Primary liver transplantation vs transplant after Kasai portoenterostomy in children with biliary atresia: A retrospective Brazilian single-center cohort

BACKGROUND Biliary atresia(BA)is the most common indication for pediatric liver transplantation,although portoenterostomy is usually performed first.However,due to the high failure rate of portoenterostomy,liver transplantation has been advocated as the primary procedure for patients with BA.It is still unclear if a previous portoenterostomy has a negative impact on liver transplantation outcomes.AIM To investigate the effect of prior portoenterostomy in infants un-dergoing liver transplantation for BA.METHODS This was a retrospective cohort study of 42 pediatric patients with BA who underwent primary liver transplantation from 2013 to 2023 at a single tertiary center in Brazil.Patients with BA were divided into two groups:Those undergoing primary liver transplantation without portoenterostomy and those undergoing liver transplantation with prior portoenterostomy.Continuous variables were compared using the Student’s t-test or the Kruskal-Wallis test,and categorical variables were compared using theχ2 or Fisher’s exact test,as appropriate.Multivariable Cox regression analysis was performed to determine risk factors for portal vein thrombosis.Patient and graft survival analyses were conducted with the Kaplan–Meier product-limit estimator,and patient subgroups were compared using the two-sided log-rank test.RESULTS Forty-two patients were included in the study(25[60%]girls),23 undergoing liver transplantation without prior portoenterostomy,and 19 undergoing liver transplantation with prior portoenterostomy.Patients with prior portoenterostomy were older(12 vs 8 months;P=0.02)at the time of liver transplantation and had lower Pediatric End-Stage Liver Disease scores(13.2 vs 21.4;P=0.01).The majority of the patients(35/42,83%)underwent livingdonor liver transplantation.The group of patients without prior portoenterostomy appeared to have a higher incidence of portal vein thrombosis(39 vs 11%),but this result did not reach statistical significance.Prior portoenterostomy was not a protective factor against portal vein thrombosis in the multivariable analysis after adjusting for age at liver transplantation,graft-to-recipient weight ratio,and use of vascular grafts.Finally,the groups did not significantly differ in terms of post-transplant survival.CONCLUSION In our study,prior portoenterostomy did not significantly affect the outcomes of liver transplantation.

Evaluation of Hepatic Fibrosis and Hepatic Steatosis by Pulse Elastography (FIBROSCAN/CAP) in Asymptomatic Patients about 170 Cases at the Donka CHU National Hospital in Conakry

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.

Primary hepatic lymphoma presenting as pyogenic liver abscess:A case report

BACKGROUND Primary hepatic lymphoma(PHL)is a lymphoproliferative disorder confined to the liver without peripheral lymph node involvement and bone marrow invasion.PHL is extremely rare in clinical practice.The etiology and pathogenesis of PHL are largely unknown.There are no common standard protocols or guidelines for the treatment of PHL.CASE SUMMARY We report the case of a 66-year-old man who presented with fever and abdominal pain for three weeks.Computed tomography and magnetic resonance imaging scans showed a pyogenic liver abscess.The patient underwent a right posterior hepatectomy.The surgical pathology revealed aggressive B-cell lymphoma,with a primary consideration of diffuse large B-cell lymphoma of non-germinal center origin.CONCLUSION This article reviews the characteristics,mechanism and treatment of PHL and provides insight into the diagnosis of PHL.

Progress in pathogenesis and treatment of type A hepatic encephalopathy in acute liver failure:a comprehensive review

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.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

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.

"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy

BACKGROUND Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment,the feasibility and safety of this approach for laparo-scopic pancreaticoduodenectomy(LPD)require further clinical evaluation and investigation.AIM To explore the application value of the"five steps four quadrants"modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD patients.METHODS A total of 52 patients who underwent LPD via the"five steps four quadrants"modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed retrospectively.The patients'body mass index(BMI),preoperative laboratory indices,intraoperative variables and postoperative complications were recorded.The relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also analyzed.RESULTS Among the 52 patients,36 were males and 16 were females,and the average age was 62.2±11.0 years.There were 26 patients with pancreatic head cancer,16 patients with periampullary cancer,and 10 patients with distal bile duct cancer.The BMI was 22.3±3.3 kg/m²,and the median total bilirubin(TBIL)concentration was 57.7(16.0-155.7)µmol/L.All patients successfully underwent the"five steps four quadrants"modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic leakage.Correlation analysis revealed significant associations between preoperative BMI(r=0.3581,P=0.0091),TBIL level(r=0.2988,P=0.0341),prothrombin time(r=0.3018,P=0.0297)and lymph node dissection time.Moreover,dissection time was significantly correlated with intraoperative blood loss(r=0.7744,P<0.0001).Further stratified analysis demonstrated that patients with a preoperative BMI≥21.9 kg/m²and a TIBL concentration≥57.7μmol/L had significantly longer lymph node dissection times(both P<0.05).CONCLUSION The"five steps four quadrants"modularized en bloc dissection technique for accessing the hepatic hilum lymph node is safe and feasible for LPD.This technique is expected to improve the efficiency of hepatic hilum lymph node dissection and shorten the learning curve;thus,it is worthy of further clinical promotion and application.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

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.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug therapy.However,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver fibrosis.Here,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying mechanism.Methods:The expression level of GPR65 was evaluated in both human and mouse fibrotic livers.Furthermore,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver fibrosis.Additionally,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated.Results:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic livers.Moreover,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-αand IL-6 via the Gαq-Ca^(2+)-JNK/NF-κB pathways,while promoted the expression of TGF-βthrough the Gαq-Ca^(2+)-MLK3-MKK7-JNK pathway.Notably,pharmacological GPR65 inhibition retarded the development of inflammation,HCs injury and fibrosis invivo.Conclusions:GPR65 is a major regulator that modulates the progression of liver fibrosis.Thus,targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.

Laparoscopic anatomical liver resection of segment 7 using a sandwich approach to the right hepatic vein (with video)

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.

Achieving laparoscopic anatomic resection for hepatocellular carcinoma by fluorescence guided positive staining of hepatic cone unit

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].

Middle hepatic vein variation provides a safe path for anterior transection of hepatocellular carcinoma in caudate lobe

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.

A rare case of hepatic vein-portal vein fistula with hepatolithiasis presenting as cholangiocarcinoma

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.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis

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.

Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease

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.

Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains unclear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.

Capsaicin alleviates the hepatic clock gene disruption and gut microbiota dysbiosis in circadian rhythm disorder mouse model

As the body’s internal clock,the circadian rhythm regulates the energy expenditure,appetite,and sleep.There exists a close relationship between the host circadian rhythm and gut microbiota.In this work,a circadian disorder mouse model induced by constant darkness(CD)was constructed to investigate the regulating effects of capsaicin(CAP)on disturbances of metabolism homeostasis and gut microbiota in the respect of circadian rhythm-related mechanisms.Our results indicated that CAP reduced weight gain induced by circadian rhythm disorder in mice by inhibiting fat accumulation in liver and adipose tissue.The rhythmic expressions of circadian clock genes and lipid-metabolism related genes in liver were also recovered by CAP.Microbial study using 16S rRNA sequencing revealed that CAP modulated the gut microbiota richness,diversity and composition,and restored diurnal oscillations of gut microbes at the phylum and family level.These results indicated that CAP could alleviate CD-induced hepatic clock gene disruption and gut microbiota dysbiosis in mice,providing theoretical basis for CAP to be used as a muti-functional ingredient with great healthpromoting effects.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

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.

HepG2.2.15-derived exosomes facilitate the activation and fibrosis of hepatic stellate cells

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.