Thirty-five consecutive pediatric living donor liver transplantation: experiences and lessons learned from a single center.

BACKGROUND/AIMS: In the last 10 years, the early patient outcome of liver transplantation in children have significantly improved. Now the overall outcomes of pediatric LT are promising. METHODOLOGY: In this study, we review the outcome of all pediatric liver transplants performed at our center and analyze our experiences with pediatric liver transplant. Of the 34 liver transplant recipients, 26 were highly urgent (19.7%). RESULTS: Actuarial patient survival rates at 6, 12, and 36 months was 82.9%, 79.8% and 72.2%, respectively. Indications for liver transplant were biliary atresia (n = 22), Wilson's disease (n = 4), glycogen storage disease (n = 3), portal vein cavernous transformation (PVCT) (n = 3), fulminant liver failure (n = 1), and cryptogenic cirrhosis (n = 1). The main complications were surgical complications (including biliary complications, portal vein or arterial complications, intestinal perforation, postoperative bleeding, of which 20% required reoperation) and infections. Cyclosporine was the primary immunosuppressive agent used in 70.6% of patients, with a 26.5% incidence of acute allograft rejection within the first six months. One children underwent re-transplant as a result of hepatic artery thrombosis. Nine children died during followup. They were related to portal vein thrombosis (one), chronic rejection (one), sepsis (one), post-transplant lymphoproliferative disease (one) and so on. CONCLUSIONS: The overall outcomes of pediatric liver transplantation at our center are promising. Advances in post-transplant care and monitoring of the recipients, technical refinements enable these results.

The pre-Kasai procedure in living donor liver transplantation for children with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a major cause of chronic cholestasis, a fatal disorder in infants. This study was undertaken to evaluate the safety and effectiveness of primary living donor liver transplantation (LDLT) in comparison with the traditional first-line treatment, the Kasai procedure. METHODS: We assessed 28 children with BA at age of less than two years (3-21.3 months) who had undergone LDLT in two hospitals in Southwest China during the period of 2008-2011. Eighteen children who had had primary LDLT were included in a primary LDLT group, and ten children who had undergone the Kasai operation in a pre-Kasai group. All patients were followed up after discharge from the hospital. The records of the BA patients and donors were reviewed. RESULTS: The time of follow-up ranged 12-44.5 months with a median of 31 months. The 30-day and 1-year survival rates were 85.7% and 78.6%, respectively. There was no significant difference in the 30-day or 1-year survival between the two groups (83.3% vs 90% and 77.8% vs 80%, P>0.05). The main cause of death was hepatic artery thrombosis. There were more patients with complications who required intensive medical care or re-operation in the pre-Kasai group (8, 80%) than in the primary LDLT group (9, 50%) (P=0.226). But no significant differences were observed in operating time (9.3 vs 8.9 hours, P=0.77), intraoperative blood loss (208.6 vs 197.0 mL, P=0.84) and blood transfusion (105.6 vs 100.0 mL, P=0.91) between the two groups. The durations of ICU and hospital stay in the primary LDLT group and pre-Kasai group were 180.4 vs 157.7 hours (P=0.18) and 27 vs 29 days (P=0.29), respectively. CONCLUSIONS: Primary LDLT is a safe and efficient management for young pediatric patients with BA. Compared with the outcome of LDLT for patients receiving a previous Kasai operation, a similar survival rate and a low rate of re-operation and intensive medical care for patients with BA can be obtained.

[Clinical analysis of early postoperative pulmonary infection in children after living donor liver transplantation].

