Objective:To evaluate the efficacy and safety of once-daily tacrolimus extended-release capsules (OD-TAC) in pediatric liver transplant recipients after conversion from twice-daily tacrolimus (TD-TAC).Methods:A retrospective analysis was performed on pediatric liver transplant recipients at Tianjin First Center Hospital between January 2014 and December 2020 who were converted from TD-TAC to OD-TAC with a follow-up of at least 12 months. After conversion, all patients received OD-TAC monotherapy. The daily dose conversion ratio from TD-TAC to OD-TAC ranged from 2∶1 to 1∶2. Clinical data including demographics, tacrolimus dosage, trough concentrations, liver function, and adverse events were collected. Continuous variables with normal distribution were expressed as Mean±SD and compared using independent-samples t-test or ANOVA; non-normally distributed variables were expressed as median ( Q1, Q3) and compared using Mann-Whitney U or Kruskal-Wallis H tests. Categorical variables were expressed as frequency and percentage, and compared using χ 2 test or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 290 children were enrolled, including 140 males (48.3%) and 150 females (51.7%). The median age at transplantation was 7.34 (6.03, 12.34) months, and the median time to conversion was 36 (29, 48) months post-transplant. Tacrolimus daily doses at 3, 6, and 12 months after conversion were slightly higher than before conversion, but without statistical significance (all P>0.05). Trough tacrolimus levels at 6 and 12 months after conversion were 2.34±1.02 μg/L and 2.23±1.07 μg/L, respectively, both lower than pre-conversion (2.77±1.43 μg/L), with statistical significance ( P=0.02 and P<0.01). Serum creatinine levels at 6 and 12 months post-conversion were 2.63±0.63 mmol/L and 2.76±0.68 mmol/L, respectively, both higher than before conversion (2.57±1.90 mmol/L, P<0.05). Triglyceride level at 12 months post-conversion was 0.87±0.25 mmol/L, significantly lower than pre-conversion (1.05±0.55 mmol/L, P<0.05). Two patients developed transient bilirubin elevation at 3 months, and another two developed transient triglyceride elevation at 6 months; all recovered without intervention. No new-onset diabetes was observed during follow-up. Thirteen patients experienced acute rejection. One patient (0.3%) died three years after conversion due to hepatic venous outflow obstruction, while all others survived. Conclusion:In pediatric liver transplant recipients, OD-TAC provides comparable efficacy and safety to TD-TAC.

Objective:To evaluate the efficacy and safety of once-daily tacrolimus extended-release capsules (OD-TAC) in pediatric liver transplant recipients after conversion from twice-daily tacrolimus (TD-TAC).Methods:A retrospective analysis was performed on pediatric liver transplant recipients at Tianjin First Center Hospital between January 2014 and December 2020 who were converted from TD-TAC to OD-TAC with a follow-up of at least 12 months. After conversion, all patients received OD-TAC monotherapy. The daily dose conversion ratio from TD-TAC to OD-TAC ranged from 2∶1 to 1∶2. Clinical data including demographics, tacrolimus dosage, trough concentrations, liver function, and adverse events were collected. Continuous variables with normal distribution were expressed as Mean±SD and compared using independent-samples t-test or ANOVA; non-normally distributed variables were expressed as median ( Q1, Q3) and compared using Mann-Whitney U or Kruskal-Wallis H tests. Categorical variables were expressed as frequency and percentage, and compared using χ 2 test or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 290 children were enrolled, including 140 males (48.3%) and 150 females (51.7%). The median age at transplantation was 7.34 (6.03, 12.34) months, and the median time to conversion was 36 (29, 48) months post-transplant. Tacrolimus daily doses at 3, 6, and 12 months after conversion were slightly higher than before conversion, but without statistical significance (all P>0.05). Trough tacrolimus levels at 6 and 12 months after conversion were 2.34±1.02 μg/L and 2.23±1.07 μg/L, respectively, both lower than pre-conversion (2.77±1.43 μg/L), with statistical significance ( P=0.02 and P<0.01). Serum creatinine levels at 6 and 12 months post-conversion were 2.63±0.63 mmol/L and 2.76±0.68 mmol/L, respectively, both higher than before conversion (2.57±1.90 mmol/L, P<0.05). Triglyceride level at 12 months post-conversion was 0.87±0.25 mmol/L, significantly lower than pre-conversion (1.05±0.55 mmol/L, P<0.05). Two patients developed transient bilirubin elevation at 3 months, and another two developed transient triglyceride elevation at 6 months; all recovered without intervention. No new-onset diabetes was observed during follow-up. Thirteen patients experienced acute rejection. One patient (0.3%) died three years after conversion due to hepatic venous outflow obstruction, while all others survived. Conclusion:In pediatric liver transplant recipients, OD-TAC provides comparable efficacy and safety to TD-TAC.

