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.

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.

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.

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

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.

Peroxisome proliferator-activated receptor agonists:A new hope towards the management of alcoholic liver disease

In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.

Dual peroxisome proliferator-activated receptorα/δagonists:Hope for the treatment of alcohol-associated liver disease?

In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions.

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).

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.

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.

Liver disease in patients with transfusion-dependentβ-thalassemia:The emerging role of metabolism dysfunction-associated steatotic liver disease

In this Editorial,we highlight the possible role that metabolism dysfunction-associated steatotic liver disease(MASLD)may play in the future,regarding liver disease in patients with transfusion-dependent β-thalassemia(TDBT).MASLD is characterized by excessive accumulation of fat in the liver(hepatic steatosis),in the presence of cardiometabolic factors.There is a strong correlation between the occurrence of MASLD and insulin resistance,while its increased prevalence parallels the global epidemic of diabetes mellitus(DM)and obesity.Patients with TDBT need regular transfusions for life to ensure their survival.Through these transfusions,a large amount of iron is accumulated,which causes saturation of transferrin and leads to the circulation of free iron molecules,which cause damage to vital organs(primarily the liver and myocardium).Over the past,the main mechanisms for the development of liver disease in these patients have been the toxic effect of iron on the liver and chronic hepatitis C,for which modern and effective treatments have been found,resulting in successful treatment.Additional advances in the treatment and monitoring of these patients have led to a reduction in deaths,and an increase in their life expectancy.This increased survival makes them vulnerable to the onset of diseases,which until recently were mainly related to the non-thalassemic general population,such as obesity and DM.There is insufficient data in the literature regarding the prevalence of MASLD in this population or on the risk factors for its occurrence.However,it was recently shown by a study of 45 heavily transfused patients with beta-thalassemia(Padeniya et al,BJH),that the presence of steatosis is a factor influencing the value of liver elastography and thus liver fibrosis.These findings suggest that future research in the field of liver disease in patients with TDBT should be focused on the occurrence,the risk factors,and the effect of MASLD on these patients.

Quantitative Assessment of Liver Fibrosis by Elastography in Patients with Chronic Liver Disease: A Cross-Sectional Study in Lomé (Togo)

Aim: To describe the two-dimensional elastographic profile according to the Shearwave (2D-SWE) technique in patients with chronic liver disease in Lom. Materials and method: Cross-sectional, descriptive study conducted over seven month at the Autel dElie Clinic in Lom, from January to August 2022, on adult patients with chronic liver disease who underwent abdominal ultrasound coupled with two-dimensional elastography. Results: The sample size was 54 patients. The mean age of the patients was 33 12 years, with extremes of 18 and 66 years. Patients aged 30 years or less accounted for 48.1% (n = 26). All patients (n = 54) had at least one transaminase assay with a mean of 69.3 78.3 IU/l (AST) and 59.3 82.8 IU/l (ALT). There was no statistically significant association between the biological parameters and the presence of fibrosis. Viral liver disease was the main cause, accounting for 81.5% (n = 44) of cases, with no significant association with the degree of fibrosis. Ultrasound revealed a dysmorphic liver (57.4%;n = 31) and portal hypertension (18.5%, n = 10). Fibrosis stages F1, F2 and F4 accounted for (48.1%, n = 26), (24.1%, n = 13) and (13%, n = 7) of cases respectively. Liver dysmorphia was significantly associated with the presence of fibrosis (p = 0.012) and portal hypertension was significantly associated with the degree of fibrosis (p = 0.0063). Conclusion: Assessment of liver fibrosis in patients with chronic liver disease using 2D-SWE elastography is essential for patient follow-up.

