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BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease in the world and was recently renamed to emphasize its metabolic component. AIMS: This article seeks to fill the gap in specific guidelines for patients with obesity and MASLD who will undergo bariatric surgery. METHODS: A systematic search for guidelines was carried out on PubMed and Embase platforms. RESULTS: A total of 544 articles were found, of which 11 were selected according to inclusion and exclusion criteria. All 11 guidelines are from clinical societies; therefore, they do not include some necessary interpretations for bariatric patients. CONCLUSIONS: We recommend that every patient undergoing bariatric and metabolic surgery be screened initially with the Fibrosis-4 (FIB-4) score, followed by transient hepatic elastography (vibration-controlled transient elastography, VCTE), especially for those with FIB-4>1.3. However, interpreting VCTE results in obese patients requires further studies to define the actual cutoff values. Enhanced Liver Fibrosis® shows promise but its availability is limited. The indication for liver biopsy during surgery needs to be individualized but it is recommended for those with changes in FIB-4 and/or VCTE. Family screening is recommended for relatives of young patients with already advanced fibrosis. Liver transplantation is an option for patients with advanced MASLD but the optimal timing for bariatric surgery with transplantation is still unclear. Regular follow-up and VCTE examination are recommended to monitor disease progression after surgery.
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Cirugía Bariátrica , Síndrome Metabólico , Obesidad , Humanos , Síndrome Metabólico/complicaciones , Obesidad/complicaciones , Obesidad/cirugía , Hígado Graso/complicaciones , Brasil , Sociedades Médicas , Diagnóstico por Imagen de ElasticidadRESUMEN
Background Attenuation coefficient (AC) and shear-wave speed (SWS) are established US markers for assessing patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while shear-wave dispersion slope (DS) is not. Purpose To assess the relationship between the multiparametric US imaging markers DS, AC, and SWS and liver histopathologic necroinflammation in patients with MASLD. Materials and Methods This international multicenter prospective study enrolled consecutive patients with biopsy-proven MASLD between June 2019 and March 2023. Before biopsy, all participants underwent multiparametric US, and measurements of DS, AC, and SWS were obtained. Multivariable linear regression analyses were performed to assess the association of clinical variables and imaging markers with pathologic findings. The diagnostic performance of imaging markers for determining inflammation grade, steatosis grade, and fibrosis stage was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 124 participants (mean age, 53 years ± 15 [SD]; 62 males) were evaluated. In multivariable regression, lobular inflammation was associated with DS (regression coefficient, 0.06; P = .02), alanine aminotransferase level (regression coefficient, 0.002; P = .002), and Hispanic or Latino ethnicity (regression coefficient, -0.68; P = .047), while steatosis was associated with AC (regression coefficient, 3.66; P < .001) and fibrosis was associated with SWS (regression coefficient, 2.02; P < .001) and body mass index (regression coefficient, 0.05; P = .02). DS achieved an AUC of 0.72 (95% CI: 0.63, 0.82) for identifying participants with inflammation grade A2 or higher (moderate to severe inflammation). AC showed excellent performance for identifying participants with grade S1 (mild) or higher steatosis (AUC, 0.92 [95% CI: 0.87, 0.97]), while SWS showed excellent performance for identifying participants with fibrosis stage F2 or higher (clinically significant fibrosis) (AUC, 0.91 [95% CI: 0.86, 0.96]). Of the three US markers, SWS showed the highest AUC (0.81 [95% CI: 0.74, 0.89]) for the diagnosis of metabolic dysfunction-associated steatohepatitis. Conclusion Of the three US imaging markers (DS, AC, and SWS), DS was most associated with lobular inflammation grade at histologic examination and demonstrated fair diagnostic performance in distinguishing moderate to severe lobular inflammation. ClinicalTrials.gov Identifier: NCT04012242 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Yin in this issue.
