AIM: To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography (CT) volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellu...AIM: To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography (CT) volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma. METHODS: CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as "CT grade" and the percentage of remnant liver volume (PRLV) [PRLV = predicted RLV/predicted total liver volume (PTLV) × 100%; PTLV (mL) = 121.75 + 16.49 × body mass (kg)] were calculated by adding slice by slice of CT liver images. The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed. RESULTS: There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV > 50% (χ2 = 4.988, P = 0.026), and between the group with CT grade 0/1 and the group with CT grade 2/3 (χ2 = 5.429, P = 0.026). With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% (1/14), and that below the line was 53.7% (22/41), indicating a significant difference between the two rates (χ2 = 9.281, P = 0.002, P < 0.05). CONCLUSION: PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidatesundergoing liver resection for judging hepatic functional reserve.展开更多
Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis t...Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.展开更多
Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be di...Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.展开更多
BACKGROUND It is controversial whether transjugular intrahepatic portosystemic shunt(TIPS)placement can improve long-term survival.AIM To assess whether TIPS placement improves survival in patients with hepaticvenous-...BACKGROUND It is controversial whether transjugular intrahepatic portosystemic shunt(TIPS)placement can improve long-term survival.AIM To assess whether TIPS placement improves survival in patients with hepaticvenous-pressure-gradient(HVPG)≥16 mmHg,based on HVPG-related risk stratification.METHODS Consecutive variceal bleeding patients treated with endoscopic therapy+nonselectiveβ-blockers(NSBBs)or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019.HVPG measurements were performed before therapy.The primary outcome was transplant-free survival;secondary endpoints were rebleeding and overt hepatic ence-phalopathy(OHE).RESULTS A total of 184 patients were analyzed(mean age,55.27 years±13.86,107 males;102 in the EVL+NSBB group,82 in the covered TIPS group).Based on the HVPG guided risk stratification,70 patients had HVPG<16 mmHg,and 114 patients had HVPG≥16 mmHg.The median follow-up time of the cohort was 49.5 mo.There was no significant difference in transplant-free survival between the two treatment groups overall(hazard ratio[HR],0.61;95%confidence interval[CI]:0.35-1.05;P=0.07).In the high-HVPG tier,transplant-free survival was higher in the TIPS group(HR,0.44;95%CI:0.23-0.85;P=0.004).In the low-HVPG tier,transplantfree survival after the two treatments was similar(HR,0.86;95%CI:0.33-0.23;P=0.74).Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier(P<0.001).The difference in OHE between the two groups was not statistically significant(P=0.09;P=0.48).CONCLUSION TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.展开更多
Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies w...Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.展开更多
BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnosti...BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.展开更多
Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s.It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area o...Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s.It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area of the liver[1–3].Anatomical liver resec-tion is considered to have potential superiority than non-anatomic resection in terms of tumor prognosis,thus it is more often rec-ommended in the treatment of hepatocellular carcinoma[4,5].Recently,laparoscopic segmental liver resection according to the Couinaud classification has been widely performed due to its ad-vantages in minimal invasiveness and tumor prognosis.展开更多
Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine gree...Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine green(ICG)-fluorescence imaging has been introduced as an effective tool for real-time intraoperative guidance[2].Liver anatomy is complex.Generally,liver is composed of 9 segments,each is composed of two to three subsegments,and each subsegment contains several hepatic cone units.A hepatic cone unit is dominated by a tertiary or quaternary hepatic pedicles[3].展开更多
To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove...To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.展开更多
To the Editor: We sincerely applaud the work by Tang et al., in which they described caudate lobe-sparing subtotal hepatectomy as treatment for intrahepatic arterioportal fistulas [ 1 ]. Compared to intrahepatic arter...To the Editor: We sincerely applaud the work by Tang et al., in which they described caudate lobe-sparing subtotal hepatectomy as treatment for intrahepatic arterioportal fistulas [ 1 ]. Compared to intrahepatic arterioportal fistulas, portal vein-hepatic vein fistulas are rarely reported. Patients typically lack clinical symptoms such as hyperammonemia, cholestatic jaundice, and hypoglycemia, unless the shunt becomes relatively large [ 2, 3 ]. Herein, we describe partial hepatectomy as a treatment for cases of left portal vein-middle hepatic vein fistulas.展开更多
Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate w...Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.展开更多
BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular carcinoma.The pathogenesis of hepatic fibrosis ...BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular carcinoma.The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis.Therefore,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic fibrosis.AIM To explore the effect of taurine on aHSC proliferation and the mechanisms involved.METHODS Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated group.Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs.Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron concen-tration.Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs.Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,ATG5,Beclin 1,PTGS2,SLC7A11,and p62.RESULTS Taurine promoted the death of aHSCs and reduced the deposition of the ECM.Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulating LC3B and Beclin 1 protein expression,and upregulating p62 protein expression.Meanwhile,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload,lipid ROS accumu-lation,glutathione depletion,and lipid peroxidation.Furthermore,bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4,exhibiting the best average binding affinity of-20.99 kcal/mol.CONCLUSION Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid drople...Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.展开更多
Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointes...Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.展开更多
BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell prolif...BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains elusive.The focus was on comprehending the relationship and influence of differentially expressed microRNAs(DE-miRNAs)within these exosomes.AIM To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell(HSC)LX2 and the progression of liver fibrosis.METHODS Exosomes from HepG2.2.15 cells,which express HBV-related proteins,were isolated from parental HepG2 and WRL68 cells.Western blotting was used to confirm the presence of the exosomal marker protein CD9.The activation of HSCs was assessed using oil red staining,whereas DiI staining facilitated the observation of exosomal uptake by LX2 cells.Additionally,we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2′-deoxyuracil staining and western blotting,respectively.DE-miRNAs were analyzed using DESeq2.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were used to annotate the target genes of DE-miRNAs.RESULTS Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells.A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 cells.GO analysis indicated that these DE-miRNA target genes were associated with cell differentiation,intracellular signal transduction,negative regulation of apoptosis,extracellular exosomes,and RNA binding.KEGG pathway analysis highlighted ubiquitin-mediated proteolysis,the MAPK signaling pathway,viral carcinogenesis,and the toll-like receptor signaling pathway,among others,as enriched in these targets.CONCLUSION These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation,proliferation,and fibrosis of LX2 cells and that DE-miRNAs within these exosomes contribute to the underlying mechanisms.展开更多
BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more effi...BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.展开更多
The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Cen...The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.展开更多
Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to pred...Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.展开更多
Objective Hepatic stellate cells(HSCs)play a crucial role in liver fibrosis.Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs.Kruppel-like factor 4(KLF4)plays a pivotal role in ...Objective Hepatic stellate cells(HSCs)play a crucial role in liver fibrosis.Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs.Kruppel-like factor 4(KLF4)plays a pivotal role in a wide array of physiological and pathological processes.This study aimed to investigate the effect of KLF4 on the proliferation,apoptosis and phenotype of quiescent HSCs Methods We designed a KLF4 lentiviral vector and a KLF4 siRNA lentiviral vector,to upregulate and silence KLF4 expression in human HSC LX-2 cells via transfection.Cell proliferation was assessed using the CCK-8 assay.Flow cytometry was used to detect the cell cycle distribution and apoptosis rate.Western blotting was used to determine the levels of some quiescence and activation markers of HSCs Results Overexpression of KLF4 significantly increased the levels of E-cadherin and ZO-1,which are quiescent HSC markers,while significantly decreased the levels of N-cadherin and a-SMA,known activated HSC markers.In contrast,cell proliferation and apoptosis rates were elevated in LX-2 cells in which KLF4 expression was silenced Conclusion KLF4 inhibits the proliferation and activation of human LX-2 HSCs.It might be a key regulatory protein in the maintenance of HSC quiescence and may serve as a target for the inhibition of hepatic fibrosis.展开更多
BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of pati...BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.展开更多
基金Supported by the Natural Science Foundation of Hainan Province, No. 30527
文摘AIM: To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography (CT) volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma. METHODS: CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as "CT grade" and the percentage of remnant liver volume (PRLV) [PRLV = predicted RLV/predicted total liver volume (PTLV) × 100%; PTLV (mL) = 121.75 + 16.49 × body mass (kg)] were calculated by adding slice by slice of CT liver images. The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed. RESULTS: There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV > 50% (χ2 = 4.988, P = 0.026), and between the group with CT grade 0/1 and the group with CT grade 2/3 (χ2 = 5.429, P = 0.026). With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% (1/14), and that below the line was 53.7% (22/41), indicating a significant difference between the two rates (χ2 = 9.281, P = 0.002, P < 0.05). CONCLUSION: PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidatesundergoing liver resection for judging hepatic functional reserve.
