RESUMEN
Background: In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. Methods: In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Conclusion: Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.
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Neoplasias Endometriales , Hiperglucemia , Hipertensión , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/epidemiología , Persona de Mediana Edad , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Anciano , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Metástasis Linfática , Pronóstico , Adulto , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/complicaciones , Estudios RetrospectivosRESUMEN
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
Metabolic-dysfunction associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is a growing global health concern with significant implications for oncogenesis. This review synthesizes current evidence on the association between MASLD and cancer risk, highlighting its role as a risk factor for both intrahepatic and extrahepatic malignancies. MASLD is increasingly recognized as a major cause of hepatocellular carcinoma (HCC), with its incidence rising in parallel with the prevalence of metabolic dysfunction. Furthermore, MASLD is associated with an elevated risk of various gastrointestinal cancers, including colorectal, esophageal, stomach, and pancreatic cancers. Beyond the digestive tract, evidence suggests that MASLD may also contribute to an increased risk of other cancers such as breast, prostate, thyroid, gynecological, renal and lung cancers. Understanding the mechanisms underlying these associations and the impact of MASLD on cancer risk is crucial for developing targeted screening and prevention strategies.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Factores de Riesgo , Neoplasias/metabolismo , Neoplasias/complicaciones , Neoplasias/epidemiología , Neoplasias/etiología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/etiología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/epidemiología , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/etiologíaRESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health problem owing to its high prevalence and associated morbidity and mortality secondary to progressive liver disease and cardiovascular events. Resmetirom, a selective thyroid hormone receptor-ß agonist has been developed as a therapeutic modality for MASLD. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of resmetirom compared to a placebo in the treatment of MASLD. Eligible studies were systematically identified by screening PubMed, Scopus, Web of Science, Cochrane library, Embase, and ClinicalTrials.gov from 2014 to 2024. Only randomized controlled trials comparing the efficacy and safety of resmetirom in the treatment of MASLD against placebo were included in the analysis. Meta-analysis was performed using RevMan 5.4 software. Four studies with low risk of bias and involving a total of 2359 participants were identified. The metanalysis included only three clinical trials with 2234 participants. A significant reduction in MRI-proton density fat fraction (MRI-PDFF) with 80 mg Resmetirom compared to that with placebo [SMD - 27.74 (95% CI - 32.05 to - 32.42), p < 0.00001] at 36-52 weeks as well as at 12-16 weeks [SMD - 30.92 (95% CI - 36.44 to - 25.40), p < 0.00001]. With Resmetirom 100 mg dose at 36-52 weeks [SMD - 36.05 (95% CI - 40.67 to - 31.43), p < 0.00001] and 12-16 weeks [SMD - 36.89 (95% CI - 40.73 to - 33.05), p < 0.00001] were observed. Resmetirom treatment was associated with a significant reduction in LDL-c triglyceride, lipoproteins. and liver enzymes. There was significant reduction FT4 and increase in SHBG and sex steroids with Resmetirom compared to placebo. There was no major difference in the overall treatment emergent adverse events at 80 mg [OR 1.55 (95% CI 0.84 to 2.87), and 100 mg [OR 1.13 (95% CI 0.78 to 1.63), doses of Resmetirom compared to placebo. However, gastrointestinal adverse events diarrhoea and nausea occurred in ≥ 10% in the Resmetirom group compared to placebo at < 12 week. Resmetirom treatment showed modest efficacy in treating MASLD with reduction in MRI-PDFF, LDL-c, triglyceride, lipoproteins, liver enzymes and NASH biomarkers without significant safety concerns. Larger and long-term RCTs may further confirm this promising outcomes of Resmetirom use in MASLD.
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Hígado Graso , Piridazinas , Receptores beta de Hormona Tiroidea , Humanos , Hígado Graso/tratamiento farmacológico , Hígado Graso/etiología , Hígado Graso/metabolismo , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/metabolismo , Piridazinas/administración & dosificación , Piridazinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores beta de Hormona Tiroidea/agonistas , Resultado del Tratamiento , Uracilo/administración & dosificación , Uracilo/efectos adversos , Uracilo/análogos & derivadosRESUMEN
Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan are unknown. Thus, we aimed to clarify these trends before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was thought to be largely attributable to an increase in that of the incidence of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusions: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.
