Cognitive function of children with biliary atresia after primary living donor liver transplantation.

BACKGROUND: The survival rate of children with biliary atresia (BA) after liver transplantation (LT) is significantly improved, and their quality of life has attracted much attention.This study aimed to investigate the cognition and its influencing factors in children with BA after primary living donor LT (BA-pLDLT) during infancy. METHODS: Children with BA were recruited 6 months after pLDLT at Children's Hospital of Chongqing Medical University (2018-2022). Demographic and clinical data were collected from the health information system. Cognition was assessed using the Chinese version of the Griffiths Mental Development scale (GMDS-C). Multivariate linear regression were used to analyze the influencing factors of their cognitive function. RESULTS: In total, 57 children with BA-pLDLT, aged 5.00(3.90-9.30) months at transplantation and 25.00(14.00-60.80) months at evaluation were included. The general developmental quotient (89.02 ± 12.07) and motor, language, eye-hand coordination, performance, and practical reasoning quotients of these children were significantly lower than the normative mean values of GMDS-C(P < 0.05). Of the 57 children, 16 (28.07%) had borderline developmental delay (DQ between 70 and 84), 3 (5.26%) had developmental delay (DQ < 70), and 11(19.29%) had language delay. Reoperation for biliary or vascular complications after pLDLT was a risk factor for decreased general development quotient and motor quotient and lower ZW at assessment was associated with decline motor quotient. CONCLUSION: Children with BA-pLDLT have varying degrees of developmental delays in early life. Reoperation and nutritional deficiencies had adverse effects on cognitive development.

A nomogram for predicting choledochal cyst with perforation.

BACKGROUND: Choledochal cyst with perforation (CC with perforation) rarely occurs, early diagnosis and timely treatment plan are crucial for the treatment of CC with perforation. This study aims to forecast the occurrence of CC with perforation. METHODS: All 1111 patients were conducted, who underwent surgery for choledochal cyst at our hospital from January 2011 to October 2022. We conducted univariate and multivariate logistic regression analysis to screen for independent predictive factors for predicting CC with perforation, upon which established a nomogram. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) curves. RESULTS: The age of children with choledochal cyst perforation is mainly concentrated between 1 and 3 years old. Logistic regression analysis indicates that age, alanine aminotransferase, glutamyl transpeptidase, C-reactive protein, vomiting, jaundice, abdominal distension, and diarrhea are associated with predicting the occurrence of choledochal cyst perforation. ROC curves, calibration plots, and DCA curve analysis curves demonstrate that the nomogram has great discriminative ability and calibration, as well as significant clinical utility. CONCLUSION: The age of CC with perforation is mainly concentrated between 1 and 3 years old. A nomogram for predicting the perforation of choledochal cyst was established.

Ursodeoxycholic acid loaded dual-modified graphene oxide nanocomposite alleviates cholestatic liver injury through inhibiting hepatocyte apoptosis.

Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.

Prediction of early recovery of graft function after living donor liver transplantation in children.

For end-stage liver disease in children, living donor liver transplantation (LDLT) is often the important standard curative treatment. However, there is a lack of research on early recovery of graft function after pediatric LDLT. This is a single-center, ambispective cohort study. We collected the demographic and clinicopathological data of donors and recipients, and determined the risk factors of postoperative delayed recovery of hepatic function (DRHF) by univariate and multivariate Logistic analyses. 181 cases were included in the retrospective cohort and 50 cases in the prospective cohort. The incidence of DRHF after LDLT in children was 29.4%, and DRHF could well evaluate the early recovery of graft function after LDLT. Through Logistic analyses and AIC score, preoperative liver function of donors, ischemia duration level of the liver graft, Ln (Cr of recipients before operation) and Ln (TB of recipients on the 3rd day after operation) were predictive indicators for DRHF after LDLT in children. Using the above factors, we constructed a predictive model to evaluate the incidence of postoperative DRHF. Self-verification and prospective internal verification showed that this prediction model had good accuracy and clinical applicability. In conclusion, we pointed many risk factors for early delayed recovery of graft function after LDLT in children, and developed a visual and personalized predictive model for them, offering valuable insights for clinical management.

