8%; P = .160). It was not different among patients undergoing transplantation during the various seasons ( P = .505). Our data confirmed the effectiveness of OLT for the treatment of BA in children with or without KP in Taiwan.

Advances in the understanding and treatment of biliary atresia

The purpose of this study is to review both the basic science and clinical advancements in the last 12 months that have furthered our understanding of biliary atresia. Early diagnosis and further understanding of the disease process may be the next major step in advancement. Stool color cards have been shown to be an accurate screening tool. Basic science developments have focused on defects in morphogenesis, immunologic dysregulation, and viral infection as the major theories of causes. There have been initial reports of minimally invasive approaches to hepatic portoenterostomy but there has been little comparative study. Postoperative corticosteroid therapy remains an area of debate without definitive data. Early postoperative testing of serum bilirubin levels and hepatobiliary scintigraphy are showing strong correlation with long-term outcomes. The comparison of regions with decentralization policies compared with those with central referral policies is providing a good forum to monitor real-time outcome data. Biliary atresia continues to represent a major challenge with many unanswered questions. The establishment of multicentered collaboration in both basic science and clinical research interests has been an important step in improving outcomes for this disease.

Universal screening for biliary atresia using an infant stool color card in Taiwan†

Biliary atresia is the most common cause of death from liver disease in children. Although the Kasai operation before 60 days of age can significantly improve prognosis, delay in referral and surgery remains a formidable problem worldwide because of difficulties in differentiating it from benign prolonged neonatal jaundice. We established a universal screening system using an infant stool color card to promote the early diagnosis and treatment of biliary atresia. After a pilot regional study in 2002-2003, a national stool color screening system was established by integrating the infant stool color card into the child health booklet given to every neonate in Taiwan since 2004. Within 24 hours of the discovery of an abnormal stool color, this event is reported to the registry center. The annual incidence of biliary atresia per 10,000 live births in 2004 and 2005 was 1.85 (40/216,419) and 1.70 (35/205,854), respectively. The sensitivity of detecting biliary atresia using stool cards before 60 days of age was 72.5% in 2004, which improved to 97.1% in 2005. The national rate of the Kasai operation before 60 days of age increased from 60% in 2004 to 74.3% in 2005. The jaundice-free rate (<2 mg/dL) at 3 months after the Kasai operation among infants with biliary atresia in 2004-2005 was 59.5% (44 of 74), significantly higher than the historical data of 37.0% in 1976-2000 before the stool card screening program (P = 0.002). Universal screening using the stool color cards can enhance earlier referral, which may ultimately lead to timely performance of the Kasai operation and better postoperative outcome in infants with biliary atresia.

Long-term outcome of hepatic portoduodenostomy with interposition of the ileocecoappendix for biliary atresia

Hepatic portoduodenostomy with interposition of the ileocecoappendix (HPI) can be used for the surgical treatment of biliary atresia (BA). The purpose of this study was to evaluate the long-term outcome of patients with HPI. The records of nine patients who had HPI performed for BA were reviewed. Mean age at portoenterostomy was 68.1 days (range 26-113 days). At the end of 2006, seven of the nine subjects were alive, although two required liver transplantation (LT). The two deaths occurred 94 days and 2 years after HPI due to varicella infection and variceal bleeding, respectively. Length of follow-up for the seven survivors ranged from 17 to 19 years (mean 18 years). Three subjects achieved normal liver function after HPI and have remained jaundice-free to date. Another three who were initially jaundice-free required Roux-en-Y jejunostomy (RYJ) to the ileocecum for severe obstructive cholestasis 6 months, 3 years, and 19 years after HPI secondary to stones in the cecum. RYJ was successful in these three cases, and liver function returned to normal within a few months. Two of these three have continued to have almost normal liver function, but one required LT 5 years after RYJ. The remaining case had LT because of liver dysfunction 14 months after HPI. There is a high risk for stone formation and obstruction with the HPI procedure because bile can stagnate in the ileocecum.

