Surgical Treatment Of Biliary Atresia Research Articles

Odevixibat: an investigational inhibitor of the ileal bile acid transporter (IBAT) for the treatment of biliary atresia

ABSTRACT Introduction Biliary atresia (BA) is a rare, non-curable cholestasis-causing disease in infancy, due to progressive ascending bile duct sclerosis. Even after restoration of bile flow following Kasai portoenterostomy, about half of these children need a liver transplant by their 2nd birthday, due to progressive fibrosis. Toxicity of bile acids may play a central role in disease progression, but drug therapies are not yet available. With ileal bile acid transporter (IBAT) inhibitors, there is a potential novel drug option that inhibits the absorption of bile acids in the small intestine. As a result of reduced bile acid accumulation in the cholestatic liver, it may be possible to delay hepatic remodeling. Areas covered This review summarizes the dataset on bile acids and the potential effects of odevixibat, an IBAT inhibitor, in children with BA. Expert opinion Systemic reduction of bile acids with the aim of preventing inflammation, and thus liver remodeling, is a novel, promising, therapeutic concept. In principle, however, the time until diagnosis and surgical treatment of BA should still be kept as short as possible in order to minimize liver remodeling before medical intervention can be initiated. IBAT inhibitors may add to the medical options in limiting disease progression in BA.

Management of biliary atresia: To transplant or not to transplant.

Kasai procedure (KP) and liver transplantation (LT) represent the only therapeutic options for patients with biliary atresia (BA), the most common indication for LT in the pediatric population. However, KP represents by no means a radical option but rather a bridging one, as nearly all patients will finally require a liver graft. More and more experts in the field of transplant surgery propose that maybe it is time for a paradigm change in BA treatment and abandon KP as transplantation seems inevitable. Inadequacy of organs yet makes this option currently not feasible, so it seems useful to find ways to maximize the efficacy of KP. In previous decades, multiple studies tried to identify these factors which opt for better results, but in general, outcomes of KP have not improved to the level that was anticipated. This review provides the framework of conditions which favor native liver survival after KP and the ones which optimize a positive LT outcome. Strategies of transition of care at the right time are also presented, as transplantation plays a key role in the surgical treatment of BA. Future studies and further organization in the transplant field will allow for greater organ availability and better outcomes to be achieved for BA patients.

Sequential Treatment of Biliary Atresia With Kasai Hepatoportoenterostomy and Liver Transplantation: Benefits, Risks, and Outcome in 393 Children.

Introduction: Surgical treatment of biliary atresia (BA) is still based on sequential strategy with Kasai hepatoportoenterostomy (KP) followed by liver transplantation (LT), in case of complicated secondary biliary cirrhosis. Concerns have been expressed regarding the risks of LT related to previous KP, suggesting primary LT as an exclusive treatment of BA.Methods: Single-center retrospective analysis including 393 pediatric patients who underwent LT for BA from 1993 to 2018, categorized into two groups: with (KP) or without (NoKP) previous KP. Pre-LT clinical condition was estimated considering age at LT, time on waiting list, pediatric end-stage liver disease score (PELD), and presence of portal vein hypoplasia. Post-LT outcome was evaluated considering patient and graft survival rates, and need for early reoperation due to abdominal or graft-related complications (<45 days after LT).Results: Two-hundred ninety-six patients (75.3%) were categorized in the KP group, and 97 (24.7%) in the NoKP group. Median age at LT was 1.14 years in the KP group and 0.85 years in the NoKP group (p < 0.0001). PELD score was significantly less severe in KP patients (p < 0.05). One-year patient survival rates were 96.9 and 96.8% in the KP and NoKP groups, respectively (p = 0.43), and the corresponding graft survival was 92.5 and 94.8% (p = 0.97). The need for early reoperation was more frequent in the KP group (29.8%) vs. NoKP group (12.4%, p = 0.01). The rate of bowel perforation was non-significantly higher in the KP group (8.1%) vs. NoKP group (3.1%, p = 0.11).Conclusions: The sequential strategy including KP and LT allowed performing LT in patients with significant older age and better clinical conditions, when compared to those transplanted without previous KP. Patient and graft survivals were not impacted by previous KP. Although previous KP was associated with an increased rate of post-LT surgical complications, bowel perforation and bleeding did not occur significantly more frequently. Such results support the current strategy based on sequential treatment.

Long-Term Effects of Kasai Portoenterostomy for Biliary Atresia Treatment in Russia.

This prospective study enrolled 144 patients after surgical treatment of biliary atresia in early infancy. We analyzed the immediate effectiveness of the surgery and the age-related structure of complications in the up to 16-year follow-up. The immediate 2-year survival rate after the surgery constituted 49.5%. At the time of this writing, 17 of the patients had celebrated their 10th birthdays with good quality of life and no indications for transplantation of the liver. The obtained results underscore the critical importance of surgical correction of biliary atresia by Kasai surgery in the first 60 days of life and subsequent dynamic follow-up of patients for the purpose of the early detection and timely correction of possible complications.