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COVID-19 , Hígado Graso , Humanos , Persona de Mediana Edad , Masculino , Femenino , Japón/epidemiología , Prevalencia , Adulto , Anciano , Hígado Graso/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , SARS-CoV-2 , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/complicaciones , Pandemias , Factores de Riesgo , Síndrome Metabólico/epidemiologíaRESUMEN
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: 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
Excessive body weight may disrupt hepatic enzymes that may be aggravated by obesity-related comorbidities. The current case-control study was designed to evaluate the extent of liver enzyme alteration in obesity-related metabolic disorders. Obese females with BMI ≥ 30 suffering from metabolic disorders were grouped according to existing co-morbidity and their hepatic enzymes were compared with non-obese healthy females. The resultant data was subjected to analysis of variance and mean difference in liver enzymes were calculated at P = 0.05. Analysis of variance indicated that obese diabetic and obese hypertensive females had almost 96% and 67% increase in the concentration of gamma-glutamyl transferase than control, respectively (P<0.0001). The obese females suffering from diabetes and hypertension exhibited nearly 54% enhancement in alanine transaminase level (P<0.0001) and a 17% increase in aspartate aminotransferase concentration (P = 0.0028). Obesity along with infertility decline liver enzyme production and a 31% significant decline in aspartate aminotransferase was observed while other enzyme concentrations were not significantly altered. Regression analysis was performed on the resultant data to understand the association between liver enzyme alteration and the development of metabolic diseases. Regression analysis indicated that obese diabetic and obese diabetic hypertensive women had 20% production of normal liver enzymes and 80% enzymes produced abnormally. Obese hypertensive and obese infertile females had only 5% and 6% normal production of liver enzymes, respectively. This research leads to the conclusion that the ability of the liver to function normally is reduced in obesity-related diabetes and hypertension. This may be due to inflamed and injured liver and poses a serious threat to developing fatty liver disease and ultimately liver cirrhosis.
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Hígado , Enfermedades Metabólicas , Obesidad , Adulto , Femenino , Humanos , Persona de Mediana Edad , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Estudios de Casos y Controles , gamma-Glutamiltransferasa/sangre , Hipertensión/complicaciones , Hígado/enzimología , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/epidemiología , Obesidad/complicaciones , Análisis de Regresión , Personas del Sur de AsiaRESUMEN
Obesity and obesity-related complications, including various metabolic diseases and cancers, are significant health problems in developed and developing countries [...].
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Obesidad , Humanos , Obesidad/complicaciones , Obesidad/metabolismo , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/complicaciones , Neoplasias/etiología , Neoplasias/metabolismoRESUMEN
There is limited research on the relationship between Life's Essential 8 (LE8) score and metabolic dysfunction-associated steatotic liver disease (MASLD). Our aim is to investigate the relationship between overall lifestyle assessed by LE-8 score and MASLD in a nationally representative sample. We employed the LE8 score to comprehensively evaluate cardiovascular health, the assessment of MASLD primarily utilized the Fatty Liver Index. The weighted logistic regression models, restrictive cubic splines (RCS), subgroup analyses and the weighted quantile sum (WQS) regression were used to evaluate the relationship between the cardiovascular health and MASLD. Logistic regression models revealed that higher LE8 scores were associated with lower odds of having MASLD. The RCS revealed a significant nonlinear dose-response relationship between LE8 scores and MASLD. The WQS regression model indicated that blood glucose contributed the most to the risk of MASLD. The subgroup analysis indicates that there are significant differences in this association across age, educational level, and poverty income ratio. Our study suggests that an inverse correlation between LE8 and the risk of MASLD. Our findings underscore the utility of the LE8 algorithm in MASLD risk assessment and provide support for MASLD prevention through the promotion of healthy lifestyles.
