Accuracy of prognostic serological biomarkers in predicting liver fibrosis severity in people with metabolic dysfunction-associated steatotic liver disease: a meta-analysis of over 40,000 participants

IntroductionA prognostic model to predict liver severity in people with metabolic dysfunction-associated steatotic liver disease (MASLD) is very important, but the accuracy of the most commonly used tools is not yet well established.ObjectiveThe meta-analysis aimed to assess the accuracy of different prognostic serological biomarkers in predicting liver fibrosis severity in people with MASLD.MethodsAdults ≥18 years of age with MASLD were included, with the following: liver biopsy and aspartate aminotransferase-to-platelet ratio (APRI), fibrosis index-4 (FIB-4), non-alcoholic fatty liver disease fibrosis score (NFS), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD score), FibroMeter, FibroTest, enhanced liver fibrosis (ELF), Forns score, and Hepascore. Meta-analyses were performed using a random effects model based on the DerSimonian and Laird methods. The study’s risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2.ResultsIn total, 138 articles were included, of which 86 studies with 46,514 participants met the criteria for the meta-analysis. The results for the summary area under the receiver operating characteristic (sAUROC) curve, according to the prognostic models, were as follows: APRI: advanced fibrosis (AF): 0.78, any fibrosis (AnF): 0.76, significant fibrosis (SF): 0.76, cirrhosis: 0.72; FIB-4: cirrhosis: 0.83, AF: 0.81, AnF: 0.77, SF: 0.75; NFS: SF: 0.81, AF: 0.81, AnF: 0.71, cirrhosis: 0.69; BARD score: SF: 0.77, AF: 0.73; FibroMeter: SF: 0.88, AF: 0.84; FibroTest: SF: 0.86, AF: 0.78; and ELF: AF: 0.87.ConclusionThe results of this meta-analysis suggest that, when comparing the scores of serological biomarkers with liver biopsies, the following models showed better diagnostic accuracy in predicting liver fibrosis severity in people with MASLD: FIB-4 for any fibrosis, FibroMeter for significant fibrosis, ELF for advanced fibrosis, and FIB-4 for cirrhosis.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD 42020180525]

Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis

Background: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. Results: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated β-galactosidase (SA-β-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. Conclusions: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis

TRF1 as a major contributor for telomeres’ shortening in the context of obesity

Obesity is a prevalent multifactorial chronic disorder characterized by metabolic dysregulation. Sustained pro-oxidative mediators trigger harmful consequences that reflect at systemic level and contribute for the establishment of a premature senescent phenotype associated with macromolecular damage (DNA, protein, and lipids). Telomeres are structures that protect chromosome ends and are associated with a six-protein complex called the shelterin complex and subject to regulation. Under pro-oxidant conditions, telomere attrition and the altered expression of the shelterin proteins are central for the establishment of many pathophysiological conditions such as obesity. Thus, considering that individuals with obesity display a systemic oxidative stress profile that may compromise the telomeres length or its regulation, the aim of this study was to investigate telomere homeostasis in patients with obesity and explore broad/systemic associations with the expression of shelterin genes and the plasma redox state. We performed a cross-sectional study in 39 patients with obesity and 27 eutrophic subjects. Telomere length (T/S ratio) and gene expression of shelterin components were performed in peripheral blood mononuclear cells by qPCR

Doença hepática não-alcoólica gordurosa e risco de cirrose = Nonalcoholic fatty liver disease and risk of cirrhosis

Objetivos: destacar a doença hepática gordurosa não-alcoólica, seus diversos graus e suas possíveis conseqüências (cirrose e hepatocarcinoma) como uma comorbidez freqüentemente não diagnosticada da obesidade. Fonte de dados: os artigos selecionados para esta revisão foram obtidos em pesquisa no PUBMED. Os principais critérios de seleção foram publicações avaliadas por pares e autores de destaque na área de obesidade e hepatologia. Síntese dos dados: artigos recentes confirmam a relação entre obesidade e doença hepática gordurosa não-alcoólica. É de interesse a possível progressão da esteatose para cirrose e carcinoma hepatocelular. Conclusões: a obesidade mórbida está associada à doença hepática gordurosa não-alcoólica que, por sua vez, determina risco de cirrose e de carcinoma hepatocelula

