Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the r...Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.展开更多
Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is ...Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.展开更多
Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.U...Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.展开更多
Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of ev...Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.展开更多
Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its...Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.展开更多
Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopath...Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.展开更多
With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn pu...With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liv...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.展开更多
BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to pre...BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyl...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.展开更多
Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which ...Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.展开更多
BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombo...BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.展开更多
Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,...Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.展开更多
Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were establi...Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.展开更多
BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are p...BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.展开更多
The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary chola...The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment ...Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.展开更多
Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute resp...Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.展开更多
Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases.In some countries,its use is restricted to radiologists,limiting access for other clinicians,su...Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases.In some countries,its use is restricted to radiologists,limiting access for other clinicians,such as gastroenterologists.Endoscopic ultrasound,as a novel technique,plays a crucial role in diagnosis and treatment of digestive diseases.However,its use is sometimes recommended for conditions where no clear advantage over percutaneous ultrasound exists,leaving the impression that clinicians sometimes resort to an endoscopic approach due to the unavailability of percutaneous options.展开更多
BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,an...BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.展开更多
文摘Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.
文摘Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.
文摘Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.
文摘Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.
文摘Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.
基金The current project is funded by Shandong Provincial Natural Science Foundation,China(ZR2020MH370)Major Science and Technology Innovation in Shandong Province(2017CXGC1307)Ji’nan Science and Technology Project(201303055)。
文摘Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.
文摘With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.
基金Supported by the Special Research Project of the Capital’s Health Development,No.2024-3-7037and the Beijing Clinical Key Specialty Project.
文摘BACKGROUND The severity of nonalcoholic fatty liver disease(NAFLD)and lipid metabolism are related to the occurrence of colorectal polyps.Liver-controlled attenuation parameters(liver-CAPs)have been established to predict the prognosis of hepatic steatosis patients.AIM To explore the risk factors associated with colorectal polyps in patients with NAFLD by analyzing liver-CAPs and establishing a diagnostic model.METHODS Patients who were diagnosed with colorectal polyps in the Department of Gastroenterology of our hospital between June 2021 and April 2022 composed the case group,and those with no important abnormalities composed the control group.The area under the receiver operating characteristic curve was used to predict the diagnostic efficiency.Differences were considered statistically significant when P<0.05.RESULTS The median triglyceride(TG)and liver-CAP in the case group were significantly greater than those in the control group(mmol/L,1.74 vs 1.05;dB/m,282 vs 254,P<0.05).TG and liver-CAP were found to be independent risk factors for colorectal polyps,with ORs of 2.338(95%CI:1.154–4.733)and 1.019(95%CI:1.006–1.033),respectively(P<0.05).And there was no difference in the diagnostic efficacy between liver-CAP and TG combined with liver-CAP(TG+CAP)(P>0.05).When the liver-CAP was greater than 291 dB/m,colorectal polyps were more likely to occur.CONCLUSION The levels of TG and liver-CAP in patients with colorectal polyps are significantly greater than those patients without polyps.Liver-CAP alone can be used to diagnose NAFLD with colorectal polyps.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)and alcohol-related liver disease(Ar-LD)constitute the primary forms of chronic liver disease,and their incidence is progressively increasing with changes in lifestyle habits.Earlier studies have do-cumented a correlation between the occurrence and development of prevalent mental disorders and fatty liver.AIM To investigate the correlation between fatty liver and mental disorders,thus ne-cessitating the implementation of a mendelian randomization(MR)study to elu-cidate this association.METHODS Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog,while information on mental disorders,including Alzheimer's disease,schizophrenia,anxiety disorder,attention deficit hyperactivity disorder(ADHD),bipolar disorder,major depressive disorder,multiple personality dis-order,obsessive-compulsive disorder(OCD),post-traumatic stress disorder(PTSD),and schizophrenia was acquired from the psychiatric genomics consor-tium.A two-sample MR method was applied to investigate mediators in signifi-cant associations.RESULTS After excluding weak instrumental variables,a causal relationship was identified between fatty liver disease and the occurrence and development of some psychia-tric disorders.Specifically,the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD(OR:5.81,95%CI:5.59-6.03,P<0.01),bipolar disorder(OR:5.73,95%CI:5.42-6.05,P=0.03),OCD(OR:6.42,95%CI:5.60-7.36,P<0.01),and PTSD(OR:5.66,95%CI:5.33-6.01,P<0.01).Meanwhile,NAFLD significantly increased the risk of developing bipolar disorder(OR:55.08,95%CI:3.59-845.51,P<0.01),OCD(OR:61.50,95%CI:6.69-565.45,P<0.01),and PTSD(OR:52.09,95%CI:4.24-639.32,P<0.01).CONCLUSION Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders,namely bipolar disorder,OCD,and PTSD,highlighting the significance of preven-tive measures against psychiatric disorders in patients with fatty liver disease.
基金supported by the grant from the National Natural Science Foundation of China (82070609)
文摘Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.
