With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, C...With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma.展开更多
Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-...Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-donor” liver transplantation allows grafts to be recovered from other liver recipients. This review summarizes the current clinical practice of “no-donor” liver transplantation, focusing on the experiences of Chinese transplant teams. Domino liver transplantation was introduced by Furtado in 1995 and implemented later in 2013 in China, and novel donor indications including some essential-to-treat inherited metabolic liver-based diseases have emerged. The concept of cross-auxiliary domino liver transplantation brings a further expansion of the domino liver graft pool, and the first pair of liver transplantation performed “rigorously without donation” was accomplished in our center in 2018. Our experience with this original transplantation procedure is hereby reviewed. In order to further promote and make successful “no-donor” liver transplantation, close co-operation between researchers, surgeons, physicians, organ procurement organizations, as well as ethical committees is required.展开更多
Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is ...Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.展开更多
Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and pote...Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.展开更多
Background:Normal bile is sterile.Studies have shown that cholangitis after liver transplantation(LT)was associated with a relatively poor prognosis.It remains unclear whether the bacteriobilia or fungibilia impact th...Background:Normal bile is sterile.Studies have shown that cholangitis after liver transplantation(LT)was associated with a relatively poor prognosis.It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients,especially with donation after circulatory death(DCD)allografts,which was correlated with a higher risk of allograft failure.Methods:This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021.All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia.The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes,especially hospital stay were analyzed.Results:Totally 135 and 171 organisms were isolated at weeks 1 and 2,respectively.Among all patients included in this analysis,83(59.7%)developed bacteriobilia or fungibilia within 2 weeks posttransplantation.The occurrence of bacteriobilia or fungibilia[β=7.43,95%CI(confidence interval):0.02 to 14.82,P=0.049],particularly the detection of Pseudomonas(β=18.84,95%CI:6.51 to 31.07,P=0.003)within 2 weeks post-transplantation was associated with a longer hospital stay.However,it did not affect the graft and patient survival.Conclusions:The occurrence of bacteriobilia or fungibilia,particularly Pseudomonas within 2 weeks posttransplantation,could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.展开更多
Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria....Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seq LDLT) after LR as a strategy for HCC patients with high-risk of recurrence.Methods:We analyzed data from 27 adult patients who underwent seq LDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS).Results:Among 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqL DLT. Five patients (19%) underwent living donor liver transplantation (LDLT) following LR as a downstaging strategy while the rest received seqL DLT as a preemptive strategy. The median age was 53.5 years with 85%males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0%and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors> 5 cm(19%), and a total tumor diameter> 10 cm (7%).Conclusions:Seq LDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seq LDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.展开更多
Background:Liver transplantations(LTs)with extended criteria have produced surgical results comparable to those obtained with traditional standards.However,it is not sufficient to predict hepatocellular carcinoma(HCC)...Background:Liver transplantations(LTs)with extended criteria have produced surgical results comparable to those obtained with traditional standards.However,it is not sufficient to predict hepatocellular carcinoma(HCC)recurrence after LT according to morphological criteria alone.The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria.Methods:Retrospective data on patients with HCC,including pathology,serological markers and followup data,were collected from January 2015 to April 2020 at Huashan Hospital,Fudan University,Shanghai,China.Logistic least absolute shrinkage and selection operator(LASSO)regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram.Receiver operating characteristic(ROC)curves,Kaplan-Meier