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Abstract Liver transplantation (LT) rejection remains the most pervasive problem associated with this procedure, while the mechanism involved is still complicated and undefined. One promising solution may involve the use of myeloid-derived suppressor cells (MDSC). However, the immunological mechanisms underlying the effects of MDSC after LT remain unclear. This study is meant to clarify the role MDSCs play after liver transplantation. In this study, we collected liver tissue and peripheral blood mononuclear cells (PBMC) from LT patients showing varying degrees of rejection, as well as liver and spleen tissue samples from mice LT models. These samples were then analyzed using flow cytometry, immunohistochemistry and multiple immunofluorescence. M-MDSCs and CD8 + T-cells extracted from C57/BL6 mice were enriched and cocultured for in vitro experiments. Results, as obtained in both LT patients and LT mice model, revealed that the proportion and frequency of M-MDSC and PD-1 + T-cells increased significantly under conditions associated with a high degree of LT rejection. Within the LT rejection group, our immunofluorescence results showed that a close spatial contiguity was present between PD-1 + T-cells and M-MDSCs in these liver tissue samples and the proportion of CD84/PD-L1 double-positive M-MDSC was greater than that of G-MDSC. There was a positive correlation between the activity of CD84 and immunosuppressive function of M-MDSCs including PD-L1 expression and reactive oxygen species (ROS) production, as demonstrated in our in vitro model. M-MDSCs treated with CD84 protein were able to induce co-cultured CD8 + T-cells to express high levels of exhaustion markers. We found that CD84 regulated M-MDSC function via expression of PD-L1 through activation of the Akt/Stat3 pathway. These results suggest that the capacity for CD84 to regulate M-MDSC induction of CD8 + T-cell exhaustion may play a key role in LT rejection. Such findings provide important, new insights into the mechanisms of tolerance induction in LT.

Abstract Background Explanted livers from patients with inherited metabolic liver diseases possess the potential to be a cell source of good-quality hepatocytes for hepatocyte transplantation (HT). This study evaluated the therapeutic effects of domino HT using hepatocytes isolated from explanted human livers for acute liver failure (ALF). Methods Isolated hepatocytes were evaluated for viability and function and then transplanted into d-galactosamine/lipopolysaccharide-induced ALF mice via splenic injection. The survival rate was analyzed by the Kaplan–Meier method and log-rank test. Liver function was evaluated by serum biochemical parameters, and inflammatory cytokine levels were measured by ELISA. The pathological changes in the liver tissues were assessed by hematoxylin–eosin staining. Hepatocyte apoptosis was investigated by TUNEL, and hepatocyte apoptosis-related proteins were detected by western blot. The localization of human hepatocytes in the injured mouse livers was detected by immunohistochemical analyses. Results Hepatocytes were successfully isolated from explanted livers of 10 pediatric patients with various liver-based metabolic disorders, with an average viability of 85.3% ± 13.0% and average yield of 9.2 × 106 ± 3.4 × 106 cells/g. Isolated hepatocytes had an excellent ability to secret albumin, produce urea, uptake indocyanine green, storage glycogen, and express alpha 1 antitrypsin, albumin, cytokeratin 18, and CYP3A4. Domino HT significantly reduced mortality, decreased serum levels of alanine aminotransferase and aspartate aminotransferase, and improved the pathological damage. Moreover, transplanted hepatocytes inhibited interleukin-6 and tumor necrosis factor-α levels. Domino HT also ameliorates hepatocyte apoptosis, as evidenced by decreased TUNEL positive cells. Positive staining for human albumin suggested the localization of human hepatocytes in ALF mice livers. Conclusion Explanted livers from patients with inheritable metabolic disorders can serve as a viable cell source for cell-based therapies. Domino HT using hepatocytes with certain metabolic defects has the potential to be a novel therapeutic strategy for ALF.

