Wei Rao

Tacrolimus-related seizure after pediatric liver transplantation – A single-center experience

To identify the risk factors for new‐onset seizures after pediatric LT and to assess their clinical implications and long‐term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non‐seizures group. Pre‐operative, intra‐operative, and post‐operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic–clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end‐stage liver disease score before surgery, Child–Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure‐free without anti‐epileptic drugs over a mean follow‐up period of 33.7 ± 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post‐operative period after pediatric LT. High PELD and Child‐Pugh scores before LT and high post‐operative serum Tbil may be contributory risk factors for TAC‐related seizures.

Outcomes in children with biliary atresia following liver transplantation

BACKGROUND Congenital biliary atresia is a rare condition characterized by idiopathic dysgenesis of the bile ducts. If untreated, congenital biliary atresia leads to liver cirrhosis, liver failure and premature death. The present study aimed to evaluate the outcomes of orthotopic liver transplantation in children with biliary atresia. METHOD We retrospectively analyzed 45 patients with biliary atresia who had undergone orthotopic liver transplantation from September 2006 to August 2012. RESULTS The median age of the patients was 11.0 months (5-102). Of the 45 patients, 41 were younger than 3 years old. Their median weight was 9.0 kg (4.5-29.0), 34 of the 45 patients were less than 10 kg. Thirty-one patients had undergone Kasai portoenterostomy prior to orthotopic liver transplantation. We performed 30 living donor liver transplants and 15 split liver transplants. Six patients died during a follow-up. The median follow-up time of surviving patients was 11.4 months (1.4-73.7). The overall 1-, 2- and 3-year survival rates were 88.9%, 84.4% and 84.4%, respectively. CONCLUSION With advances in surgical techniques and management, children with biliary atresia after liver transplantation can achieve satisfactory survival in China, although there remains a high risk of complications in the early postoperative period.

Occult hepatitis B virus infection predicts de novo hepatitis B infection in patients with alcoholic cirrhosis after liver transplantation.

Occult hepatitis B virus infection (OBI) in patients undergoing liver transplantation (LT) is a suspected source of de novo hepatitis B virus (HBV) infection after LT. This study aimed to investigate the prevalence of OBI in liver transplant recipients with alcoholic cirrhosis and demonstrate the association between OBI and de novo HBV infection after LT in these patients.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

The Population Pharmacokinetic Models of Tacrolimus in Chinese Adult Liver Transplantation Patients.

Aim. The aim of this study was to establish population pharmacokinetic models of tacrolimus in Chinese adult liver transplantation patients. Methods. Tacrolimus dose and concentration data (n = 435) were obtained from 47 Chinese adult liver transplant recipients, and the data were analyzed using a nonlinear mixed-effect modeling (NONMEM) method. Results. The structural model was a two-compartment model with first-order absorption. The typical population values of tacrolimus for the pharmacokinetic parameters of apparent clearance (CL/F), apparent distribution volume of the central compartment (V 2/F), intercompartmental clearance (Q/F), apparent distribution volume of the peripheral compartment (V 3/F), and absorption rate (k a) were 11.2 L/h, 406 L, 57.3 L/h, 503 L, and 0.723 h−1, respectively. The interindividual variabilities of these parameters were 16.2%, 163%, 19.7%, 199%, and 74.3%, respectively, and the intraindividual variability of observed concentration was 26.54%. The covariates retained in the final models were postoperative days (POD) and dosage per day (DOSE) on CL/F. Conclusion. Population pharmacokinetic models of tacrolimus were developed in Chinese adult liver transplant patients. These results could provide the interpretation of the outcome of pharmacokinetics modeling and the impact of covariate tested on individualized tacrolimus therapy.

A limited sampling strategy for tacrolimus in liver transplant patients.

To develop limited sampling strategy (LSS) equations to estimate area under the curve (AUC0-12) in Chinese adult transplant patients. 26 adult liver transplant patients were included in this study. The blood samples, collected within 12 hours, were analyzed by microparticle enzyme immunoassay. By multiple stepwise linear regression analysis, LSS equations were identified. The predictive performance of these models was validated by the jackknife technique. As a result, the two sampling time point (trough and 4 hours postdose) model accurately predicted AUC0-12. (R2 = 0.949, ICC = 0.976). The two-point LSS equation (AUC0-12 = 7.26 + (2.17·C0) + (8.30·C4)) can be used as a predictable measure of AUC0-12 of tacrolimus in Chinese liver transplant patients.

Risk factors for de novo hepatitis B infection in pediatric living donor liver transplantation.

AIM To investigate the incidence of de novo hepatitis B virus (HBV) infection after pediatric living donor liver transplantation (LDLT) and to analyze the risk factors associated with this de novo HBV infection. METHODS The clinical and laboratory data of children who underwent LDLT from June 2010 to September 2012 in First Center Hospital in Tianjin, China, were retrospectively included in the study. Intrahepatic HBV DNA in donors and recipients was quantified by real-time polymerase chain reaction using DNA extracted from formalin-fixed, paraffin-embedded tissues. RESULTS Between June 2010 to September 2012, 32 consecutive pediatric patients underwent LDLT in our institute. Thirty LDLT patients (13 girls and 17 boys) were followed up for a median of 15 mo, of whom 53.3% (16/30) were hepatitis B core antibody (HBcAb) positive and 36.7% (11/30) were hepatitis B surface antibody (HBsAb)/HBcAb positive before transplantation. Sixteen of the children received HBcAb-positive allografts, and 43.7% (7/16) of the grafts were found to be intrahepatic HBV DNA positive. De novo HBV infection developed in 16.1% (5/30) of the children within a median of 11 mo after transplantation. All five of the HBV-infected children had received HBcAb-positive allografts, four of which were intrahepatic HBV DNA positive. Two of the children developed de novo HBV infection despite the preoperative presence of both HBsAb and HBcAb CONCLUSION In pediatric recipients, positive intrahepatic HBV DNA in allografts could be a risk factor for de novo HBV infection from HBcAb-positive allografts. HBsAb/HBcAb positivity in pediatric LDLT patients before transplantation exhibited only weak effectiveness in protecting them against de novo HBV infection from HBcAb-positive allografts.

Successful percutaneous transluminal balloon dilatation for hepatic venous outflow obstruction after pediatric liver transplantation: A series of cases.

Whether percutaneous transluminal balloon dilatation (PTBD) or stent placement should be used in children with hepatic venous outflow obstruction (HVOO) is still controversial. The aim of the present study was to retrospectively describe experience in diagnosis and treatment of HVOO and to evaluate the outcome of PTBD in HVOO patients after pediatric liver transplantation (P‐LT).