文摘Introduction: Fibroscan is a recent, non-invasive and non-irradiating diagnostic method. It is based on the principle of ultrasound, which enables liver tissue elasticity to be quantified using a probe, and fibrosis to be assessed. Fibroscan measures both elasticity correlated with hepatic fibrosis and CAP correlated with steatosis. The aim of this study was to evaluate hepatic fibrosis and steatosis using pulse elastometry (Fibroscan/CAP). Methods: This was a descriptive and analytical cross-sectional study in which 170 patients were included. It was conducted from October 1 2021 to December 31 2023, i.e. 27 months, in an outpatient clinic in the hepato-gastroenterology department of the Donka national hospital of the CHU Conakry. Results: Of the 170 patients identified, 87 were male (51%) and 83 female (49%), giving a M/F sex ratio of 1.04. The average age of our patients was 40. The 30 - 50 age group was the most affected, with a frequency of 58.23% (n = 99), followed by the 50 age group with a frequency of 29.41% (n = 50). Hepatomegaly, steatotic liver on ultrasonography, transaminase elevation and obesity were the main indications, respectively: (21.76%), (17.65%), (14.71%), and (13.53%). The examinations were requested by hepatogastroenterologists (47.06%), diabetologists (35.88%) and general practitioners (29%). Of the 170 patients, 100 patients (58.82%) had no significant fibrosis F0F1, 39 (22.94%) had moderate fibrosis F2, 20 patients (11.76%) had severe fibrosis F3 and 11 patients (6.47%) had fibrosis F4. Hepatic steatosis: 62 patients (36.47%) had no S0 steatosis;29.41% had S1 steatosis, 20% had S2 steatosis and 24 patients (14.11%) had S3 steatosis. Abdominal ultrasound revealed a normal liver in 67.05% of patients, hepatic steatosis in 29.41% and non-decompensated cirrhosis in 6 cases. Thus, 108 patients had the parameters required to calculate the Fatty Liver Index (FLI), steatosis was present in 20% of our patients, while 29.41% had an undetermined status and 24 14.11% had a normal FLI. Conclusion: Identifying subjects at risk of metabolic steatopathy, diagnosing and managing these patients is a public health issue and one of the future challenges of hepato-gastroenterology. Fibroscan is an increasingly popular screening tool for hepatic fibrosis and steatosis. The fight against obesity must be a priority.
基金supported by the National Nature Science Foundation of China(Grants 81974533,81530098).
文摘Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.
基金Supported by the National Natural Science Foundation of China,No.81900552Nanjing Health Science,Technology Development Special Fund Project-Key project,No.ZKX19015+1 种基金Outstanding Youth Fund project,No.JQX20005Funding for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University,No.2022-LCYJ-MS-13.