curves,decision curve analyses(DCAs),calibration diagrams,net reclassification indices(NRIs)and integrated discrimination improvement(IDI)values were used to assess the prognostic capacity of the nomogram.Results:A total of 301 patients with HCC who underwent LT were enrolled in the study.The nomogram was constructed,and the ROC curve showed good performance in predicting survival in both the development set(2/3)and the validation set(1/3)(the area under the curve reached 0.748 and 0.716,respectively).According to the median value of the risk score,the patients were categorized into the high-and low-risk groups,which had significantly different recurrence-free survival(RFS)rates(P<0.01).Compared with the Milan criteria and University of California San Francisco(UCSF)criteria,DCA revealed that the new nomogram model had the best net benefit in predicting 1-,3-and 5-year RFS.The nomogram performed well for calibration,NRI and IDI improvement.Conclusions:The nomogram,based on the Milan criteria and serological markers,showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.展开更多
BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical...BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.展开更多
To the Editor:With the popularity of liver transplantation(LT)and the inspiration for long-time survival,issues related to evaluating the liver allograft have increased in recent years[1-3].Although there has been ren...To the Editor:With the popularity of liver transplantation(LT)and the inspiration for long-time survival,issues related to evaluating the liver allograft have increased in recent years[1-3].Although there has been renewed interest in non-invasive methods to evaluate diffuse liver disease,liver biopsy is still the golden standard in clinical practice,particularly for liver transplant recipients(LTRs).The liver biopsy has always been performed in LTRs as a part of standard procedure in cases whose liver function was normal,named as protocol liver biopsy,or to identify histological abnormalities for abnormal liver function and provide guidance for the adjustment of immunosuppressive regimen[4,5].Percutaneous liver biopsy(PLB)has been frequently conducted in LTRs;however,the clinical implementation of protocol liver biopsy by PLB in LTRs is challenging due to their suboptimal compliance,particularly in China[6].Besides,the PLB procedure has been associated with discomfort and potentially life-threatening complications in the general population,as reported in the literature[7,8].展开更多
BACKGROUND Liver transplant(LT)candidates face a heightened risk of infection both pre-and post-transplant,owing to immunosuppressive therapy and complications from chronic liver disease.Infections during the pre-tran...BACKGROUND Liver transplant(LT)candidates face a heightened risk of infection both pre-and post-transplant,owing to immunosuppressive therapy and complications from chronic liver disease.Infections during the pre-transplant period,such as lymphorrhea-induced cellulitis,can cause significant delays in transplantation and increase mortality while on the waiting list.Lymphorrhea,characterized by substantial lymphatic leakage and recurrent skin infections,presents a significant challenge in managing patients who are already immunocompromised.Effective preoperative infection control is critical to enhancing the prospects for a successful liver transplantation.CASE SUMMARY We report the case of a 50-year-old female diagnosed with Hepatitis C virusrelated cirrhosis(Child-Pugh C)and recurrent cellulitis due to lymphorrhea in her left lower leg.She suffered repeated episodes of cellulitis over five years,which prevented her from undergoing LT.Initial conservative treatments were unsuccessful in managing the lymphatic leakage and accompanying infections.In February 2019,she underwent supermicrosurgical lymphaticovenous anastomoses(LVA)to address her lymphorrhea.This procedure,which created multiple lymphatic-venous connections in the lower limb,led to significant improvements in her condition.After the LVA,she experienced no further episodes of cellulitis.Eighteen months later,she successfully underwent a deceased donor liver transplantation.Postoperative complications,including a wound hematoma,were effectively managed,and she was discharged 3 months post-operation.At her 3-year follow-up,her liver function was stable,with no recurrence of cellulitis.CONCLUSION Despite numerous challenges,the patient achieved a successful recovery with satisfactory graft function and was free from lymphorrhea/lymphedema in her left lower limb 3 years post-transplantation.This case underscores the importance of robust infection control during both the pre-and post-transplantation phases and highlights the potential of LVA as a treatment option for managing lymphorrhea and infections in patients with liver cirrhosis.