Objective:To explore the effects of graft recipient weight ratio (GRWR) on the early prognosis (within 1 year after operation) of recipients of different ages after split liver transplantation (SLT) in children.Methods:From April 2015 to December 2022, the relevant clinical data were retrospectively reviewed for 188 children aged under 12 years undergoing initial SLT. Based upon operative age, they were assigned into groups of L (age≤18 months, 123 cases) and H (18 months< age≤12 years, 65 cases). Draw receiver operating characteristic (ROC) curves for predicting survival rates in H and L groups using GRWR and determine the cut-off value, and subgroup dassification was based the value. Compare the general condition, intraoperative condition, postoperative condition, and major complications of recipients. Follow-ups were conducted until 12 months post-SLT, death or retransplantation within 12months post-SLT. Kaplan-Meier survival rate analysis was utilized for comparing early postoperative survival rate of recipient/graft. The incidence of major early postoperative complications was examined by χ2 test or Fisher exact probability method. Results:The survival rate of recipients at Month 12 post-SLT was 92.6% (174/188), and graft survival rate was 91.0% (171/188). The survival rate of recipients in group L at Month 12 post-SLT was 94.3% (116/123), and graft survival rate was 92.7% (114/123). The GRWR value determined of 3.1 %. According to the level of GRWR, group L was divided into groups of L-L (GRWR≤3.1%, 36 cases) and L-H (GRWR>3.1%, 87 cases) while group H groups of H-L (GRWR≤3.1%, 55 cases) and H-H (GRWR>3.1%, 10 cases). The survival rates of recipients in groups L-L/L-H were 88.9% (32/36) and 96.6% (84/87) at Month 12 post-SLT. Inter-group difference was not statistically significant ( P=0.077). Graft survival rates were 83.3% (30/36) and 96.6% (84/87 ). Inter-group difference was statistically significant ( P=0.007). The intraoperative cold ischemia time were 479.0 (194.0, 593.0) min and 204.0 (122.0, 495.0) min in groups L-L/L-H. Inter-group difference was statistically significant ( P=0.002 ). The incidence of hepatic artery thrombosis were 13.9 % (5/36) and 2.3 % (2/87) in groups L-L/L-H. Inter-group difference was statistically significant ( P=0.036). The survival rate of recipients in group H at Month 12 post-SLT was 89.2% (58/65), and graft survival rate was 87.7% (57/65). No significant inter-group difference existed during surgery ( P>0.05 ). The survival rates of recipients in group H-L/H-H at Month 12 post-SLT were 92.7 % (51 /55) and 70.0 % (7/10 ). Inter-group difference was statistically significant ( P=0.019). Graft survival rates were 90.9% (50/55) and 70.0% (7/10). Inter-group difference was statistically significant ( P=0.036). No significant inter-group difference existed in the incidence of complications ( P>0.05) . Conclusion:During pediatric SLT, recipients of different ages have different requirements for GRWR. GRWR≤3.1 % implies poor early prognosis of recipients aged ≤18 months and GRWR>3.1% is associated with poor early prognosis of recipients aged between 18 months and 12 years.

