The diagnosis of biliary atresia (BA) is mainly based on clinical manifestations, screening, and related biochemistry tests. In recent years, the development of blood biomarkers and the improvement in ultrasound examination have made it possible for BA to be diagnosed at a younger age. In particular, matrix metalloproteinase-7 shows high sensitivity and specificity and has a higher diagnostic efficiency than existing biochemical parameters, thereby holding a promise for clinical application. Sound touch elastography can increase the diagnostic efficiency for BA in terms of diagnosis and prognostic evaluation. Surgery is still the only method for the treatment of BA at present, with the preferred surgical treatment regimen of Kasai portoenterostomy combined with pharmacotherapies for alleviating infection and inflammation, and the patients who fail Kasai portoenterostomy or have liver dysfunction may require liver transplantation to save their lives. Therefore, the current research on BA should focus on the biomarkers for early diagnosis, specifically targeted drugs, and drugs for preventing progressive liver fibrosis. This article reviews the current diagnosis and treatment methods for BA and discusses the potential research directions.
Humans ; Biliary Atresia/therapy* ; Portoenterostomy, Hepatic/methods* ; Liver Transplantation/methods* ; Prognosis ; Biomarkers

OBJECTIVETo summarize experience of pediatric intensive care and explore the incidence of complications, the involved pathogens among liver recipients to determine the effective strategies for preventing complications.

METHODSBetween June 2006 and July 2009, 35 children under the age of 14 yr received 35 liver transplantations (LTs) performed at the center. A retrospective review of 22 infants weighing 8.8 kg or less underwent 23 transplants was conducted. Indication for transplantation was biliary atresia. Central venous pressure and arterial blood pressure were monitored continuously and fluid monitoring was performed every 2 hours in the first postoperative week. Blood loss, ascites, and intraoperative transudate loss were primarily replaced with 5% albumin and crystalloids to maintain a central venous pressure between 4 and 6 cm H(2)O. Oral food intake was allowed as soon as possible. To identify vascular or biliary complications, liver doppler ultrasound was performed intraoperatively immediately after reperfusion and after closure of the abdominal wall and postoperatively, twice daily during the first week after surgery. Immunosuppression was initially cyclosporine based, in combination with steroids. Cyclosporine was begun one day prior to transplantation at a dose of 10 mg/(kg·d) divided into two doses, except for cases with hepatic encephalopathy and severe infection. The subsequent doses were adjusted on the basis of recommended trough blood concentrations at different stages. Steroids were eventually discontinued at a time point exceeding 6 months after transplantation. The diagnosis of rejection was confirmed by histology on needle biopsy specimens. Acute graft rejection episodes were treated with a 3-day scheme of IV methylprednisolone 10 mg/(kg·d) followed by recycling doses during the following 3 days (7.5, 5 and 2.5 mg/(kg·d).

RESULTSThe most common postoperative complications were infections (18 cases), gastrointestinal bleeding (3 cases), and vascular complications (4 cases). Rejection occurred in 25% of patients. There was one perioperative death from primary graft non-function. The most common isolated bacteria of the pathogen spectrum were Staphylococcus epidermidis. The median length of stay (LOS) in the PICU for 22 patients (23 transplants) was 10 days (range 5 - 21) and the mean length of stay in the hospital was (18.5 ± 116) days (range, 11 - 48 days). Mean requirement for artificial ventilation was 37.6 h. Mean use of dobutamine, prostaglandin E1 and dopamine was 3.3, 7.5 and 8.8 days, respectively. Preoperatively, 3 children had gastrointestinal bleeding, 18 had ascites, 2 had encephalopathy, 22 had jaundice, and 16 had coagulopathy. There were multiple early operative complications in these infants, including one graft with primary non-function (4.5%). Two patients (9.1%) returned for a total of three times for gastrointestinal bleeding or intra-abdominal hematoma. Three patients (13.6%) had early postoperative intestinal perforations related to adhesions or enterotomy, one was associated with a bowel obstruction. There were 26 episodes of bacterial or fungal infections in 18 (81.8%) patients in the early postoperative period, and infection was the direct/contributing cause of death in one infant. These infections included pneumonia, intra-abdominal abscess or sepsis. All of the bacterial and fungal infections were successfully treated with the appropriate antibacterial and antifungal agents, except for one patient who developed overwhelming sepsis after small bowel perforation. Four (18.2%) patients developed five episodes of acute allograft rejection during the first 15 days after LT. Three of the four patients who developed rejection were transplanted before 2007. All episodes of rejection were treated successfully with intravenous steroid pulse and optimization of cyclosporine levels or FK506 conversion. Of the 20 survivors beyond the perioperative period, two cases (10%) had hypertension requiring therapy.

CONCLUSIONSLiver transplantation in infants with biliary atresia appears technically demanding but acceptable. There should be essentially no age or size restriction for infants and transplantation can be performed with good outcome, although the frequency of complications is much higher than that seen in older children. The improvement in medical and nursing expertise in this group of very sick infants is based on judicious preoperative donor and recipient selection, meticulous surgical technique (vascular reconstruction and abdominal closure), immediate detection and prompt intervention of complications, and keen postoperative surveillance, which reflect a learning curve for both the technical aspects of liver transplantation and post-operative care of these very small patients in our institution. Liver transplantation for infants can be technically challenging.

