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Homozygous familial hypercholesterolemia (HoFH) is a rare and serious autosomal genetic metabolic disease. Patients without intervention often die younger than 30 years old from early atherosclerotic cardiovascular disease (ASCVD)incurred by extremely high levels of low-density lipoprotein cholesterol (LDL-C). We present a case of HoFH, a child with compound heterozygous mutation in this study. The effect of conventional lipid-lowering therapy through diet control and lipid-lowering drugs was unsatisfactory. The blood-lipid purification proves effective but has poor compliance and difficult to maintain for a longer time. The patient received orthotopic liver transplantation and had been followed for 2 years, with the patient shows normal LDL-C, well growth and development. We hope the case will provide the clinician with better understanding of the diagnosis and treatment of the rare disease of HoFH.
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Small-for-size syndrome is one of the most common and dangerous complications of partial liver transplantation. With the accumulation of clinical experiences and basic researches developed in recent years, new knowledge about the pathogenesis, pathophysiological process, prevention and treatment of small-for-size syndrome has been established. This article summarizes the progress of research on the small-for-size syndrome in recent years to help better diagnosis, prevention and treatment, thus improving the prognosis and long-term survival of patients.
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Objective:To explore health utility value, evaluate health-related quality-of-life(QOL)of pediatric liver transplantation(LT)recipients and examine its influencing factors to provide rationales for related health economic evaluations.Methods:This cross-sectional QOL was conducted through a questionnaire in pediatric LT recipients aged 5-17 years.The interviewees undergoing initial LT from June 2013 to September 2021 were reviewed regularly.Those children and their parents unwilling to participate or failing to understand the contents of questionnaire were excluded.The questionnaire was designed on the basis of Child Health Utility 9D Instrument(CHU9D)and answered online by one of primary caregiver.Chinese score system of CHU9D was employed for converting the responses into health utility values and the influencing factors were analyzed.Univariate analysis was performed by nonparametric tests and multivariate analysis by multiple linear regression model. P<0.05 was deemed as statistically significant. Results:A total of 140 valid questionnaires were obtained.Mean age of pediatric LT recipients was(7.95±2.74)years and mean postoperative time(4.90±2.17)years.Among them, 19 cases had experienced acute rejection and 101(72.1%)cases were living-related LT recipients.CHU9D scale indicated that average health utility value was(0.85±0.14)points.Univariate analysis revealed that age( P=0.008), education level( P<0.001)and primary disease( P=0.010)influenced the postoperative level of QOL.Multivariate analysis indicated that QOL was correlated with education level(behind schedule: 95% CI: -0.146, -0.034, P=0.002; leave of absence: 95% CI: -0.251, -0.068, P=0.001). Conclusions:Health utility of pediatric LT recipients is high with an excellent QOL.Poor QOL is associated with absence from school or dropping out of school.
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Objective:To investigate the application value of single-port laparoscopic left lateral donor liver acquisition in pediatric living donor liver transplantation (PLDLT).Methods:The retrospective and descriptive study was conducted. The clinical data of the donor and recipient who were admitted to Beijing Friendship Hospital of Capital Medical University for PLDLT in January 2020 were collected. The donor was a male, aged 28 years with body mass as 62 kg, height as 174 cm and body mass index (BMI) as 20.5 kg/m 2. The recipient was the daughter of the donor, aged 1 year with body mass as 9 kg, height as 75 cm and BMI as 16.0 kg/m 2. The donor underwent single-port laparoscopic left lateral donor liver acquisition. The recipient underwent living donor liver trans-plantation by the same operation team. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Results:(1) Intraoperative conditions. The donor under-went single-port laparoscopic left lateral donor liver acquisition successfully, with the single-port access system being placed through a transumbilical incision. The operation time, the warm ischemia time of the donor liver and volume of intraoperative blood loss were 240 minutes, 3 minutes and 40 mL, respectively, of the donor. The weight of the donor liver was 233.6 g, and the corrected graft-to-recipient body weight ratio was 2.60%. The recipient underwent living donor liver transplantation successfully. (2) Postoperative conditions. The donor began to take liquid diet at postoperative day 1, and results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT) and total bilirubin (TBil) of the donor was 239 U/L, 116 U/L, 53 U/L and 22.57 μmol/L. The donor began to take diet with high quality proteins at postoperative day 2, and to get for out-of-bed activities moderately. The donor′s peritoneal drainage fluid was light red at postoperative day 3, and no fluid accumulation was found in the operation area after abdominal B-ultrasound examination, so the peritoneal drainage tube was removed. The donor was discharged at postoperative day 4. The liver function of the recipient recovered to normal level 2 weeks after the operation. (3) Follow-up. The donor was followed up by outpatient examination 2 weeks after discharged, and results of laboratory examination showed that the ALT, AST, GGT and TBil was 44 U/L, 25 U/L, 53 U/L and 9.22 μmol/L, respectively. Neither the donor nor the recipient had complication ≥Ⅱ grade of the Clavien-Dino classification, such as biliary fistula and vascular complication during the 6 months after operation.Conclusion:Single-port laparoscopic left lateral donor liver acquisition can be used into the PLDLT.
