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.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.
Antimalarials/pharmacology* ; China/epidemiology* ; Drug Combinations ; Drug Resistance/genetics* ; Folic Acid Antagonists/pharmacology* ; Humans ; Mutation ; Plasmodium vivax/genetics* ; Prevalence

Objective:To explore the potential immune mechanism of pediatric ABOi-LDLT presenting low humoral immune response to donor specific blood group antigen.Methods:From June 2013 to December 2020, clinical data were retrospectively reviewed for 29 patients of long-term surviving pediatric ABOi-LDLT.There were A to O ABOi-LDLT( n=10)and B to O ABOi-LDLT( n=19). Graft types included left lateral lobe( n=26)and left hemi-liver( n=3). The median age of liver transplantation was 10 months, the median weight 8.0 kg and the median follow-up time 41.9 months.The titers of donor specific blood group antibodies and non-donor specific blood group antibodies(IgG, IgM)were continuously monitored before transplantation and at 1, 3, 6, 12, 24, 36 months post-transplantation.Protocol or event-based liver biopsy was performed to determine whether or not there was antibody-mediated rejection. Results:The titer of donor specific blood group antibody in recipients was significantly lower than that of non-donor specific blood group antibody( P<0.001). Among 18 protocol liver pathological biopsies, two cases were C4d positive for vascular endothelium.Five abnormal event-based liver biopsies were completed and one was C4d positive in bile duct endothelium.No pathological sign of typical blood group antibody mediated antigen-antibody complex mediated cascade immune reaction was detected in liver pathological biopsy.Typical pathological signs of blood group antibody mediated rejection were absent in protocol liver biopsy. Conclusions:Donor specific blood group antibody is expressed at a low level in pediatric ABOi-LDLT recipients.It presents as incomplete immune tolerance to donor specific blood group antigen.

Objective:To study the hepatic hemodynamics changes and pathophysiological mechanisms of the use of a functional shunt after auxillary liver transplantation to treat portal hypertension associated with a small-for-size graft.Methods:A retrospective analysis of the clinical data of patients with portal hypertension treated with functional shunting of small-volume grafts from a living donor liver at the Beijing Friendship Hospital, Capital Medical University from July 2014 to December 2018, and a total of 6 patients were included as the research objects, including 4 males and 2 females, with a median age of 35.5 (29.0-52.0) years old. Blood flow monitoring data were collected during and after operation, and the characteristics of liver hemodynamics were analyzed.Results:The portal venous blood flow of the remnant native liver gradually decreased to no flow. As a buffer response, the flow velocity of hepatic artery increased. The portal venous blood flow of the graft gradually increased in the early postoperative period and then gradually decreased from post-operation Day 5 to 10 due to gradual increase in portal venous resistance. However, the portal venous perfusion gradually increased from Day 10 after the operation, reached to a level and declined to a stable level about 1 month after the operation. The volume of abdominal drainage slowly decreased after the peak level at Day 5-10 after the operation, and disappeared completely at Day 30 after operation.Conclusions:When using auxiliary liver transplantation for functional shunting to treat portal hypertension, autologous residual liver can act as a guide buffer for the pressure gradient of portal vein hyperperfusion in liver transplantation, and reach a steady state of blood flow distribution about 1 month after surgery, while relying on autologous remnant liver hepatic artery buffer response prevents small liver syndrome.

Objective:To review our experience in the use of "Full right-Full left" split liver transplantation in adult-to adult or adult-to adult-size child.Methods:The clinical data of liver donors to 4 recipients of full right-full left split liver transplantation performed at Beijing Friendship Hospital of Capital Medical University from January to December 2019 were reviewed. The surgical methods of split liver transplantation, cold ischemia time, operation time, intraoperative blood transfusion, and postoperative complications and prognosis were analyzed.Results:The 4 recipients of complete right hepatic-left hepatic split liver transplantation included 3 adults and 1 heavy child (45 kg). Their ages ranged from 14 to 48 years, and body weight ranged from 45 to 61 kg. The end-stage liver disease model score were 21, 12, 41, and 30 points. The ratios of graft mass to recipient's body mass ranged from 0.85% to 1.35%. The cold ischemia time was 457-650 min, and the operation time was 460-575 min. Early liver function recovered smoothly in all the 4 patients after transplantation, and no small liver syndrome occurred. Patients were followed up to 6 months after operation. One patient developed anastomotic biliary leak, which was cured by endoscopic retrograde cholangiopancreatographic treatment. Another patient developed biliary stricture presenting with repeated biliary tract infection despite percutaneous transhepatic puncture biliary drainage. A third patient died six months from lung infection.Conclusion:In properly selected patients, using full right-full left hemiliver by split liver transplantation increased organ utilization and provided patients with increased treatment opportunities.