3D-printed PCL/ß-TCP/CS composite artificial bone and histocompatibility study.

BACKGROUND: Tissue-engineered bone materials are an effective tool to repair bone defects. In this study, a novel biodegradable polycaprolactone (PCL)/ß-tricalcium phosphate (ß-TCP)/calcium sulfate (CS) composite scaffold was prepared by using three-dimensional (3D) printing technology. METHODS: Scanning electron microscopy, gas expansion displacement, and contact goniometry were used to examine the 3D-printed PCL/ß-TCP/CS composite scaffolds. The results showed that the PCL/ß-TCP/CS scaffolds possessed controllable porosity, hydrophobicity, biodegradability, and suitable apatite mineralization ability. To confirm the bone regenerative properties of the fabricated composite scaffolds, scaffold extracts were prepared and evaluated for their cytotoxicity to bone marrow mesenchymal stem cells (BMSCs) and their ability to induce and osteogenic differentiation in BMSCs. RESULTS: The PCL/ß-TCP/CS composite scaffolds induced a higher level of differentiation of BMSCs than the PCL scaffolds, which occurred through the expression of bone metastasis-related genes. The New Zealand white rabbit radial defect experiment further demonstrated that PCL/ß-TCP/CS scaffolds could promote bone regeneration. CONCLUSIONS: In summary, the 3D-printed PCL/ß-TCP/CS composite porous artificial bone has good cytocompatibility, osteoinductivity, and histocompatibility, which make it an ideal bone material for tissue engineering.

High expression of RPL27A predicts poor prognosis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the digestive system with rapid progression and poor prognosis. Recent studies have shown that RPL27A could be used as a biomarker for a variety of cancers, but its role in HCC is not clear. METHOD: We analyzed the expression of RPL27A in the pan-cancer analysis and analyzed the relationship between the expression of RPL27A and the clinical features and prognosis of patients with HCC. We evaluated the expression difference of RPL27A in HCC tissues and paired normal adjacent tissues using immunohistochemistry. Furthermore, we analyzed the co-expression genes of RPL27A and used them to explore the possible mechanism of RPL27A and screen hub genes effecting HCC. In addition, we studied the role of RPL27A in immune infiltration and mutation. RESULTS: We found that the expression level of RPL27A increased in a variety of cancers, including HCC. In HCC patients, the high expression of RPL27A was related to progression and poor prognosis as an independent predictor. We also constructed a protein interaction network through co-expression gene analysis of RPL27A and screened 9 hub genes. Enrichment analysis showed that co-expression genes were associated with ribosome pathway, viral replication, nuclear-transcribed mRNA catabolic process, and nonsense-mediated decay. We found that the expression level of RPL27A was closely related to TP53 mutation and immune infiltration in HCC. CONCLUSION: RPL27A might become a biomarker in the diagnosis, treatment, and follow-up of patients with HCC.

Early life growth and developmental trajectory in children with biliary atresia undergoing primary liver transplantation.

Objective: To clarify the early growth and developmental characteristics of children with biliary atresia (BA) undergoing primary liver transplantation (pLT). Methods: A prospective cohort study, which specifically focused on BA-pLT children, was conducted after the diagnosis of BA by following the children at the time of pLT and 1, 3, 5, 7 months and 1 year after pLT for growth and developmental monitoring. The growth parameters were calculated according to the WHO standard, and the developmental status was assessed using Denver Developmental Screening Tests. Results: A total of 48 BA children who received pLT at the age of 5.00 ± 0.94 months were analyzed. The weight-for-age Z-value (ZW) and length-for-age Z-value (ZL) were higher than the head circumference-for-age Z-value (ZHC) at pLT (P = 0.002 and 0.02), but they were all lower than the WHO growth standard (Z = 0) (P < 0.001). The ZW and ZHC decreased first and then returned to the population level at 1 year after pLT, while the ZL only returned to the preoperative status and was lower than the ZW and ZHC (P < 0.001). Developmental screening showed that 35% (17/48) of the children were defined as suspicious and 15% (7/48) were abnormal at 1-4 months after pLT, the most likely time to be suspected of developmental delay. At 1 year after pLT, gross motor skill delay still existed (12/45, 27%), and language skill delay began to appear (4/45, 9%). Conclusions: BA-pLT children suffer from growth and developmental problems. Low ZHC is the main growth problem before pLT, while low ZL is the problem after pLT. Developmental delays are significant after pLT, especially in motor and language skills. The current study suggested that further studies are warranted to clarify the long-term growth and developmental outcomes of BA-pLT children, to compare them with children undergoing the Kasai procedure and to explore their influencing factors and possible mechanisms.