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Hígado Graso , Cirrosis Hepática , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Cirrosis Hepática/diagnóstico por imagen , Hígado Graso/diagnóstico por imagen , Hígado Graso/complicaciones , Ultrasonografía/métodos , Adulto , Hígado/diagnóstico por imagen , Hígado/patología , Anciano , Inflamación/diagnóstico por imagen , Biomarcadores/sangreRESUMEN
OBJECTIVE: The association of appendicular skeletal muscle mass (ASM), grip strength and fat-to-muscle ratio (FMR) and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) are not well known. MATERIALS AND METHODS: This study included participants older than 40 years who underwent bioelectrical impedance assessment in Prevalence of Metabolic Diseases and Risk Factors in Shunde (SPEED-Shunde). We measured grip strength with an electronic grip strength metre. ASM and grip strength were adjusted by dividing body mass index (BMI). FMR was calculated as total fat mass to total muscle mass. Liver steatosis and liver fibrosis were evaluated by vibration-controlled transient elastography. Multifactorial logistic regression was used to analyse the relationship between ASM, grip strength, FMR, and MASLD or MASLD-associated liver fibrosis. We performed subgroup analyses according to sex, age and BMI. Interaction tests and linear trend tests were also conducted. RESULTS: This study included a total of 3277 participants. FMR was positively associated with MASLD (OR: 1.89, 95% CI: 1.66-2.15) and MASLD-associated liver fibrosis (OR: 1.70, 95% CI: 1.22-2.37). While ASM/BMI (OR: 0.59, 95% CI: 0.52-0.67) or grip strength/BMI (OR: 0.72, 95% CI: 0.66-0.78) were negatively associated with MASLD. Interactions were observed between ASM/BMI and age, grip strength and sex in MASLD, as well as FMR and MASLD-associated liver fibrosis. CONCLUSION: In a middle-to-elderly aged population, FMR was positively associated with the risk of MASLD and MASLD-associated liver fibrosis, and muscle mass and grip strength were negatively associated with MASLD, rather than MASLD-associated liver fibrosis.
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Índice de Masa Corporal , Fuerza de la Mano , Músculo Esquelético , Humanos , Masculino , Fuerza de la Mano/fisiología , Femenino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Músculo Esquelético/diagnóstico por imagen , Anciano , Hígado Graso/fisiopatología , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Factores de Riesgo , Cirrosis Hepática/fisiopatología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Estudios Transversales , Diagnóstico por Imagen de Elasticidad , Adulto , Impedancia Eléctrica , Tejido Adiposo/diagnóstico por imagen , Composición CorporalRESUMEN
BACKGROUND: Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We analyzed regional cortical thickness and area obtained from brain MRI in 29,051 participants in UK Biobank. Liver fat amount was computed as proton density fat fraction (PDFF) from liver MRI scans. We examined the relationship between brain structure and PDFF, adjusting for sociodemographic, physical, lifestyle, and environmental factors, as well as alcohol intake and a spectrum of cardiometabolic covariates. Finally, we compared patterns of brain alterations in SLD/MASLD and major depressive disorder (MDD) using previously published results. RESULTS: PDFF-related gray matter alterations were region-specific, involving both increases and decreases in cortical thickness, and increased cortical area. In several regions, PDFF effects on gray matter could also be attributed to cardiometabolic covariates. However, PDFF was consistently associated with lower cortical thickness in middle and superior temporal regions and higher cortical thickness in pericalcarine and right frontal pole regions. PDFF-related alterations for the SLD and the MASLD group correlated with those observed in MDD (Pearson r = 0.45-0.54, p < 0.01). CONCLUSION: These findings suggest the presence of shared biological mechanisms linking MDD to SLD and MASLD. They might explain the well-known elevated risk of depression in these groups and support early lifestyle interventions and treatment of metabolic risk factors for the successful management of the interconnected diseases depression and SLD/MASLD.