OBJECTIVE: To analyze the condition of early (≤ 30 d) postoperative pulmonary infection in children after living donor liver transplantation (LDLT). METHOD: The clinical data of 36 cases undergoing LDLT in Children's Hospital of Chongqing Medical University were analyzed retrospectively from June 2006 to December 2009. RESULT: Of 36 cases without preoperative respiratory disease, 17 were boys, 19 were girls. Their age ranged from 2 months to 14 years. Pulmonary infection developed in 24 patients, of whom 4 cases died (17%) and 3 deaths were related to pulmonary infection. Pulmonary infection occurred in 17 of 20 infants (85%) and 10 of 11 cases (91%) with liver function of Child-Pugh grade C. Twenty cases (83%) developed pulmonary infection within first 2 weeks after LDLT. Totally 65 pathogenic strains of microorganisms were isolated, in which Gram-negative bacteria, Gram-positive bacteria and fungi were 46 strains, 5 strains, 14 strains respectively. The most frequently isolated bacteria were Pseudomonas aeruginosa (14 strains), Klebsiella pneumoniae (8 strains) and Acinetobacter baumannii (8 strains). Pseudomonas aeruginosa showed a resistance rate of almost 100% to cotrimoxazole, tetracycline, chloramphenicol, ampicillin, the first, the second and some of the third generation cephalosporins. Klebsiella pneumoniae producing extended spectrum beta-lactamase had a resistance rate of almost 100% to beta-lactams except carbapenems. Acinetobacter baumannii was exquisitely susceptible to carbapenems, but showed a high resistance to penicillins and cephalosporins. Candida albicans, which was the most common fungus, showed a susceptibility rate of 100% to amphotericin B. In the LDLT recipients of pulmonary infection, cytomegalovirus (CMV) infections occurred in 2 patients and Epstein Barr virus (EBV) infection in 1 patient. CONCLUSION: The incidence of early postoperative pulmonary infection was high in children undergoing LDLT, especially in infants. And the mortality should not be ignored. The high risk period for infection was within the first 2 weeks after operation. The pathogens were mainly Gram-negative bacteria, which showed high and multidrug resistance.

Combinatory effects of hepatic CD8+ and NK lymphocytes in bile duct injury from biliary atresia.

INTRODUCTION: To our knowledge, elucidating the immune pathogenesis of disease, especially characteristic T-cell and natural killer (NK) cell expansions, has not been performed before now. We investigated the role of T lymphocytes and NK lymphocytes in the destruction of extrahepatic bile ducts of patients with biliary atresia. METHODS: Lymphocytes from the liver and extrahepatic bile duct remnants of patients with biliary atresia were characterized by immunofluorescence staining, fluorescence-activated cell sorter analysis, and real-time reverse-transcriptase PCR. Cholangiocyte lysis assays were performed to confirm cytotoxicity of activated hepatic NK lymphocytes or CD8(+) cells. RESULTS: The inflammatory milieu from portal tracts and/or biliary remnants consisted of greater numbers of Kupffer cells, T lymphocytes, and NK lymphocytes in the patients with biliary atresia as compared with the cholestatic and noncholestatic controls. In patients with biliary atresia, expression of NK or CD8+ costimulatory molecules was upregulated as compared with controls. Hepatic NK lymphocytes or CD8(+) cells from patients with biliary atresia were demonstrated to be cytotoxic to the duct epithelium. DISCUSSION: Specific immune responses from NK and CD8(+) cells were involved in the injury to the duct epithelium and play a significant role in the phenotype of experimental biliary atresia.

Sixty-four-slice computed tomography in surgical strategy of portal vein cavernous transformation.

AIM: To investigate the role of 64-slice computed tomography (CT) in portal vein cavernous transformation to determine surgical strategy. METHODS: The site of lesions and extent of collateral circulation in 12 pediatric cases of cavernous transformation of the portal vein with surgical treatment were analyzed. RESULTS: Eleven of 12 children had esophageal varices and were treated with lower esophageal and gastric devascularization and splenectomy, and the other case was only treated with splenectomy. There were eight cases with spontaneous spleen/stomach-renal shunt, four with Retzius vein opening, which was reserved during surgery. Three cases of lesions involving the intrahepatic portal vein (PV) were treated with living donor liver transplantation. One patient died from PV thrombosis after liver transplantation, and the rest had no significant complications. CONCLUSION: The PV, its branches and collateral circulation were clearly seen by 64-slice spiral CT angiography, which helped with preoperative surgical planning.

Usage of 64-detector-row spiral computed tomography volumetry in preoperative volume prediction in living donor liver transplantation in children.