Incidence trends and predictive model of hepatic malignant tumors in children: a population-based study.

OBJECTIVE: To analyze the incidence trend and establish a model to predict the prognosis of hepatic malignant tumors in children (CHMTs). METHODS: We analyzed the incidence data of CHMTs from 1975 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database, and evaluated the incidence trends based on different demographic and pathological features. We also analyzed clinicopathologic data from 2000 to 2018 from the SEER database. Univariate and multivariate Cox regression analyses were performed to explore prognostic factors related to overall survival (OS). Then, we established nomograms based on independent predictors and verified them using receiver operating characteristic curves, calibration plots, and decision curve analysis plots. RESULTS: The incidence of CHMTs increased significantly, from 0.1 per 100,000 in 1975 to 0.4 per 100,000 in 2018. Incidences among different races and genders were increasing and converging. The incidence of hepatoblastoma (HB) increased, while that of hepatocellular carcinoma (HCC) was relatively stable. The 1-, 3-, 5-, and 10-year OS rates were 86.2%, 77.5%, 74.2%, and 70.2%, respectively. Being Spanish-Hispanic-Latino, HB, surgery, and systemic therapy were independent predictors of longer OS, whereas regional and distant stages were independent predictors of shorter OS. Nomograms with good predictive ability and clinical utility were established to evaluate the prognosis of children with HB or HCC. CONCLUSION: The incidence of CHMTs is increasing, especially for HB and in younger children. This study identified independent predictors and developed nomograms that could provide a personalized and accurate prognosis for CHMTs.

[Clinical Analysis of ABO-Incompatible Living-Donor Liver Transplantation in Children].

Objective: To evaluate the safety and clinical efficacy of ABO-incompatible living-donor liver transplantation (LDLT) in children. Methods: The clinical data of 62 children who underwent for the first time living donor liver transplantation in our hospital from April 2019 to July 2020 were retrospectively analyzed. According to the blood type matching of donor and recipient, the patients were divided into 3 groups, ABO-identical (ABO-Id, n=33), ABO-compatible (ABO-C, n=10) and ABO-incompatible (ABO-In, n=19), the median age of recipients in the three groups being 5 months. In the ABO-In group, 4 recipients whose condition was combined with liver failure and 2 recipients who had blood group antibody titers≥1∶32 received preoperative plasma exchange. All ABO-incompatible recipients had preoperative blood group antibody titers<1∶32. All recipients in the three groups underwent piggyback liver transplantation and received immunosuppressive and anticoagulation therapy. Postoperative follow-up was 5 to 20 months, the median being 12 months, measured until December 31, 2020 or until the date of death. Baseline clinical data, postoperative survival, and postoperative complications of recipients in the three groups were analyzed. Results: There were no significant differences in age, gender, underlying disease, operation history, Child Pugh score, donor age, graft to recipient weight ratio (GR/WR), cold ischemia time, warm ischemia time, duration of surgery, intraoperative blood loss and the use of immunosuppressants among the recipients in the three groups (all P>0.05). There was one death in the perioperative period and two deaths in the postoperative period in the ABO-Id group. There was one death in the postoperative period in the ABO-C group. There was one death in the perioperative period and one death in the postoperative period in the ABO-In group. There was no significant difference in the overall cumulative survival rate among the three groups ( P>0.05). There were no significant differences in the incidence of postoperative infection, acute rejection, biliary anastomotic stenosis and vascular complications among the three groups ( P>0.05). Conclusion: ABO-In LDLT is an effective and safe treatment option that can effectively expand the pool of live donors for liver transplantation and save the life of children with end-stage liver disease.

