Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver disea...MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
Liver diseases remain a global health crisis,with limited safe therapeutic options.Cornus officinalis,a traditional medicinal-edible plant,has demonstrated significant hepatoprotective potential.This review systematic...Liver diseases remain a global health crisis,with limited safe therapeutic options.Cornus officinalis,a traditional medicinal-edible plant,has demonstrated significant hepatoprotective potential.This review systematically summarizes its liver-protective mechanisms and explores its potential as a functional food.Data were collected from scientific databases such as Pub Med,Science Direct,Elsevier,Google Scholar,and relevant literature.Key bioactive compounds—including iridoids,polyphenols,and polysaccharides—contribute to hepatoprotection by mitigating oxidative stress,inflammation,steatosis,apoptosis,and by regulating gut microbiota.As critical quality markers,iridoids exhibit suboptimal bioavailability,necessitating targeted technological interventions—nanoencapsulation for liver-specific delivery and microbial fermentation for controlled aglycone conversion are proposed to enhance their pharmacokinetic properties and bioactivity.Future research could adopt encapsulation and fermentation technologies for C.officinalis processing,aiming to develop targeted functional food products with enhanced bioactivity of its active components.This review,for the first time,establishes a“component-pathway-integration”model,providing a theoretical framework for evidence-based CO-derived functional food development and highlighting the need for further research on iridoid metabolic transformation to advance liver health management.展开更多
Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsul...Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical nee...To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.展开更多
BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver fu...BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.展开更多
Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine...Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.展开更多
This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid acc...This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.展开更多
BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diag...BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,g...Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,given the substantial global prevalence of chronic hepatitis B(CHB),instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios.Both conditions can lead to liver fibrosis,cirrhosis,and potentially hepatocellular carcinoma(HCC).However,the intrica-cies of the dual etiology,consequential outcomes,and associated risks of CHB concurrent with MASLD are still not fully understood.Data sources:A literature search was conducted on PubMed for articles published up to March 2024.The search keywords included nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,chronic hepatitis B,liver fibrosis,hepatocellular carcinoma,nuclear factor erythroid 2-related factor 2,and oxidative stress.Results:This review examined recent studies on the interplay between MASLD and CHB.The coexis-tence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus(HBV)replication.Conversely,individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD.Nevertheless,these observations do not necessarily indicate universally positive outcomes.Indeed,MASLD and CHB may synergistically act as“co-conspirators”to exacerbate clinical manifestations,particularly liver fibrosis and HCC.Conclusions:As our understanding of the interaction between steatosis and HBV infection becomes clearer,we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD.These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.展开更多
This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integri...This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.展开更多
Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al report...Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related cACLD.Differently from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood count.RPR is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is non-specific.The second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades.Cardiovascular disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related mortality.Therefore,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers.Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.展开更多
BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but da...BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.展开更多
Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in ...Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in our hospital from May 2022 to July 2024 were selected as the research subjects.All patients underwent a B-ultrasound examination.According to the severity of the disease,they were divided into group A(mild,n=35),group B(moderate,n=44),and group C(severe,n=26).Another 30 healthy residents who came to the hospital for physical examination during the same period were selected as group D.The differences in blood lipids,blood glucose,and liver function indicators between groups were compared.Results:The triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL)levels in groups A,B,and C were higher than those in group D,while the high-density lipoprotein cholesterol(HDL)level was lower(P<0.05).The fasting plasma glucose(FPG)levels in groups B and C were higher than those in group D(P<0.05).The TG,LDL,and FPG levels in groups B and C were higher than those in group A(P<0.05).The TC level in group C was higher than that in group A,while the HDL level was lower(P<0.05).The TC and FPG levels in group C were higher than those in group B(P<0.05).The total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in groups A,B,and C were higher than those in group D(P<0.05).The TBil and ALT levels in groups B and C were higher than those in group A(P<0.05).The AST level in group C was higher than that in group A(P<0.05).The AST and ALT levels in group C were higher than those in group B(P<0.05).Conclusion:Patients with non-alcoholic fatty liver disease have disordered glucose and lipid metabolism.Blood lipids,blood glucose,and liver function are closely related to the severity of the disease.Strengthening exercise and dietary intervention early on can help control the progression of simple fatty liver disease and reduce the risk of severe liver diseases such as steatohepatitis and cirrhosis.展开更多
BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patien...BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.展开更多
In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut...In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD.Currently,the gut microbiota has become one of the important entry points for the research of this disease.Therefore,the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD,including the changes and differences in the microbiota between the healthy liver and the diseased liver.Meanwhile,considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis(such as mild fibrosis and severe fibrosis)during the disease progression,we also conduct a comparison of the microbiota in these states and use them as markers of disease progression.It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota,and the impact of lipopolysaccharide from Gram-negative bacteria on the disease.In addition,the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics(including new-generation probiotics)will be explored,which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota.This will achieve important progress in preventing and combating this disease.展开更多
Liver-directed therapies such as resection,ablation,and embolization offer potentially curative options for patients with primary and metastatic liver tumors as part of multidisciplinary oncology care.However,these tr...Liver-directed therapies such as resection,ablation,and embolization offer potentially curative options for patients with primary and metastatic liver tumors as part of multidisciplinary oncology care.However,these treatments pose significant hepatic decompensation risks,particularly with underlying liver disease and chemotherapy-associated steatohepatitis.Accurate assessment of liver function and portal hypertension(PH)is critical for candidate selection.While Child-Pugh score and model for end-stage liver disease are commonly used,they have substantial limitations.Hepatic venous pressure gradient(HVPG)measurement remains the gold standard for assessing PH but is invasive and not widely available.Endoscopic ultrasound(EUS)guided portal pressure gradient(PPG)measurement has emerged as a promising minimally invasive alternative.EUSPPG demonstrates excellent technical success rates,safety profile,and correlation with HVPG in early studies.By providing direct portal pressure measurement,EUS-PPG offers several advantages over existing methods for prognostication and risk stratification prior to liver-directed therapies,particularly in detecting presinusoidal hypertension.Furthermore,it has potential applications in assessing response to neoadjuvant treatments and guiding adjuvant therapies.However,research is needed to validate its predictive performance and cost-effectiveness in larger prospective cohorts and to establish its accuracy compared to non-invasive assessment of liver function.展开更多
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金funded by the Program of China Scholarships Council(No.202206785007)“Four New”Experimental Teaching Curriculum Reform Project of Jinan University in China(SYJG202235),the Teaching QualityTeaching Reform Project of Undergraduate University of Guangdong in China(2020).
文摘MASLD in China:an under-recognized public health problem Epidemic characteristics of metabolic dysfunction-associated steatotic liver disease(MASLD)in China As one of the most common chronic non-infectious liver diseases,metabolic dysfunction-associated steatotic liver disease(MASLD),previously known as non-alcoholic fatty liver disease(NAFLD),affects one quarter of the world’s population,is closely related to diabetes and obesity[1,2].
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
基金funded by the Major Science and Technology Project of Henan Province(231100310200)the National Key Research and Development Program(2023YFF1103804).
文摘Liver diseases remain a global health crisis,with limited safe therapeutic options.Cornus officinalis,a traditional medicinal-edible plant,has demonstrated significant hepatoprotective potential.This review systematically summarizes its liver-protective mechanisms and explores its potential as a functional food.Data were collected from scientific databases such as Pub Med,Science Direct,Elsevier,Google Scholar,and relevant literature.Key bioactive compounds—including iridoids,polyphenols,and polysaccharides—contribute to hepatoprotection by mitigating oxidative stress,inflammation,steatosis,apoptosis,and by regulating gut microbiota.As critical quality markers,iridoids exhibit suboptimal bioavailability,necessitating targeted technological interventions—nanoencapsulation for liver-specific delivery and microbial fermentation for controlled aglycone conversion are proposed to enhance their pharmacokinetic properties and bioactivity.Future research could adopt encapsulation and fermentation technologies for C.officinalis processing,aiming to develop targeted functional food products with enhanced bioactivity of its active components.This review,for the first time,establishes a“component-pathway-integration”model,providing a theoretical framework for evidence-based CO-derived functional food development and highlighting the need for further research on iridoid metabolic transformation to advance liver health management.