Abstract Background Postreperfusion hyperkalemia (PRHK) has garnered increasing attention in regard to deceased liver transplantation (LT), especially for LT using the expanded criteria donor grafts. However, the impact of the effluent potassium (eK+) concentration on PRHK has been largely overlooked. We evaluated whether elevated eK+ concentrations are associated with PRHK in deceased LT. Methods In this single-institution, retrospective cohort study, we included all adults who underwent deceased LT with intraoperative eK+ concentration monitoring between November 2016 and December 2018. The eK+ concentrations were obtained from the effluent samples collected following a standard portal vein flush. PRHK was defined as any serum potassium (sK+) level of > 5.5 mmol/L following reperfusion. Logistic regression was performed to identify predictors for PRHK, and linear regression was used to examine predictors of the maximum percentage increase in the sK+ level following reperfusion. Results Of the 86 patients who met the inclusion criteria, 54 (62.8%) developed PRHK. Independent predictors for PRHK included greater graft weight (OR 1.283 [95% CI 1.029–1.599] per 100 g, P = 0.027), an elevated eK+ concentration (OR 1.291 [95% CI 1.068–1.561] per mol/L, P = 0.008), and a higher sK+ level before reperfusion (OR 4.459 [95% CI 1.543–12.884] per mol/L, P = 0.006). An eK+ concentration of more than 6.9 mmol/L had a sensitivity of 59.26% and a specificity of 78.12% for predicting PRHK (area under the receiver operating characteristic curve, 0.694). Multiple linear regression analyses indicated that the eK+ and sK+ levels before reperfusion were significant predictors of the maximum percentage increase in the sK+ level following reperfusion. In addition, PRHK was associated with an increased risk of postreperfusion significant arrhythmias, severe postreperfusion syndrome, and postoperative early allograft dysfunction. Conclusions This study shows that the eK+ concentration could predict the risk of PRHK in deceased LT. Further prospective studies are warranted to clarify these associations.

Abstract Background Current world experience regarding living donor liver transplantation (LDLT) in the treatment of propionic acidemia (PA) is limited, especially in terms of using obligate heterozygous carriers as donors. This study aimed to evaluate the clinical outcomes of LDLT in children with PA. Methods From November 2017 to January 2020, 7 of the 192 children who underwent LDLT at our institution had been diagnosed with PA (median age, 2.1 years; range, 1.1–5.8 years). The primary indication for transplantation was frequent metabolic decompensations in 6 patients and preventative treatment in 1 patient. Of the seven parental living donors, six were genetically proven obligate heterozygous carriers. Results During a median follow-up of 23.9 months (range, 13.9–40.2 months), all patients were alive with 100% allograft survival, and no severe transplant-related complications occurred. In the case of liberalized protein intake, they did not suffer metabolic decompensation or disease-related complications and made progress in neurodevelopmental delay and body growth, as well as blood and urinary metabolite levels. In one patient with pre-existing mild dilated cardiomyopathy, her echocardiogram results completely normalized 13.8 months post-transplant. All living donors recovered well after surgery, with no metabolic decompensations or procedure-related complications. Western blotting revealed that the hepatic expressions of PCCA and PCCB in one of the heterozygous donors were comparable to those of the normal healthy control at the protein level. Conclusions LDLT using partial liver grafts from asymptomatic obligate heterozygous carrier donors is a viable therapeutic option for selected PA patients, with no negative impact on donors’ and recipients' clinical courses.

Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.