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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.
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Objective:To investigate the role of signal lymphocyte activating molecule family member 5 (SLAMF5) in liver transplantation rejection in SD rats.Methods:Forty-five male SD rats without special pathogens, weight 260-300 g, aged 10-12 weeks were included. Among them, forty male SD rats (20 donors and 20 recipients respectively) were established with reference to the " two cuff" method. 15 liver transplantation model rats were randomly divided into 1 week (LT-1W) group, 2 weeks (LT-2W) group and 3 weeks (LT-3W) group, with 5 rats in each group, and 5 normal rats were taken as the normal control group. The expressions of SLAMF5, CD4 and CD8 were detected by polymerase chain reaction (PCR), Western blot and immunohistochemistry. The correlations between SLAMF5 expression in the lymphocyte infiltration area and the rejection activity index was analyzed.Results:The levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin were significantly higher in LT-1W group, LT-2W group and LT-3W group than those in the normal control group (all P<0.05). PCR results showed that the relative expression of SLAMF5 mRNA were (5.44±1.11), (4.69±1.12), (2.18±0.68) respectively, which were increased in LT-1W group, LT-2W group and LT-3W group than those in normal control group (1.01±0.23), and the differences were statistically significant (all P<0.05). Immunohistochemical staining showed that SLAMF5 and CD4, CD8 positive T cells were mainly distributed in the portal area, hepatic lobule area and around the proliferative bile duct, and there was a certain overlap. Correlation analysis showed that there was a positive correlation between the expression of SLAMF5 in the lymphocyte infiltration area and the rejection activity index ( r=0.519, P=0.048). Conclusion:The expression of SLAMF5 is increased after liver transplantation in SD rats, and there is a correlation between SLAMF5 expression and liver transplantation rejection in rats.
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V set and Ig domain containing 4 (VSIG4), a co-inhibitory molecule expressed by macrophages, is a B7 family-related protein. It can serve as the second signal of T cell activation and regulate the function of T cells. It has been found that VSIG4 is essential in maintaining immune tolerance. Moreover, VSIG4 can also act as a complement receptor, playing a role in recognizing pathogens, regulating the complement alternative pathway and inhibiting inflammatory response. This review summarized the expression of VSIG4 and its role in the immune system.