A role for laparoscopic approach in the treatment of biliary atresia and choledochal cysts

Background/Purpose Indications for a laparoscopic approach in the management of biliary atresia and choledochal cysts in children are not clearly defined. We present our initial experience with 9 consecutive laparoscopic cases, and compare them to the traditional open approach. Methods A retrospective comparison of all consecutive operations for biliary atresia and choledochal cysts from January 2000 to May 2006 was undertaken. We evaluated the patient's age at operation, operative time, return of bowel function postoperatively, length of hospital stay, complications, and the need for subsequent liver transplantation. Mann-Whitney U test was used for statistical analysis. Results A total of 45 portoenterostomies and choledochojejunostomies were performed, including 9 laparoscopic and 36 open procedures. Patients with choledochal cysts were older than patients with biliary atresia. All the compared parameters were similar and there was no difference in outcomes between the laparoscopic and the open groups. Conclusions Our initial experience is encouraging and indicates that the laparoscopic approach is technically feasible, safe, and effective, with a low morbidity and a comparable outcome to the open technique. Longer follow-up of a larger patient cohort is needed.

Obstructive jaundice caused by biliary stone formation around the stent after liver transplantation

We report an unusual case of obstructive jaundice caused by a biliary stone, which developed in the stump of a Roux-en-Y hepaticojejunostomy after undergoing LT. The patient was a 13-yr-old male. At 74 days after birth, a hepaticojejunostomy (Kasai's procedure) was performed for the treatment of biliary atresia. He underwent a reduced size deceased donor LT in the left subphrenic space twice at the age of one and three years in Australia. Eleven years after his second LT, he developed liver dysfunction and jaundice with a low grade fever. Computed tomography showed a marked jejunal loop enlargement by a rugby ball-shaped stone and the bile duct in the graft was thus dilated. A surgical exploration revealed the jejunal loop to be bent sharply while its stump side was dilated by stagnated bile including a biliary stone. The stone included a stent that had been previously used for the hepaticojejunostomy. This case suggests that a retained stent used for hepaticojejunostomy had thus caused biliary stone formation because of a combination of various conditions in the jejunal loop.

Imaging of the jaundiced child

In both infants and older children ultrasound should be the initial radiological investigation and further imaging dependent upon the findings.Imaging primarily aims to differentiate extrahepatic from intrahepatic causes.Any neonate with jaundice persisting beyond 2 weeks of age warrants investigation.The diagnosis and treatment of biliary atresia should be performed prior to 8 weeks of age to achieve the best long term surgical success.Gallstones are increasing prevalent in older children and underlying choledochal cysts should be sought when bile duct stones found.Hepatic masses are an important differential in the investigation of jaundice and usually require evaluation with CT or MRI.

Treatment for Biliary Atresia in 2003

Treatment for Biliary Atresia in 2003

Biliary atresia and orthotopic liver transplantation. 11 years of experience in Geneva.

Biliary atresia (BA) is a congenital malformation or an evolutive inflammatory process which, without treatment, leads to cirrhosis, hepatic failure and death within two years of birth. The literature gives a survival rate of 60% at five years and 25% to adulthood after an initial operation performed for BA. 30% of children do not survive beyond two years of age. BA has become the most frequent indication for liver transplantation (LT) in children. With LT, survival expectancy is 90%. Results of the operation designed for BA remain unsatisfactory, and seem to depend on the age of the infants, as well as on other factors such as liver histology, and centre experience. Since 1989, onset of the paediatric hepatic transplantation program in Geneva, to July 2000, 20 children have been referred for initial treatment of BA, and 26 for possible hepatic transplantation after initial treatment done in another centre. The aim of the current study is to analyse our own results of the initial operation and to present the results of liver transplantation in this particular group of patients. All the patients with a BA are included in this study. The initial operation for BA yielded 43% favourable outcome at five years and the survival in this group following LT reached 91.3% survival. The importance of the age of the patient at time of initial operation is underlined.