BackgroundHepatic ischemia-reperfusion injury (HIRI) is largely unavoidable during liver transplantation (LT). Dexmedetomidine (DEX), an α2-adrenergic agonist, exerts a variety of organ-protective effects in pediatric populations. However, evidence remains relatively limited about its hepatoprotective effects in pediatric living-related LT.MethodsA total of 121 pediatric patients undergoing living-related LT from June 2015 to December 2018 in our hospital were enrolled. They were classified into DEX or non-DEX groups according to whether an infusion of DEX was initiated from incision to the end of surgery. Primary outcomes were postoperative liver graft function and the severity of HIRI. Multivariate logistic regression and propensity score matching (PSM) analyses were performed to identify any association.ResultsA 1:1 matching yielded 35 well-balanced pairs. Before matching, no significant difference was found in baseline characteristics between groups except for warm ischemia time, which was longer in the non-DEX group (44 [38–50] vs. 40 [37–44] min, p = 0.017). After matching, the postoperative peak lactic dehydrogenase levels decreased significantly in the DEX group than in the non-DEX group (622 [516–909] vs. 970 [648–1,490] IU/L, p = 0.002). Although there was no statistical significance, a tendency toward a decrease in moderate-to-extreme HIRI rate was noted in the DEX group compared to the non-DEX group (68.6% vs. 82.9%, p = 0.163). Patients in the DEX group also received a significantly larger dosage of epinephrine as postreperfusion syndrome (PRS) treatment (0.28 [0.17–0.32] vs. 0.17 [0.06–0.30] µg/kg, p = 0.010). However, there were no significant differences between groups in PRS and acute kidney injury incidences, mechanical ventilation duration, intensive care unit, and hospital lengths of stay. Multivariate analysis revealed a larger graft-to-recipient weight ratio (odds ratio [OR] 2.657, 95% confidence interval [CI], 1.132–6.239, p = 0.025) and intraoperative DEX administration (OR 0.333, 95% CI, 0.130–0.851, p = 0.022) to be independent predictors of moderate-to-extreme HIRI.ConclusionThis study demonstrated that intraoperative DEX could potentially decrease the risk of HIRI but was associated with a significant increase in epinephrine requirement for PRS in pediatric living-related LT. Further studies, including randomized controlled studies, are warranted to provide more robust evidence.

Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.

The Micro-Electromechanical System (MEMS) optical switches in power systems may be affected by optical control signals during fiber switching, which may cause damage to Optical Time-Domain Reflectometer (OTDR). In order to solve this problem, this paper proposes a method to optimize the switching path of MEMS optical switches in power systems. After the optical switch performing a complete scan, the accurate optical signal channel power contour map is obtained, and then the switching path is optimized and controlled. Therefore, the MEMS optical switch can achieve the highest relative channel isolation of incident light along the premise of balancing the control channel switching time. The best path for switching control can also be used to minimize the impact of the MEMS optical switch on other channels when switching under the premise of ensuring the switching time, and it will not be affected even in a very complicated channel environment.

Biliary Atresia, a common basis for neonatal cholestasis and primary indication for Liver Transplantation, accounts for 60% of pediatric Liver Transplantations. While the pathogenesis of Biliary Atresia remains obscure, abnormalities within bile ducts and the liver, inflammation, fibrosis and cilia defects are thought to comprise the pathological basis for this condition. The findings of genetic variants in Biliary Atresia, such as Copy Number Variations and Single Nucleotide Polymorphism, are considered as essential factors in the development of this condition. In this review, we summarize and analyze these Biliary Atresia variants from a perspective of their pathological characteristics. In conclusion, such analyses may offer novel insights into the pathogenesis of Biliary Atresia and provide a foundation for future studies directed toward a better understanding and treatment of Biliary Atresia.

BackgroundIn living donor liver transplantation (LDLT), graft-to-recipient weight ratio (GRWR) 1.03 g/mL). For the donors, there were significant differences in donor age, graft type, liver size, GRWR, and GSVR (P < 0.05). Following the surgical factors, there were significant differences in blood loss and CRBC transfusion (P < 0.05). The low GSVR has demonstrated had a significant relationship with ascites drainage and portal venous flow after LDLT (P < 0.05). Meanwhile, low GSVR heralds worse results which covered platelet count, international normalized ratio (INR), and portal venous velocity. Kaplan–Meier analysis showed that there was a significant difference between the two groups, while the low GSVR group demonstrated worse recipients survival compared with the normal GSVR group (P < 0.05).ConclusionsWithout splenectomy, low GSVR was an important predictor of portal hypertension and impaired graft function after LDLT.