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Bancos de Muestras Biológicas , Hígado Graso , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Reino Unido/epidemiología , Estudios de Cohortes , Anciano , Hígado Graso/patología , Hígado Graso/diagnóstico por imagen , Hígado Graso/complicaciones , Depresión/patología , Adulto , Trastorno Depresivo Mayor/patología , Trastorno Depresivo Mayor/diagnóstico por imagen , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Biobanco del Reino UnidoRESUMEN
Given the global high prevalence of MASLD and its poor CVD prognosis, it is essential to perform risk stratification for MASLD patients. The specific impact of High Sensitivity Troponins (hs-cTn ) on mortality in MASLD patients remains unexplored. The NHANES databases from 1999 to 2004, which include data on high-sensitivity cardiac troponin (hs-cTn) levels and comorbidities, were linked with the most recent mortality dataset. Myocardial injury was determined using the 99th upper reference limits (URL) for hs-cTn. Our study included 3460 MASLD patients. The mean follow-up duration was 192 months, during which 1074 (23%) MASLD participants died from all-cause mortality, and 363 (7.3%) died from CVD mortality. Our findings indicate that MASLD patients with elevated levels of hs-cTnT (> 99th URL) exhibit increased risks of all-cause mortality [adjusted hazard ratio (aHR) = 1.93] and CVD mortality (aHR = 2.4). Similar results were observed for hs-cTnI, where the aHRs for all-cause mortality and CVD mortality were 2.03 and 2.97, respectively. Furthermore, we identified a nonlinear dose-response relationship between hs-cTn levels and the risk of mortality (P for nonlinearity < 0.001). Our findings suggest that hs-cTn can predict mortality risk in MASLD, aiding clinicians in risk-stratifying this population. Therefore, we recommend considering hs-cTn detection in individuals with MASLD to effectively assess their future mortality risk.
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Enfermedades Cardiovasculares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Biomarcadores/sangre , Hígado Graso/mortalidad , Hígado Graso/sangre , Hígado Graso/complicaciones , Adulto , Pronóstico , Troponina/sangre , Troponina/metabolismo , Troponina T/sangreRESUMEN
INTRODUCTION: Despite superior outcomes with liver transplantation, cirrhotic patients with HCC may turn to other forms of definitive treatment. To understand perioperative outcomes, we examined perioperative mortality and major morbidity after hepatectomy for HCC among cirrhotic and non-cirrhotic patients. METHOD: ology: The American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) database was queried for liver resection for HCC. Multivariable logistic regression was performed to determine the association between liver texture and risk of major non-infectious morbidity, post-hepatectomy liver failure (PHLF) and 30-day mortality. RESULTS: From 2014 to 2018, 2203 patients underwent hepatectomy: 58.6 % cirrhotic, 12.8 % fatty and 28.6 % normal texture. Overall 30 day-mortality was 2.1 % (n = 46), although higher among fatty liver (2.8 %) and cirrhotic (2.6 %; p = 0.025) patients. The incidence of PHLF was 6.9 %, with hepatectomy type, cirrhosis, and platelet count as major risk factors. Age, resection type, and platelet count were associated with major complications. Trisegmentectomy and right hepatectomy (OR = 3.60, OR = 3.46, respectively) conferred a greater risk of major noninfectious morbidity compared to partial hepatectomy. Among cirrhotics alone, hepatectomy type, platelet count, preoperative sepsis and ASA class were associated with major morbidity. DISCUSSION: Hepatic parenchymal disease/texture and function, presence of portal hypertension, and the extent of the liver resection are critical determinants of perioperative risk among HCC patients.
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Carcinoma Hepatocelular , Hepatectomía , Cirrosis Hepática , Neoplasias Hepáticas , Complicaciones Posoperatorias , Humanos , Hepatectomía/mortalidad , Hepatectomía/efectos adversos , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Masculino , Femenino , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugía , Cirrosis Hepática/patología , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Anciano , Hígado Graso/patología , Hígado Graso/cirugía , Hígado Graso/complicaciones , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant and ever-increasing health and economic burden worldwide. Substantial epidemiological evidence shows that MASLD is a multisystem disease that is associated not only with liver-related complications but is also associated with an increased risk of developing cardiometabolic comorbidities and extrahepatic cancers (principally gastrointestinal [GI] cancers). GI cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. In this narrative review, we provide an overview of the literature on (a) the epidemiological data on the risk of non-liver GI cancers in MASLD, (b) the putative mechanisms by which MASLD (and factors linked with MASLD) may increase this risk, and (c) the possible pharmacotherapies beneficially affecting both MASLD and extrahepatic GI cancer risk. There are multiple potential pathophysiological mechanisms by which MASLD may increase extrahepatic GI cancer risk. Although further studies are needed, the current evidence supports a possible extrahepatic carcinogenic role for MASLD, regardless of obesity and diabetes status, thus highlighting the potential role of tailoring cancer screening for individuals with MASLD. Although there are conflicting data in the literature, aspirin, statins and metformin appear to exert some chemo-preventive effects against GI cancer.
