In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of h UC-MSCs. Histopathology was assessed by hematoxylin and eosin(H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.RESULTS We demonstrated that the infused h UC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of h UC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted h UC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. h UC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

Unraveling the Impact of Direct-Acting Antivirals on Hepatitis-Linked Cirrhosis: A Comprehensive Analysis of Fibrosis, Child Score, and Disease Progression

The treatment of hepatitis C has undergone a significant boom since the advent of direct acting antivirals (DAA). Indeed, the interferon-ribavirin combination that has been used to treat hepatitis C has a virological response in only 45% of cases with significant side effects. The advent of direct-acting antivirals has changed the prognosis of cirrhotic patients with hepatitis C. DAAs have ensured a sustained viral response in the majority of patients. Our work aims to see the evolution of hepatitis C patients at the cirrhosis stage under DAA. We conducted a retrospective study over 15 years (January 2009, January 2024) including all patients with post-viral cirrhosis C, whom we divided into two groups: group A, cirrhotic patients who received ribavirin and interferon, and group B, patients on DAA. From January 2009 to January 2024, we conducted a study of 182 patients with viral hepatitis C, including 102 cirrhotic patients. The mean age was 55 years. 66% of patients were initially treated with the ribavirin interferon combination, while 34% received direct-acting antivirals (DAAs). Since the introduction of DAAs, the most commonly used regimens have been sofosbuvir/daclatasvir with or without ribavirin and sofosbuvir/ledipasvir with or without ribavirin. Group A achieved sustained virological response (SVR) in 60% of cases, with notable side effects. In Group B, SVR was 98.18%, with improved tolerability and fewer side effects than previous treatments. Fifteen patients developed hepatocellular carcinoma (HCC), with a significantly lower mortality rate in those treated with DAAs compared with pegylated dual therapy (p: 0.001).

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.

From liver to hormones:The endocrine consequences of cirrhosis

Hepatocrinology explores the intricate relationship between liver function and the endocrine system.Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption.Despite its importance,assessing endocrine issues in cirrhotic patients is frequently neglected.This article provides a comprehensive review of the epidemiology,pathophysiology,diagnosis,and treatment of endocrine disturbances in liver cirrhosis.The review was conducted using the PubMed/Medline,EMBASE,and Scielo databases,encompassing 172 articles.Liver cirrhosis is associated with endocrine disturbances,including diabetes,hypoglycemia,sarcopenia,thyroid dysfunction,hypogonadotropic hypogonadism,bone disease,adrenal insufficiency,growth hormone dysfunction,and secondary hyperaldosteronism.The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system,respectively.Sarcopenia can be assessed through imaging and functional tests,while other endocrine disorders are evaluated using hormonal assays and imaging studies.Treatment options include metformin,glucagon-like peptide-1 analogs,sodium-glucose co-transporter-2 inhibitors,and insulin,which are effective and safe for diabetes control.Established standards are followed for managing hypoglycemia,and hormone replacement therapy is often necessary for other endocrine dysfunctions.Liver transplantation can address some of these problems.

Fat necrosis of liver in a patient with mixed type liver cirrhosis

To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to progress through various stages, from steatosis or necrosis with inflammation and hepatocyte damage to the development of fibrosis and eventual cirrhosis with an increased risk of carcinoma [ 2, 3 ].

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.

Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology.The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis.Here,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human studies.Angiotensin-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of HCC.Finally,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.In this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this pathway.However,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function

We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.

Encapsulating taurine into liposomes:A promising therapeutic for liver fibrosis

We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 light chain 3 Beta,and autophagy-related gene 5 to inhibit autophagy,binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy,and interacts with glutathione peroxidase 4 to promote iron apoptosis.There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation.From a pharmaceutical point of view,there are certain requirements for Tau protein delivery systems,such as loading efficiency,stability,and targeting.Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency.Since Tau is a hydrophilic molecule with high water solubility,liposomes,micelles,and amphiphilic polymer nanoparticles may represent a superior choice.The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs,respectively,whereas Tau is expected to be loaded into the water region.In addition,a representative method of actively targeting hematopoietic stem cells is introduced.A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes(lecithin plus cholesterol).