To analyzed a case of pediatric patient with propionic acidemia combined with dilated cardiomyopathy retrospectively, who underwent living donor liver transplantation at the Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University in March 2019.A 2 years and 6 months female child was admitted to hospital for propionic acidemia.The pretransplant echocardiogram showed left ventricular dilatation and systolic dysfunction, and thus dilated cardiomyopathy was considered.A living donor liver transplant was performed using her mother′s left latera-llobe.On the 14 months postoperatively, the child was on a liberated protein diet, but still required levocarnitine supplementation.Her hepatic and cardiac function returned normal, but growth retardation was still present.During the follow-up period, further propionic acidemia-related complications like metabolic decompensation, or any transplant-related complications were not reported.This case report suggested that liver transplantation is effective on pediatric propionic acidemia combined with cardiomyopathy, which reverses cardiomyopathy, improves cardiac function, relieves strict protein restriction, reduces the risk of metabolic decompensation, and significantly improves quality of life.

Objective:To explore the clinical feasibility and efficacy of using donated liver procured from donors complicated with intra-peritoneal widespread dissecting aneurysm.Methods:One case of liver donation was assigned to our center from COTRS. Intra-peritoneal widespread dissecting aneurysm was detected intraoperatively with an involvement of coeliac trunk until artery superior to bifercation of HA (hepatic artery). HA reconstruction was extremely challenging. With the final attempt of using donors artery next to hilus lienis as a bridge vessel, success of reconstruction was achieved.Results:During an early postoperative period, satisfactory graft blood flow was established without surgical complications, the patient was discharged smoothly. At Month 13, blood flow of graft remained decent.Conclusions:Through a review of the relevant articles, a few cases have been successful using of donated liver from donors with intra-peritoneal dissecting aneurysm as long as proper hepatic artery is not involved and the difficulty of HA reconstruction remains relatively low. As for widespread intra-peritoneal dissecting aneurysm, donor liver should be employed cautiously.

Objective To analyze the clinical characteristics, pathogenic causes and therapeutic experience of right diaphragmatic hernia after pediatric living donor liver transplantation. Methods Clinical data of 3 recipients with right diaphragmatic hernia after pediatric living donor liver transplantation were retrospectively analyzed. The clinical characteristics, diagnosis and treatment process and therapeutic experience were analyzed and summarized. Results The primary diseases of 3 children with diaphragmatic hernia after living donor liver transplantation were biliary atresia. The diaphragmatic hernia occurred at 4-6 months after liver transplantation. The contents of diaphragmatic hernia included the intraperitoneal and interperitoneal tissues and organs. Diaphragmatic defects were all located in the posterior medial area of the right diaphragm. The primary stage intermittently suturing repair was performed during intraoperative period. No diaphragmatic hernia recurred during long-term follow-up. Conclusions The clinical manifestations of right diaphragmatic hernia after pediatric living donor liver transplantation are diverse. The risk factors include malnutrition, low body weight, surgical trauma, chemical erosion caused by bile leakage, focal infection and pleural-peritoneal pressure gradient, etc. Surgical intervention is the preferred treatment strategy for diaphragmatic hernia after liver transplantation.

Objective To analyze the donor specific antibody (DSA) in liver transplantation,and discuss the therapeutic schemes.Methods We retrospectively analyzed prospectively collected samples from 139 cases of liver transplantation from September 1,2013 to July 1,2015.Luminex assays were applied to determine human leukocyte antigen,panel reactive antibody (PRA).For PRA positive cases,DSA,C1q and C4d were detected,and liver biopsy was done.Results Of 139 cases enrolled,there were 12 cases positive for DSAs,including 2 cases of PreDSA:1 case of Ⅰ DSA (HLA-A mismatch),and 1 case of Ⅱ DSA (HLA-DQ mismatch).Ten cases of de novo DSA (including 1 case of PreDSA) all were HLA-DQ mismatch.The liver biopsy on 5 cases showed hepatic fibrosis,early rejection and intrahepatic cholestasis,and only 2 cases showed positive C4d.Of 6 cases of DSA,5 cases showed positive C1q.In the patients positive for DSA,tacrolimus dose was adjusted postoperatively,adding mycophenolatemofetil or increasing its dose,or methylprednisolone and immunoglobulin given.Conclusion DSAs are important indicators of sensitized recipients in liver transplantation,associated with trends toward worse outcomes in patients or allografts.The monitoring of DSA is requisite in order to adjust the immunosuppressant.

Objective To Analyze the clinical outcomes of pediatric liver transplantation (LT) for liver-based metabolic disorders.Methods We conducted a retrospective analysis on 42 pediatric patients with liver-based metabolic disorders from June 2013 to March 2017,and analyzed the pediatric end stage liver disease model (PELD),growth and development,type of transplant,postoperative complications and prognosis of patients.Results There were 42 children with liver-based metabolic disorders (15.56%) out of all the 270 children who underwent LT.The median age was 51.0 months (range,3.4-160.9 months).Of the 42 children,19 received living donor liver transplantation (LDLT),18 cases received deceased donor liver transplantation (DDLT) and 5 cases received domino liver transplantation.1-,2-and 3-year cumulative survival rate of 42 recipients was 97.7%,93.6% and 93.6%,and that of the grafts was 95.3%,91.4% and 91.4%,respectively.As compared with the 194 children with biliary atresia who underwent LT,significant difference was found in PELD and weight Z-score between the two groups.Conclusion Liver transplantation is a valuable option for children with metabolic disorders,and it has gained a better prognosis.