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Hígado Graso , Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/etiología , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/complicaciones , Neoplasias Gastrointestinales/patología , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hígado Graso/etiología , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/etiología , Factores de RiesgoRESUMEN
Physical activity is a cornerstone of a healthy lifestyle, with benefits in managing chronic diseases. This study investigates the relationship between physical activity and liver-related outcomes with or without steatotic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD and increased alcohol intake (MetALD). The primary outcomes of interest were overall survival in the entire population, individuals without steatotic liver disease, patients with MASLD, and those with MetALD. The secondary outcomes included the incidence of liver cirrhosis. Participants were categorized based on physical activity frequency and Kaplan-Meier survival curves and Cox proportional hazards models were used for analysis. Higher physical activity was associated with significantly better survival in the overall cohort and MASLD cohort before and after inverse probability of treatment weighting (IPTW). In participants without steatotic liver disease and the MetALD cohort, higher physical activity showed significant survival improvement after IPTW. For the incidence of liver cirrhosis, higher physical activity showed significant associations before IPTW in the overall cohort and MASLD cohort, but these associations were not significant after IPTW. Marginal significance was observed in the MetALD cohort before and after IPTW. In conclusion. promoting physical activity may be key in improving liver-related outcomes.
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Ejercicio Físico , Hígado Graso , Cirrosis Hepática , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Incidencia , Hígado Graso/mortalidad , Hígado Graso/terapia , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Estudios de Cohortes , Adulto , Anciano , Modelos de Riesgos Proporcionales , Estimación de Kaplan-MeierRESUMEN
Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
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Síndrome Metabólico , Micronutrientes , Obesidad , Humanos , Masculino , Proyectos Piloto , Método Doble Ciego , Femenino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/dietoterapia , Adulto , Micronutrientes/uso terapéutico , Micronutrientes/administración & dosificación , Síndrome Metabólico/complicaciones , Síndrome Metabólico/dietoterapia , Hígado Graso/complicaciones , Hígado Graso/dietoterapia , Suplementos DietéticosRESUMEN
BACKGROUND AND AIMS: Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. METHODS: We analyzed data from all consecutive first adult full-graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation-free survival were studied through survival analyses. RESULTS: Of 12 174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p < 0.001) and donor DM (aHR 1.157, p = 0.004) were independently associated with impaired retransplantation-free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p = 0.0185]; steatosis alone, aHR: 1.200 [p < 0.001]; both steatosis and DM, aHR: 1.381 [p < 0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation-free survival within 7 days. CONCLUSIONS: Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high-risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation.