文摘Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金Supported by Japan Society for the Promotion of Science KAKENHI,No.25K11274.
文摘To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.
文摘BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.
基金supported by the Budgeted Fund of Shanghai University of Traditional Chinese Medicine(Natural Science)(No.2021LK037)the Open Project of Qinghai Province Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation(No.2021-ZY-03).
文摘Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.
文摘This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.
基金Supported by the National Natural Science Foundation of China,No.82202185and Shanghai Science and Technology Development Foundation,No.22Y11911500.
文摘BACKGROUND Hepatic steatosis,characterized by fat accumulation in hepatocytes,can result from metabolic dysfunction-associated steatotic liver disease(MASLD),infections,alcoholism,chemotherapy,and toxins.MASLD is diagnosed via imaging or biopsy with metabolic criteria and may progress to metabolic dysfunction–asso-ciated steatohepatitis,potentially leading to fibrosis,cirrhosis,or cancer.The coexistence of hepatic steatosis with chronic hepatitis B(CHB)is mainly related to metabolic factors and increases mortality and cancer risks.As a noninvasive method,attenuation imaging(ATI)shows promise in quantifying liver fat,demonstrating strong correlation with liver biopsy.AIM To investigate the disparity of ATI for assessing biopsy-based hepatic steatosis in CHB patients and MASLD patients.METHODS The study enrolled 249 patients who underwent both ATI and liver biopsy,including 78 with CHB and 171 with MASLD.Hepatic steatosis was classified into grades S0 to S3 according to the proportion of fat cells present.Liver fibrosis was staged from 0 to 4 according to the meta-analysis of histological data in viral hepatitis scoring system.The diagnostic performance of attenuation coefficient(AC)values across different groups was compared for each grade of steatosis.Factors associated with the AC values were determined through linear regression analysis.A multivariate logistic regression model was established to predict≥S2 within the MASLD group.RESULTS In both the CHB and the MASLD groups,AC values increased significantly with higher steatosis grade(P<0.001).In the CHB group,the areas under the curve(AUCs)of AC for predicting steatosis grades≥S1,≥S2 and S3 were 0.918,0.960 and 0.987,respectively.In contrast,the MASLD group showed AUCs of 0.836,0.774,and 0.688 for the same steatosis grades.The diagnostic performance of AC for detecting≥S2 and S3 indicated significant differences between the two groups(both P<0.001).Multivariate linear regression analysis identified body mass index,trigly-cerides,and steatosis grade as significant factors for AC.When the steatosis grade is≥S2,it can progress to more serious liver conditions.A clinical model integrating blood biochemical parameters and AC was developed in the MASLD group to enhance the prediction of≥S2,achieving an AUC of 0.848.CONCLUSION The AC could effectively discriminate the degree of steatosis in both the CHB and MASLD groups.In the MASLD group,when combined with blood biochemical parameters,AC exhibited better predictive ability for moderate to severe steatosis.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金supported by a grant from the Scientific Re-search Program of Furong Laboratory(No.2023SK2108).
