简介：Nonalcoholicfattyliverdisease(NAFLD),definedasabnormalaccumulation(>5%)ofhepatictriglyceridewithoutexcessalcoholintake,isthemostcommonformofchronicliverdiseaseinadultsandchildrenintheUnitedStates.NAFLDencompassesaspectrumofhistologicfindingsincludinguncomplicatedsteatosis,steatosiswithinflammationandsteatohepatitis[nonalcoholicsteatohepatitis(NASH)];thelattercanadvancetocirrhosisandhepatocellularcarcinoma.NASHiscurrentlyacceptedasthehepaticmanifestationofthesetofcardiovascularriskfactorscollectivelyknownasmetabolicsyndrome.In1999asystemforhistologicgradingandstagingforNASHwasproposed;thiswasrevisedbytheNASHClinicalResearchNetworkin2005fortheentirespectrumoflesionsinNAFLD,includingthelesionsandpatternsofpediatricNAFLD,andforapplicationinclinicalresearchtrials.Diagnosisremainsdistinctfromgradeandstage.ArecentEuropeanproposalseparatessteatosisfromactivitytoderiveanumericdiagnosisofNASH.Eventhoughtherehavebeenpromisingadvancementsinnon-invasivetesting,thesetestsarenotyetdetailedenoughtoreplacethefullrangeoffindingsprovidedbyliverbiopsyevaluation.Limitationsofbiopsyareacknowledged,butliverbiopsyremainsthe'goldstandard'fordiagnosisanddeterminationofamountsofnecroinflammatoryactivity,andlocationoffibrosis,aswellasremodelingoftheparenchymainNASH.ThisreviewfocusesonthespecifichistologiclesionsofNAFLDandNASH,gradingandstaging,differentialdiagnosestobeconsidered,andthecontinuingroleoftheliverbiopsyinthisimportantliverdisease.

简介：TheJanuskinase-signaltransducersandactivatorsoftranscription(JAK-STAT)signalingpathway,activatedbymorethan50cytokinesorgrowthfactors,playscriticalrolesinawidevarietyofcellularfunctionsinthehematopoietic,immune,neuronalandhepaticsystems.Intheliver,thissignalingpathway,activatedbymorethan20cytokines,growthfactors,hormones,andhepatitisviralproteins,playscriticalrolesinantiviraldefense,acutephaseresponse,hepaticinjury,repair,inflammation,transformation,andhepatitis.ThisarticlereviewsthebiologicalsignificanceofSTAT1,2,3,4,5,6inhepaticfunctionsanddiseases.Cellular&MolecularImmunology.2005;2(2):92-100.

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简介：SulfatechitosanderivativeshavegoodsolubilityandtherapeuticeffectonthecellmodelofNAFLD.TheaimofthisstudywastoexaminethetherapeuticeffectofsulfatechitosanderivativesonNAFLD.ThemaleWistarratswereorallyfedhighfatemulsionandreceivedsulfatechitosanderivativesfor5weekstodeterminethepre-treatmenteffectofsulfatechitosanderivativesonNAFLD.ToevaluatethetherapeuticeffectofsulfatechitosanderivativesonNAFLD,theratswereorallyfedwithhighconcentrationemulsionfor5weeks,followedbysulfatechitosanderivativesfor3weeks.Histologicalanalysisandbiomedicalassaysshowedthatsulfatechitosanderivativescandramaticallypreventthedevelopmentofhepaticsteatosisinhepatocytecells.Inanimalstudies,pre-treatmentandtreatmentwithsulfatechitosanderivativessignificantlyprotectedagainsthepaticsteatohepatitisinducedbyhighfatdietaccordingtohistologicalanalysis.Furthermore,increasedTC,ALT,MDA,andLEPinNAFLDweresignificantlyamelioratedbypre-treatmentandtreatmentwithsulfatechitosanderivatives.Furthermore,increasedTG,AST,andTNF-αinNAFLDweresignificantlyamelioratedbytreatmentwithsulfatechitosanderivatives.Sulfatechitosanderivativeshavegoodpre-treatmentandtherapeuticeffectonNAFLD.

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简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

简介：AbstractFor the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

简介：AbstractNonalcoholic fatty liver disease (NAFLD) is becoming increasingly common as the global economy grows and living standards improve. Timely and effective preventions and treatments for NAFLD are urgently needed. Retinol-binding protein-4 (RBP4), the protein that transports retinol through the circulation, was found to be positively related to diabetes, obesity, cardiovascular disease, and other metabolic diseases. Observational studies on the association between serum RBP4 level and the prevalence of NAFLD found contradictory results. Some of the underlying mechanisms responsible for this association have been revealed, and the possible clinical implications of treating NAFLD by targeting RBP4 have been demonstrated. Future studies should focus on the predictive value of RBP4 on NAFLD development and its potential as a therapeutic target in NAFLD.

