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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：Overthepastfewdecades,non-alcoholicfattyliverdisease(NAFLD)hasbecomeone,ifnotthemostcommon,causeofchronicliverdiseaseaffectingbothadultsandchildren.Theincreasingnumberofcasesatanearlyageisthemostworryingaspectofthispathology,sinceitprovidesmoretimeforitsevolution.Thespectrumofthisdiseaserangesfromliversteatosistosteatohepatitis,fibrosisandinsomecases,hepatocellularcarcinoma.NAFLDmaynotalwaysbeconsideredabenigndiseaseandhepatologistsmustbecautiousinthepresenceoffattyliver.Thisshouldprompttheuseoftheavailableexperimentalmodelstounderstandbetterthepathogenesisandtodeveloparationaltreatmentofadiseasethatisdangerouslyincreasing.Inspiteofthegrowingefforts,thepathogenesisofNAFLDisstillpoorlyunderstood.InthepresentarticlewereviewthemostrelevanthypothesesandevidencethataccountfortheprogressionofNAFLDtonon-alcoholicsteatohepatitis(NASH)andfibrosis.TheavailableinvitroandinvivoexperimentalmodelsofNASHarediscussedandrevisedintermsoftheirvalidityintranslationalstudies.Thesestudiesmustbeaimedatthediscoveryofthestillunknowntriggersormediatorsthatinducetheprogressionofhepaticinflammation,apoptosisandfibrosis.

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：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：Oysterextractisaneffectivebioactivitycomponent.Ithasabundantnutritionalvalueandantiviral,antitumorandimmunedefensefunctions.Theroleofoysterextractintreatingliverinjuryhasbeenpaidmoreattention.WeuseWistarratstomakealcoholicliverdiseasemodelthroughinjectingalcoholintorats'stomachs.Theseratswererandomlydividedintofivegroups:modelgroup,controlgroup,low-dose,middle-doseandhigh-doseexperimentalgroupwithadoseof0.12gkg-1,0.40gkg-1,and1.20gkg-1alcoholic.Afternineweeks,serumbiomarkers(ALT,AST,TGandTCHO),malondialdehyde(MDA),glutathione(GSH),C3a,C5a,IL-17,TNF-ɑ,anti-MAA-HASIgG,CD3+,CD4+,CD8+,NKcellactivationandzinccontentwereassessed.Theresultsshowedthattheserumbiomarkers(ALT,AST,TGandTCHO),MDAcontent,anti-MAA-HSAIgG,serumC3a,C5aIL-17andTNF-ɑlevelsofoysterextracttreatmentgroupsweresignificantlydecreasedincomparisonwithmodelgroup.Onthecontrary,GSHshowedadversetrend.SerumCD3+,CD4+andNKcellactivationweresignificantlyincreasedinmiddle-dosegroupandhigh-dosegroupcomparedwithmodelgroup,andtherewasdecreaseofCD8+activityinhigh-dosegroup.PlasmaZnlevelwasdecreasedinmodelgroupcomparedwiththatincontrolgroup.Meanwhile,MeanplasmaZnlevelsincreaseddramaticallyfollowingthedoseincreaseofagivenoysterextract.

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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

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简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is a disorder of lipid metabolism. The lipotoxic intermediates of lipid metabolism cause mitochondrial dysfunction and endoplasmic reticulum stress. Organelle-specific autophagy is responsible for the removal of dysfunctional organelles to maintain intracellular homeostasis. Lipophagy contributes to lipid turnover by degrading lipid droplets. The level of autophagy changes during the course of NAFLD, and the activation of hepatocyte autophagy might represent a method of treating NAFLD.

简介：AbstractChronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.

简介：AbstractBackground:The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.Methods:A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.Results:Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years.Conclusions:The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.Registration:PROSPERO, No. CRD42020171104.