PURPOSE: To investigate the correlation between the graft volume calculated by 64-detector-row spiral computed tomography (CT) and the graft weight measured during the living donor liver transplantation (LDLT) operation, and try to get an equation to help determine the possible weight of graft before operation. METHODS: 23 donors with left lateral lobe LDLT were enrolled to undergo 64-detector-row spiral CT and the imaging data at the hepatic venous phase was used for whole and partial liver volumetric measurement on a dedicated image postprocessing workstation. The resected part of donor liver was weighed during the operation. Statistical analysis with SPSS15.0 was used to analyze the correlation between the estimated liver volume by CT and the actual graft weight. RESULTS: The graft volume calculated preoperatively by CT (293.35 ± 53.43 ml) was significantly larger than measured graft weight during the operation (252.82 ± 50.96 g) (P < 0.05). All corresponding pre- and intraoperative data correlated significantly (R = 0.885) (P < 0.001). Intraoperatively expected weight (W (intraop)) in grams and volume calculated preoperatively by CT (V (preop)) in milliliters can be calculated with the equation W (intraop) (g) = 0.844 × V (preop) (ml) + 5.271. CONCLUSION: Liver volume calculated by 64-detector-row spiral CT preoperatively can predict the actual graft weight, which is very useful in donor selection in LDLT.

Analysis of biliary epithelial-mesenchymal transition in portal tract fibrogenesis in biliary atresia.

BACKGROUND: The cellular origin of myofibroblast in the liver fibrosis remains unclear. This study was designed to investigate whether biliary epithelial cells (BECs) undergoing epithelial-mesenchymal transition (EMT) might be found in patients with biliary atresia, thereby serving as a source of fibrotic myofibroblasts. METHODS: Liver sections from patients with biliary atresia were evaluated to detect antigen for the BECs marker 4 and cytokeratin-7 (CK-7), proteins (fibroblast-specific protein 1, also known S100A4; the collagen chaperone heat shock protein 47, HSP47) characteristically expressed by cells undergoing EMT, as well as myofibroblasts marker a-smooth muscle actin (a-SMA). RESULTS: Normal bile ducts BECs could express CK-7 and low levels of a-SMA; they did not express S100A4 and HSP47. However, BECs from biliary atresia resulted in increased expression of a-SMA, S100A4, with concurrent transition to a fibroblast-like morphology and decreased expression of AK-7. Furthermore, BECs in biliary atresia were associated with significant bile ductular proliferation and coexpressed both epithelial and mesenchymal markers. CONCLUSIONS: From significant histologic evidence, the BECs forming small- and medium-sized bile ducts undergoing EMT may account for prominent bile ductular proliferation and directly contribute to fibrogenesis in BA.

[Clinical study of 28 patients with adult-to-infant living donor liver transplantation].

OBJECTIVE: To summarize our experience in adult-to-infant living donor liver transplantation (A-ILDLT) and to analyze the efficacy and complications of A-ILDLT. METHODS: The clinical data, surgical strategies and complications of 28 adult donors and infantile recipients who underwent A-ILDLT from April 2006 to December 2009 were retrospectively analyzed. These 28 patients (14 boys and 14 girls) aged from 80 days to 11.5 months with body weights of 3.08 to 10.3 kg at the time of operation . They suffered from biliary atresia with decompensated cirrhosis. The living donors were 15 mothers, 9 fathers, 3 grandma and 1 elder brother with ABO compatible with the infantile recipients. 27 Donor organs were the left lateral lobe grafts (segment II, III) and 1 graft was segment II. All patients were followed up for 5 to 24 months. RESULTS: These grafts were orthotopically transplanted into the infantile recipients. The average length of stay was 9.3 days for the donor group without any complications. Postoperative immunosuppression included prednisone, Cyclosporin and mycophenolate mofetil (MMF). A total of 24 postoperative complications occurred in 20 recipients, including 5 vascular complications, 4 bleeding, 7 pneumonia, 2 bowel obstruction, 4 intestinal perforation and 3 rejection. Three recipients died of hepatic arterial thrombosis (HAT). The perioperative mortality rate of recipients was 10.7% (3/28) and the survival rate was 89.3% in peroperative period. One died of stricture of hepatic vein and 1 of accidental asphyxia during follow-up term. At present, 23 cases are still alive. CONCLUSION: A-ILDLT has become an effective method to infants with end-stage liver disease. The postoperative vascular complication is the predominant cause of death.