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)has a high global incidence and associated with increased lipid accumulation in hepatocytes,elevated hepatic enzyme levels,liver fibrosis,and hepatic carc...Metabolic dysfunction-associated steatotic liver disease(MASLD)has a high global incidence and associated with increased lipid accumulation in hepatocytes,elevated hepatic enzyme levels,liver fibrosis,and hepatic carcinoma.Despite decades of research and significant advancements,the treatment of MASLD still faces formidable challenges.Nanoprobes for diagnostics and nanomedicine for targeted drug delivery to the liver present promising options for MASLD diagnosis and treatment,enhancing both imaging contrast and bioavailability.Here,we review recent advances in nanotechnology applied to MASLD diagnosis and treatment,specifically focusing on drug delivery systems targeting hepatocytes,hepatic stellate cells,Kupffer cells,and liver sinusoidal endothelial cells.This review aims to provide an overview of nanomedicine’s potential in early MASLD diagnosis and therapeutic interventions,addressing related complications.展开更多
Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality r...Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.展开更多
BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patien...BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.展开更多
Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-c...Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.展开更多
AIM:To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.METHODS:Between April 2002 and July 2008,220hepatocellular carcinoma(HCC)patients who w...AIM:To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.METHODS:Between April 2002 and July 2008,220hepatocellular carcinoma(HCC)patients who were diagnosed with HCC and underwent liver transplantation(LT)at our liver transplantation center were included.These patients were divided into three groups according to the characteristics of their tumors(tumor diameter,tumor number):the Milan criteria group(Group 1),the in up-to-seven group(Group 2)and the out up-toseven group(Group 3).Then,we compared long-term survival and tumor recurrence of these three groups.RESULTS:The baseline characteristics of transplant recipients were comparable among these three groups,except for the type of liver graft(deceased donor liver transplant or live donor liver transplantation).There were also no significant differences in the pre-operativeα-fetoprotein level.The 1-,3-,and 5-year overall survival and tumor-free survival rate for the Milan criteriagroup were 94.8%,91.4%,89.7%and 91.4%,86.2%,and 86.2%respectively;in the up-to-seven criteria group,these rates were 87.8%,77.8%,and 76.6%and 85.6%,75.6%,and 75.6%respectively(P<0.05).However,the advanced HCC patients’(in the group out of up-to-seven criteria)overall and tumor-free survival rates were much lower,at 75%,53.3%,and 50%and65.8%,42.5%,and 41.7%,respectively(P<0.01).CONCLUSION:Considering that patients in the up-toseven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group,the up-to-seven criteria should be used carefully and selectively.展开更多
AIM:To validate the"Metroticket"predictor using a large cohort of liver transplantation(LT)patients with hepatocellular carcinoma(HCC)in China.METHODS:In total,230 cases of LT for HCC treatment at our center...AIM:To validate the"Metroticket"predictor using a large cohort of liver transplantation(LT)patients with hepatocellular carcinoma(HCC)in China.METHODS:In total,230 cases of LT for HCC treatment at our center,from July 2000 to August 2008,were included in the present study.The predicted 1-,3-and 5-year post-LT survival rates were calculated using the Metroticket model(http://89.96.76.14/metroticket/calculator/).The predicted and observed long-term survival rates were then compared and analyzed.RESULTS:The predicted survival rates for all 230cases,as calculated by the Metroticket model,were64.7%and 56.2%at 3 and 5 years,respectively,and the observed survival rates for these patients were71.3%and 57.8%,respectively.For the 23 cases with macrovascular invasion,the predicted 5-year survival rate was 43.5%,whereas the observed 5-year survival rate was only 8.7%.For the 42 cases with microvascular invasion but an absence of macrovascular invasion,the predicted 5-year survival rate was 44.9%,and the observed 5-year survival rate was 50%.For the remaining 165 patients without any vascular invasion,the predicted 5-year survival rate was 65.8%,and the observed 5-year survival rate was 66.7%.CONCLUSION:The Metroticket model can be used to accurately predict survival in HCC-related LT cases with an absence of macrovascular invasion.展开更多
BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end...BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive(HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of China's Mainland. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.AIM To evaluate the safety of using hepatitis B virus(HBV) core antibody-positive donors for liver transplantation in Chinese patients.METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative(HBcAb-) liver grafts. The 1-, 3-and 5-year survival rates in patients and grafts between the two groups were similar(patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3-and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcA b+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive(HBsAg+) and HBsA g negative(HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg-patients with HBcAb+ liver grafts(13.23%), in which HBV naive recipients suffered most(31.82%), although this difference did not affect patient and graft survival(P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody(anti-HBs) titer(more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. CONCLUSION HBcA b+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.展开更多
AIM： To discuss the safety of donors during living donor liver transplantation （LDLT） and the authors＇ experience with 50 cases. METHODS： Between January 1995 and March 2006, 50 patients with end-stage liver dise...AIM： To discuss the safety of donors during living donor liver transplantation （LDLT） and the authors＇ experience with 50 cases. METHODS： Between January 1995 and March 2006, 50 patients with end-stage liver disease received LDLT in our department. Donors （at the age of 27-58 years） were healthy and antibody （ABO）-compatible. The protocol of evaluation and selection of donors, choice of surgical methods and strategy applied in the safety evaluation of donors were analyzed. RESULTS： A total of 115 candidate donors were evaluated for LDLT at our center. Of these, 50 underwent successful hepatectomy for living donation. The elimination rate for donors was 43.5%. Positive hepatitis serology and ABO incompatibility were the main factors for excluding candidates. All donors recovered uneventfully. The follow-up time ranged from 3 to 135 too. The incidence of major and minor medical complications was 12.0% and 28.0%, respectively. CONCLUSION： LDLT provides an excellent approach to the problem of donor shortage in China. With a thorough and complete preoperative workup and meticulous intra-and postoperative management, LDLT can be performed with minimal donor morbidity.展开更多
Biliary complications have always been a dreaded cause of morbidity after living donor liver transplantation.While intrinsic variations in both graft and recipient biliary anatomy remain a significant factor to the di...Biliary complications have always been a dreaded cause of morbidity after living donor liver transplantation.While intrinsic variations in both graft and recipient biliary anatomy remain a significant factor to the difficulty of biliary reconstruction,our institution has taken advantage of its high volume of cases to critically review and evaluate modifiable operative risk factors,in particular,our surgical protocols.We present herein,the evolution of our reconstructive biliary technique from conventional methods to our current standard of microsurgical biliary reconstruction for both graft and recipient ducts.Over this period of transition,our center has created a classification system for biliary reconstruction that decreased the biliary complication rates from 40.0%to 10.2%.展开更多
文摘With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma.
基金supported by grants from Capital’s Funds for Health Improvement and Research (2024–1–2022)Beijing Nat-ural Science Foundation (7244318)。
文摘Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-donor” liver transplantation allows grafts to be recovered from other liver recipients. This review summarizes the current clinical practice of “no-donor” liver transplantation, focusing on the experiences of Chinese transplant teams. Domino liver transplantation was introduced by Furtado in 1995 and implemented later in 2013 in China, and novel donor indications including some essential-to-treat inherited metabolic liver-based diseases have emerged. The concept of cross-auxiliary domino liver transplantation brings a further expansion of the domino liver graft pool, and the first pair of liver transplantation performed “rigorously without donation” was accomplished in our center in 2018. Our experience with this original transplantation procedure is hereby reviewed. In order to further promote and make successful “no-donor” liver transplantation, close co-operation between researchers, surgeons, physicians, organ procurement organizations, as well as ethical committees is required.