Objective:To explore the risk factors and treatments of portal vein thrombosis (PVT) in children after pediatric living donor liver transplantation (pLDLT) .Method:From January 2014 to December 2021, the relevant clinical data were retrospectively reviewed for 975 LDLT children at Department of Pediatric Organ Transplantation of Tianjin First Central Hospital. Based upon the postoperative occurrence of PVT, they were assigned into two groups of PVT (19 cases) and non-PVT (956 cases). Univariate and multivariate analyses were performed for screening the risk factors of PVT post-LDLT and discussing the managements and prognoses of PVT.Result:Among them, overall incidence of PVT post-LDLT was 1.9% (19/975), and median time for an initial occurrence of PVT 8 (1-495) day. Single-factor analysis indicated that donor height ( P=0.014), operative duration ( P=0.002) and vascular interposition ( P=0.001) were correlated with the occurrence of postoperative PVT post-pLDLT. Multifactorial analysis revealed that operative duration ( P=0.008) and vascular interposition ( P<0.01) were independent risk factors for PVT post-pLDLT. For 19 cases of postoperative PVT, the measures included surgical thrombectomy (8 cases), urokinase thrombolysis plus warfarin anticoagulation (3 cases), interventional treatment (3 cases), warfarin anticoagulation (4 cases) and retransplantation (1 cases). After treatment, the outcomes were a disappearance of PVT (15 cases), symptomatic improvement (2 cases) and unrelated mortality (2 cases) . Conclusion:During pLDLT, intraoperative placement of blood vessels and operative duration are independent risk factors for the occurrence of PVT. Timely standardized treatment may achieve satisfactory therapeutic outcomes.

Mice ; Animals ; Tandem Mass Spectrometry ; Alpha-Amanitin ; Chromatography, Liquid ; Metabolomics ; Chromatography, High Pressure Liquid/methods*

Objective:To evaluate the effect of parental liver donation on early acute cellular rejection(ACR)after liver transplantation(LT)in children aged under one year.Methods:From January 2018 to January 2021, retrospective review is conducted for clinical data of living donor LT recipients and donors aged under 1 year at Tianjin First Central Hospital.Donor livers are assigned into two groups of paternal donor liver(156 cases)and maternal donor liver(206 cases)according to the source of donor liver, Clinical characteristics and postoperative ACR occurrence of two groups are analyzed.Results:The rates of ACR during early postoperative period is 14.9%(54/362), 20.5%(32/156)in paternal liver donor group and 10.7%(22/206)in maternal liver donor group.There is statistically significant difference(λ 2=6.763, P=0.009).In analysis of gender matching of donor recipients, the rates of ACR is 22.6% in paternal donor group and 10.3% in maternal donor group.There is statistically significant difference(λ 2=5.411, P=0.020).Median time of initial postoperative ACR is 13.00(8.25~20.25)day in paternal liver donor group and 17.00(9.00~28.25)day in maternal donor group.The difference is not statistically significant( P>0.05). ACR is mostly mild-to-moderate in two groups . Conclusions:In living donor LT for children aged under 1 year, the rates of early ACR is lower for maternal donor than that for paternal donor, especially in female recipients.