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Objective To evaluate the efficacy of liver transplantation for acute liver failure (ALF) in children. Methods Clinical data of 15 children with ALF who underwent liver transplantation were collected and retrospectively analyzed. The proportion of ALF among children undergoing liver transplantation during the same period was calculated. The characteristics, postoperative complications and clinical prognosis of ALF children receiving liver transplantation were analyzed. Results In the same period, the proportion of ALF was 2.0% (15/743) among pediatric recipients undergoing liver transplantation. All 15 children had acute onset of ALF, and most of them were accompanied by fever, diarrhea and progressive yellowing of skin and sclera. Thirteen children were complicated with hepatic encephalopathy before operation (6 cases of stage Ⅳ hepatic encephalopathy), and two children were complicated with myelosuppression and granulocytopenia before liver transplantation. Ten children underwent living donor liver transplantation with relative donor liver, 4 received liver transplantation from donation after cardiac death (DCD), and 1 underwent Domino donor-auxiliary liver transplantation. Of 15 children, 12 recipients had the same blood type with their donors, 1 recipient had compatible blood type with the donor and 2 cases had different blood type with their donors. Among 15 children, 10 cases developed postoperative complications. Postoperative cerebral edema occurred in 5 cases, of whom 4 cases died of diffuse cerebral edema, and the remaining case was in a persistent vegetative state (eyes-open coma). Postoperative cytomegalovirus (CMV) infection was seen in 5 cases. Two children presented with aplastic anemia and survived after bone marrow transplantation, 1 case died of CMV hepatitis and viral encephalitis, and 2 cases died of diffuse brain edema. One child developed graft-versus-host disease (GVHD) after liver transplantation, and died of septic shock after bone marrow transplantation. Nine children survived and obtained favorable liver function during postoperative follow-up. Conclusions Liver transplantation is an efficacious treatment for ALF in children, which may enhance the survival rate. Brain edema is the main cause of death in ALF children following liver transplantation, and treatment such as lowering intracranial pressure, improving brain metabolism and blood purification should be actively performed. Liver transplantation should be promptly performed prior to the incidence of irreversible neurological damage in ALF children, which might prolong the survival and enhance long-term prognosis.
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BACKGROUND@#Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression.@*METHODS@#The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation.@*RESULTS@#CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2.@*CONCLUSIONS@#CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.
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Animais , Humanos , Camundongos , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Proliferação de Células/genética , China , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , RNA Circular/genética , RNA MensageiroRESUMO
Objective:To explore the characteristics and significance of Epstein-Barr virus-infected lymphocyte cell types in peripheral blood mononuclear cells(PBMC)in post-transplant lymphoproliferative disorder(PTLD)after pediatric liver transplantation.Methods:From June 2013 to March 2021, retrospective data analysis was performed for 14 pediatric liver transplant recipients with PTLD.The determination of EBV-DNA in PBMC, plasma and TBNK lymphocyte cells was analyzed.Results:EBV-DNA in PBMC showed a high viral load(>10 4 copies/ml)and plasma EBV-DNA was >10 3 copies/ml( n=8). There were dominant B-cell-type infection( n=12)and T/NK-cell-type infection( n=2). After treatment, EBV-DNA in PBMC and plasma turned negative in 7 patients with a decline( n=6)and an increase( n=1). EBV-DNA in B lymphocyte became negative( n=10)with a decline( n=3). In one case, EBV-DNA increased in T, B and NK cells with a high viral load.The remainders recovered after treatment.One case of hemophagocytic syndrome died from a progression of PTLD. Conclusions:A large majority of EBV-related PTLD are dominated by B-cell-type infection and a few belong to T or NK-cell-type infection.Patients with T/NK-cell-type infection have a worse response to therapy and poorer prognosis than those with B-cell-type infection.Determination of EBV-infected lymphocyte cell types is of vital research value for treatment and prognosis.
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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.
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Argininemia is a rare autosomal recessive inherited disease, characterized by complex and diverse clinical symptoms.Its pathogenesis remains unclarified.The oligodendrocytes and neuro injury caused by energy meta-bolism disorders may account for neurosystem damage.The basic treatment methods for argininemia are the low-protein diet and nitrogen scavenger, which, however, cannot effectively prevent the progress of the neurological damage.Enzyme replacement or gene therapy is an ideal regimen for argininemia.However, gene editing therapy has not been applied in clinical practice.Liver transplantation (LT) is currently a practical option for argininemia treatment.Although LT cannot repair genetic defects in patients, but it can supplement arginase I, normalize plasma arginine and its metabolites, prevent progressive damage, relieve neurological symptoms, and improve the patients quality of life.For the low incidence of argininemia, it is not fully understood.In this paper, the clinical characteristics, pathogenesis, diagnosis, and treatment of argininemia were reviewed, in order to further more people′s understanding of this disease.