基金supported by funding from the National Key Research and Development Program of China(Grant No.2021 YFA1100500)The Major Research Plan of the National Natural Science Foundation of China(Grant No.92159202)+3 种基金Key Program,National Natural Science Foundation of China(Grant No.81930016)National Natural Science Foundation of China(Grant No.82300743)Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23H160044)Key Research&Development Program of Zhejiang Province(Grant Nos.2019C03050,2022C03108,and 2021C03118)。
文摘Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be determined.This study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with HCC.Methods:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were analyzed.The associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further studied.Results:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male donors.Multivariate analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(P<0.05).Conclusions:Our findings highlighted that the post-LT outcomes of female recipients were significantly superior to those of male recipients,and the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival.Livers from male donors may provide the most benefit to female recipients.Our results indicate that sex should be considered as a critical factor in organ allocation.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018–028)the nuclear energy development projects of China during the 13thFive Year Plan periodthe key research and development project of the Sichuan Provincial Department of Science and Technology(No.18ZDYF1466)。
文摘Radioactive microspheres have demonstrated excellent therapeutic effects and good tolerance in the treatment of unresectable primary and secondary liver malignancies.This is attributed to precise embolization and potent anti-tumor effect.However,certain limitations such as unstable loading,perfusion stasis,heterogeneous distribution,ectopic distribution,and insufficient dosage,restrict their clinical application.Herein,a novel personalized Y-90 carbon microsphere with high uniformity,high specific activity and high availability(^(90)Y-HUACM)is presented.It is synthesized through planar molecular complex adsorption and chemical deposition solidification.^(90)Y-HUACM exhibited controllable size,excellent biocompatibility,outstanding in vitro and in vivo stability.The radiolabeling efficiency of Y-90 exceeded 99%and the leaching rate of Y-90 is far below 0.1%.Furthermore,the excellent anti-tumor effect,nuclide loading stability,anti-reflux characteristics,precise embolization,and biosafety of^(90)Y-HUACM were validated in a rabbit VX2liver tumor model.In summary,this new,high-performance,and customizable radioactive microsphere provides a superior choice for selective internal radiation treatment of advanced liver cancer is expected to be rapidly applied in clinical practice.
基金supported by grants from Shanghai Municipal Health Commission(201940032)National Key Research and Development Program of China(2023YFC2505900).
文摘Background:Normal bile is sterile.Studies have shown that cholangitis after liver transplantation(LT)was associated with a relatively poor prognosis.It remains unclear whether the bacteriobilia or fungibilia impact the patient outcomes in LT recipients,especially with donation after circulatory death(DCD)allografts,which was correlated with a higher risk of allograft failure.Methods:This retrospective study included 139 LT recipients of DCD grafts from 2019 to 2021.All patients were divided into two groups according to the presence or absence of bacteriobilia or fungibilia.The prevalence and microbial spectrum of postoperative bacteriobilia or fungibilia and its possible association with outcomes,especially hospital stay were analyzed.Results:Totally 135 and 171 organisms were isolated at weeks 1 and 2,respectively.Among all patients included in this analysis,83(59.7%)developed bacteriobilia or fungibilia within 2 weeks posttransplantation.The occurrence of bacteriobilia or fungibilia[β=7.43,95%CI(confidence interval):0.02 to 14.82,P=0.049],particularly the detection of Pseudomonas(β=18.84,95%CI:6.51 to 31.07,P=0.003)within 2 weeks post-transplantation was associated with a longer hospital stay.However,it did not affect the graft and patient survival.Conclusions:The occurrence of bacteriobilia or fungibilia,particularly Pseudomonas within 2 weeks posttransplantation,could influence the recovery of liver function and was associated with prolonged hospital stay but not the graft and patient survival.
文摘Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seq LDLT) after LR as a strategy for HCC patients with high-risk of recurrence.Methods:We analyzed data from 27 adult patients who underwent seq LDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS).Results:Among 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqL DLT. Five patients (19%) underwent living donor liver transplantation (LDLT) following LR as a downstaging strategy while the rest received seqL DLT as a preemptive strategy. The median age was 53.5 years with 85%males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0%and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors> 5 cm(19%), and a total tumor diameter> 10 cm (7%).Conclusions:Seq LDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seq LDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.