Adult-to-adult living donor liver transplantation with small partial liver grafts often requires intraoperative portal inflow modulation to prevent portal hyperperfusion and subsequent small-for-size syndrome (SFSS). However, there are concerns about the specific morbidity of these modulation techniques. This study aims to lower post-perfusion portal venous pressure and correct severe hypersplenism in a patient with end-stage liver cirrhosis by simultaneous subtotal splenectomy during auxiliary partial orthotopic liver transplantation (APOLT). A 29-year-old man was diagnosed with cryptogenic cirrhosis and severe portal hypertension suffered recurrent acute variceal bleeding, severe thrombocytopenia, and massive ascites before admission to our hospital. After the recipient's left liver was resected, we performed APOLT using his 51-year-old father's left lobe graft with a graft-to-recipient weight ratio of 0.55%. Intraoperatively, simultaneous subtotal splenectomy was performed to lower graft post-perfusion portal vein pressure below 15 mmHg and correct severe hypersplenism-related pancytopenia. The recipient's postoperative hospital course was uneventful with no occurrence of SFSS and procedure-related complications. Platelet and leukocyte counts remained in the normal ranges postoperatively. The living donor was discharged 6 days after the operation and recovered well-with no complications. After a follow-up period of 35.3 months, both the recipient and donor live with good liver function and overall condition. This is the first case report of simultaneous subtotal splenectomy during APOLT using small-for-size living-donated left liver lobes, which is demonstrated to be a viable procedure for modulating portal inflow and correcting severe hypersplenism in selected adult patients with end-stage liver cirrhosis. APOLT using a small-for-size liver graft may be a safe and feasible treatment option for selected adult patients with end-stage liver cirrhosis.

Abstract Background Stem cell therapy is becoming an emerging therapeutic option for chronic liver disease (CLD). However, whether stem cell therapy is more effective than conventional treatment remains questionable. We performed a large-scale meta-analysis of randomized controlled trials (RCTs) to evaluate the therapeutic effects and safety of stem cell therapy for CLD. Methods We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases for the period from inception through March 16, 2020. Primary outcomes were all-cause mortality and adverse events related to stem cell therapy. Secondary outcomes included the model for end-stage liver disease score, total bilirubin, albumin, alanine aminotransferase, prothrombin activity, and international normalized ratio. The standardized mean difference (SMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated using a random-effects model. Results Twenty-four RCTs were included and the majority of these studies showed a high risk of bias. The meta-analysis indicated that compared with conventional treatment, stem cell therapy was associated with improved survival and liver function including the model of end-stage liver disease score, total bilirubin, and albumin levels. However, it had no obvious beneficial effects on alanine aminotransferase level, prothrombin activity, and international normalized ratio. Subgroup analyses showed stem cell therapy conferred a short-term survival benefit for patients with acute-on-chronic liver failure (ACLF), a single injection was more effective than multiple injections, hepatic arterial infusion was more effective than intravenous infusion, and bone marrow-derived stem cells were more effective than those derived from the umbilical cord. Thirteen trials reported adverse events related to stem cell therapy, but no serious adverse events were reported. Conclusions Stem cell therapy is a safe and effective therapeutic option for CLD, while patients with ACLF benefit the most in terms of improved short-term survival. A single injection administration of bone marrow-derived stem cells via the hepatic artery has superior therapeutic effects.

Abstract Background Patients with isolated methylmalonic acidemia (MMA) usually experience recurrent episodes of acute metabolic decompensation or metabolic stroke, require frequent hospitalization, and have a relatively high mortality rate. The aim of our study was to assess factors predicting the in-hospital death of pediatric patients with isolated MMA. We performed a retrospective study using data from the Hospital Quality Monitoring System, a national inpatient database in China collected from 2013 to 2017. All patients under 18 years old with a diagnosis of isolated MMA were included. Demographic, hospital-related, and clinical features were collected. Poisson regression was performed to identify potential influencing variables associated with in-hospital death. Results From 2013 to 2017, among 2317 admissions for pediatric patients diagnosed with isolated MMA, 1.77% had the outcome of death. In the univariate analysis, patients aged under 1 year had a higher risk of death than did those aged 1 year or older (odds ratio [OR] = 2.63, 95% confidence interval [CI]: 1.36–5.07). There was a higher risk of in-hospital death for patients admitted through emergency departments or via referrals than for those admitted through other routes (OR = 3.76, 95% CI: 1.84–7.67). Deaths were higher in hospitals with volumes of less than 50 patients with isolated MMA during the five study years (OR = 2.92, 95% CI: 1.46–5.83). Moreover, the risk of in-hospital death gradually decreased over time (OR = 0.72, 95% CI: 0.57–0.90). In the multivariate analysis, the abovementioned associations with the risk of in-hospital death remained statistically significant. However, no significant associations were observed between specific clinical signs and in-hospital death in either the univariate or the multivariate analysis. Conclusions Younger age, admission to hospitals with low patient volumes, and admission through emergency departments or referrals are associated with higher risk of in-hospital death. The co-existence of specific clinical signs appears to have no effect on in-hospital death.