文摘BACKGROUND It is controversial whether transjugular intrahepatic portosystemic shunt(TIPS)placement can improve long-term survival.AIM To assess whether TIPS placement improves survival in patients with hepaticvenous-pressure-gradient(HVPG)≥16 mmHg,based on HVPG-related risk stratification.METHODS Consecutive variceal bleeding patients treated with endoscopic therapy+nonselectiveβ-blockers(NSBBs)or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019.HVPG measurements were performed before therapy.The primary outcome was transplant-free survival;secondary endpoints were rebleeding and overt hepatic ence-phalopathy(OHE).RESULTS A total of 184 patients were analyzed(mean age,55.27 years±13.86,107 males;102 in the EVL+NSBB group,82 in the covered TIPS group).Based on the HVPG guided risk stratification,70 patients had HVPG<16 mmHg,and 114 patients had HVPG≥16 mmHg.The median follow-up time of the cohort was 49.5 mo.There was no significant difference in transplant-free survival between the two treatment groups overall(hazard ratio[HR],0.61;95%confidence interval[CI]:0.35-1.05;P=0.07).In the high-HVPG tier,transplant-free survival was higher in the TIPS group(HR,0.44;95%CI:0.23-0.85;P=0.004).In the low-HVPG tier,transplantfree survival after the two treatments was similar(HR,0.86;95%CI:0.33-0.23;P=0.74).Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier(P<0.001).The difference in OHE between the two groups was not statistically significant(P=0.09;P=0.48).CONCLUSION TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.
文摘Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.
文摘BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.
基金This study was supported by a grant from the Natural Science Foundation of Zhejiang Province(LY20H160023).
文摘Full laparoscopic liver resection has been performed widely since it was introduced in the early 1990s.It has been expanded from initial for partial resection of the anterolateral segments to non-restriction of area of the liver[1–3].Anatomical liver resec-tion is considered to have potential superiority than non-anatomic resection in terms of tumor prognosis,thus it is more often rec-ommended in the treatment of hepatocellular carcinoma[4,5].Recently,laparoscopic segmental liver resection according to the Couinaud classification has been widely performed due to its ad-vantages in minimal invasiveness and tumor prognosis.
基金from Health Commission of Zhejiang Province(JBZX-202004)the National Natural Science Foundation of China(82002925)the National Key Research and Development Program of China(2022YFC2407304).
文摘Laparoscopic anatomical liver resection has been increasingly reported worldwide,but how to demarcate the resection planes is technically challenging[1].Positive staining technique with intraoperative indocyanine green(ICG)-fluorescence imaging has been introduced as an effective tool for real-time intraoperative guidance[2].Liver anatomy is complex.Generally,liver is composed of 9 segments,each is composed of two to three subsegments,and each subsegment contains several hepatic cone units.A hepatic cone unit is dominated by a tertiary or quaternary hepatic pedicles[3].
基金the Natural Science Foundation of Zhejiang Province(LQ22H160058).
文摘To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.
基金supported by a grant from the Sichuan Province Science and Technology Planning Project (2022NSFSC0767)。
文摘To the Editor: We sincerely applaud the work by Tang et al., in which they described caudate lobe-sparing subtotal hepatectomy as treatment for intrahepatic arterioportal fistulas [ 1 ]. Compared to intrahepatic arterioportal fistulas, portal vein-hepatic vein fistulas are rarely reported. Patients typically lack clinical symptoms such as hyperammonemia, cholestatic jaundice, and hypoglycemia, unless the shunt becomes relatively large [ 2, 3 ]. Herein, we describe partial hepatectomy as a treatment for cases of left portal vein-middle hepatic vein fistulas.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81970563)the Medical Health Science and Technology Project of Health Commission of Zhejiang Province(2019RC055).
文摘Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.
基金Supported by Guangxi Natural Science Foundation Program,No.2020GXNSFAA297160 and No.2018GXNSFBA050050Guipai Xinglin Youth Talent Project of Guangxi University of Chinese Medicine,No.2022C042.
文摘BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular carcinoma.The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis.Therefore,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic fibrosis.AIM To explore the effect of taurine on aHSC proliferation and the mechanisms involved.METHODS Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated group.Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs.Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron concen-tration.Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs.Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,ATG5,Beclin 1,PTGS2,SLC7A11,and p62.RESULTS Taurine promoted the death of aHSCs and reduced the deposition of the ECM.Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulating LC3B and Beclin 1 protein expression,and upregulating p62 protein expression.Meanwhile,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload,lipid ROS accumu-lation,glutathione depletion,and lipid peroxidation.Furthermore,bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4,exhibiting the best average binding affinity of-20.99 kcal/mol.CONCLUSION Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.