Lead exposure as a causative factor for metabolic associated fatty liver disease (MAFLD) and a lead exposure related nomogram for MAFLD prevalence.

The relationship between lead exposure and neurological disorders has been extensively studied, but the effects of lead exposure on hepatotoxicity are unknown. Metabolically related fatty liver disease (MAFLD) is an update of previous non-alcoholic fatty liver disease (NAFLD). It redefines the diagnostic conditions and emphasizes metabolic factors while considering non-alcoholic factors. Lead can affect the endocrine system and metabolism, so we believe that lead exposure may contribute to MAFLD. 41,723 individuals who had undergone blood lead testing from 2005 to 2018 in the National Health and Nutrition Examination Survey (NHANES) database were selected for this study. The characteristics of population lead exposure in the last decade or so, the effect of lead exposure on liver function and whether lead exposure can cause MAFLD were analyzed. Co-variates were adjusted according to age, ethnicity, body mass index (BMI), waist circumference, visceral adiposity index (VAI), poverty indices (PIR), diabetes, hypertension, and hyperlipidemia. The results showed that blood lead concentrations stabilized at a low level after a decreasing trend from year to year. The differences in blood lead concentrations were associated with differences in age, sex, race, education level, and PIR. Lead exposure was an independent risk factor for MAFLD, and lead and nine other factors were used as independent risk factors for MAFLD, so a nomogram was established to predict the prevalence probability of MAFLD.

Competitive risk analysis of the therapeutic value of liver transplantation for liver cancer in children: A population-based study.

Background: Liver transplantation (LT) is one of the most important treatments for children with liver cancer (CLCa) and has been increasingly used. However, there is a lack of large-scale and multicenter studies on the trend in the application and value of LT for the treatment of CLCa. Methods: We analyzed the clinicopathological data of CLCa from 2000 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. We explored the trend in the application of LT for the treatment of CLCa. LASSO Cox regression and the Log-Rank test were used to explore prognostic factors, and we built a nomogram using the screened factors. Propensity score matching was used to balance the baseline data of patients undergoing LT and other surgeries, and then the Log-Rank test was used to evaluate the therapeutic value of LT for CLCa. Results: The 1-year, 3-year, 5-year, and 10-year overall survival (OS) rates of CLCa were 88.7%, 80.6%, 76.8%, and 73.0%, respectively. Then, we established a nomogram using many variables including age of diagnosis, regional lymph node metastasis, summary stage, and therapy. Internally validated and externally verified, our nomogram had good predictive power and clinical applicability. LT was increasingly being used to treat CLCa. There was no statistically significant difference in the OS of CLCa between the LT and other surgeries groups. After LT, the hepatoblastoma group had a better prognosis than the hepatocellular carcinoma group. Conclusion: We built a well-performing nomogram to predict the OS of CLCa. LT could improve the prognosis of CLCa as other surgeries and could be considered an effective treatment choice for CLCa.

A sewing needle in the liver in children: A case report and literature review.

RATIONALE: In clinical practice, foreign bodies (FBs) in the digestive tract are more common in children, but intrahepatic FBs are rare, especially those that can cause infection, bleeding, bile leakage, and other complications. However, there is no consensus on its diagnosis and treatment due to the lack of large-scale cohort studies. PATIENT CONCERNS: Case 1 is a 4-years 8-months-old girl, who at the age of 10 months, showed an X-ray finding of a striped FB in her liver, with no symptoms. However, the patient's parents refused surgery. After nearly 4 years of active surveillance, the patient visited our hospital for surgery. Case 2, a 2-year-old male, reported a sewing needle that completely pierced into the right upper abdomen due to an accidental fall that took place half-a-day before admission. He only had right upper abdominal pain. CT showed a striped FB in the liver. DIAGNOSIS: FB in the liver (sewing needle). INTERVENTIONS: Both the patients were injected with human tetanus immunoglobulin and underwent surgical removal. OUTCOMES: Both patients recovered smoothly and had no complications during follow-up. LESSONS: Active surveillance might be considered for cases with no symptoms or complications and no displacement of the FB, but surgery should be the first choice. If the patient's condition is complicated, it is recommended to use ultrasound or X-ray to help decision-making during the operation. Additionally, tetanus, child safety, and family education are important supportive measures.