Hazards of hepatic portocholecystostomy in biliary atresia.

A hepatic portocholecystostomy (HPC) has been recommended to avoid postoperative cholangitis in the case of a patent distal extrahepatic bile duct (PDEBD) for the treatment of biliary atresia (BA). We investigated the efficacy and clinical problems of HPC in BA. The clinical records of eight patients with BA and PDEBD were reviewed. The diameter of the common bile duct was compared between the patients with BA and PDEBD and age-matched patients with neonatal hepatitis (NH). Five of 8 patients with PDEBD underwent HPC. One patient had to be converted to a cholecystojejunostomy because of common bile duct stenosis at 19 years of age. The other two patients underwent a reoperation by a hepatic portojejunostomy due to poor bile drainage after HPC. Another patient became jaundice-free one month after HPC, but died of sepsis due to bile leakage 3 months thereafter. The mean diameter of the common bile duct in BA with PDEBD was significantly smaller than that of NH (0.76 +/- 0.16 mm (n = 8) in BA vs. 1.90 +/- 0.39 mm (n = 11) in NH, p<0.01). HPC was thus found to be an excellent operative method for preventing postoperative cholangitis in BA, however, many clinical problems still need to be overcome for such a narrow distal duct.

Prognostic value of hepatobiliary functional scintigraphy in diagnosis and after-care of biliary atresia

To investigate the prognostic relevance of hepatobiliary scintigraphy (HBS) in newborns suffering from biliary atresia (BA) for establishing the primary diagnosis and in the postoperative follow-up after portoenterostomy (Kasai). Twenty newborns with direct hyperbilirubinemia and 6 children after operative treatment of BA (Kasai) underwent HBS with Tc-99m-DEIDA. In patients without intestinal drainage, hepatocellular extraction was estimated visually and calculated semiquantitatively by means of liver/heart-ratio 5 min p.i. 10/20 patients with hyperbilirubinemia did not display biliary drainage; 6 had BA, 3 intrahepatic hypoplasia, and one showed a bile plug syndrome. 4/6 with BA but none of the 4 children with diagnoses other than BA presented with a good extraction. All of the 4 children with BA, who had either pre- or postoperatively a bad extraction, needed liver transplantation due to liver failure. Both of the two newborns with BA and favourable outcome after Kasai had a good extraction in the preoperative HBS and demonstrated good intestinal drainage in the postoperative scan. HBS rules out BA with high accuracy by demonstrating drainage of bile into the intestine. In newborns without drainage a good extraction favours the diagnosis of BA. In newborns with BA a bad extraction seems to indicate a poor postoperative prognosis after Kasai operation. HBS might therefore help to select those children who will not benefit from portoenterostomy. Postoperatively, HBS can easily and quickly confirm the successful hepatobiliary anastomosis by demonstrating biliary drainage into the intestine.

Surgical Treatment of Biliary Atresia in the Liver Transplantation Era

Surgical Treatment of Biliary Atresia in the Liver Transplantation Era

Long-term results and clinical problems after portoenterostomy in patients with biliary atresia.

From January 1962 through December 1986, 71 cases of biliary atresia were operated on. Nine of these patients underwent only an exploratory laparotomy. A hepatic portoenterostomy (Kasai's operation) was performed on 62 infants with biliary atresia. Of these 62 children, 18 survived more than 10 years. However, 4 of the 18 died shortly thereafter because of persistent or recurrent jaundice and hepatic failure. Fourteen patients, however, are still alive more than ten years after portoenterostomy, today the actual 10-year survival rate is thus 22.5%. Six of them have no severe complications and their serum total bilirubin is less than 1.0 mg/dl. However, 8 patients, whose serum total bilirubin is more than 1.0 mg/dl, demonstrated numerous clinical problems such as esophageal varices, hypersplenism and recurrent jaundice after cholangitis. One of the patients in the latter group eventually underwent a liver transplantation because of the recurrent jaundice and hepatic insufficiency. In the treatment of biliary atresia, a close and careful follow-up is therefore essential especially for patients whose serum total bilirubin is more than 1.0 mg/dl.