Transient elastography and diffusion-weighted magnetic resonance imaging for assessment of liver fibrosis in children with chronic hepatitis C

BACKGROUND Chronic hepatitis C(CHC)is a health burden with consequent morbidity and mortality.Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment.Noninvasive altern-atives for liver biopsy such as transient elastography(TE)and diffusion-weighted magnetic resonance imaging(DW-MRI)are critical needs.AIM To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.METHODS This prospective cross-sectional study initially recruited 100 children with CHC virus infection.Sixty-four children completed the full set of investigations including liver stiffness measurement(LSM)using TE and measurement of apparent diffusion coefficient(ADC)of the liver and spleen using DW-MRI.Liver biopsies were evaluated for fibrosis using Ishak scoring system.LSM and liver and spleen ADC were compared in different fibrosis stages and correlation analysis was performed with histopathological findings and other laboratory parameters.RESULTS Most patients had moderate fibrosis(73.5%)while 26.5%had mild fibrosis.None had severe fibrosis or cirrhosis.The majority(68.8%)had mild activity,while only 7.8%had moderate activity.Ishak scores had a significant direct correlation with LSM(P=0.008)and were negatively correlated with both liver and spleen ADC but with no statistical significance(P=0.086 and P=0.145,respectively).Similarly,histopatho-logical activity correlated significantly with LSM(P=0.002)but not with liver or spleen ADC(P=0.84 and 0.98 respectively).LSM and liver ADC were able to significantly discriminate F3 from lower fibrosis stages(area under the curve=0.700 and 0.747,respectively)with a better performance of liver ADC.CONCLUSION TE and liver ADC were helpful in predicting significant fibrosis in children with chronic hepatitis C virus infection with a better performance of liver ADC.

Regression of hepatic fibrosis after pharmacological therapy for nonalcoholic steatohepatitis

The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix,leading to fibrosis.Hepatocyte ballooning is a key catalyst for fibrosis progression,potentially advancing to cirrhosis and its decompensated state.Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD;therefore,those with substantial fibrosis require timely intervention.Although liver biopsy is the most reliable method for fibrosis detection,it is associated with certain risks and limitations,particularly in routine screening.Consequently,various noninvasive diagnostic techniques have been introduced.This review examines the increasing prevalence of NAFLD,evaluates the noninvasive diagnostic techniques for fibrosis,and assesses their efficacy in staging the disease.In addition,it critically appraises current and emerging antifibrotic therapies,focusing on their mechanisms,efficacy,and potential in reversing fibrosis.This review underscores the urgent need for effective therapeutic strategies,given the dire consequences of advanced fibrosis.

Ensemble for evaluating diagnostic efficacy of non-invasive indices in predicting liver fibrosis in untreated hepatitis C virus population

BACKGROUND Hepatitis C virus(HCV)infection progresses through various phases,starting with inflammation and ending with hepatocellular carcinoma.There are several invasive and non-invasive methods to diagnose chronic HCV infection.The invasive methods have their benefits but are linked to morbidity and complications.Thus,it is important to analyze the potential of non-invasive methods as an alternative.Shear wave elastography(SWE)is a non-invasive imaging tool widely validated in clinical and research studies as a surrogate marker of liver fibrosis.Liver fibrosis determination by invasive liver biopsy and non-invasive SWE agree closely in clinical studies and therefore both are gold standards.AIM To analyzed the diagnostic efficacy of non-invasive indices[serum fibronectin,aspartate aminotransferase to platelet ratio index(APRI),alanine aminotransferase ratio(AAR),and fibrosis-4(FIB-4)]in relation to SWE.We have used an Artificial Intelligence method to predict the severity of liver fibrosis and uncover the complex relationship between non-invasive indices and fibrosis severity.METHODS We have conducted a hospital-based study considering 100 untreated patients detected as HCV positive using a quantitative Real-Time Polymerase Chain Reaction assay.We performed statistical and probabilistic analyses to determine the relationship between non-invasive indices and the severity of fibrosis.We also used standard diagnostic methods to measure the diagnostic accuracy for all the subjects.RESULTS The results of our study showed that fibronectin is a highly accurate diagnostic tool for predicting fibrosis stages(mild,moderate,and severe).This was based on its sensitivity(100%,92.2%,96.2%),specificity(96%,100%,98.6%),Youden’s index(0.960,0.922,0.948),area under receiver operating characteristic curve(0.999,0.993,0.922),and Likelihood test(LR+>10 and LR-<0.1).Additionally,our Bayesian Network analysis revealed that fibronectin(>200),AAR(>1),APRI(>3),and FIB-4(>4)were all strongly associated with patients who had severe fibrosis,with a 100% probability.CONCLUSION We have found a strong correlation between fibronectin and liver fibrosis progression in HCV patients.Additionally,we observed that the severity of liver fibrosis increases with an increase in the non-invasive indices that we investigated.