Abstract Background Methylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China. Methods The data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data. Results Among all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013 (0.76% for MMA; 0.13% for PA) to 2017 (1.61% for MMA; 0.32% for PA). For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high (RMB 7388.53 for MMA; RMB 4999.66 for PA). Moreover, most patients hospitalized in tertiary class A hospitals (MMA: 80.96%, PA: 76.21%); and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization. Conclusions The study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed.

Background and Objectives: Liver transplantation (LT) has been accepted as a life-saving option as a last resort for children with homozygous familial hypercholesterolemia (HoFH). Perioperative management of LT for HoFH poses extra challenges for clinicians largely due to premature atherosclerotic cardiovascular diseases (ASCVDs). We aimed to analyze our data of pediatric LT recipients with HoFH, with special attention paid to perioperative management and clinical outcomes. Materials and Methods: After obtaining approval from the local ethics committee, the clinical data of pediatric patients with HoFH who underwent LT at our institution between January 2014 and February 2021 were retrospectively studied. Results: Six pediatric LT recipients with HoFH were included in the analysis. Although ASCVDs were common before LT, all children with HoFH survived the perioperative period without in-hospital mortality. However, one patient experienced acute myocardial infarction two months following LT and was successfully treated with medical interventions. Post-LT metabolic improvement was shown by declines in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in the early post-LT period (for TC: 14.7 ± 3.2 mmol/L vs. 5.5 ± 1.8 mmol/L, p < 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 3.6 ± 1.2 mmol/L, p < 0.001, respectively) and at the last follow-up (for TC: 14.7 ± 3.2 mmol/L vs. 4.5 ± 0.9 mmol/L, p = 0.001; for LDL-C: 10.6 ± 2.2 mmol/L vs. 2.8 ± 0.6 mmol/L, p = 0.001, respectively). Dietary restrictions could be lifted after LT. However, three patients required restarting lipid-lowering therapy after LT due to suboptimal LDL-C levels and progression of ASCVDs. Conclusions: Our data suggest that LT can be a safe and feasible therapeutic option for well-selected patients with HoFH, offering relaxed dietary restrictions and remarkable reductions in LDL-C levels. However, concerns remain regarding progression of ASCVDs after LT.

Background and AimsBiliary atresia is the most common cause of liver disease and liver transplantation in children. The accumulation of bile acids in hepatocytes and the stimulation of the intestinal microbiome can aggravate the disease progression. This study investigated changes in the composition of the gut microbiota and its metabolites in biliary atresia and the possible effects of these changes on disease progression.MethodsStool samples of biliary atresia at different disease stages and matched control individuals were collected (early stage: 16 patients, 16 controls; later stage: 16 patients, 10 controls). Metagenomic sequencing was performed to evaluate the gut microbiota structure. Untargeted metabolomics was performed to detect and analyze the metabolites and bile acid composition.ResultsA disturbed gut microbiota structure occurred in the early and later stages of biliary atresia. Klebsiella, Streptococcus, Veillonella, and Enterococcus have always been dominant. The abundance of V. atypica displayed significant changes between the early and later stages of biliary atresia. Combined with clinical indicators, Spearman’s analysis showed that Klebsiella and Veillonella atypica strongly correlated with liver enzymes. Enterococcus faecium had an enormously positive relationship with lithocholic acid derivatives. Metabolites involved in tryptophan metabolism were changed in the patients with biliary atresia, which had a significant association with stool V. atypica and blood total bilirubin (p < 0.05).ConclusionsThe liver damage of biliary atresia was directly or indirectly exacerbated by the interaction of enriched Klebsiella (K. pneumoniae), Veillonella (V. atypica), and Enterococcus (E. faecium) with dysmetabolism of tryptophan and bile acid.