Learning Curve Analysis of Microvascular Hepatic Artery Anastomosis for Pediatric Living Donor Liver Transplantation: Initial Experience at A Single Institution.

Background: The incidence of hepatic artery thrombosis in pediatric living donor liver transplantation (LDLT) is significantly higher than that in adults, and is closely related to the surgeon's experience with hepatic artery anastomosis. However, there are few studies on the learning curve of hepatic artery anastomosis among surgeons. Methods: We collected data related to 75 patients who underwent pediatric LDLT and hepatic artery anastomosis independently by the same surgeon. Cumulative sum method (CUSUM) was used to analyse the duration of hepatic artery anastomosis and determine the cut-off value. Patients were divided into two phases according to CUSUM. We analysed the intraoperative and postoperative data and survival outcomes of the included patients. Results: Total anastomosis duration decreased with an increased number of completed procedures, and the average duration was 42.4 ± 2.20 min. A cut-off value and two phases were identified: 1-43 cases and 44-75 cases. Intraoperative blood loss was significantly lower in phase 2 than in phase 1. The immediate functional changes of total bilirubin (TBIL) and direct bilirubin (DBIL) were significantly also lower in phase 2 than in phase 1. Other functional outcomes, postoperative complications, and the long-term survival rate were not significantly different between the two phases. Conclusions: Technical competence in pediatric LDLT hepatic artery anastomosis may be achieved after completing 43 cases. It is a safe procedure with a surgical loupe that can be systematized and adopted by pediatric surgeons with sufficient experience via a relatively long learning curve.

The Bioinformatic Study Uncovers Probable Critical Genes Involved in the Pathophysiology of Biliary Atresia.

Background: Biliary atresia (BA) is an uncommon illness that causes the bile ducts outside and within the liver to become clogged in babies. If left untreated, the cholestasis causes increasing conjugated hyperbilirubinemia, cirrhosis, and hepatic failure. BA has a complicated aetiology, and the mechanisms that drive its development are unknown. The objective of this study was to show the role of probable critical genes involved in the pathophysiology of biliary atresia. Methods: We utilised the public Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE46960 to find differentially expressed genes (DEGs) in 64 biliary atresia newborns, 14 infants with various causes of intrahepatic cholestasis, and 7 deceased-donor children as control subjects in our study. The relevant information was looked into. The important modules were identified after functional enrichment, GO and KEGG pathway analyses, protein-protein interaction (PPI) network analyses, and GSEA analysis. Results: The differential expression analysis revealed a total of 22 elevated genes. To further understand the biological activities of the DEGs, we run functional enrichment analyses on them. Meanwhile, KEGG analysis has revealed significant enrichment of pathways involved in activating cross-talking with inflammation and fibrosis in BA. SERPINE1, THBS1, CCL2, MMP7, CXCL8, EPCAM, VCAN, ITGA2, AREG, and HAS2, which may play a significant regulatory role in the pathogenesis of BA, were identified by PPI studies. Conclusion: Our findings suggested 10 hub genes and probable mechanisms of BA in the current study through bioinformatic analysis.

Immune Characteristics in Biliary Atresia Based on Immune Genes and Immune Cell Infiltration.