Correlation of image textures of a polarization feature parameter and the microstructures of liver fibrosis tissues

Mueller matrix imaging is emerging for the quantitative characterization of pathological microstructures and is especially sensitive to fibrous structures.Liver fibrosis is a characteristic of many types of chronic liver diseases.The clinical diagnosis of liver fibrosis requires time-consuming multiple staining processes that specifically target on fibrous structures.The staining proficiency of technicians and the subjective visualization of pathologists may bring inconsistency to clinical diagnosis.Mueller matrix imaging can reduce the multiple staining processes and provide quantitative diagnostic indicators to characterize liver fibrosis tissues.In this study,a fibersensitive polarization feature parameter(PFP)was derived through the forward sequential feature selection(SFS)and linear discriminant analysis(LDA)to target on the identification of fibrous structures.Then,the Pearson correlation coeffcients and the statistical T-tests between the fiber-sensitive PFP image textures and the liver fibrosis tissues were calculated.The results show the gray level run length matrix(GLRLM)-based run entropy that measures the heterogeneity of the PFP image was most correlated to the changes of liver fibrosis tissues at four stages with a Pearson correlation of 0.6919.The results also indicate the highest Pearson correlation of 0.9996 was achieved through the linear regression predictions of the combination of the PFP image textures.This study demonstrates the potential of deriving a fiber-sensitive PFP to reduce the multiple staining process and provide textures-based quantitative diagnostic indicators for the staging of liver fibrosis.

Intervention effect of Zhuangfang Rugan Huaxian Granules on CCl_(4)compound factor‑induced liver fibrosis rat model and its effect on the expression ofα‑SMA and E‑Cadherin

Objective:To study the intervention effect of Zhuangfang Soft Liver and Fibrous Granules on CCl_(4)compound factor-induced liver fibrosis rat model and its effect onα-SMA and E-Cadherin protein expression.Methods:Forty-eight male Wistar rats were randomly divided into a blank group,a pathological model group and a group of 16 rats in each group.The rats in the pathological model group and the pellet group were injected subcutaneously with 40%carbon tetrachloride(CCl_(4))oil combined with peanut oil to establish an animal model of rat liver fibrosis,and the pellets were administered by gavage three times a week for 8 weeks from the 5th week.The expression of oxidative stress oxidase dismutase(SOD)and malondialdehyde(MDA)was detected by enzyme-linked immunoassay(ELISA),and the expression ofα-smooth muscle actin(α-SMA)and E-calmodulin(E-Cadherin)was detected by RT-PCR andWestern Blot.expression.Results:Compared with the blank group,the serum ALT and AST levels of the rats in the pathological model group were significantly increased,and the serum ALT and AST levels of the rats in the soft liver and fibrous pellet group were significantly decreased(P<0.001).In the pathological model group,the lobular structure of liver tissue was mutilated and numerous liver fibrous tissues were abnormally proliferated,and the collagen fibers formed by the proliferation were confluent into dense fibrous intervals,thus turning into pseudolobular structure,and a large number of fatty degenerated hepatocytes of different shapes and sizes appeared inside the pseudolobular structure,and the diffuse infiltration of inflammatory cells was significant.Compared with the pathological model group,the degree of destruction of hepatic lobular structure was significantly reduced in the LBP group,and there were different degrees of proliferation of collagen fibrous tissue concentrated in the area from the central vein to the confluent area,and the fibrous septum was relatively loose,with a small amount of inflammatory cell infiltration,and the degree of infiltration was reduced compared with the pathological model group.Compared with the pathological model group,the SOD level was significantly higher in the group of liver softener and fibrous pellets compared with the pathological model group and the blank group(P<0.001),the MDA level was significantly lower in the group of liver softener and fibrous pellets compared with the pathological model group(P<0.001),the expression level ofα-SMA was significantly lower in the group of liver softener and fibrous pellets(P<0.001),and the expression level of E-Cadherin was significantly higher in the group of liver softener and fibrous pellets(P<0.001).Conclusion:Soft Liver Fibro Pellets can effectively inhibit liver fibrous tissue proliferation and reduce the serum ALT and AST levels in rats with CCl_(4)combined with peanut oil compound solution induced liver fibrosis,and its anti-liver fibrosis mechanism may be through protecting liver function,reducing the level of oxidative stress,down-regulating the expression ofα-SMA protein,up-regulating the expression of E-cadherin protein,and inhibiting epithelial-mesenchymal transition epithelial mesenchymal transformation(EMT)and thus exerting therapeutic effects on CCl_(4)compound-induced hepatic fibrosis in rats.