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Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Hígado Graso/epidemiología , Estilo de Vida , Factores de Riesgo , Anciano , Estados Unidos/epidemiología , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/complicaciones , Medición de RiesgoRESUMEN
BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increased clinical attention. However, most of those current studies involve cross-sectional studies and meta-analyses, and experimental mechanistic exploration still needs to be improved. This study aimed to investigate the mechanisms by which H. pylori impacts MASLD. METHODS: We established two H. pylori-infected (Cag A positive and Cag A negative) mouse models with 16 weeks of chow diet (CD) or high-fat diet (HFD) feeding. Body weight, liver triglyceride, blood glucose, serum biochemical parameters, inflammatory factors, and insulin resistance were measured, and histological analysis of liver tissues was performed. Mouse livers were subjected to transcriptome RNA sequencing analysis. RESULTS: Although H. pylori infection could not significantly affect serum inflammatory factor levels and serum biochemical parameters in mice, serum insulin and homeostatic model assessment for insulin resistance levels increased in CD mode. In contrast, H. pylori Cag A + infection significantly aggravated hepatic pathological steatosis induced by HFD and elevated serum inflammatory factors and lipid metabolism parameters. Hepatic transcriptomic analysis in the CD groups revealed 767 differentially expressed genes (DEGs) in the H. pylori Cag A + infected group and 1473 DEGs in the H. pylori Cag A- infected group, and the "nonalcoholic fatty liver disease" pathway was significantly enriched in KEGG analysis. There were 578 DEGs in H. pylori Cag A + infection combined with the HFD feeding group and 820 DEGs in the H. pylori Cag A- infected group. DEGs in the HFD groups were significantly enriched in "fatty acid degradation" and "PPAR pathway." Exploring the effect of different Cag A statuses on mouse liver revealed that fatty acid binding protein 5 was differentially expressed in Cag A- H. pylori. DEG enrichment pathways were concentrated in the "PPAR pathway" and "fatty acid degradation." CONCLUSIONS: Clinicians are expected to comprehend the impact of H. pylori on MASLD and better understand and manage MASLD. H. pylori infection may exacerbate the development of MASLD by regulating hepatic lipid metabolism, and the H. pylori virulence factor Cag A plays a vital role in this regulation.
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Hígado Graso , Infecciones por Helicobacter , Helicobacter pylori , Metabolismo de los Lípidos , Ratones Endogámicos C57BL , Transcriptoma , Animales , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/metabolismo , Metabolismo de los Lípidos/genética , Transcriptoma/genética , Hígado Graso/complicaciones , Hígado Graso/microbiología , Hígado Graso/metabolismo , Hígado Graso/genética , Hígado Graso/patología , Masculino , Dieta Alta en Grasa , Hígado/metabolismo , Hígado/patología , Resistencia a la Insulina , Perfilación de la Expresión Génica , Ratones , Enfermedades Metabólicas/microbiología , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/genética , Redes y Vías Metabólicas/genéticaRESUMEN
Sarcopenia and cardiometabolic diseases have become important public health problems affecting the health and quality of life of the elderly. Reducing the incidence of sarcopenia is of positive significance for preventing and treating cardiometabolic diseases. This paper reviews the diagnostic criteria of sarcopenia in the elderly, the relationship between sarcopenia and cardiometabolic diseases, and the possible mechanisms. It provides support for the prevention and control of sarcopenia combined with cardiometabolic diseases.
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Enfermedades Cardiovasculares , Sarcopenia , Humanos , Sarcopenia/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/complicaciones , Calidad de VidaRESUMEN
BACKGROUND/AIM: To examine the relationship between the body surface area (BSA) and body composition in patients with metabolic dysfunction-associated steatotic liver disease (MASLD, 2,141 men and 986 women). MATERIALS AND METHODS: BSA and body composition parameters were examined. RESULTS: The median body mass index (BMI) was 25.0 kg/m2 for both men and women (p=0.7754). The median body surface area (BSA) was 1.854 m2 for men and 1.618 m2 for women (p<0.0001). In men, the median fat mass was 17.7 kg, whereas in women, it was 22.1 kg (p<0.0001). Additionally, the median fat-free mass was 55.4 kg in men and 39.3 kg in women (p<0.0001).). In male cases, BSA significantly correlated with fat mass (r=0.82, p<0.0001) and fat-free mass (r=0.95, p<0.0001). In female cases, BSA significantly correlated with fat mass (r=0.87, p<0.0001) and fat-free mass (r=0.94, p<0.0001). CONCLUSION: BSA could be a useful marker for the estimation of body composition in patients with MASLD.
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Composición Corporal , Índice de Masa Corporal , Superficie Corporal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Hígado Graso/metabolismo , Hígado Graso/patología , Hígado Graso/complicaciones , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/etiologíaRESUMEN
The worldwide epidemics of obesity, hypertriglyceridemia, dyslipidaemia, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic dysfunction-associated steatohepatitis (MASH) represent a major economic burden on healthcare systems. Patients with at-risk MASH, defined as MASH with moderate or significant fibrosis, are at higher risk of comorbidity/mortality, with a significant risk of cardiovascular diseases and/or major adverse liver outcomes. Despite a high unmet medical need, there is only one drug approved for MASH. Several drug candidates have reached the phase III development stage and could lead to several potential conditional drug approvals in the coming years. Within the armamentarium of future treatment options, FGF21 analogues hold an interesting position thanks to their pleiotropic effects in addition to their significant effect on both MASH resolution and fibrosis improvement. In this review, we summarise preclinical and clinical data from FGF21 analogues for MASH and explore additional potential therapeutic indications.