基金Discipline Key Special ProjectGrant/Award Number:XKZDQY202001+7 种基金Henan Provincial Key R&D and Promotion Special ProjectGrant/Award Number:212102310033Henan Provincial Medical Science and Technology Tackling ProgramGrant/Award Number:LHGJ20220557Key R&D Program of ChinaGrant/Award Number:2020YFC2006100,2020YFC2009000 and 2020YFC2009006National Natural Science Foundation of ChinaGrant/Award Number:31471330 and 81870408。
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally.Hepatic stellate cells(HSCs)are the major effector cells of liver fibrosis.HSCs contain abundant lipid droplets(LDs)in their cytoplasm during quiescence.Perilipin 5(PLIN 5)is a LD surface-associated protein that plays a crucial role in lipid homeostasis.However,little is known about the role of PLIN 5 in HSC activation.Methods:PLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection.At the same time,PLIN 5 gene knockout mice were constructed and fed with a high-fat diet(HFD)for 20 weeks to study the role of PLIN 5 in NAFLD.The corresponding reagent kits were used to measure TG,GSH,Caspase 3 activity,ATP level,and mitochondrial DNA copy number.Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC-MS/MS.AMPK,mitochondrial function,cell proliferation,and apoptosis-related genes and proteins were detected by western blotting and qPCR.Results:Overexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria,inhibition of cell proliferation,and a significant increase in cell apoptosis through AMPK activation.In addition,compared with the HFD-fed C57BL/6J mice,PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition,decreased LD abundance and size,and reduced liver fibrosis.Conclusion:These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.
文摘Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.
基金Supported by The Spring City Plan:The High-level Talent Promotion and Training Project of Kunming,No.2022SCP002The Research of Key Techniques and Application of Liver-Kidney Organ Transplantation,No.202302AA310018.
文摘BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains elusive.The focus was on comprehending the relationship and influence of differentially expressed microRNAs(DE-miRNAs)within these exosomes.AIM To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell(HSC)LX2 and the progression of liver fibrosis.METHODS Exosomes from HepG2.2.15 cells,which express HBV-related proteins,were isolated from parental HepG2 and WRL68 cells.Western blotting was used to confirm the presence of the exosomal marker protein CD9.The activation of HSCs was assessed using oil red staining,whereas DiI staining facilitated the observation of exosomal uptake by LX2 cells.Additionally,we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2′-deoxyuracil staining and western blotting,respectively.DE-miRNAs were analyzed using DESeq2.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were used to annotate the target genes of DE-miRNAs.RESULTS Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells.A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 cells.GO analysis indicated that these DE-miRNA target genes were associated with cell differentiation,intracellular signal transduction,negative regulation of apoptosis,extracellular exosomes,and RNA binding.KEGG pathway analysis highlighted ubiquitin-mediated proteolysis,the MAPK signaling pathway,viral carcinogenesis,and the toll-like receptor signaling pathway,among others,as enriched in these targets.CONCLUSION These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation,proliferation,and fibrosis of LX2 cells and that DE-miRNAs within these exosomes contribute to the underlying mechanisms.
基金This study was reviewed and approved by the Ethics Committee of Zhongshan People’s Hospital(Approval No.2022-029).
文摘BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.
文摘The Baveno VII criteria redefine the management of decompensated liver cirrhosis,introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline.Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies,including antivirals and lifestyle modifications.Studies on alcohol,hepatitis C virus,and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes.Transjugular intrahepatic portosystemic shunt(TIPS)emerges as a promising intervention,effectively resolving complications of portal hypertension and facilitating recompensation.However,optimal timing and patient selection for TIPS remain unresolved.Despite challenges,TIPS offers renewed hope for hepatic recompensation,marking a significant advancement in cirrhosis management.Further research is needed to refine its implementation and maximize its benefits.In conclusion,TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.
基金Supported by the Research Fund of Beijing Tsinghua Changgung Hospital,No.12021C11016.
文摘Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.
基金supported by the National Natural Science Foundation of China(No.81071541).