文摘Background:In recent years,the rising prevalence of obesity and metabolic syndrome has led to an increased number of individuals developing metabolic dysfunction-associated steatotic liver disease(MASLD).Furthermore,given the substantial global prevalence of chronic hepatitis B(CHB),instances of MASLD coexisting with CHB are becoming increasingly commonplace in clinical scenarios.Both conditions can lead to liver fibrosis,cirrhosis,and potentially hepatocellular carcinoma(HCC).However,the intrica-cies of the dual etiology,consequential outcomes,and associated risks of CHB concurrent with MASLD are still not fully understood.Data sources:A literature search was conducted on PubMed for articles published up to March 2024.The search keywords included nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,chronic hepatitis B,liver fibrosis,hepatocellular carcinoma,nuclear factor erythroid 2-related factor 2,and oxidative stress.Results:This review examined recent studies on the interplay between MASLD and CHB.The coexis-tence of these conditions may facilitate the clearance of hepatitis B surface antigen from the serum and impede hepatitis B virus(HBV)replication.Conversely,individuals with coexisting CHB tend to exhibit a lower rate of hypertriglyceridemia and reduced serum triglyceride levels compared with those only having NAFLD.Nevertheless,these observations do not necessarily indicate universally positive outcomes.Indeed,MASLD and CHB may synergistically act as“co-conspirators”to exacerbate clinical manifestations,particularly liver fibrosis and HCC.Conclusions:As our understanding of the interaction between steatosis and HBV infection becomes clearer,we can better assess the risk of advanced liver disease in patients with concurrent CHB and MASLD.These insights will support the exploration of potential underlying mechanisms and may provide recommendations for improving patient outcomes.
基金Supported by the National Natural Science Foundation of China,No.82104525Open Foundation of Key Laboratory of Tropical Plant Resource Chemistry of Hainan Province,No.rdzw2024s01.
文摘This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.
文摘Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical decisions.The paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related cACLD.Differently from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood count.RPR is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is non-specific.The second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for decades.Cardiovascular disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related mortality.Therefore,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic cancers.Adequately sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.
文摘BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.
文摘Objective:To study the clinical value of combined detection of blood lipids,blood glucose,and liver function in non-alcoholic fatty liver disease.Methods:105 patients with non-alcoholic fatty liver disease treated in our hospital from May 2022 to July 2024 were selected as the research subjects.All patients underwent a B-ultrasound examination.According to the severity of the disease,they were divided into group A(mild,n=35),group B(moderate,n=44),and group C(severe,n=26).Another 30 healthy residents who came to the hospital for physical examination during the same period were selected as group D.The differences in blood lipids,blood glucose,and liver function indicators between groups were compared.Results:The triglyceride(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL)levels in groups A,B,and C were higher than those in group D,while the high-density lipoprotein cholesterol(HDL)level was lower(P<0.05).The fasting plasma glucose(FPG)levels in groups B and C were higher than those in group D(P<0.05).The TG,LDL,and FPG levels in groups B and C were higher than those in group A(P<0.05).The TC level in group C was higher than that in group A,while the HDL level was lower(P<0.05).The TC and FPG levels in group C were higher than those in group B(P<0.05).The total bilirubin(TBil),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels in groups A,B,and C were higher than those in group D(P<0.05).The TBil and ALT levels in groups B and C were higher than those in group A(P<0.05).The AST level in group C was higher than that in group A(P<0.05).The AST and ALT levels in group C were higher than those in group B(P<0.05).Conclusion:Patients with non-alcoholic fatty liver disease have disordered glucose and lipid metabolism.Blood lipids,blood glucose,and liver function are closely related to the severity of the disease.Strengthening exercise and dietary intervention early on can help control the progression of simple fatty liver disease and reduce the risk of severe liver diseases such as steatohepatitis and cirrhosis.
基金Supported by WBE Liver Foundation,No.WBE20220182022 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYY-YN-2022-092023 Young and Middle-aged Talents Incubation Project(Youth Innovation)of Beijing Youan Hospital,Capital Medical University,No.BJYAYYYN2023-14.