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Objective To evaluate the effect of liver transplantation on intestinal microflora in children with biliary atresia. Methods The fecal samples and liver function indexes of 16 children with biliary atresia before and 6 months after liver transplantation were collected, and 10 healthy children were selected as the healthy controls. DNA extraction and metagenome sequencing were carried out in the fecal samples. Statistical analysis was performed by software packages, such as R language. The changes of species structure and functional composition of intestinal microflora after liver transplantation were analyzed. The recovery of intestinal microflora in children with biliary atresia after liver transplantation was assessed. The relationship between intestinal microflora and liver function indexes was investigated. Results Following liver transplantation, the number of species of intestinal microflora in children with biliary atresia was increased. The opportunistic pathogens were the dominant species of intestinal microflora in children with biliary atresia before liver transplantation. The abundance of opportunistic pathogens was decreased and the abundance of short-chain fatty acid-producing bacteria was increased after liver transplantation (all P < 0.05). Following liver transplantation, lipid metabolism, amino acid metabolism, carbohydrate metabolism, energy metabolism, metabolism of cofactors and vitamins were enhanced, whereas infectious diseases of bacterial, immune diseases and drug resistance were weakened. Compared with the healthy control group, there were no statistically significant differences in the diversity and structure of intestinal microflora in the post-liver transplant group, but different species were observed between two groups. The liver function indexes of children with biliary atresia after liver transplantation tended to decline (all P < 0.000 1). The abundance of beneficial intestinal microflora was negatively correlated with liver function indexes, whereas the abundance of opportunistic pathogens was positively correlated with liver function indexes (all P < 0.05). Conclusions Liver transplantation may significantly improve the structure and functional composition of intestinal microflora in children with biliary atresia.
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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.
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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.
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Gastroesophageal varices hemorrhage is a common complication of portal hypertension. Drug and endoscopic therapy have become the basic treatments for varices. Transjugular intrahepatic portal venous shunt is recommended for the management of refractory or recurrent variceal hemorrhage. Liver transplantation will be considered when variceal hemorrhage becomes fatal and traditional therapies are with high risk, contraindicated, or have unsatisfactory results. Patients who received traditional treatments can achieve short-term efficacy and even stabilize the disease for a long time. However, if these treatments lead to complications such as portal vein thrombosis and hepatorenal syndrome, it may increase the risk of liver transplantation complications and affect the patient’s prognosis. Elevated portal venous pressure has a variety of adverse effects on systemic circulation, which can cause hepatopulmonary syndrome, portal pulmonary hypertension, refractory ascites, etc. In these cases, liver transplantation should be performed as early as possible. Conventional treatments are unsatisfactory. In addition, frailty may be worsened after traditional treatment, which will significantly increase the risk of liver transplantation. With the increase of model for end-stage liver disease, the requirement for donor liver volume will also has been increased, which will also affect the implementation of living donor liver transplantation. Some patients with portal hypertension may have poor quality of life and it may also become a clinical indication for liver transplantation. These liver transplant-related issues should be evaluated when administering traditional therapies. Traditional therapies aimed at improving the patient's condition, delaying or controlling complications should not interfere with the consequent implementation of liver transplantation. Improving the long-term overall survival rate and quality of life of patients with portal hypertension is the ultimate standard of all treatments.
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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.