Impact of human leukocyte antigen mismatching on outcomes of liver transplantation: a meta-analysis.

AIM: To assess the effect of human leukocyte antigen (HLA) mismatching on liver graft outcome and acute rejection from a meta-analysis of available cohort studies. METHODS: Articles in PubMed/MEDLINE, EMBASE and the Cochrane database from January 1970 to June 2009, including non-English literature identified in these databases, were searched. Only studies comparing HLA or sub-phenotype matching with mismatching were extracted. The percentage of graft survival was extracted by "Engauge Digitizer" from survival curves if the raw data were not displayed. A meta-analysis was performed when at least 3 studies provided data. RESULTS: Sixteen studies met the inclusion criteria. A lower number of HLA mismatches (0-2 vs 3-6) did reduce the incidence of acute rejection (relative risk: 0.77, P = 0.03). The degree of HLA mismatching (0-2 vs 3-6) had no significant effect on 1-year [hazard ratio (HR): 1.04, P = 0.68] and 5-year (HR: 1.09, P = 0.38) graft survival. In sub-phenotype analysis, the degree of HLA-A, B and DR mismatching (0 vs 1-2) had no significant effect on 1-year and 5-year graft survival, either. The HRs and P-values were 0.95, 0.71 (HLA-A, 1-year); 1.06, 0.60 (HLA-A, 5-year); 0.77, 0.16 (HLA-B, 1-year); 1.07, 0.56 (HLA-DR, 1-year); 1.18, 0.23 (HLA-DR, 5-year), respectively. CONCLUSION: The results of this systematic review imply that good HLA compatibility can reduce the incidence of acute rejection in spite of having no influence on graft outcomes. To obtain a short recovery time and minimize rejection post transplantation, HLA matching studies should be considered before the operation.

[Establishment and identification of bone morrow specific transgenic mouse model with tumorigenesis by mutant Myc retrovirus infection.].

OBJECTIVE: To establish a novel Myc gene transgenic mouse model for spontaneously forming B-lymphoma and assessing its tumorigenesis potential. METHODS: Freshly isolated hematopoietic progenitor cells served as the target for Myc gene transfer mediated by a retrovirus vector. These cells were engrafted into C57BL/6 mice with (60)Co-gamma ray radiation in advance. Tumor latency was measured and the tumor loaded mice were followed for survival time. Tumor was identified with histology and immunostaining. The exogenous Myc gene was detected by Western blot (in liver, spleen, tumor tissue) and flow cytometry (FCM) \[in bone marrow (BM)\]. RESULTS: Mice BM-infected with mutant Myc gene more readily gave rise to B-cell lymphomas than those infected with wild type Myc gene did Myc gene was expressed highly in BM and tumor tissues but not in liver and spleen. CONCLUSION: Our model will be a tool in assessing the transforming potential of Myc mutants and in studying cooperation between Myc and other oncogenes. Mutant Myc is more effective than wild-type Myc in promoting B cell lymphomagenesis in mice.

[Retrospective analysis of maternal and infant birth features of hepatoblastoma patients].

OBJECTIVE: To explore the risk factors for hepatoblastoma. METHODS: A case-cohort study using Logistic regression multiple variables analysis of medical record data sets was conducted to examine infant and perinatal risk factors for hepatoblastoma. RESULTS: Birth weight less than 1,000 g was associated with a strongly increased risk of hepatoblastoma (odds risk, OR = 26.0, 95% confidence interval, CI: 14.0 to 65.7). After adjustment of birth weight, a moderately increased risk of hepatoblastoma was found for older maternal age ( > 35 years vs. 20 to 34 years: OR = 2.6, 95% CI: 0.9 to 5.9), maternal smoking (OR = 2.9, 95% CI: 1.1 to 4.2) and higher maternal pregnancy body mass index (OR = 3.2, 95% CI: 1.0 to 6.7). CONCLUSION: Very low birth weight and maternal characteristics including overweight, smoking are associated with hepatoblastoma risk.