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

Despite achieving a high cure rate with the direct-acting antivirals(DAAs)in hepatitis C treatment,further research is needed to identify additional benefits of the DAA therapy.The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs,who also achieved sustained virologic response.By the fibrosis-4(FIB-4)index,patients were categorized based on their baseline fibrosis levels,and the improvement in fibrosis was analyzed in both short-term(9-26 weeks)and long-term(≥36 weeks)follow-up.The results showed a significant decrease in the FIB-4 index,indicating an improvement in liver fibrosis,in 63.0%and 67.6%of the patients during the short-term and long-term follow-up,respectively.Short-term improvement was associated with factors including ribavirin usage,blood cholinesterase levels,alanine transaminase levels,albumin levels,and the baseline FIB-4 index,while long-term improvement was associated with factors such as aspartate transaminase levels,total protein level,and the baseline FIB-4 index.The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis,which will provide crucial insights for enhancing patient care in hepatitis C management.

Alpha-1 antitrypsin deficiency and Pi^(*)Z allele as important co-factors in the development of liver fibrosis

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and Pi*Z allele is the most clinically relevant mutation.AIM To evaluate the impact of clinical parameters and AATD phenotypes,particularly the Pi*Z allele,in liver fibrosis.METHODS Cross-sectional cohort study including consecutive patients with AATD followed in Pulmonology or Hepatology consultation.RESULTS Included 69 patients,49.3%had Pi*MZ phenotype and 10.1%Pi*ZZ.An age≥55 years,age at diagnosis≥41 years and AAT at diagnosis<77 mg/dL predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,P<0.001;AUC=0.836,P<0.001;AUC=0.681,P=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,P<0.001;AUC=0.795,P<0.001).Patients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(P<0.001,P=0.002,P=0.008,P<0.001,P=0.033).Patients with at least one Pi*Z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kPa(P=0.040).CONCLUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one Pi*Z allele,and AAT value at diagnosis<77 mg/dL.We created an algorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

Assessment of Liver Fibrosis in HBsAg-Negative and Anti HBc Positive Patients

Background: Surface antigen (HBsAg) is the mean marker of hepatitis B virus infection. During the course of the infection, some patients lose the HBsAg and only the presence of anti-HBc antibody indicates previous contact with the virus. Among these patients, some have detectable viral load (occult infection) but most without viral replication. There is no guideline regarding these patients. The aim of this study was to assess hepatic fibrosis in patients with only the hepatitis B virus contact marker “total anti-HBc”. Patients and methods: it was a descriptive and analytical cross-sectional study, conducted in three private hospitals from January to August 2022. Were included HBsAg-negative and HBc-positive patients, consulting in Gastroenterology departments. Noninvasive methods (APRI, FIB-4 and FIBROSCAN) were used to evaluate liver stiffness because of their easy accessibility and low-cost. The hepatic fibrosis was considered significant when the score determined by APRI, FIB-4 and FIBROSCAN® tests was respectively greater than 1.5;2.67 and 8 kPa corresponding to fibrosis level 2 (F2). Results: A total of 63 HBsAg-negative/total HBcAg-positive patients were included. The mean age was 49.9 ± 13.4 years. The male/female sex ratio was 1.78. Of the 63 patients, 19 had significant liver fibrosis (30.1%) among which 9 patients had HCC. The FIB-4 score outperformed the APRI score in assessing liver fibrosis, with a sensitivity of 84.2%, a specificity of 100% and a negative predictive value of 93.6%. In univariate analysis, there was a significant association between the occurrence of significant liver fibrosis and age over 40 years, dyslipidaemia, obesity, alcohol consumption, smoking, herbal medicine, negative anti-HBs immunological status and detectable viral load. Conclusion: Our study revealed a high prevalence of significant to severe hepatic fibrosis in anti-HBc positive patients. In most of the cases, the fibrosis was severe. Progression to HCC has also been possible. There is no consensus on the follow-up strategy for those patients. However, screening for hepatic fibrosis using noninvasive methods should be recommended for patients aged over 40 years, alcohol or herbal medicine users, patients with metabolic syndrome or occult hepatitis B. In HBsAg-negative/anti-HBc-positive patients, liver stiffness should be evaluated and if it is greater than F2, HCC screening should be started.