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Objective:To study the effect of microRNA (miR)-330-3p on hepatic ischemia-reperfusion injury (IRI) in mice, meanwhile, and to determine potential molecular mechanism.Methods:Eighty male C57BL/6 mice, aged 7-8 weeks, 23-25 g, specific pathogen free, were randomly divided into 8 groups (10 mice in each group) using random number table: reperfusion 2 h group, 6 h group, 12 h group, 24 h group, sham group, miR-330-3p agomir group (preoperative injection of agonist), miR-330-3p antagomir group (preoperative injection of inhibitor) and miRNA-NC group. Except for the sham group, the hepatic IRI model were established in mice. Polymerase chain reaction (PCR), Western blot and immunohistochemistry were used to detect the expression of miR-330-3p and phosphoglycerate mutase family member 5 (PGAM5), cleave caspase-1 and GSDMD. Luciferase reporter assay was performed to investigate whether miR-330-3p directly targets PGAM5. At the same time, AML12 cells were also treated with miR-330-3p mimics/inhibitor or PGAM5 siRNA, then the expression of PGAM5, NLRP3, cleave caspase-1 and GSDMD were detected by Western blot analysis.Results:Level of miR-330-3p gradually decreased after reperfusion, however, mRNA level of PGAM5 was increased thereafter ( P<0.05) as compared with the sham group. Serum level of AST and ALT were decreased in miR-330-3p agomir group while that of were increased in miR-330-3p antagomir group as a function of time following reperfusion, and the differences were statistically significant (all P<0.05). Cleave caspase-1 expression was decreased in miR-330-3p agomir group but was increased in miR-330-5p antagomir group ( P<0.05). Luciferase reporter assay was performed to determine PGAM5 was a target gene of miR-330-3p. SiRNA-mediated knockdown of PGAM5 decreased level of GAM5 (0.24±0.09), NLRP3(0.12±0.07), cleave caspase-1 (0.15±0.07) and GSDMD (1.08±0.08) as compared with the siRNA-NC group (1.17±0.14), (0.36±0.09), (0.68±0.09), (1.36±0.08), and the differences were statistically significant (all P<0.05). Conclusion:MiR-330-3p can alleviate hepatic IRI in mice, which may be related to inhibition of PGAM5-induced pyroptosis.
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There are significant differences in origin and development between pediatric liver malignancies and adult liver malignancies, and even for the same type of liver cancer, there are still differences in its development, progression, therapies, and treatment outcome between children and adults. The histological manifestation and anatomical location of pediatric liver malignancies can reflect the characteristics of invasion and metastasis, the difficulty in surgical treatment, and the sensitivity of drug therapy. Therefore, treatment modalities should be selected based on these characteristics. Pediatric liver malignancies are more sensitive to adjuvant therapy such as chemotherapy, and the combination with adjuvant therapies, such as chemotherapy, before or after liver transplantation may achieve satisfactory results and thus expand the indications for liver transplantation. Among pediatric liver malignancies, hepatoblastoma, hepatocellular carcinoma, and undifferentiated embryonal sarcoma is more common and can be treated by liver transplantation with satisfactory prognosis. Liver transplantation should be considered for children with malignant liver tumors confined to the liver and poor response to liver resection.
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Objective To summarize the incidence, diagnostic and therapeutic experience of hepatic sinusoidal obstruction syndrome (HSOS) after liver transplantation. Methods Clinical data of 4 patients with HSOS after liver transplantation were retrospectively analyzed. The incidence, clinical manifestations, imaging and pathological characteristics of HSOS after liver transplantation were collected, and the treatment methods and clinical outcomes of patients with HSOS were analyzed. Results The incidence of HSOS after liver transplantation was 0.8%(2/239), and the median time of onset was 4.5(1.7, 9.0) months after liver transplantation. The clinical manifestations of HSOS mainly included abdominal distension, ascites, hepatomegaly, increased bilirubin, and renal insufficiency in partial cases. Enhanced abdominal CT scan of 4 patients with HSOS showed uneven spot-like enhancement and the liver histopathological examination mainly showed the signs of hepatic sinusoidal dilatation complicated with congestion. Four patients were administered with an adjusted regime of immunosuppressant by replacing tacrolimus (Tac) with ciclosporin and adding anticoagulant therapy with warfarin. One patient received transjugular intrahepatic portosystemic shunt (TIPS). After treatment, the symptoms of 3 patients were completely relieved, and 1 patient died. One of the 3 surviving patients died from pulmonary infection and gastrointestinal bleeding. Conclusions HSOS is a rare and fatal complication after liver transplantation. Timely diagnosis and treatment can avoid the incidence of graft failure and improve clinical prognosis of the patients.