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简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

简介：AIM:Toinvestigatewhetherliversteatosisreductionduetoasix-monthdietaryinterventionresultsinsignificantchangesintheconcentrationsoffattyacids.METHODS:Agroupof35Caucasianindividualsdiagnosedwithdifferentlevelsofsteatosiswereprospectivelyenrolledinthepresentstudy.Analysisofthefattyacidprofileswasperformedaccordingtochangesinliversteatosis(liversteatosisreductionbyoneortwodegrees)afterasix-monthdietaryintervention.Thediethelpedreducebodymassinobeseandoverweightpatients,andstabilizebothglycemiaanddyslipidemia.FattyacidswereextractedaccordingtotheFolchmethodandanalyzedbygaschromatography.RESULTS:Thisstudyshowedsignificantchangesinfattyacidprofilesinpatientswhohadreducedliversteatosisbyoneaswellastwodegrees.Areductioninliversteatosisbyonedegreecausedasignificantincreaseinthelevelofthen-3family:eicosapentaenoicacid(P<0.055),docosapentaenoicacid-C22:5(P<0.05)anddocosahexaenoicacid(P<0.05).Areductioninliversteatosisbytwodegreescausedasignificantdecreaseinserumpalmitoleicacid-C16:1(P<0.05).CONCLUSION:Liversteatosisreductionisassociatedwithchangesinfattyacidprofiles,andthesechangesmayreflectanalterationinfattyacidsynthesisandmetabolism.Thesefindingsmayhelpbetterunderstandregressionofnonalcoholicfattyliverdisease.

简介：hepatocellular癌(HCC)的发展被归因于几个因素，包括长期的病毒的感染，白酒消费，到黄麴毒素B1的暴露和新陈代谢的混乱。几份最近的报告证明了HCC能当另外的内在的高风险的肝疾病不在时与长期的Crohns疾病(CD)发生在病人。然而，可以在CD和hepatocarcinogenesis之间有一个协会为这的精确机制要求进一步的调查。

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简介：AbstractBackground:Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease. China has the world’s largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization (WHO) of eliminating hepatitis B virus (HBV) as a global health threat by 2030. This study aimed to analyze data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO’s goal.Methods:Annual deaths and age-standardized mortality rates (ASMRs) of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019. We calculated the percentage changes in deaths and estimated annual percentage changes (EAPCs) of ASMRs of liver disease due to hepatitis B.Results:In China, deaths of total liver disease due to hepatitis B decreased by 29.13% from 229 thousand in 2016 to 162 thousand in 2019, and ASMR decreased by an average of 4.92% (95% confidence interval [CI]: 4.45–5.39%) per year in this period. For the spectrum of liver disease due to hepatitis B, deaths decreased by 74.83%, 34.71%, and 23.34% for acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer from 1990 to 2019, respectively, and ASMRs of acute hepatitis (EAPC = –7.63; 95% CI: –8.25, –7.00), cirrhosis and other chronic liver diseases (EAPC= –4.15; 95% CI: –4.66, –3.65), and liver cancer (EAPC = –5.17; 95% CI: –6.00, –4.33) decreased between 1990 and 2019. The proportions of older adults aged ≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019. Deaths of liver cancer due to hepatitis B increased by 7.05% from 2015 to 2019.Conclusions:Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019, China still faces challenges in achieving the WHO’s goal of eliminating HBV as a public threat by 2030. Therefore, efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B, especially of liver cancer due to hepatitis B, are warranted in China.

简介：AbstractBackground:The global prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The pathogenesis of NAFLD is multifaceted, and the underlying mechanisms are elusive. We conducted data mining analysis to gain a better insight into the disease and to identify the hub genes associated with the progression of NAFLD.Methods:The dataset GSE49541, containing the profile of 40 samples representing mild stages of NAFLD and 32 samples representing advanced stages of NAFLD, was acquired from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the R programming language. The Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database were used to perform the enrichment analysis and construct protein-protein interaction (PPI) networks, respectively. Subsequently, transcription factor networks and key modules were identified. The hub genes were validated in a mice model of high fat diet (HFD)-induced NAFLD and in cultured HepG2 cells by real-time quantitative PCR.Results:Based on the GSE49541 dataset, 57 DEGs were selected and enriched in chemokine activity and cellular component, including the extracellular region. Twelve transcription factors associated with DEGs were indicated from PPI analysis. Upregulated expression of five hub genes (SOX9, CCL20, CXCL1, CD24, and CHST4), which were identified from the dataset, was also observed in the livers of HFD-induced NAFLD mice and in HepG2 cells exposed to palmitic acid or advanced glycation end products.Conclusion:The hub genes SOX9, CCL20, CXCL1, CD24, and CHST4 are involved in the aggravation of NAFLD. Our results offer new insights into the underlying mechanism of NAFLD progression.