Bi?psia hep?tica em cunha ou com agulha em cirurgia bari?trica convencional

Made available in DSpace on 2015-04-14T13:36:01Z (GMT). No. of bitstreams: 1 342393.pdf: 4328263 bytes, checksum: ea9e357d61bd62332eb1ddd87f4e394b (MD5) Previous issue date: 2005-12-12Introdu??o: Pacientes obesos m?rbidos, mesmo na presen?a de provas laboratoriais normais e sem evid?ncia cl?nica de doen?a, apresentam alta preval?ncia de altera??es na histologia hep?tica. A bi?psia hep?tica ? indicada para definir diagn?stico, gradua??o, estadiamento e evolu??o de doen?as hep?ticas, ajudando a definir o manejo cl?nico. Discute-se qual a melhor t?cnica para coleta de tecido hep?tico, que costuma apresentar fibrose na regi?o sub-capsular, exigindo coleta de material mais profundo. M?todo: Estudo transversal, envolvendo 264 pacientes obesos m?rbidos, submetidos ? redu??o g?strica, com deriva??o em Y de Roux convencional de julho 2001 a setembro de 2004, nos quais a bi?psia hep?tica foi realizada como procedimento de rotina no transoperat?rio. As primeiras 107 bi?psias foram realizadas em cunha e as 157 seguintes por agulha. Foram avaliados os resultados histol?gicos nas duas t?cnicas baseando-se no grau de esteatose hep?tica, presen?a de fibrose e adequabilidade do material. Resultados: N?o houve diferen?a significativa quanto ao grau de esteatose entre as duas t?cnicas (p=0,132). A presen?a de fibrose foi significativamente maior nos casos em que a bi?psia foi realizada em cunha (41 = 46,1%), quando comparados ? t?cnica por agulha (20 = 13,7%): p<0,001. As bi?psias por agulha foram significativamente menores que as em cunha: p<0,001, mas n?o houve diferen?a quanto ? adequabilidade das amostras: p=0,95, nas diferentes t?cnicas. Conclus?o: A bi?psia por agulha mostrou os mesmos resultados obtidos com a bi?psia em cunha em rela??o ao grau de esteatose. A presen?a de fibrose foi significativamente menor na t?cnica por agulha

Influ?ncia da zona doadora na concentra??o de c?lulas-tronco derivadas do tecido adiposo em mulheres

Made available in DSpace on 2015-04-14T13:34:33Z (GMT). No. of bitstreams: 1 404135.pdf: 1490615 bytes, checksum: b5509cc2d05c00816334141421e9d2b2 (MD5) Previous issue date: 2008-06-27Introdu??o: Recentemente, o tecido adiposo obtido atrav?s da lipoaspira??o foi identificado como uma fonte alternativa de c?lulas-tronco adultas. A facilidade de obten??o e a abund?ncia de material facilitam n?o s? a pesquisa, mas principalmente a aplica??o cl?nica destas c?lulas. Os estudos que tratam deste assunto n?o avaliam de forma precisa a exist?ncia ou n?o de diferen?a na concentra??o destas c?lulas nas diferentes poss?veis zonas de coleta do corpo. Objetivo: Avaliar a influ?ncia da zona doadora na concentra??o de c?lulas-tronco derivadas do tecido adiposo em mulheres. M?todo: Estudo transversal prospectivo. Foram inclu?dos no estudo 25 pacientes com indica??o de lipoaspira??o em 4 ou mais zonas diferentes em um mesmo procedimento cir?rgico. Ap?s a lipoaspira??o seletiva, o material foi processado para a dissocia??o do tecido e extra??o das c?lulas-tronco adultas para posterior quantifica??o. Foram avaliadas as seguintes zonas de coleta: abdome superior, abdome inferior, zona trocant?rica, zona crural, joelho e flanco. A concentra??o celular obtida em cada zona foi comparada atrav?s de an?lise de vari?ncia para modelos mistos. Resultados: Verificou-se diferen?a significativa na concentra??o celular obtida nas diferentes zonas doadoras. A concentra??o celular no abdome inferior foi superior ?s demais; por?m, n?o apresentou diferen?a significativa em rela??o ? zona crural. Conclus?o: O abdome inferior e a zona crural parecem ter maiores concentra??es de c?lulas-tronco derivadas do tecido adiposo