文摘Objective Hepatic stellate cells(HSCs)play a crucial role in liver fibrosis.Early-stage liver fibrosis is reversible and intimately associated with the state of HSCs.Kruppel-like factor 4(KLF4)plays a pivotal role in a wide array of physiological and pathological processes.This study aimed to investigate the effect of KLF4 on the proliferation,apoptosis and phenotype of quiescent HSCs Methods We designed a KLF4 lentiviral vector and a KLF4 siRNA lentiviral vector,to upregulate and silence KLF4 expression in human HSC LX-2 cells via transfection.Cell proliferation was assessed using the CCK-8 assay.Flow cytometry was used to detect the cell cycle distribution and apoptosis rate.Western blotting was used to determine the levels of some quiescence and activation markers of HSCs Results Overexpression of KLF4 significantly increased the levels of E-cadherin and ZO-1,which are quiescent HSC markers,while significantly decreased the levels of N-cadherin and a-SMA,known activated HSC markers.In contrast,cell proliferation and apoptosis rates were elevated in LX-2 cells in which KLF4 expression was silenced Conclusion KLF4 inhibits the proliferation and activation of human LX-2 HSCs.It might be a key regulatory protein in the maintenance of HSC quiescence and may serve as a target for the inhibition of hepatic fibrosis.
基金Supported by Natural Science Foundation of Xinjiang Uygur Autonomous Region,China,No.2022D01D17.
文摘BACKGROUND Lymph node metastasis is a specific type of metastasis in hepatic alveolar echinococcosis(AE).Currently,there is a scarcity of describing the clinical characteristics and lymph node metastasis rules of patients with hepatic AE combined with lymph node metastasis and its mechanism and management are still controversial.Radical hepatectomy combined with regional lymph node dissection is a better treatment.AIM To analyse the clinical features of hepatic AE combined with lymph node metastasis to explore its treatment and efficacy.METHODS A total of 623 patients with hepatic AE admitted to the First Affiliated Hospital of Xinjiang Medical University from 1 January 2012 to 1 January 2022 were retrospectively analysed.Fifty-five patients with combined lymph node metastasis were analysed for their clinical data,diagnosis and treatment methods,follow-up efficacy,and characteristics of lymph node metastasis.Finally,we comparatively analysed the lymph node metastasis rates at different sites.Categorical variables are expressed as frequencies and percentages,and the analysis of difference was performed using theχ2 test.The Bonferroni method was used for pairwise comparisons when statistical differences existed between multiple categorical variables.RESULTS A lymph node metastasis rate of 8.8%(55/623)was reported in patients with hepatic AE,with a female predilection(69.1%)and a statistically significant sex difference(χ2=8.018,P=0.005).Of the 55 patients with lymph node metastasis,72.7%had a parasite lesion,neighbouring organ invasion,and metastasis stage of P3N1M0 and above,of which 67.3%,78.2%,and 34.5%of hepatic AE lesions invaded the bile ducts,blood vessels,and distant metastases,respectively.Detection rates of lymph node metastasis of 16.4%,21.7%,and 34.2%were reported for a preoperative abdominal ultrasound,magnetic resonance imaging,and computed tomography examinations.All patients were intraoperatively suspected with enlarged lymph nodes and underwent radical hepatectomy combined with regional lymph node dissection.After surgery,a routine pathological examination was conducted on the resected lymph nodes.A total of 106 positive lymph nodes were detected in six groups at various sites,including 51 single-group metastasis cases and four multi-group metastasis cases.When the metastasis rates at different sites were statistically analysed,we observed that the metastasis rate in the para-hepatoduodenal ligament lymph nodes was significantly higher than that of the other sites(χ^(2)=128.089,P=0.000<0.05).No statistical difference was observed in the metastasis rate between the five other groups.Clavien-Dindo grade IIIa complication occurred in 14 cases,which improved after administering symptomatic treatment.Additionally,lymph node dissection-related complications were not observed.Recurrence after 2 years was observed in one patient.CONCLUSION Lymph node metastasis is a rare form of metastasis in hepatic AE,which is more frequent in women.Parahepatoduodenal ligament lymph nodes are commonly observed.Radical hepatectomy combined with regional lymph node dissection is a safe,effective,and feasible treatment for liver AE combined with lymph node metastasis.