文摘BACKGROUND Autoimmune liver diseases,including primary biliary cholangitis(PBC),autoi-mmune hepatitis(AIH),and their overlap syndrome(OS),involve immune-mediated liver injury,with OS occurring in 1.2%-25%of PBC patients.OS carries a higher risk of cirrhosis,hepatocellular carcinoma,and reduced survival.While its pathogenesis remains unclear,gut microbiota dysbiosis and serum metabolite alterations may play key roles.This study uses 16S rRNA sequencing and liquid chromatography-mass spec-trometry(LC-MS)metabolomics to compare gut microbiota and serum metabolites among PBC,AIH,and OS patients,and explores their associations with liver function.AIM To differentiate OS from PBC and AIH based on gut microbiota,serum metabolites,and liver function.METHODS Gut microbiota profiles were analyzed using 16S rRNA sequencing,while untargeted serum metabolomics was conducted via LC-MS.Comparative analyses were performed to identify differences in microbial composition and serum metabolite levels among PBC,AIH,and OS groups.Correlation analyses and network visualization tech-niques were applied to elucidate the interactions among liver function parameters,gut microbiota,and serum metabolites in OS patients.RESULTS Compared to patients with PBC or AIH,OS patients demonstrated significantly reduced microbial diversity and richness.Notable taxonomic shifts included decreased abundances of Firmicutes,Bacteroidetes,and Actinobacteria,alongside increased levels of Proteobacteria and Verrucomicrobia.Distinct serum metabolites,such as pentadecanoic acid and aminoimidazole carboxamide ribonucleotide,were identified in OS patients.Correlation analysis revealed that aspartate aminotransferase(AST)levels were negatively associated with the bacterial genus Fusicatenibacter and the metabolite L-Tyrosine.A microbial-metabolite network diagram further confirmed a strong association between Fusicatenibacter and L-Tyrosine in OS patients.CONCLUSION OS patients show decreased gut microbiota diversity and unique serum metabolites.Multi-omics linked AST,Fusicatenibacter,and L-Tyrosine,revealing OS mechanisms and diagnostic potential.
基金Supported by Natural Science Foundation of Chongqing,No.cstc2021jcyj-msxmx0848Chongqing Bishan Scientific Research Project,No.BSKJ2022006+1 种基金National Natural Science Foundation of China,No.81773954National College Students Innovation and Entrepreneurship Program,No.202310617015.
文摘In the current era,metabolic dysfunction-associated steatotic liver disease(MASLD)has gradually developed into a major type of chronic liver disease that is widespread globally.Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD.Currently,the gut microbiota has become one of the important entry points for the research of this disease.Therefore,the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD,including the changes and differences in the microbiota between the healthy liver and the diseased liver.Meanwhile,considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis(such as mild fibrosis and severe fibrosis)during the disease progression,we also conduct a comparison of the microbiota in these states and use them as markers of disease progression.It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota,and the impact of lipopolysaccharide from Gram-negative bacteria on the disease.In addition,the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics(including new-generation probiotics)will be explored,which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota.This will achieve important progress in preventing and combating this disease.
文摘Liver-directed therapies such as resection,ablation,and embolization offer potentially curative options for patients with primary and metastatic liver tumors as part of multidisciplinary oncology care.However,these treatments pose significant hepatic decompensation risks,particularly with underlying liver disease and chemotherapy-associated steatohepatitis.Accurate assessment of liver function and portal hypertension(PH)is critical for candidate selection.While Child-Pugh score and model for end-stage liver disease are commonly used,they have substantial limitations.Hepatic venous pressure gradient(HVPG)measurement remains the gold standard for assessing PH but is invasive and not widely available.Endoscopic ultrasound(EUS)guided portal pressure gradient(PPG)measurement has emerged as a promising minimally invasive alternative.EUSPPG demonstrates excellent technical success rates,safety profile,and correlation with HVPG in early studies.By providing direct portal pressure measurement,EUS-PPG offers several advantages over existing methods for prognostication and risk stratification prior to liver-directed therapies,particularly in detecting presinusoidal hypertension.Furthermore,it has potential applications in assessing response to neoadjuvant treatments and guiding adjuvant therapies.However,research is needed to validate its predictive performance and cost-effectiveness in larger prospective cohorts and to establish its accuracy compared to non-invasive assessment of liver function.