Biliary Atresia ; surgery ; therapy ; Child, Preschool ; Critical Care ; methods ; Humans ; Infant ; Liver Transplantation ; Living Donors ; Parenteral Nutrition ; Postoperative Care ; methods ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the growth of children in weight and height before and after liver transplantation and the relation between malnutrition and postoperative time.

METHODGrowth was assessed for children who received liver transplantation from July 2007 to December 2012 after operation during follow-up. Weight and height were measured for 51 children in May 30, 2013. Weight and height percentiles of each child were calculated in accordance with data surveying on physical development of children in nine provinces/municipalities. Underweight was defined as weight less than the third percentile of same age and sex groups. Growth retardation was defined as height less than the third percentile of same age and sex groups. Children were set into 2 groups (before liver transplantation group, after liver transplantation group). The incidence of underweight and growth retardation were analyzed by chi-square test. Children were divided into 4 groups according to the length of time from operation time to May 30, 2013: 1 year after liver transplantation (1-365 days); 2 years after liver transplantation (366-730 days); 3 years after liver transplantation (731-1 095 days) ; 4 years or more after liver transplantation (1 096-2 133 days) . The underweight and growth retardation were analyzed by hierarchical log linear model.

RESULTThe mean age of 51 children was 44.78 months (range 13 months to 13 years old), 26 of them were male and 25 female. The number of children with underweight and growth retardation were 20 (39%) and 35 (69%) respectively before transplantation and were 5 (10%) and 14 (27%) respectively after transplantation. There was a significant difference between underweight incidence before and after operation (χ(2) = 10.385, P = 0.001). There was significant difference between growth retardation incidence before and after operation (χ(2) = 15.710, P = 0.000). The subjects included 10 patients at 1 year after operation (underweight n = 3, growth retardation n = 3), 19 patients at 2 years (underweight n = 1, growth retardation n = 9), 10 patients at 3 years (underweight n = 1, growth retardation n = 2), 12 patients at 4 years and above (underweight n = 0, growth retardation n = 0). Parameter analysis of hierarchical log linear estimates: underweight at 1 year = 0.661, underweight at 2 years = -0.214, underweight at 3 years = 0.119, underweight at 4 years and above = -0.566. Growth retardation at 1 year = 0.282, at 2 years = 0.613, at 3 years = 0.051, at 4 years and above = -0.946.

CONCLUSIONCompared with after liver transplantation, obvious malnutrition existed in patients before transplantation. Patients have the ability to catch-up growth after liver transplantation. Reduced effect of underweight occurred in second year after liver transplantation. Reduced effect of growth retardation occurred in third year after liver transplantation.

Adolescent ; Biliary Atresia ; therapy ; Body Height ; Body Weight ; Child ; Child Development ; Child, Preschool ; Female ; Growth Disorders ; epidemiology ; Humans ; Infant ; Liver Cirrhosis ; therapy ; Liver Transplantation ; Male ; Malnutrition ; epidemiology ; Postoperative Period ; Retrospective Studies ; Thinness ; epidemiology ; Time Factors

Pediatric liver transplantation is the standard of care for treatment of liver failure in children. The aim of this study was to identify the characteristics of pediatric liver transplantation in centers located in Korea and determine factors that influence outcomes. This retrospective study was performed using data from between 1988 and 2010 and included all recipients 18 yr old and younger who underwent pediatric liver transplantation in Korea during that period. Our data sources were hospital medical records and the outcome measure was overall patient survival. Univariate and multivariate statistical analyses were undertaken using the Cox proportional hazards model. Five hundred and thirty-four pediatric liver transplantations were performed in 502 children. Median age and average pediatric end-stage liver disease (PELD) score were 20 months and 18 point, respectively. Biliary atresia (57.7%, 308/534) was the most common cause of liver disease. Eighty-two (15.3%) were deceased donor liver transplantations and 454 (84.7%) were living donor liver transplantations. Retransplantation was performed in 32 cases (6%). Overall, 1-, 5-, and 10-yr patient survival rates were 87.8%, 82.2%, and 78.1%, respectively. In multivariate analysis, independent significant predictors of poor patient survival were chronic rejection and retransplantation. This study presents the epidemiologic data for nearly all pediatric liver transplantation in Korea and shows that the independent prognostic factors in patient survival are chronic rejection and retransplantation.
Adolescent ; Biliary Atresia/epidemiology ; Child ; Child, Preschool ; End Stage Liver Disease/epidemiology/mortality/*therapy ; Female ; Graft Survival ; Humans ; Infant ; *Liver Transplantation ; Male ; Prognosis ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome

PURPOSE: To assess the feasibility of the use of spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) in livers of children and young adults. MATERIALS AND METHODS: Patients (≤ 20 years old) who underwent 3T SE-EPI MRE were included retrospectively. Subjects were divided into three groups according to the purpose of the liver MRI: suspicion of fatty liver or focal fat deposition in the liver (FAT group), liver fibrosis after receiving a Kasai operation from biliary atresia (BA group), and hepatic iron deposition after receiving chemotherapy or transfusions (IRON group). Technical failure of MRE was defined when a stiffness map showed no pixel value with a confidence index higher than 95%, and the patients were divided as success and failure groups accordingly. Clinical findings including age, gender, weight, height, and body mass index and magnetic resonance imaging results including proton density fat fraction (PDFF), T2*, and MRE values were assessed. Factors affecting failure of MRE were evaluated and the image quality in wave propagation image and stiffness map was evaluated using the appropriate scores. RESULTS: Among total 240 patients (median 15 years, 211 patients in the FAT, 21 patients in the BA, and 8 patients in the IRON groups), technical failure was noted in six patients in the IRON group (6/8 patients, 75%), while there were no failures noted in the FAT and BA groups. These six patients had T2* values ranging from 0.9 to 3.8 ms. The image quality scores were not significantly different between the FAT and BA groups (P > 0.999), while the scores were significantly lower in the IRON group (P < 0.001). CONCLUSION: The 3T SE-EPI MRE in children and young adults had a high technical success rate. The technical failure was occurred in children with decreased T2* value (≤ 3.8 ms) from iron deposition.
Biliary Atresia ; Body Mass Index ; Child ; Drug Therapy ; Echo-Planar Imaging ; Elasticity Imaging Techniques ; Fatty Liver ; Humans ; Iron ; Liver Cirrhosis ; Liver ; Magnetic Resonance Imaging ; Protons ; Retrospective Studies ; Young Adult

Biliary Atresia ; diagnosis ; etiology ; therapy ; Bilirubin ; blood ; Biomarkers ; blood ; Calcium-Binding Proteins ; deficiency ; Cholangiopancreatography, Magnetic Resonance ; Cholestasis, Intrahepatic ; diagnosis ; etiology ; therapy ; Citrullinemia ; diagnosis ; etiology ; therapy ; DNA Mutational Analysis ; Humans ; Infant ; Jaundice ; diagnosis ; etiology ; therapy ; Liver Function Tests ; Male ; Mitochondrial Membrane Transport Proteins ; genetics ; Mutation ; Organic Anion Transporters ; deficiency

OBJECTIVETo summarize the clinical characteristics, early diagnosis, comprehensive treatment and prognosis of 6 cases of children with post-transplantation lymphoproliferative disorder (PTLD) after liver transplantation.

METHODData of 6 cases with PTLD seen between January 2011 and December 2013 were retrospectively analyzed. The anti-rejection drug dose adjustments, the effect of rituximab, antiviral therapy and comprehensive treatment program after surgery were explored.

RESULT(1) The diagnosis of PTLD was confirmed by histologic findings. Six cases of PTLD including 3 males and 3 females were diagnosed as congenital biliary atresia and underwent split liver transplantation. The occurrence rate of PTLD was 2.9%. (2) The median time to the development of PTLD was less than 6 months. The initial symptom of PTLD in all patients was fever and clinical manifestations of PTLD were non-specific, depending on the involving organs. Five cases of PTLD developed gastrointestinal symptoms, including diarrhea, abdominal pain, and abdominal distension. One case developed respiratory symptoms, including cough and tachypnea. Three cases had lymph node involvement. In 2 cases pathophysiology involved polymorphic lymphocyte proliferation and in 4 cases B lymphocyte proliferation. (3) Two cases died, in whom EBV DNA was not detected and were diagnosed as PTLD by surgical pathology before death. Four survived cases had high EBV-DNA load and then were diagnosed as PTLD by biopsy pathology. (4) Of the 6 cases of PTLD, 2 cases died and 4 cases survived. The overall mortality was 33%. The dead cases were only treated with laparotomy because of intestinal obstruction or perforation and the survived cases were treated with tacrolimus at reduced doses or discontinuation and rituximab. In 2 cases antiviral therapy (acyclovir) was continued, including 1 cases of intestinal obstruction treated with surgical repair. All the survived patients were followed up for 4 months to 1 year and no evidence has been found.

CONCLUSIONEBV infection is the high risk factor for PTLD after liver transplantation. Close clinical surveillance of EBV DNA for pediatric liver transplantation was important for the early diagnosis of PTLD. Reducing doses of immunosuppressive agents and rituximab is the initial therapy for PTLD. A reduction in the dose of tacrolimus is suggested. Operation therapy can also play a role in the management of local complications.

Antiviral Agents ; administration & dosage ; Biliary Atresia ; therapy ; DNA, Viral ; analysis ; Drug Therapy, Combination ; Early Diagnosis ; Epstein-Barr Virus Infections ; diagnosis ; therapy ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; Infant ; Liver Transplantation ; adverse effects ; Lymphoproliferative Disorders ; diagnosis ; etiology ; mortality ; therapy ; Male ; Pediatrics ; Postoperative Complications ; Retrospective Studies ; Survival Rate ; Tacrolimus ; administration & dosage