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简介：AIM:Toinvestigatetheproteinexpressionofphosphataseandtensinhomolog(PTEN)inhumanliverbiopsiesofpatientswithalcoholicandnon-alcoholicliverdisease.METHODS:PTENproteinexpressionwasassessedbyimmunohistochemistryinformalin-fixed,paraffinembeddedliversectionsofpatientswithnon-alcoholicfattyliverdisease(NAFLD)(n=44)oralcoholicliverdisease(ALD)(n=25).Liverresectionsobtainedfrom3healthysubjectscandidateforpartialliverdonationservedascontrols.Histologicalevaluationswereperformedbytwoexperiencedpathologists,anddiagnosesestablishedbasedoninternationalcriteria.TheintensityofthePTENstaininginnucleiwascomparedbetweensteatoticandnon-steatoticareasofeachliverfragmentanalyzed.Foreachliverspecimen,theantibody-stainedsectionswereexaminedandscoredblindlybythreeindependentobservers,whowereunawareofthepatients’clinicalhistory.RESULTS:Inhealthyindividuals,PTENimmunostainingwasintenseinboththecytoplasmandnucleiofallhepatocytes.However,PTENwasstronglydownregulatedinboththenucleusandthecytoplasmofhepatocytesfromsteatoticareasinpatientswithNAFLD,independentlyofthediseasestage.Incontrast,nochangesinPTENproteinexpressionwereobservedinpatientswithALD,regardlessofthepresenceofsteatosisorthestageofthedisease.ThedegreeofPTENdownregulationinhepatocytesofpatientswithNAFLDcorrelatedwiththepercentageofsteatosis(r=0.3061,P=0.0459)andtheBMI(r=0.4268,P=0.0043).Hovewer,inpatientswithALD,PTENexpressionwasnotcorrelatedwiththepercentageofsteatosiswithorwithoutobesityasaconfoundingfactor(P=0.5574).Finally,PTENexpressionlevelinsteatoticareasofALDpatientswassignificantlydifferentfromthatseeninsteatoticareasofNAFLDpatients(P<0.0001).CONCLUSION:PTENproteinexpressionisdownregulatedearlyinNAFLD,butnotinALD.PTENimmunohistochemicaldetectioncouldhelpinthedifferentialdiagnosisofN

简介：瞄准：评估影响多囊肝疾病的非侵略、侵略的治疗的结果的因素。方法：有到2006年6月的从1986年7月的完全的后续的病人的临床的文件的分析。结果：41个病人(男性，7；女性，34)，11.9年变老的47.8+/-，和5.7+/-6.7年后续，被学习。硷性磷酸酯酶(AP)举起(15%病人)与侵略治疗的要求被联系(信息技术，P=0.005)。信息技术率是更高的在比非征兆的病人征兆(65.4%对14.3%，P=0.002)，并且在拿神经质的代替治疗(HRT)的女人(P=0.001)。包囊复杂并发症(CC)是更经常的(22%)在征兆的病人组织(P=0.023)。有身体质量的病人索引(BMI)>(59%)25在它以后有一个趋势到复杂并发症(P=0.075)。腹的疼痛为信息技术(78%)是最普通的症状(56%)和指示。十九个病人(46%)要求了第一种信息技术：12开的开窗术()，4laparoscopic开窗术(LF)和有肝的切除术(FHR)的3开窗术。三要求了第二种信息技术，并且一个人要求了第三个过程。复杂并发症在32%由于第一种信息技术被发现(16.7%，LF25%，FHR66.7%)，并且在在66.7%的第二种信息技术(100%)。后续死亡率是0。结论：症状，提高的AP，和CC的存在与信息技术要求被联系。HRT与症状和信息技术要求的存在被联系。有BMI>的病人25有一个趋势产生信息技术复杂并发症。复杂并发症的比例在FHR和秒信息技术组是更高的。RS是更经常的在以后。

简介：AbstractBackground:Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China.Methods:A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression.Results:The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years).Conclusions:HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions.Trial registration:NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.