Background and Aims: Biliary atresia (BA) is the most common cholestatic liver disease in neonates. Although the Kasai procedure can improve temporary biliary drainage in some cases, complications and liver fibrosis still develop. Liver transplantation is the ultimate treatment. The current study aimed to investigate the effect of previous Kasai surgery on gut microbiota and bile acid in BA with end-stage liver disease.Methods: Patients with BA with end-stage liver disease were divided into two groups according to whether they had previously undergone Kasai surgery (non-Kasai: n = 8, post-Kasai: n = 8). Metagenomic sequencing and ultraperformance liquid chromatography/tandem mass spectrometry were performed to identify the gut microbiota and bile acid.Results: Previous Kasai surgery had some effects on gut microbiota and bile acid in BA with end-stage liver disease. In the gut microbiome, the differential species were mainly distributed at the species level. Veillonella atypica had a significant increase in the non-Kasai group (P < 0.05). Bacteroides spp., Prevotella spp., Barnesiella spp., Parabacteroides spp., Heliobacterium spp., Erysipelatoclostridium spp. and Diaporthe spp. were increased in the post-Kasai group (P < 0.05). Concerning functional profiles, methionine biosynthesis was enriched in the non-Kasai group, while pyridoxal biosynthesis and riboflavin biosynthesis were enriched in the post-Kasai group (linear discriminant analysis > 2, P < 0.05). In stools, 17 bile acids were distinctly elevated in the post-Kasai group, such as cholic acid, chenodeoxycholic acid, β-muricholic acid and tauro α-muricholate (P < 0.05). Spearman correlation test showed that V. atypica had an enormously positive correlation with liver enzymes. Faecalibacterium prausnitzii and Escherichia coli were associated with derivatives of the alternative pathway of bile acid metabolism.Conclusion: Previous Kasai surgery can improve the gut microbiota and bile acid in patients with BA with end-stage liver disease. This improvement contributes to maintaining the intestinal barrier.

Background and AimsBiliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.MethodsPatients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.ResultsThe Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.ConclusionLT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.

Abstract. Background:. Although a number of technical problems and donor safety issues associated with living donor liver transplantation (LDLT) have been resolved, some initial clinical studies showed an increased risk of hepatocellular carcinoma (HCC) recurrence in LDLT. This meta-analysis was conducted to assess differences in tumor recurrence between LDLT and deceased donor liver transplantation (DDLT). Methods:. After systematic retrievals of studies about LDLT and DDLT for HCC, articles were selected with a rationale of emphasizing inter-group comparability. Results from multivariate analyses were combined and discussed together with univariate analyses. In subgroup analysis, the impact of organ allocation policy was taken into consideration. Results:. Seven articles were included in the meta-analysis. Overall, a salient result that emerged from the seven studies was a significant increased risk of HCC recurrence in the LDLT group than in the DDLT group (P = 0.01). The most significant increase in hazard ratio was found in studies where organs tended to be allocated to non-tumor patients. Conclusions:. An increased risk for HCC recurrence in LDLT as compared with DDLT patients was found. The relatively shorter preoperative observation windows in LDLT may lead to fewer cases of HCC with invasive features being screened out, which may provide a possible explanation for the high rates of HCC recurrence.

Abstract. Background:. Portosystemic shunts, including surgical portosystemic shunts and transjugular intra-hepatic portosystemic shunt (TIPS), may have benefit over endoscopic therapy (ET) for treatment of variceal bleeding in patients with cirrhotic portal hypertension; however, whether there being a survival benefit among them remains unclear. This study was to compare the effect of three above-mentioned therapies on the short-term and long-term survival in patient with cirrhosis. Methods:. Using the terms “variceal hemorrhage or variceal bleeding or variceal re-bleeding” OR “esophageal and gastric varices” OR “portal hypertension” and “liver cirrhosis,” the Cochrane Central Register of Controlled Trials, PubMed, Embase, and the references of identified trials were searched for human randomized controlled trials (RCTs) published in any language with full texts or abstracts (last search June 2017). Risk ratio (RR) estimates with 95% confidence interval (CI) were calculated using random effects model by Review Manager. The quality of the included studies was evaluated using the Cochrane Collaboration's tool for the assessment of the risk of bias. Results:. Twenty-six publications comprising 28 RCTs were included in this analysis. These studies included a total of 2845 patients: 496 (4 RCTs) underwent either surgical portosystemic shunts or TIPS, 1244 (9 RCTs) underwent either surgical portosystemic shunts or ET, and 1105 (15 RCTs) underwent either TIPS or ET. There was no significant difference in overall mortality and 30-day or 6-week survival among three interventions. Compared with TIPS and ET, separately, surgical portosystemic shunts were both associated with a lower bleeding-related mortality (RR = 0.07, 95% CI = 0.01–0.32; P

