Pediatric liver transplantation for Alagille syndrome: a single-center experience / 器官移植

Objective To evaluate the clinical efficacy of liver transplantation in children with Alagille syndrome (ALGS). Methods Clinical data of 12 children with ALGS were collected and retrospectively analyzed. Clinical characteristics of children with ALGS, pathological characteristics of liver tissues, characteristics of liver transplantation, postoperative complications and follow-up of children with ALGS were analyzed. Results JAG1 gene mutation and typical facial features was present in all 12 children. Jaundice was the most common initial symptom, which occurred at 7 (3, 40) d after birth. Upon liver transplantation, the Z scores of height and body weight were calculated as -2.14 (-3.11, -1.83) and -2.32 (-3.12, -1.12). Five children developed severe growth retardation and 4 children with severe malnutrition. Eight of 12 children were diagnosed with cardiovascular abnormalities. Pathological examination showed that the lobular structure of the diseased livers of 4 children was basically maintained, and 8 cases of nodular liver cirrhosis in different sizes including 1 case of single early moderately-differentiated hepatocellular carcinoma. Three children were misdiagnosed with biliary atresia and underwent Kasai portoenterostomy. Eight children underwent living donor liver transplantation, three children underwent cadaveric donor liver transplantation (two cases of split liver transplantation and one case of cadaveric total liver transplantation), and one child underwent domino liver transplantation (donor liver was derived from a patient with maple syrup urine disease). during the follow-up of 30.0(24.5, 41.7) months, the survival rates of the children and liver grafts were both 100%. During postoperative follow-up, the Z scores of height and body weight were calculated as -1.24 (-2.11, 0.60) and -0.83 (-1.65, -0.43), indicating that the growth and development of the children were significantly improved after operation. Conclusions Liver transplantation is an efficacious treatment for children with ALGS complicated with decompensated cirrhosis, severe itching and poor quality of life. For children with ALGS complicated with cardiovascular abnormalities, explicit preoperative evaluation should be delivered, and consultation with pediatric cardiologists should be performed if necessary.

Guía de práctica clínica en atresia de las vías biliares / Clinical practice guidelines in biliary atresia

Basada en la mejor evidencia científica disponible, se presenta la guía de práctica clínica en atresia de vías biliares, la cual se define como una obstrucción progresiva de las vías biliares intra- o extrahepáticas en recién nacidos y lactantes pequeños y causa ictericia colestásica grave y cirrosis hepática. Es una enfermedad poco frecuente, de etiología desconocida, con mayor incidencia en países asiáticos. Clínicamente se expresa por ictericia obstructiva, acolia, coluria y hepatoesplenomegalia. Los complementarios expresan una hiperbilirrubinemia directa con aumento de las enzimas hepáticas, y el diagnóstico se confirma en nuestro hospital con la colangiografía, generalmente en el curso de una laparoscopía. El tratamiento es quirúrgico y consiste en la portoenterostomía de Kasai, con mejores resultados en cuanto al drenaje biliar si se realiza antes de los 60 días de vida, así como el trasplante hepático. La enfermedad tiene un curso progresivo hacia la cirrosis hepática en etapas tempranas de la vida, sobre todo si no se realiza el diagnóstico y tratamiento quirúrgico precozmente, con implicaciones en la supervivencia y calidad de vida de estos pacientes. Por tanto, referir precozmente al paciente con sospecha de atresia de vías biliares a un centro especializado es la piedra angular de la actitud médica. La presente guía de práctica clínica pretende ofrecer las herramientas técnicas estandarizadas para mejorar los resultados a los pacientes con esta enfermedad, así como contribuir con la docencia y las investigaciones(AU)

Based on the best scientific evidence available, it is presented the clinical practice guidelines on biliary atresia. This disease is defined as a progressive obstruction of the intra and/or extrahepatic bile ducts in newborns and young infants, causing severe cholestatic jaundice and cirrhosis of the liver. It is a rare disease of unknown etiology, with a higher incidence in Asian countries. It is clinically expressed by obstructive jaundice, acholia, choluria and hepatosplenomegaly. Laboratory tests show a direct hyperbilirubin and elevated liver enzymes, and in our hospital, the diagnosis is confirmed by a cholangiography, usually during a laparoscopy procedure. It has surgical treatment and it involves a Kasai portoenterostomy, with better results regarding biliary drainage if it is performed before 60 days of life, as well as liver transplant. This condition has a progressive course towards liver cirrhosis in early stages of life, mainly if the diagnosis and surgical treatment are not made timely, with implications for the survival and quality of life of these patients. Therefore, early referral of the patient with suspected biliary atresia to a specialized center is the cornerstone of the medical attitude. This clinical practice guidelines aims to offer standardized technical tools to improve the outcome for patients with this disease, as well as to contribute to teaching and research(AU)

The Prognostic Value of CD8⁺ and CD45RO⁺ T Cells Infiltration and Beclin1 Expression Levels for Early Postoperative Cholangitis of Biliary Atresia Patients after Kasai Operation