基金supported by grants from the National Key Research and Development Program of China(2023YFC2505900)the National Natural Science Foundation of China(82241225,81873874 and 82071797)。
文摘Background:Liver transplantations(LTs)with extended criteria have produced surgical results comparable to those obtained with traditional standards.However,it is not sufficient to predict hepatocellular carcinoma(HCC)recurrence after LT according to morphological criteria alone.The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria.Methods:Retrospective data on patients with HCC,including pathology,serological markers and followup data,were collected from January 2015 to April 2020 at Huashan Hospital,Fudan University,Shanghai,China.Logistic least absolute shrinkage and selection operator(LASSO)regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram.Receiver operating characteristic(ROC)curves,Kaplan-Meier curves,decision curve analyses(DCAs),calibration diagrams,net reclassification indices(NRIs)and integrated discrimination improvement(IDI)values were used to assess the prognostic capacity of the nomogram.Results:A total of 301 patients with HCC who underwent LT were enrolled in the study.The nomogram was constructed,and the ROC curve showed good performance in predicting survival in both the development set(2/3)and the validation set(1/3)(the area under the curve reached 0.748 and 0.716,respectively).According to the median value of the risk score,the patients were categorized into the high-and low-risk groups,which had significantly different recurrence-free survival(RFS)rates(P<0.01).Compared with the Milan criteria and University of California San Francisco(UCSF)criteria,DCA revealed that the new nomogram model had the best net benefit in predicting 1-,3-and 5-year RFS.The nomogram performed well for calibration,NRI and IDI improvement.Conclusions:The nomogram,based on the Milan criteria and serological markers,showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.
文摘BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.
基金supported by a grant from 2021 Shandong Provincial Social Science Popularization and Application Research Project (2021-SKZC-18)。
文摘To the Editor:With the popularity of liver transplantation(LT)and the inspiration for long-time survival,issues related to evaluating the liver allograft have increased in recent years[1-3].Although there has been renewed interest in non-invasive methods to evaluate diffuse liver disease,liver biopsy is still the golden standard in clinical practice,particularly for liver transplant recipients(LTRs).The liver biopsy has always been performed in LTRs as a part of standard procedure in cases whose liver function was normal,named as protocol liver biopsy,or to identify histological abnormalities for abnormal liver function and provide guidance for the adjustment of immunosuppressive regimen[4,5].Percutaneous liver biopsy(PLB)has been frequently conducted in LTRs;however,the clinical implementation of protocol liver biopsy by PLB in LTRs is challenging due to their suboptimal compliance,particularly in China[6].Besides,the PLB procedure has been associated with discomfort and potentially life-threatening complications in the general population,as reported in the literature[7,8].
文摘BACKGROUND Liver transplant(LT)candidates face a heightened risk of infection both pre-and post-transplant,owing to immunosuppressive therapy and complications from chronic liver disease.Infections during the pre-transplant period,such as lymphorrhea-induced cellulitis,can cause significant delays in transplantation and increase mortality while on the waiting list.Lymphorrhea,characterized by substantial lymphatic leakage and recurrent skin infections,presents a significant challenge in managing patients who are already immunocompromised.Effective preoperative infection control is critical to enhancing the prospects for a successful liver transplantation.CASE SUMMARY We report the case of a 50-year-old female diagnosed with Hepatitis C virusrelated cirrhosis(Child-Pugh C)and recurrent cellulitis due to lymphorrhea in her left lower leg.She suffered repeated episodes of cellulitis over five years,which prevented her from undergoing LT.Initial conservative treatments were unsuccessful in managing the lymphatic leakage and accompanying infections.In February 2019,she underwent supermicrosurgical lymphaticovenous anastomoses(LVA)to address her lymphorrhea.This procedure,which created multiple lymphatic-venous connections in the lower limb,led to significant improvements in her condition.After the LVA,she experienced no further episodes of cellulitis.Eighteen months later,she successfully underwent a deceased donor liver transplantation.Postoperative complications,including a wound hematoma,were effectively managed,and she was discharged 3 months post-operation.At her 3-year follow-up,her liver function was stable,with no recurrence of cellulitis.CONCLUSION Despite numerous challenges,the patient achieved a successful recovery with satisfactory graft function and was free from lymphorrhea/lymphedema in her left lower limb 3 years post-transplantation.This case underscores the importance of robust infection control during both the pre-and post-transplantation phases and highlights the potential of LVA as a treatment option for managing lymphorrhea and infections in patients with liver cirrhosis.