文摘BACKGROUND Peripherally inserted central catheters(PICCs)are commonly used in hospitalized patients with liver cancer for the administration of chemotherapy,nutrition,and other medications.However,PICC-related thrombosis is a serious complication that can lead to morbidity and mortality in this patient population.Several risk factors have been identified for the development of PICC-related thrombosis,including cancer type,stage,comorbidities,and catheter characteristics.Understanding these risk factors and developing a predictive model can help healthcare providers identify high-risk patients and implement preventive measures to reduce the incidence of thrombosis.AIM To analyze the influencing factors of PICC-related thrombosis in hospitalized patients with liver cancer,construct a predictive model,and validate it.METHODS Clinical data of hospitalized patients with liver cancer admitted from January 2020 to December 2023 were collected.Thirty-five cases of PICC-related thrombosis in hospitalized patients with liver cancer were collected,and 220 patients who underwent PICC placement during the same period but did not develop PICC-related thrombosis were randomly selected as controls.A total of 255 samples were collected and used as the training set,and 77 cases were collected as the validation set in a 7:3 ratio.General patient information,case data,catheterization data,coagulation indicators,and Autar Thrombosis Risk Assessment Scale scores were analyzed.Univariate and multivariate unconditional logistic regression analyses were performed on relevant factors,and the value of combined indicators in predicting PICC-related thrombosis in hospitalized patients with liver cancer was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Univariate analysis showed statistically significant differences(P<0.05)in age,sex,Karnofsky performance status score(KPS),bedridden time,activities of daily living impairment,parenteral nutrition,catheter duration,distant metastasis,and bone marrow suppression between the thrombosis group and the non-thrombosis group.Other aspects had no statistically significant differences(P>0.05).Multivariate regression analysis showed that age≥60 years,KPS score≤50 points,parenteral nutrition,stage III to IV,distant metastasis,bone marrow suppression,and activities of daily living impairment were independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer(P<0.05).Catheter duration of 1-6 months and catheter duration>6 months were protective factors for PICC-related thrombosis(P<0.05).The predictive model for PICC-related thrombosis was obtained as follows:P predictive probability=[exp(Logit P)]/[1+exp(Logit P)],where Logit P=age×1.907+KPS score×2.045+parenteral nutrition×9.467+catheter duration×0.506+tumor-node-metastasis(TNM)staging×2.844+distant metastasis×2.065+bone marrow suppression×2.082+activities of daily living impairment×13.926.ROC curve analysis showed an area under the curve(AUC)of 0.827(95%CI:0.724-0.929,P<0.001),with a corresponding optimal cut-off value of 0.612,sensitivity of 0.755,and specificity of 0.857.Calibration curve analysis showed good consistency between the predicted occurrence of PICC-related thrombosis and actual occurrence(P>0.05).ROC analysis showed AUCs of 0.888 and 0.729 for the training and validation sets,respectively.CONCLUSION Age,KPS score,parenteral nutrition,TNM staging,distant metastasis,bone marrow suppression,and activities of daily living impairment are independent risk factors for PICC-related thrombosis in hospitalized patients with liver cancer,while catheter duration is a protective factor for the disease.The predictive model has an AUC of 0.827,indicating high predictive accuracy and clinical value.
文摘Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
基金supported by the National Natural Science Foundation of China(81971875,82300661)Natural Science Foundation of Anhui province(2308085QH246)+3 种基金Natural Science Foundation of the Anhui Higher Education Institutions(KJ2021A0205)Basic and Clinical Cooperative Research Program of Anhui Medical University(2019xkjT002,2019xkjT022,2022xkjT013)Talent Training Program,School of Basic Medical Sciences,Anhui Medical University(2022YPJH102)National College Students Innovation and Entrepreneurship Training Program of China(202210366024)。
文摘Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.
文摘BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.
文摘The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.
基金the National Natural Science Foundation of China,No.82070588 and No.82370577.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.
文摘Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
文摘Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases.In some countries,its use is restricted to radiologists,limiting access for other clinicians,such as gastroenterologists.Endoscopic ultrasound,as a novel technique,plays a crucial role in diagnosis and treatment of digestive diseases.However,its use is sometimes recommended for conditions where no clear advantage over percutaneous ultrasound exists,leaving the impression that clinicians sometimes resort to an endoscopic approach due to the unavailability of percutaneous options.
基金Supported by the National Natural Science Foundation of China,No.81372595 and No.81972696.
文摘BACKGROUND At present,liver transplantation(LT)is one of the best treatments for hepatocellular carcinoma(HCC).Accurately predicting the survival status after LT can significantly improve the survival rate after LT,and ensure the best way to make rational use of liver organs.AIM To develop a model for predicting prognosis after LT in patients with HCC.METHODS Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated.The expression levels of alphafetoprotein(AFP),des-gamma-carboxy prothrombin,Golgi protein 73,cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer.The best cutoff value of biomarkers was determined using the Youden index.Cox regression analysis was used to identify the independent risk factors.A forest model was constructed using the random forest method.We evaluated the accuracy of the nomogram using the area under the curve,using the calibration curve to assess consistency.A decision curve analysis(DCA)was used to evaluate the clinical utility of the nomograms.RESULTS The total tumor diameter(TTD),vascular invasion(VI),AFP,and cytokeratin-18 epitopes M30(CK18-M30)were identified as important risk factors for outcome after LT.The nomogram had a higher predictive accuracy than the Milan,University of California,San Francisco,and Hangzhou criteria.The calibration curve analyses indicated a good fit.The survival and recurrence-free survival(RFS)of high-risk groups were significantly lower than those of low-and middle-risk groups(P<0.001).The DCA shows that the model has better clinical practicability.CONCLUSION The study developed a predictive nomogram based on TTD,VI,AFP,and CK18-M30 that could accurately predict overall survival and RFS after LT.It can screen for patients with better postoperative prognosis,and improve longterm survival for LT patients.