Clinical study on the relationship between liver cirrhosis,ascites,and hyponatremia

BACKGROUND Cirrhosis is a common liver disease,and ascites is one of the common clinical conditions.However,the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied.AIM To explore the clinical manifestations,prognostic factors,and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies.METHODS In this study,we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022.Patients were divided into two groups:ascites combined with hyponatremia group and ascites group.We compared the general characteristics,degree of hyponatremia,complications,treatment,and prognosis between the two groups.RESULTS In the study results,patients in the ascites combined with hyponatremia group showed an older average age(58.2±8.9 years),64.4%were male,and had a significantly longer hospitalization time(12.7±5.3 d).Hyponatremia was more severe in this group,with a mean serum sodium concentration of 128.5±4.3 mmol/L,which was significantly different from the ascites group of 137.6±2.1 mmol/L.Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy(56.2%vs 39.0%),renal impairment(45.2%vs 28.6%)and infection(37.0%vs 23.4%).Regarding treatment,this group more frequently used diuretics(80.8%vs 62.3%)and salt supplements(60.3%vs 38.9%).Multiple logistic regression analysis identified older age[Odds ratio(OR)=1.06,P=0.025]and male gender(OR=1.72,P=0.020)as risk factors for hyponatremia combined with ascites.Overall,patients with ascites and hyponatremia present a clear high-risk status,accompanied by severe complications and poor prognosis.CONCLUSION In patients with cirrhosis,ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in the presence of liver fibrosis,increases the risk of cardiovascular morbidity and mortality,but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus(T2DM)is not fully understood.AIM To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis.METHODS T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle,anthropometric measurements,vital signs,an extensive laboratory panel,and a standard echocardiography.Liver fibrosis was evaluated using two scores[Fibrosis-4(FIB4)and Non-alcoholic fatty liver disease-Fibrosis Score(NFS)],and subjects were classified as having advanced fibrosis,no fibrosis,or an indeterminate risk.The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses.Statistical significance was set at P<0.05.RESULTS Data from 267 T2DM-MASLD subjects with complete assessment was analyzed.Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular(LV)posterior wall thickness,atrial diameters,LV end-systolic volume,LV mass index(LVMi),and epicardial adipose tissue thickness(EATT).Their mean ejection fraction(EF)was significantly lower(49.19%±5.62%vs 50.87%±5.14%vs 52.00%±3.25%;P=0.003),and a smaller proportion had an EF≥50%(49.40%vs 68.90%vs 84.21%;P=0.0017).Their total and mid LV wall motion score indexes were higher(P<0.05).Additionally,they had markers of diastolic dysfunction,with a higher E/e’ratio[9.64±4.10 vs 8.44(2.43-26.33)vs 7.35±2.62;P=0.026],and over 70%had lateral e’values<10 cm/second,though without significant differences between groups.In multiple regression analyses,FIB4 correlated with left atrium diameter(LAD;β=0.044;P<0.05),and NFS with both LAD(β=0.039;P<0.05)and right atrium diameter(β=0.041;P<0.01),Moreover,LVMi correlated positively with age and EATT(β=1.997;P=0.0008),and negatively with serum sex-hormone binding protein(SHBP)concentrations(β=-0.280;P=0.004).SHBP also correlated negatively with LAD(β=-0.036;P<0.05).CONCLUSION T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy.Additionally,LVMi and LAD correlated negatively with serum SHBP concentrations.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.

sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.