Although orthotopic liver transplantation remains the only proven treatment for end-stage liver disease and inherited metabolic liver disease, its application has been limited by the scarcity of donor organs available for transplantation. Among feasible approaches developed to expand the donor organ pool, domino liver transplantation is a strategy in which explanted genetically defective livers of liver transplant recipients are used as grafts in other patients. Another promising therapeutic strategy is hepatocyte transplantation, an alternative to liver transplantation for certain groups of patients. However, the availability of primary hepatocytes is also hindered by the shortage of donor liver tissues. Against this background, domino hepatocyte transplantation, a strategy that utilizes the hepatocytes derived from the explanted livers of liver transplant recipients with noncirrhotic inherited metabolic liver diseases as the source of primary hepatocytes, may help increase the supply of liver cells available for transplantation. In this review, we focus on the status quo of domino liver transplantation and domino hepatocyte transplantation. We also describe recent innovative transplant strategies based on domino transplantation.

Background: The outcome of pediatric deceased donor liver transplantation (LT) has not been well studied, especially pediatric deceased donor livers used in adult transplantation. This study aimed to evaluate the efficacy of LT using pediatric deceased donor livers and compare the outcomes between pediatric-to-pediatric LT and pediatric-to-adult LT. Methods: A retrospective review of LT using pediatric deceased donor livers from June 2013 to August 2016 was performed. The patients were divided into the pediatric-to-pediatric LT group and pediatric-to-adult LT group based on the ages of the recipients. The survival and incidence of early vascular complications (VCs) were observed between the two groups. We also analyzed the risk factors of early VCs in pediatric LT and the effect of donor hypernatremia on the prognosis of recipients. Results: There were 102 cases of LT using pediatric deceased donor livers in our hospital from June 2013 to August 2016, 83 pediatric-to-pediatric LT (recipients' age ≤13 years) and 19 pediatric-to-adult LT (recipients' age ≥19 years). The ratio of early VC was similar in the two groups (19.3% vs. 10.6%, P = 0.514). Low body weight of recipient was an independent risk factor of early VC in pediatric LT (odds ratio: 0.856, 95% confidence interval: 0.752–0.975, P = 0.019). The 1-year cumulative survival rates of grafts and patients were 89.16% and 91.57% in pediatric-to-pediatric LT and 89.47% and 94.74% in pediatric-to-adult LT, respectively (all P > 0.05). In all cases, patients using donors with hypernatremia (serum sodium levels ≥150 mmol/L) had worse graft survival (χ2=4.330, P = 0.037). Conclusions: Pediatric-to-pediatric LT group has similar graft and patient survival rates with those of pediatric-to-adult LT group. Low body weight of recipients is an independent risk factor of early VC in pediatric LT. Patients using donors with hypernatremia have worse graft survival.

Abstract The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.

OBJECTIVE To analyze the expression and levels of serum proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), and interleukin (IL)-6 in patients with hepatocellular carcinoma (HCC), who received orthotopic liver transplantation (OLT). METHODS The blood samples of 20 consecutive HCC patients who underwent liver transplantation were detected and analyzed for the clinical serum biochemical parameters, TNF-α and IL-6. Blood samples were drawn from the radial artery at planned time points: preoperatively, intraoperatively, and postoperatively. Levels of serum TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS The levels of serum TNF-α and IL-6 increased significantly at reperfusion phase compared with those detected preoperatively (P < 0.01), and the level of serum IL-6 remained significantly higher until the third day after the liver transplantation. There was a significant correlation between TNF-α and IL-6 (P < 0.001).CONCLUSION This research into the effects of the proinflammatory cytokines on liver transplantation has provided new insights into the mechanisms of ischemia and reperfusion injury to OLT.