Background: Biliary atresia (BA) is a serious biliary disease in infancy. Jaundice is the most visual and prominent symptom, and it mainly involves bile duct cells leading to the loss of intrahepatic and extrahepatic bile ducts. If left untreated, it will eventually progress to liver cirrhosis. The pathogenesis of BA is not clear, and it is now generally accepted that BA is an autoimmune disease. However, few studies have revealed the infiltration of immune cells in the liver of BA from a global perspective. We used liver tissue sequencing data to predict the infiltration and relative content of immune cells in BA. Methods: The BA datasets GSE46960, GSE15235, and GSE84044, and patient information were downloaded from the Gene Expression Omnibus (GEO) database. After batch normalization, the differentially expressed immune genes (DE-IGs) in BA liver, normal liver, and hepatitis B liver were analyzed with the cut-off value of |log2fold change (log2FC)| >1 and false discovery rate (FDR) <0.05. CIBERSORT software was used to predict the proportions of 22 immune cells in all samples of the datasets. Results: 73 DE-IGs have been screened out between BA and normal tissue; among them, 20 genes were highly expressed and another 53 were expressed at a low level. A total of 30 DE-IGs existed between inflammation and fibrosis livers of BA, and all of them were expressed at low levels in fibrosis livers of BA. In GO term analysis, these DE-IGs were mainly associated with the MHC protein complex, cytokine, chemokine activity, and MHC-II receptor activity. In KEGG pathway analysis, the DE-IGs were mainly enriched in pathways of Th1 and Th2 cell differentiation, Th17 cell differentiation, IL-17 signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, and autoimmune diseases. There were significant differences in immune infiltration among different pathological types of BA, and there were also obvious differences in immune infiltration of hepatitis B as a disease control of BA. Conclusion: Based on immune genes and immune cell infiltration, this study reveals the immune characteristics of BA from a global point of view, which provides a new perspective for understanding the pathogenesis of BA and provides a direction for the diagnosis and treatment of BA.

Incidence Trend and Competing Risk Analysis of Patients With Intrahepatic Cholangiocarcinoma: A Population-Based Study.

Background: Intrahepatic cholangiocarcinoma (ICCA) is a primary liver cancer characterized by rapid progression and poor prognosis. There are few effective tools for evaluating the prognosis of ICCA patients, and the use of liver transplantation (LT) of the treatment for ICCA is still controversial. Methods: We analyzed ICCA incidence data and clinicopathological data from the Surveillance, Epidemiology, and End Results database. Prognostic predictors were identified by univariate and multivariate Cox regression analyses and then used to establish a nomogram. The prediction performance of the nomogram was evaluated with receiver operating characteristic (ROC) curves, calibration plots and decision curve analysis (DCA) plots. Propensity score matching (PSM) was used to balance the baseline data of patients undergoing LT and other operations, and then, univariate Cox regression analysis was used to evaluate the therapeutic value of LT for ICCA. Results: The incidence of ICCA increased significantly, from 0.6 per 100,000 in 2,000 to 1.3 per 100,000 in 2018. The median overall survival (OS) of the patients was 13 months, and the 1-, 3-, and 5-year OS rates were 51.40, 22.14, and 13.79%, respectively. Cox regression analysis showed that age under 60 years old, female, tumor size ≤ 50 mm, better differentiation, smaller range of tumor invasion, lack of distant metastasis, regional lymph node surgery and treatment were associated with a better prognosis. The ROC curves, calibration plots, and DCA plots showed that the nomogram had good discrimination and calibration power, as well as clinical utility. After PSM, the univariate Cox regression analysis showed no significant difference in OS between patients treated with LT and patients treated with other operations. Conclusion: The incidence of ICCA increased significantly. A nomogram with good predictive performance was developed to predict the OS of ICCA patients. LT might be considered as a potential option for some ICCA patients.

Super-Selective Partial Splenic Embolization for Hereditary Spherocytosis in Children: A Single-Center Retrospective Study.

Background: Hereditary spherocytosis (HS) is the most common hemolytic anemia due to erythrocyte membrane defects. Total splenectomy is the most effective treatment for moderate or severe HS. As a conservative alternative, partial splenic embolization (PSE) can preserve part of the spleen's function, thus reducing the risk of overwhelming post-splenectomy infection (OPSI) or sepsis, especially for pediatric patients. However, it is not easy to precisely control the scope of interventional embolization, limiting PSE applications. The present study aims to optimize the PSE procedure on smaller, which is named super-selective PSE (SPSE), to improve the controllability and assess the feasibility and effectiveness of SPSE. Results: This study was conducted by retrospectively reviewing clinical data from HS patients treated by surgical treatments, which were diagnosed at the children's hospital of Chongqing medical university from January 2015 to December 2019. Patients were divided into two groups according to their treatment preference: SPSE (16 patients) group and total splenectomy (41 patients) group. The mean proportion range of splenic embolism by SPSE was 82.4%, close to the expected value (70-85%). The average hemoglobin value was increased significantly from 6.85 (5.6-8.0) g/dl before SPSE to 12.4 (10.4-13.3) g/dl after SPSE (p < 0.001). All children after SPSE suffered mild post-embolization syndrome, such as pain, fever, and vomiting, which could easily be controlled with appropriate supportive therapy. Conclusions: Super-selective partial splenic embolization is a safe and effective treatment for moderate or severe HS in children. However, with a longer follow-up, more patients further assess the value of SPSE.