基金supported in part by Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0508800)National Natural Science Foundation of China(32401171)+4 种基金the Key Research and Development Program of Jiangsu Province(BE2023767a)Fundamental Research Fund of Southeast University(3290002406A2)Research Personnel Cultivation Programme of Zhongda Hospital,Southeast University(CZXM-GSP-RC125)Distinguished Medical Specialists in Jiangsu Province(CZXM-RC-43)Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University(2023YJXYYRCPY03).
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has a high global incidence and associated with increased lipid accumulation in hepatocytes,elevated hepatic enzyme levels,liver fibrosis,and hepatic carcinoma.Despite decades of research and significant advancements,the treatment of MASLD still faces formidable challenges.Nanoprobes for diagnostics and nanomedicine for targeted drug delivery to the liver present promising options for MASLD diagnosis and treatment,enhancing both imaging contrast and bioavailability.Here,we review recent advances in nanotechnology applied to MASLD diagnosis and treatment,specifically focusing on drug delivery systems targeting hepatocytes,hepatic stellate cells,Kupffer cells,and liver sinusoidal endothelial cells.This review aims to provide an overview of nanomedicine’s potential in early MASLD diagnosis and therapeutic interventions,addressing related complications.
基金supported by grants from the Research Foundation–Flanders(11A6420N,1268823N to WC and LVH)a FWO Junior Research Project Grant(G055121N to REV)VIB.AG is a senior clinical researcher of the Research Foundation–Flanders(1805718N)。
文摘Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.
基金Supported by WBE Liver Foundation,No.WBE20220182022 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYY-YN-2022-092023 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYYYN2023-14.
文摘BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
基金supported by grants from the Natural Science Research Project of Shanxi Basic Research Program [20210302123246]the Scientific Research Project of Shanxi Provincial Health Commission [2020079]+1 种基金the Natural Science Foundation Youth Fund of Hebei Province[C2022402032]the Shanxi Province Higher Education “Billion Project” Science and Technology Guidance Project [BYJL036]。
文摘Objective To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrowderived mesenchymal stem cells(BMSCs) against cholestatic liver fibrosis in mice.Methods BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells(HSCs).HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation(BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.Results BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore,BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell(HSC) activation and collagen fiber formation.Conclusion The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
文摘AIM:To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.METHODS:Between April 2002 and July 2008,220hepatocellular carcinoma(HCC)patients who were diagnosed with HCC and underwent liver transplantation(LT)at our liver transplantation center were included.These patients were divided into three groups according to the characteristics of their tumors(tumor diameter,tumor number):the Milan criteria group(Group 1),the in up-to-seven group(Group 2)and the out up-toseven group(Group 3).Then,we compared long-term survival and tumor recurrence of these three groups.RESULTS:The baseline characteristics of transplant recipients were comparable among these three groups,except for the type of liver graft(deceased donor liver transplant or live donor liver transplantation).There were also no significant differences in the pre-operativeα-fetoprotein level.The 1-,3-,and 5-year overall survival and tumor-free survival rate for the Milan criteriagroup were 94.8%,91.4%,89.7%and 91.4%,86.2%,and 86.2%respectively;in the up-to-seven criteria group,these rates were 87.8%,77.8%,and 76.6%and 85.6%,75.6%,and 75.6%respectively(P<0.05).However,the advanced HCC patients’(in the group out of up-to-seven criteria)overall and tumor-free survival rates were much lower,at 75%,53.3%,and 50%and65.8%,42.5%,and 41.7%,respectively(P<0.01).CONCLUSION:Considering that patients in the up-toseven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group,the up-to-seven criteria should be used carefully and selectively.