Should We Offer Surgery for Biliary Atresia in Low-Resource Settings? Surgical Outcomes in Rwanda

BackgroundIn many resource-limited settings, patients with biliary atresia present too late for surgical correction to be offered, and the diagnosis is fatal. As pediatric surgical and anesthesia capabilities have improved, patients in Rwanda have been offered surgical exploration. This study explores initial outcomes. MethodsPatients presenting with direct hyperbilirubinemia and clinical suspicion of biliary atresia were identified at the main university teaching hospital in Kigali, Rwanda, from January 2016 to June 2019. Patient demographics, referral history, geographic location, preoperative imaging, preoperative laboratory studies, operative details, postoperative laboratory studies, in-hospital complications, length of stay, and survival were abstracted from retrospective chart review. Descriptive analysis was performed, and univariate analysis evaluated survival and complications. ResultsSeventeen patients were identified with biliary atresia, and thirteen were offered surgery. The median age of admission was 77 d (interquartile range [IQR] 63-92 d), with the median time wait for the operation being 19 d (IQR 9-27 d). The median age at operation was 93 d (IQR 76-123 d). In-hospital postoperative mortality was 15.4% (n = 2) and postoperative complications occurred in 46.2% (n = 6). Eleven patients survived to hospital discharge (84.6%), with a median length of stay of 8 d (IQR 6-13 d). ConclusionsWhile future studies are needed to evaluate the long-term outcomes, this series shows that surgical treatment of biliary atresia can be safely performed in Rwanda. Early referral of direct hyperbilirubinemia is essential, particularly as limited resources and personnel may impact the time from diagnosis to operation.

Remote results of treatment of biliary atresia in children

The objective. To analyze early and long-term results of surgical treatment of biliary atresia in children. 120 patients with biliary atresia underwent Kasai procedure from 2000 to 2018. The follow-up course varied from 6 months to 15 years. The authors assessed the survival rate of children with native liver and the survival rate without indications for liver transplantation in different age periods, as well as the frequency of surgical complications, bacterial cholangitis, portal hypertension, etc. The results. The survival rate of children with native liver within 1 year was 82.7%; within 2 years – 57.72%; 3 years – 49.6%; 5 years – 42.1%; over 10 years – 33.25%. In case of effective surgery the authors noted the restoration of stool color, jaundice relief and gradual normalization of bilirubin level during the 1st year. The activity of gamma-glutamyl transferase and transaminases in most children increased in the early postoperative period and, then, gradually decreased. The most frequent postoperative complications were episodes of cholangitis and portal hypertension. During the first year, episodes of cholangitis were detected in 50 (42.3%) of 119 children, regardless of the effectiveness of the Kasai procedure. 56 children (47.75%) had signs of portal hypertension during the first year of life; its frequency increased to 70% by the age of 5–10 years. Conclusion. In most cases, Kasai procedure prolongs life with the native liver, allowing you to postpone transplantation and it is an effective method of treatment of biliary atresia in children. The most frequent complications are cholangitis and portal hypertension, the early detection and timely correction of them is an integral part of the treatment of these patients.

Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia.

The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow‐up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme‐linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real‐time reverse‐transcription PCR. Liver expression of MMP‐7 and cytokeratin‐7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP‐7 (29‐fold, p < 0.001), MMP‐2 (3.1‐fold, p < 0.001), MMP‐14 (1.7‐fold, p = 0.007), and TIMP‐1 (1.8‐fold, p < 0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin‐7, expression of MMP‐7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p < 0.001) in relation to controls. BA patients had 6‐fold higher serum levels of MMP‐7 (p < 0.001), which correlated positively with hepatic MMP‐7 gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression. Patients showed a positive correlation between biliary MMP‐7 expression and Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r = 0.606, p = 0.001). Neither similarly increased MMP‐7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure‐associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered hepatic expression of MMP‐7 in the progression of liver fibrosis after successful PE and introduce a potential therapeutic target to pharmacologically extend native liver survival by inhibiting MMP‐7 hyperactivity. Serum MMP‐7 may be a valuable postoperative prognostic tool in BA.

Surgical treatment of biliary atresia with patent distal extra hepatic bile ducts: Is hepatic portocholecystostomy the right choice?

Purpose:To report the results of surgical treatment of biliary atresia with patent distal extra hepatic bile ducts (BA with PDEBD) with special reference to hepatic portocholecystostomy (HPC) operation.Materials and Methods:The study reviews records of children operated for BA with PDEBD. The type of operation, results of surgery, postoperative course and complications during follow-up are noted.Results:Five children (mean age 83 days) underwent surgery for biliary atresia with patent extra hepatic bile ducts. The diagnosis was confirmed by intraoperative cholangiography in each case. Three children underwent HPC and two had standard hepatic portoenterostomy (HPE) as HPC was not technically feasible. The operation was considered successful in three of five children (60%, two HPC and one HPE), partially successful in one. The mean follow-up was 22 months. None of the children with HPC had cholangitis at follow-up; one child with HPE had recurrent cholangitis.Conclusions:Biliary atresia (BA) with PDEBD may be a variant with a fair chance for surgical success. When feasible, HPC may be a good treatment option in this group with acceptable results and practically no risk of postoperative cholangitis.