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Hígado Graso , Supervivencia de Injerto , Trasplante de Hígado , Complicaciones Posoperatorias , Sistema de Registros , Donantes de Tejidos , Humanos , Femenino , Masculino , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Persona de Mediana Edad , Hígado Graso/patología , Hígado Graso/etiología , Hígado Graso/complicaciones , Hígado Graso/cirugía , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Adulto , Europa (Continente)/epidemiología , Tasa de Supervivencia , Diabetes Mellitus , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Estudios Retrospectivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related cirrhosis has been increasing these last decades. There are no data regarding the prevalence of MASLD-related cirrhosis in intensive care unit (ICU). METHODS: Prospective single-centre study in a cohort of patients hospitalized in the ICU of Hepatology La Pitié-Salpêtrière Hospital between January 2019 and September 2021. We analysed three groups of patients: MASLD-cirrhosis (alcohol ≤210 g for men and 140 g weekly for women), ALD (alcohol-related liver disease, alcohol>140 g weekly for women or >210 g for men)-cirrhosis alone and MetALD (metabolic and alcohol-related liver disease)-cirrhosis. Endpoints were 1-year transplant-free survival (TFS), further acute decompensation (AD) and re-admission. RESULTS: A total of 410 patients were hospitalized, and 315 analysed: 39 in MASLD, 160 in ALD and 116 in MetALD groups. The global prevalence was 10% for MASLD, 41% ALD and 29.7% for MetALD. Patients in the MASLD group were significantly older (65 vs. 57 and 59 years, p < 0.001), and had lower Child-Pugh (8 vs. 11 vs. 10, p < 0.001) and MELD score (17 vs. 22 vs. 21, p < 0.001). The 1-year TFS was not different between groups (53% vs. 54% vs. 54%, p = 0.96). Cardiovascular mortality was <5% in all groups. The 1-year probability of developing hepatic encephalopathy was significantly higher in the MASLD group (73% vs. 27% and 21%, p < 0.001). There was no difference regarding the development of other complications between groups. CONCLUSION: MASLD or MetALD was responsible for 1/3 of the causes of cirrhosis in the ICU. MASLD-related cirrhosis is as severe as ALD-related cirrhosis. Liver transplantation should be rapidly discussed.
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Hospitalización , Unidades de Cuidados Intensivos , Cirrosis Hepática , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Francia/epidemiología , Prevalencia , Cirrosis Hepática/complicaciones , Cirrosis Hepática/mortalidad , Cirrosis Hepática/epidemiología , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pronóstico , Hospitalización/estadística & datos numéricos , Hígado Graso/epidemiología , Hígado Graso/complicaciones , AdultoRESUMEN
Epidemiological studies have reported an association between metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of urolithiasis. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between MASLD and urolithiasis. We systematically searched PubMed, Scopus, and Web of Science from database inception to March 31, 2024, using predefined keywords to identify relevant observational studies in which imaging methods or survey questionnaires diagnosed MASLD and urolithiasis. Meta-analysis was performed using random-effects modelling. We identified seven cross-sectional studies and one prospective cohort study with aggregate data on 248,936 adults from different countries. MASLD was significantly associated with an increased risk of prevalent urolithiasis (pooled random-effects odds ratio 1.87, 95% CI 1.34-2.60; I2 = 91%). This association remained significant in those studies whose results were adjusted for age, sex, ethnicity, obesity, diabetes, and other potential confounders. There was a positive graded association between the ultrasonographic severity of MASLD and urolithiasis. Meta-analysis of the single prospective cohort study showed that MAFLD was not associated with risk of developing incident urolithiasis (pooled random-effects hazard ratio 1.08, 95% CI 0.90-1.30), although a significant association was reported in men. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. This updated meta-analysis provides evidence for a significant association between MASLD and the presence of urolithiasis. Whether MASLD is associated with a higher risk of developing incident urolithiasis remains to be established.