文摘AIM:To validate the"Metroticket"predictor using a large cohort of liver transplantation(LT)patients with hepatocellular carcinoma(HCC)in China.METHODS:In total,230 cases of LT for HCC treatment at our center,from July 2000 to August 2008,were included in the present study.The predicted 1-,3-and 5-year post-LT survival rates were calculated using the Metroticket model(http://89.96.76.14/metroticket/calculator/).The predicted and observed long-term survival rates were then compared and analyzed.RESULTS:The predicted survival rates for all 230cases,as calculated by the Metroticket model,were64.7%and 56.2%at 3 and 5 years,respectively,and the observed survival rates for these patients were71.3%and 57.8%,respectively.For the 23 cases with macrovascular invasion,the predicted 5-year survival rate was 43.5%,whereas the observed 5-year survival rate was only 8.7%.For the 42 cases with microvascular invasion but an absence of macrovascular invasion,the predicted 5-year survival rate was 44.9%,and the observed 5-year survival rate was 50%.For the remaining 165 patients without any vascular invasion,the predicted 5-year survival rate was 65.8%,and the observed 5-year survival rate was 66.7%.CONCLUSION:The Metroticket model can be used to accurately predict survival in HCC-related LT cases with an absence of macrovascular invasion.
文摘BACKGROUND Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive(HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of China's Mainland. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal.AIM To evaluate the safety of using hepatitis B virus(HBV) core antibody-positive donors for liver transplantation in Chinese patients.METHODS We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study.RESULTS In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative(HBcAb-) liver grafts. The 1-, 3-and 5-year survival rates in patients and grafts between the two groups were similar(patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3-and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcA b+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive(HBsAg+) and HBsA g negative(HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg-patients with HBcAb+ liver grafts(13.23%), in which HBV naive recipients suffered most(31.82%), although this difference did not affect patient and graft survival(P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody(anti-HBs) titer(more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. CONCLUSION HBcA b+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.
文摘AIM： To discuss the safety of donors during living donor liver transplantation （LDLT） and the authors＇ experience with 50 cases. METHODS： Between January 1995 and March 2006, 50 patients with end-stage liver disease received LDLT in our department. Donors （at the age of 27-58 years） were healthy and antibody （ABO）-compatible. The protocol of evaluation and selection of donors, choice of surgical methods and strategy applied in the safety evaluation of donors were analyzed. RESULTS： A total of 115 candidate donors were evaluated for LDLT at our center. Of these, 50 underwent successful hepatectomy for living donation. The elimination rate for donors was 43.5%. Positive hepatitis serology and ABO incompatibility were the main factors for excluding candidates. All donors recovered uneventfully. The follow-up time ranged from 3 to 135 too. The incidence of major and minor medical complications was 12.0% and 28.0%, respectively. CONCLUSION： LDLT provides an excellent approach to the problem of donor shortage in China. With a thorough and complete preoperative workup and meticulous intra-and postoperative management, LDLT can be performed with minimal donor morbidity.
文摘Biliary complications have always been a dreaded cause of morbidity after living donor liver transplantation.While intrinsic variations in both graft and recipient biliary anatomy remain a significant factor to the difficulty of biliary reconstruction,our institution has taken advantage of its high volume of cases to critically review and evaluate modifiable operative risk factors,in particular,our surgical protocols.We present herein,the evolution of our reconstructive biliary technique from conventional methods to our current standard of microsurgical biliary reconstruction for both graft and recipient ducts.Over this period of transition,our center has created a classification system for biliary reconstruction that decreased the biliary complication rates from 40.0%to 10.2%.