Epidemiologic Study of Infants With Biliary Atresia

To the Editor. Yoon et al1 present an epidemiologic study of 57 infants with biliary atresia born over a 25-year period in the Atlanta area. This data was analyzed using seven variables including month of birth, from which a predilection for the winter months December through March was shown.King's College Hospital, London, is a tertiary referral unit for hepatobiliary diseases predominantly but not exclusively from the south of England. We have specialized in the treatment of biliary atresia since the 1970s and our experience has been reported recently both in general2 and specifically with the biliary atresia splenic malformation syndrome (or sequence).3 Since 1973, we have treated 380 infants with biliary atresia (nonsyndromic, n = 346; syndromic, n = 34) and have data on their month of birth. Using Yoon's own criteria for season (April through July, August through November, and December through March), we found neither predilection nor trend for season (χ2 = 0.56, df = 2:P = 0.75) in these two groups. The Figure illustrates our cases by month of birth in the two types of biliary atresia.Although our series is not from a well-defined area, is heterogenous (but predominantly white), and has no data on the population from which the cases arose, it has the irrefutable advantage of being large. We feel that it is too easy in such studies to infer statistical relationships where none actually exist. A statistical test for seasonality was applied to an average of only 4.7 cases per month and this is clearly a major weakness. Indeed, the wide confidence intervals quoted support this interpretation. The evidence for a viral etiology of biliary atresia is contradictory and, it is true, would be advanced if seasonality could be shown. However, this is not the study that has shown it.In Reply. Using data from a hospital-based case series of patients with biliary atresia, Drs Davenport and Dhawan show that there is no seasonal variation in the births of these patients with biliary atresia. However, in order to meaningfully examine seasonal variation, one needs to look at variation in birth prevalence rates because seasonal variation in births has been shown to exist in most populations.1-1 Drs Davenport and Dhawan may find that because seasonal variation is likely in the population (denominator), the lack of seasonality in the births of their case infants (the numerator) will result in prevalence rates for biliary atresia that are seasonal. In our study,1-2 we used the Walter and Elwood test for seasonality of events with a variable population at risk1-3 to show that there was seasonal variation in the birth rates of infants in metropolitan Atlanta with biliary atresia. To determine the magnitude of the seasonal variation and whether the difference we found was significant, we divided the year into three seasons and used these in a multivariate logistic regression model. Drs Davenport and Dhawan suggest that because the number of cases we studied was small and our confidence limits were wide, we should not infer a statistical relationship between the occurrence of biliary atresia and season. However, we would like to point out that confidence intervals account for the statistical uncertainty, which is related to sample size and any result with a confidence interval that excludes 1.0 is by definition statistically significant.1-4 Our study, which clearly showed that the occurrence of biliary atresia in metropolitan Atlanta was 2.6 times greater from December through March than from April through July, had a 95% confidence interval of 1.2 to 5.9 even when we controlled for other covariates.We would also like to point out that in addition to geographic and climatic variation, the metropolitan Atlanta population differs considerably from the British population with respect to race and other socioeconomic factors. All of these factors could affect the susceptibility of fetuses and infants to biliary atresia or to an environmental agent that might precipitate biliary atresia. Although much can be said for large sample sizes, population-based studies such as we conducted have a number of advantages over hospital-based studies, particularly when it comes to using study estimates to make inferences about the population at large. In summary, although the data presented by Drs Davenport and Dhawan are interesting, we believe the findings from our study support further investigation of the association between biliary atresia and environmental agents such as viruses.

Treatment of Biliary Atresia by the Kasai Procedure : Experience Over 24 Years

Treatment of Biliary Atresia by the Kasai Procedure : Experience Over 24 Years