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.

Surgical Treatment of Biliary Atresia in the Liver Transplantation Era

Surgical Treatment of Biliary Atresia in the Liver Transplantation Era

Differential Diagnosis of Extrahepatic Biliary Atresia from Neonatal Hepatitis

SummaryThe clinical presentations of cholestasis in infancy caused by neonatal hepatitis and biliary atresia are very similar. Diagnosis may be difficult on many occasions, but the surgical treatment of biliary atresia should be performed as early as possible. We established a 3‐day workup protocol for the differential diagnosis of biliary atresia and neonatal hepatitis and compared the diagnostic accuracy, sensitivity, specificity, and predictive values of various methods. One hundred and twenty‐six infants, including 84 with neonatal hepatitis (age, 65.1 ± 24.1 days) and 42 with biliary atresia (age, 60.3 ± 31.1 days), were studied prospectively from July 1982 to December 1990. The diagnostic accuracy of various methods was as follows: liver histology, 96.8%; color of duodenal juice, 91.6%; peak radioisotope count in duodenal juice, 84.2%; ultrasonographic examination of the hepatobiliary system, 80.2%; and persistence of clay‐colored stool, 80.2%. After stepwise logistic regression, the diagnostic methods of significance were liver biopsy, color of duodenal juice, abdominal ultrasonography, and stool color. However, stool color and the onset of jaundice could not differentiate severe neonatal hepatitis from biliary atresia. The diagnostic methods of significance then were liver biopsy and duodenal juice color. With this 3‐day protocol, no biliary atresia was missed although four cases of neonatal hepatitis were misdiagnosed, resulting in unnecessary laparotomy; we found an overall diagnostic accuracy of 96.8%. We conclude that this 3‐day diagnostic protocol is very helpful in the differential diagnosis of neonatal hepatitis and biliary atresia. Liver histologic examination is the most reliable single test for the differential diagnosis.

Long-term results of surgical treatment of biliary atresia: M. Odievre. World J Surg 2:589–594, (September), 1978

Long-term results of surgical treatment of biliary atresia: M. Odievre. World J Surg 2:589–594, (September), 1978

Long-term results of surgical treatment of biliary atresia.

AbstractThe long‐term results of surgical treatment of biliary atresia are presented from a series of 111 “noncorrectable” cases treated by the Kasai procedure. Thirty‐four patients displayed some degree of restoration of bile flow for at least 1 year after surgery. Almost all of them still have some manifestations of cholestasis, abnormal intrahepatic bile ducts, persistent hepatic fibrosis, or portal hypertension. Despite this continuous liver dysfunction, many of these patients are able to carry on an almost normal life.

Surgery of biliary atresia. Current status.

Currently, no single area in pediatric surgery arouses more heated controversy than does the surgical treatment of biliary atresia. Because of reports (few have been published) of spontaneous resolution of biliary atresia, only limited operations have been recommended to avoid damage to unrecognized ductal structures. Conversely, because of other reports of correctable lesions missed at operation and subsequently discovered at autopsy, a thorough surgical exploration has been urged. The dilemma has not been helped any by communications from Japan about another operation for biliary atresia in which the extrahepatic bile ducts are removed entirely. For a while, most American pediatric surgeons simply ignored the Japanese communications. This action, or lack of action, was subsequently believed fully justified after the initial pessimistic report in the United States by Campbell and associates. 1 After experiencing ten outright failures in ten successive patients, the authors legitimately concluded ... that hepatic portoenterostomy appears

Surgical treatment of biliary atresia

Among 87 proven cases of biliary atresia, 20 were of “correctable” types and the remaining 67 of “incorrectable” types. Complete cure was obtained in 3 of 16 “correctable” cases on which an anastomosis was carried out. Postoperative excretion of bile was poor or absent in many cases of “correctable” types. Fifty-three of 67 cases of the “incorrectable” type underwent hepatic portoenterostomy. Nineteen of them showed excellent or fair excretion of bile after operation and 6 are living and well without jaundice from 1 year, 2 months to 13 years after operation. The histologic study of extrahepatic bile ducts showed that tiny but patent bile duct exists in the porta hepatis of nearly all cases of “incorrectable” types examined and that good excretion of bile was obtained usually in cases which had bile ducts with a diameter of more than 200 μ in the porta hepatis. From these results, it was concluded that “correctable” cases of biliary atresia are not necessarily curable while not a few cases of “incorrectable” types might be cured by hepatic portoenterostomy if the operation is performed before 4 months of age.