Objective:To explore the relationship between serum lactate level and early prognosis after liver transplantation (LT) in children.Methods:Between January 1, 2018 and December 31, 2020, 675 pediatric LT recipients were recruited. Clinical data were retrospectively reviewed, early postoperative serum lactate level and clearance rate recorded and receiver operating characteristic (ROC) curve plotted for determining optimal cut-off values. The inter-group differences in early postoperative complications and patient/graft survival rates were compared.Results:According to ROC, blood lactate levels >1.99 mmol/L at 12 h postoperatively were associated with early postoperative graft loss (AUC 0.73, 95% CI: 0.62-0.84, P=0.01). Age and weight of recipients in high-level group were 7.17(5.70-10.40) month and 7.00(6.00-8.60) kg and both were significantly lower than those in low-level group [7.80(6.21-13.58) month and 7.20(6.45-9.00) kg]. The inter-group differences were statistically significant ( P=0.017, P=0.034). Blood plasma transfusion volume, red blood cell transfusion volume, portal vein pressure pre-closure, postoperative intensive care unit (ICU) stay, ventilator use time, early allograft dysfunction rate, early postoperative pulmonary infection rate and recipient mortality rate in high-level group were 400 (200-400) ml, 2.00 (2.00-4.00) U, (15.71±4.44) mmHg, 2.50(2.00-3.00) day, 3.81(2.47-8.50) hour, 22.95%(42/185), 16.76%(31/185) and 6.49%(12/185) respectively. The above values were significantly higher than those in low-level group 200(100-400) ml, 2.00 (2.00-3.00) U, (14.69±4.68) mmHg, 2.00(2.00-3.00) day, 3.53(2.34-6.12) hour, 14.69%(72/490), 11.02%(54/490) and 1.43%(7/490) respectively. The inter-group differences were statistically significant ( P<0.001, P=0.014, P=0.015, P=0.037, P=0.043, P=0.011, P=0.045 & P<0.001). The incidence of early postoperative acute cellular rejection was significantly lower in high-level group than that in low-level group [11.89%(22/185) vs 22.86%(112/490)]. The inter-group difference was statistically significant ( P=0.01). The 1/3-month cumulative survival rates of patient/graft were 94.6%, 94.1% and 92.4%, 91.4% in high-level group versus 99.2%, 98.6% and 99.0%, 98.4% in low-level group. There were significant inter-group differences ( P=0, P<0.000 1). With a rising level of lactate at 12 h postoperatively, risk of early graft loss and early recipient mortality spiked markedly ( P<0.05). Conclusions:Serum lactate level post-operation is a valid predictor of early prognosis after LT in children.

Objective:To explore the predictive value of psoas muscle index(PMI)on early survival and complications after liver transplantation(LT)in children with biliary atresia(BA).Methods:Between January 1, 2016 and September 30, 2020, the relevant clinical data are retrospectively reviewed for 244 BA children undergoing LT at Department of Pediatric Liver Transplantation, Tianjin First Central Hospital.Total psoas muscle area(PMA)at the level of the third lumbar endplate is measured based upon preoperative abdominal computed tomography(CT)and normalized by the square of length for obtaining the value of PMI.According to the survival at Year 1 post-LT, receiver operating characteristic(ROC)curve is plotted and the cut-off value calculated.According to the cut-off value, they are divided into two groups of high PMI(173 cases)and low PMI(71 cases). Then the clinical data of 2 groups are compared.Kaplan-Meier survival curves at Year 1 post-LT are analyzed.And Cox proportional hazard model is utilized for conducting a multivariate analysis of early death.Results:The cut-off value of PMI is 534.6 mm 2/m 2.Two groups are compared in terms of age, gender, weight-for-age Z-score(WAZ), length-for-age Z-score(LAZ)and preoperative laboratory parameters ( P>0.05). Significant inter-group differences existed in the types of donors and surgery( P<0.05), and the median age of recipients in low PMI is higher than high PMI group(7.77months vs 6.57 months, P<0.01). The proportion of children with a history of Kasai surgery in low PMI group(78.87% vs 53.76%, P<0.01)and the median length of stay in hospital(23 d vs 20 d, P=0.03)is higher in low PMI group, but recipients(88.7% vs 97.1%, P<0.01)and grafts(87.3% vs 96%, P=0.01)1-year survival rate are lower.Multivariate analysis indicated that high PMI is a protective factor for early postoperative survival( HR=0.132, 95% CI: 0.028~0.626, P=0.011). Conclusions:PMI is an independent predictor of early survival post-LT and has a certain predictive value for early graft loss in BA children.

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ² test,or Fisher's exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.
Adolescent ; Adult ; Bilirubin ; Child ; End Stage Liver Disease/surgery* ; Fatty Liver/surgery* ; Female ; Graft Survival ; Humans ; Infant ; Infant, Newborn ; Liver ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Tissue Donors ; Young Adult

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ²=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ²=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ²=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ²=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.
Child ; Female ; Male ; Humans ; Hodgkin Disease ; Retrospective Studies ; Neoplasm Recurrence, Local ; China ; Antineoplastic Combined Chemotherapy Protocols ; Prognosis ; Disease-Free Survival