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Hígado Graso , Factores de Crecimiento de Fibroblastos , Animales , Humanos , Hígado Graso/tratamiento farmacológico , Hígado Graso/etiología , Hígado Graso/metabolismo , Factores de Crecimiento de Fibroblastos/agonistas , Factores de Crecimiento de Fibroblastos/metabolismo , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/tratamiento farmacológicoRESUMEN
Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that CMD is an independent predictor of cardiac morbidity and mortality in patients with obesity and metabolic disease. CMD is comprised of functional, structural, and mechanical impairments that synergize and ultimately reduce coronary blood flow in metabolic disease and in other co-morbid conditions, including transplant, autoimmune disorders, chemotherapy-induced cardiotoxicity, and remote injury-induced CMD. This review summarizes the contemporary state-of-the-field related to CMD in metabolic and these other co-morbid conditions based on mechanistic data derived mostly from preclinical small- and large-animal models in light of available clinical evidence and given the limitations of studying these mechanisms in humans. In addition, we also discuss gaps in current understanding, emerging areas of interest, and opportunities for future investigations in this field.
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Comorbilidad , Enfermedades Metabólicas , Humanos , Animales , Enfermedades Metabólicas/complicaciones , Enfermedades Metabólicas/epidemiología , Circulación Coronaria , Microvasos/patología , Microvasos/metabolismoRESUMEN
In recent years, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been steadily rising, emerging as a major chronic liver disease of global concern. The course of MASLD is varied, spanning from MASLD to metabolic dysfunction associated steatohepatitis (MASH). MASH is an important contributor to cirrhosis, which may subsequently lead to hepatocellular carcinoma. It has been found that PANoptosis, an emerging inflammatory programmed cell death (PCD), is involved in the pathogenesis of MASLD and facilitates the development of NASH, eventually resulting in inflammatory fibrosis and hepatocyte death. This paper reviews the latest research progress on PANoptosis and MASLD to understand the mechanism of MASLD and provide new directions for future treatment and drug development.
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Hígado Graso , Humanos , Hígado Graso/complicaciones , Hígado Graso/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Necroptosis , Enfermedades Metabólicas/complicacionesAsunto(s)
Hígado Graso , Humanos , Hígado Graso/diagnóstico , Hígado Graso/terapia , Hígado Graso/etiología , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/terapia , Enfermedades Metabólicas/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. METHODS: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage [F], lobular inflammation grade [LI], hepatocyte ballooning grade [HB], and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. RESULTS: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0-1 vs. F3: 0.22 [95% CI: 0.12-0.42]), LI1 versus LI2-3 (0.42 [0.19-0.97]), and HB1 versus HB2 (0.20 [0.08-0.50]). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0-1: 0.12 [0.05-0.25]), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. CONCLUSIONS: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.
Asunto(s)
Cirrosis Hepática , Hígado , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/patología , Hígado/patología , Adulto , Biopsia , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Anciano , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/complicaciones , Hígado Graso/patología , Enfermedades Cardiovasculares/etiologíaRESUMEN
BACKGROUND: Metabolic disorders and inflammatory bowel diseases (IBD) have captured the globe during Westernisation of lifestyle and related dietary habits over the last decades. Both disease entities are characterised by complex and heterogeneous clinical spectra linked to distinct symptoms and organ systems which, on a first glimpse, do not have many commonalities in clinical practice. However, experimental studies indicate a common backbone of inflammatory mechanisms in metabolic diseases and gut inflammation, and emerging clinical evidence suggests an intricate interplay between metabolic disorders and IBD. OBJECTIVE: We depict parallels of IBD and metabolic diseases, easily overlooked in clinical routine. DESIGN: We provide an overview of the recent literature and discuss implications of metabolic morbidity in patients with IBD for researchers, clinicians and healthcare providers. CONCLUSION: The Western lifestyle and diet and related gut microbial perturbation serve as a fuel for metabolic inflammation in and beyond the gut. Metabolic disorders and the metabolic syndrome increasingly affect patients with IBD, with an expected negative impact for both disease entities and risk for complications. This concept implies that tackling the obesity pandemic exerts beneficial effects beyond metabolic health.
Asunto(s)
Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Enfermedades Metabólicas , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Metabólicas/complicaciones , Microbioma Gastrointestinal/fisiología , Síndrome Metabólico/complicaciones , Estilo de Vida , Obesidad/complicacionesRESUMEN
Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.