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Urolitiasis , Humanos , Urolitiasis/complicaciones , Hígado Graso/complicaciones , Factores de Riesgo , Enfermedades Metabólicas/complicacionesRESUMEN
BACKGROUND AND AIMS: Sarcopenia is a common complication in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prevalence and its impact on the survival of sarcopenia in patients with MASLD is unknown. In this study, we aimed to assess the prevalence and effects of sarcopenia in patients with MASLD. METHODS: Systematic review and meta-analysis of full texts of relevant studies were searched from inception until June 12, 2024 in five databases (PubMed, Cochrane Library, Embase, Web of Science, and the China National Knowledge Infrastructure). Next, we assessed the prevalence of sarcopenia in MASLD, and calculated the ORs and HRs between sarcopenia and MASLD based on the adjusted data from individual studies. Statistical analyses were performed using Stata 11.0. RESULTS: Of the 2984 records considered, 29 studies recruiting 63,330 patients were included. The pooled prevalence of sarcopenia in patients with MASLD was 23.5% overall (95% CI; 19.1%-27.9%, I2 = 99.6%), and was higher in Asian patients, male, cross-sectional studies, when BIA were employed to measure muscle mass, one criterion of diagnosis sarcopenia, MASLD was diagnosed employing MRI, and moderate-quality studies. Sarcopenia was associated with MASLD patients (adjusted odds ratio [aOR] 2.08, 95% CI 1.58-2.74, I2 = 93.6%) with similar findings in subgroups stratified by age, study design, methods for measuring muscle mass, assessment method to detect sarcopenia, and study quality. The association between all-cause mortality further supports the association between sarcopenia and poor prognosis with MASLD (aHR 1.59, 95% CI 1.33-1.91, I2 = 0%). CONCLUSIONS: Sarcopenia was strongly associated with MASLD progression and was a risk factor not only for MASLD pathogenesis but was also markedly correlated with MASLD-associated mortality.
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Sarcopenia , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Humanos , Prevalencia , Masculino , Femenino , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Persona de Mediana Edad , Anciano , Factores de RiesgoRESUMEN
BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.
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Colesterol , Progresión de la Enfermedad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , China/epidemiología , Colesterol/sangre , Estudios Transversales , Pueblos del Este de Asia , Hígado Graso/sangre , Hígado Graso/complicaciones , Estudios LongitudinalesRESUMEN
Autophagy is an evolutionarily conserved process that plays a pivotal role in the maintenance of cellular homeostasis and its impairment has been implicated in the pathogenesis of various metabolic diseases including obesity, type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review synthesizes the current evidence from human studies on autophagy alterations under these metabolic conditions. In obesity, most data point to autophagy upregulation during the initiation phase of autophagosome formation, potentially in response to proinflammatory conditions in the adipose tissue. Autophagosome formation appears to be enhanced under hyperglycemic or insulin-resistant conditions in patients with T2D, possibly acting as a compensatory mechanism to eliminate damaged organelles and proteins. Other studies have proposed that prolonged hyperglycemia and disrupted insulin signaling hinder autophagic flux, resulting in the accumulation of dysfunctional cellular components that can contribute to ß-cell dysfunction. Evidence from patients with MASLD supports autophagy inhibition in disease progression. Nevertheless, given the available data, it is difficult to ascertain whether autophagy is enhanced or suppressed in these conditions because the levels of autophagy markers depend on the overall metabolism of specific organs, tissues, experimental conditions, or disease duration. Owing to these constraints, determining whether the observed shifts in autophagic activity precede or result from metabolic diseases remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more studies investigating autophagy impairment are required to gain a more comprehensive understanding of its role in the pathogenesis of obesity, T2D, and MASLD and to unveil novel therapeutic strategies for these conditions.
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Autofagia , Diabetes Mellitus Tipo 2 , Obesidad , Humanos , Autofagia/fisiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/metabolismo , Obesidad/complicaciones , Obesidad/fisiopatología , Obesidad/metabolismo , Hígado Graso/fisiopatología , Hígado Graso/complicacionesRESUMEN
BACKGROUND: Cleavage products from collagen formation and degradation hold potential as first-line biomarkers for the risk of advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we evaluated the performance of PRO-C3, PRO-C6, C4M, PRO-C18L, and the clinical score ADAPT (age, diabetes, PRO-C3, and platelet count) to detect patients with an LSM >8 kPa or >12 kPa in comparison to the Fibrosis-4 Index (FIB-4). METHODS: Serum from patients with MASLD (n = 269) from six Swedish University Hospitals was analyzed using enzyme-linked immunosorbent assay-based methods. Liver stiffness measurement (LSM) by vibration-controlled transient elastography was performed. The area under the curve (AUC), calibration curves, and net benefit analysis were used. RESULTS: An LSM >8 kPa was found in 108 (40.1%) patients. PRO-C3, PRO-C6, C4M, and PRO-C18L had AUCs ranging from 0.48 to 0.62. ADAPT had the highest AUC (0.73, 95% confidence interval [CI] = 0.67-0.79) to detect patients >8 kPa, compared to FIB-4 (0.71, (95%CI = 0.64-0.77, p = 0.35), and had a higher net benefit compared to FIB-4 from a probability threshold of 15%. FIB-4 and ADAPT performed equally well to detect patients with an LSM >12 kPa, AUC 0.76 versus 0.76, p = 0.93. CONCLUSIONS: ADAPT seems to be marginally better than FIB-4 in identifying patients with an LSM >8 kPa. However, the clinical utility of ADAPT as a first line test is uncertain, especially in low-risk populations. The overall performance of FIB-4 was similar to that of ADAPT in detecting patients with an LSM of >12 kPa. Altogether, the results suggest that ADAPT might be useful to detect earlier stages of fibrosis in MASLD, but that FIB-4 remains a first-line test for advanced fibrosis.