Study Protocol: Design and Implementation of the Pediatric Liver Transplantation Biobank.

Background: Early treatment of neonatal biliary atresia (BA) and other end-stage liver diseases can delay or prevent the necessity of liver transplantation (LT). The establishment of a standardized clinical pediatric liver transplantation (PLT) biobank is the prerequisite for scientific research, which helps to provide a qualified sample resource platform for research. Methods: Following standardized procedures to establish biobanks, the operational processes and quality control system were formulated. Liver tissue, blood, and stool samples undergoing LT were regularly collected, managed, and stored. Systematic management was conducted in collected specimens and corresponding clinical information. Results: Since implementation in August 2018, we have enrolled 49 unique subjects (0-18 years of age); the biobank contains nearly 3000 biospecimen aliquots. The most common LT diagnosis is BA (61.23%). Conclusion: The establishment of this biobank is a valuable resource that incorporates detailed clinical and biological information. It will help accelerate the pace of PLT discovery research. ClinicalTrials.gov ID: NCT04477967.

The current status and outcomes of pediatric liver transplantation in western China: A multi-center retrospective study.

This retrospective study was conducted to examine the development and current status of pediatric liver transplantation (LT) in western China. Clinical, demographic, morbidity, and mortality data were collected to analyze. It included 260 consecutive pediatric LTs performed at three centers in western China between January 2000 and May 2019. Kaplan-Meier graft survival rates at 1, 3, 5, and 10 years were 82.1%, 77.2%, 76.6%, and 76.6%, respectively; corresponding patient survival rates were 84.7%, 80.7%, 80.0%, and 80.0%, respectively. More patients underwent living donor liver transplantation (LDLT; n = 188 (73.4%)) than deceased-donor liver transplantation (DDLT; n = 68 (26.6%)). Survival was better after LDLT (91.5%, 86.6%, and 80.6% at 1, 3, and 5 years, respectively) than after DDLT (80.9%, 72.4%, and 63.9%, respectively; P < .05). Biliary atresia was the leading LT indication (n = 141 (55.1%)), followed by metabolic disease (n = 36 (14.1%)), which was associated with the best recipient survival (88.5% at 5 years). The transplant era and graft-to-recipient body weight ratio (GRWR) also significantly predicted overall survival. Survival rates at 5 years were worst in 2000-2005 (54.5%) and best for GRWRs of 0.8%-4% (80.4%). The development of pediatric LT in western China began slowly, but the quantity and quality of pediatric LT has progressed in recent years. This procedure is now a promising and reliable treatment for children with end-stage liver disease in western China.

Decellularized human liver scaffold-based three-dimensional culture system facilitate hepatitis B virus infection.

Hepatitis B virus (HBV) study is hampered by lacking of idea cell model which support effective HBV infection and meanwhile recapitulate hepatocyte biology function in vivo. In this study, we developed decellularized human liver scaffolds for cell culture and further applied for HBV infection. As a result, primary human hepatocytes (PHHs) engrafted into liver scaffolds and maintained differentiation with stable albumin secretion and liver-specific gene expression. Comparing to mono-layer cell culture, scaffold-based three-dimensional (3D) culture system significantly augment HBV DNA (including cccDNA), RNA level as well as HBsAg secretion. Moreover, HepG2-NTCP cells cultured on 3D system exhibited higher infection efficiency and longer infection period in vitro. In addition, HBV DNA level was suppressed when anti-HBV medicine Entecavir (ETV) introduced into HepG2-NTCP 3D system. Herein, we evaluated the potential of decellularized human liver scaffold-based in 3D cell culture and disclosed that scaffold-based 3D culture system can facilitate HBV infection in vitro. This 3D culture system could be further applied in HBV-related study. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1744-1753, 2019.