BACKGROUND: Postoperative cholangitis is a common but severe complication after Kasai portoenterostomy for biliary atresia (BA). This study aimed to identify its prognostic factors. METHODS: Two sets of liver paraffin-embedded tissue samples were collected from BA patients who received Kasai portoenterostomy (n = 25 and n = 31, respectively). Patients were divided into non-cholangitis and cholangitis groups. The infiltration of CD4+, CD8+, CD45RO+, CD68+ cells and expression of Beclin1 were quantitatively evaluated in immunohistochemical analysis. RESULTS: Cholangitis group had a significantly lower CD8+ T cell infiltration but a higher CD45RO+ cell infiltration, and a lower Beclin1 level than non-cholangitis group (all P < 0.01). Multivariate logistic regression analysis indicated that infiltration of CD8+ cells (odds ratio [OR], 0.112; 95% confidence interval [CI], 0.022–0.577) and CD45RO+ cells (OR, 3.88; 95% CI, 1.37–11.03), and Beclin1 level (OR, 0.088; 95% CI, 0.018–0.452) were independent influence factors for early postoperative cholangitis. Receiver operating characteristic (ROC) analysis showed that area under ROC curve (AUROC) values for CD8+ cells, CD45RO+ cells and Beclin1 were 0.857, 0.738 and 0.900, respectively. CONCLUSION: Our findings demonstrated the CD8+ cells, CD45RO+ cells and Beclin1 level possessed the prognostic value for early postoperative cholangitis following Kasai operation, which may be helpful to develop new prevention and treatment strategies for postoperative cholangitis.

Recent Trends in the Diagnosis and Management of Biliary Atresia in Developing Countries.

Need and purpose of review: Biliary atresia is a progressive obstructive cholangiopathy and is fatal if left untreated within 2 years of life. Delay in referral is because of difficulties in differentiating it from physiologic jaundice and identifying an abnormal stool color. This paper presents an overview on the diagnosis and discusses the current strategies in the management of this disease in developing countries. Methods: Articles were retrieved from the PubMed database using the terms ‘biliary atresia’, ‘Kasai portoenterostomy’ and ‘pediatric liver transplantation’. Contents of the article are also based on personal experience of the authors. Conclusion: A national screening program using stool color cards as part of standard care in the neonatal period will greatly improve early detection of biliary atresia. Outcomes will improve if it is diagnosed at the earliest after birth, the child is referred to an experienced pediatric hepatobiliary unit for evaluation, and undergoes an early Kasai procedure. If an early Kasai portoenterostomy is performed, nearly half of all children survive into adolescence, and about one-third are likely to have a long-term, symptom-free life with normal liver biochemistry. Sequential treatment combining Kasai as first line and liver transplantation as second line results in 90% survival for children with biliary atresia.

Long-term Outcome and Prognostic Factors after Kasai Operation for Biliary Atresia

BACKGROUND: Kasai portoenterostomy has been the standard operative procedure in cases of biliary atresia (BA) since Kasai reported the first successful operative case in 1959. However, BA is still one of the pediatric surgical lesions that does not always show satisfactory operative results. METHODS: To evaluate the long-term results and the prognostic factors influencing the survival with the Kasai portoenterostomy for BA, we reviewed 80 BA patients treated at Department of Pediatric Surgery, Seoul National University Hospital from 1980 to 1990. Kaplan-Meier method and Log-rank test were used for statistical analysis. RESULTS: Overall 5-year and 10-year survival rates were 42% and 37%, respectively. Thirty-one patients underwent surgery at ages under 60 days, 31 at ages between 60 and 90 days, 11 at ages between 90 and 120 days and 7 at ages beyond 120 days. There were no statistically significant differences in survival rates among the age groups. In the liver biopsy, minimal hepatic fibrosis was noted in 2 patients, moderate fibrosis in 13, severe fibrosis in 25 and cirrhosis in 5. There were no statistically significant differences in the survival rates according to the degree of hepatic fibrosis but there was a statistically significant difference between patients with cirrhosis and without cirrhosis (p= .03). The size of the bile ductules at the porta hepatis was less than 50 micrometers in 18 patients, between 50 and 100 micrometers in 19 patients, between 100 and 200 micrometers in 4 patients and greater than 200 micrometers in 3 patients. There were no statistically significant differences in the survival rates according to the size of the bile ductules at the porta hepatis. Out of the 12 long-term survivors, survival of more than 10 years, 5 patients had abnormal liver function and 7 patients showed clinical manifestations of portal hypertension. CONCLUSIONS: Kasai portoenterostomy offers reasonable long-term survival and should be the initial procedure for biliary atresia, but a significant portion of the long-term survivors has abnormal liver functionand portal hypertension. Continuous and careful follow-up is needed not to miss the proper time for liver transplantation. Liver cirrhosis at the time of the operation was the only statistically significant prognostic factor influencing the survival.