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Biomarcadores , Colágeno , Diagnóstico por Imagen de Elasticidad , Humanos , Biomarcadores/sangre , Masculino , Femenino , Persona de Mediana Edad , Colágeno/metabolismo , Hígado Graso/diagnóstico , Hígado Graso/diagnóstico por imagen , Hígado Graso/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Anciano , Hígado/diagnóstico por imagen , Hígado/patología , AdultoRESUMEN
BACKGROUND: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Humanos , Polimorfismo de Nucleótido Simple/genética , Masculino , Femenino , Herencia Multifactorial/genética , Factores de Riesgo , Persona de Mediana Edad , Hígado Graso/genética , Hígado Graso/complicaciones , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedades Metabólicas/genética , Enfermedades Metabólicas/complicaciones , Estudios de Cohortes , Estimación de Kaplan-Meier , Anciano , Modelos de Riesgos Proporcionales , Puntuación de Riesgo GenéticoRESUMEN
BACKGROUND: This study aimed to assess the frequency and intensity of anxious and depressive symptoms in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This is a descriptive and cross-sectional study, resulting from 106 patients from the Hepatology outpatient clinic at the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil without a history of alcohol abuse, verified by the alcohol use disorders identification test (AUDIT). These were assessed using the sociodemographic data sheet, Hospital Anxiety and Depression Scale (HADS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Scale (HAM-D). RESULTS: A total of 69.8% were women and 30.2% were men, with a mean age of 61 years. The majority (71.7%) discovered MASLD through routine exams, presenting as comorbidities: Type 2 diabetes mellitus (59.4%), Dyslipidemia (49.1%), Arterial hypertension (68.9%), Obesity (61.3%) and Metabolic syndrome [MetS (63.2%)]. The HADS scale indicates 34% probability of anxiety and 33% depressive symptoms. The Hamilton's scales of intensity indicates 63.9% severe anxiety and 54.3% severe depression. There is also a relationship between anxiety, depression and the female gender, as well as between depression and MetS. CONCLUSION: The findings point to the presence of anxiety and depression in more than one third of MASLD patients, most with severe symptoms. The group is concentrated in the elderly, with many comorbidities, including MetS. There was a positive correlation between anxiety, depression and being female; also, being significant between MetS and depression.
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Ansiedad , Depresión , Síndrome Metabólico , Humanos , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Depresión/etiología , Ansiedad/etiología , Ansiedad/epidemiología , Síndrome Metabólico/complicaciones , Síndrome Metabólico/psicología , Anciano , Adulto , Hígado Graso/complicaciones , Hígado Graso/psicología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Brasil/epidemiología , Factores SocioeconómicosRESUMEN
OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.
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Enfermedades Inflamatorias del Intestino , Síndrome Metabólico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Prevalencia , Adulto , Factores de Riesgo , Síndrome Metabólico/epidemiología , Síndrome Metabólico/complicaciones , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Centros de Atención Terciaria , Brasil/epidemiología , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Índice de Masa Corporal , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.