The diagnostic value of transient elastography combined with serum SAA and IL-6 in the degree of hepatitis B liver fibrosis

Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infection that were admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Hainan Medical College from January 2020 to May 2022 with informed consent and underwent liver biopsy puncture were selected.According to the pathological results,they were divided into no obvious fibrosis group,obvious fibrosis group and liver cirrhosis group.Comparison of liver stiffness measurement(LSM),serum amyloid A(SAA0,IL-6 levels between different groups.This study drawed was conducted draw the receiver operating characteristic(ROC)curve of each index to diagnose significant liver fibrosis and liver cirrhosis,and compared the area under the ROC curve(AUC)and diagnostic efficacy of each non-invasive fibrosis diagnostic model.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 In different degrees of liver fibrosis.Results:According to the degree of liver fibrosis,the levels of SAA,IL-6,and LSM in the no significant fibrosis group(n=140),the significant fibrosis group(n=134),and the cirrhosis group(n=60)were statistically significant difference(All P<0.001).SAA,IL-6 and LSM were significantly correlated with the degree of liver fibrosis(rs=0.456,rs=0.482,rs=0.602,All P<0.001).The AUC of SAA and IL-6 for the diagnosis of significant fibrosis in hepatitis B were 0.738 and 0.809,respectively.And the AUC for the diagnosis of liver cirrhosis were 0.813 and 0.823,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.930 and 0.964,respectively.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 in different degrees of liver fibrosis(All P<0.001).Conclusion:LSM combined with serum SAA and IL-6 has great diagnostic value for different degrees of hepatitis B liver fibrosis.

Correlation between the triglyceride glucose index and the degree of steatosis and liver fibrosis in nonalcoholic fatty liver disease

Objective:To investigate the relationship between triglyceride glucose index(TyG)and the degree of steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease(NAFLD).Methods:Totally 2054 patients hospitalized in the second affiliated hospital of Xinjiang Medical University from September 2020 to September 2021 were retrospectively selected.According to abdominal ultrasound were divided into NAFLD group and non-NAFLD group.In accordance with the degree of steatosis,NAFLD patients were separated into mild group,moderate group and severe group.According to the liver stiffness,NAFLD patients were divided into liver fibrosis group and non-liver fibrosis group.We used the logistic regression to examine the correlation between TyG index and the the degree of steatosis and liver fibrosis.ROC curve was drawn to evaluate the diagnostic value of TyG index for NAFLD and liver fibrosis.Results:The prevalence of NAFLD increased with the increase of the interquartile of TyG index(Q_(1)44.1%,Q_(2)58.7%,Q_(3)71.9%,Q_(4)84.6%,P<0.001);The prevalence of liver fibrosis increased with the increase of the interquartile of TyG index(Q_(1)25.8%,Q_(2)30.2%,Q_(3)38.6%,Q_(4)44.3%,P<0.001).After adjusting for confounders,there was a correlation between TyG index and the degree of steatosis in NAFLD patients(the OR values of mild,moderate and severe groups were 1.383,2.450 and 3.070,P<0.001).TyG index was associated with liver fibrosis(OR=1.132,P<0.001).The ROC curve of TyG index predicted NAFLD was 0.701,with an optimal cutoff value of TyG is 8.57.However,the ROC curve of TyG index predicted liver fibrosis was 0.595.TyG index may not be a reliable predictor of liver fibrosis.Conclusion:TyG index was positively correlated with the degree of steatosis and liver fibrosis in NAFLD.