RESUMEN
The natural history of metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), is complex and long. A minority of patients develop inflammation and risk progressive fibrosis that can result in cirrhosis. Progression to cirrhosis occurs in 3-5% of patients and often takes more than 20 years. This narrative review presents an update on the natural history of MASLD, discussing studies and risk estimates for progression to severe outcomes, such as decompensated cirrhosis or hepatocellular carcinoma. We highlight the dynamic progression of liver damage, how to identify patients whose disease progresses over time, and how risk factors might be mitigated to reduce the risk for disease progression.
Asunto(s)
Progresión de la Enfermedad , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Factores de Riesgo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/complicaciones , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologíaRESUMEN
BACKGROUND: Frailty is associated with obesity-related comorbidities, but the relationship with nonalcoholic fatty liver disease (NAFLD) in people with HIV has been incompletely described. Our objective was to assess the associations between NAFLD and frailty. METHODS: Cross-sectional and longitudinal analysis of men in the Multicenter AIDS Cohort Study. NAFLD was defined as a liver/spleen ratio <1.0 on abdominal computed tomography scans; frailty was defined by the frailty phenotype as having 3 of the following: weakness, slowness, weight loss, exhaustion, and low physical activity. RESULTS: Men without (n = 200) and with HIV (n = 292) were included. NAFLD prevalence was 21% vs 16% and frailty 12% vs 17%, respectively. Among men with NAFLD, frailty was more prevalent in men without HIV (21% vs 11%). In multivariate analysis, NAFLD was significantly associated with frailty after controlling for significant variables. Men without HIV and NAFLD had 2.6 times higher probability [95% confidence interval (CI): 1.2- to 5.7] of frailty relative to men with neither HIV nor NAFLD. This association was not seen in men with HIV. The probability of frailty was higher among men without HIV with NAFLD (27% vs 10% in men without NAFLD) but lower among men with HIV with NAFLD (14% vs 19% in men without NAFLD). No significant relationships were found in longitudinal analyses. CONCLUSIONS: NAFLD was independently associated with frailty among men without HIV but not men with HIV, despite increased prevalence of frailty among men with HIV. The mechanisms of the muscle-liver-adipose tissue axis underlying NAFLD might differ by HIV serostatus.
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Fragilidad , Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Fragilidad/epidemiología , Persona de Mediana Edad , Estudios Transversales , Infecciones por VIH/complicaciones , Adulto , Estudios Longitudinales , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Prevalencia , Seropositividad para VIH/complicacionesRESUMEN
BACKGROUND AND AIM: Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients. PATIENTS AND METHODS: The study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3-F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves. RESULTS: The BAST score increased significantly with fibrosis progression from F1 to F3-F4. In differentiating advanced fibrosis (F2-F3) from mild/moderate fibrosis (F1-F2), the BAST score at cutoff ≤ - 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ - 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV. CONCLUSIONS: The BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Masculino , Femenino , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/patología , Diagnóstico por Imagen de Elasticidad/métodos , Adulto , Índice de Severidad de la Enfermedad , Curva ROC , AncianoRESUMEN
Background: The TyG index, or triglyceride-glucose index, is primarily used as a marker to assess insulin resistance and metabolic health. It increases mortality risk in patients with NAFLD, atherosclerosis, ischemic stroke, or heart failure. However, its association with Carotid Atherosclerosis (CAS) risk in NAFLD patients remains uncertain. Methods: This retrospective cohort study enrolled 739 individuals who participated comprehensive health evaluations at a large public hospital in Yangzhou, China, between January 2021 and December 2023. Among them, 436 were men and 303 were women, and their mean (SD) age was 51.53 ± 11.46 years. The individuals were categorized into three tertiles (Q1, Q2, and Q3), according to the baseline TyG index. Our investigation focused on exploring the correlativity between the TyG and the occurrence of CAS utilizing Cox regression and RCS analyses. Results: During a 3-year follow-up period, 199 patients developed CAS (cumulative incidence rate: 26.93%). A statistical model, adjusted for age, gender, BMI, and other confounders indicated that the HR (95%CI) values for CAS risk in the Q2 and Q3 groups were 3.11(1.87-5.17) and 4.51(2.69-7.56), respectively, with P-values <0.001 for both groups. A sensitivity analysis confirmed these results. Kaplan-Meier survival analysis revealed that CAS risk varied across the groups (P non-linear < 0.05). Conclusion: In individuals diagnosed as NAFLD, the possibility for CAS escalates with the elevation of the TyG value. Therefore, the TyG index is an effective marker for assessing the risk of CAS within this demographic. Large-sample prospective studies are needed to confirm this conclusion in the future.
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Glucemia , Enfermedades de las Arterias Carótidas , Enfermedad del Hígado Graso no Alcohólico , Triglicéridos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/epidemiología , Triglicéridos/sangre , Adulto , Factores de Riesgo , Glucemia/análisis , Glucemia/metabolismo , China/epidemiología , Resistencia a la Insulina , Estudios de Seguimiento , Incidencia , Estudios de Cohortes , Biomarcadores/sangreRESUMEN
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an important etiology of hepatocellular carcinoma (HCC), and there is no established therapy for this syndrome. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD(NET)) is an extremely rare syndrome considered to be life-threatening, with death occurring around 10 years of age. We present the oldest known autopsy case of this syndrome that developed HCC. This case provided important information on not only improving the course of this syndrome, but also understanding the natural history and therapeutic modalities of NASH and HCC. METHODS: The patient was diagnosed with ROHHAD(NET) syndrome in childhood, and liver cirrhosis due to NASH was diagnosed at age 17. HCC was detected at age 20, and embolization and irradiation were performed. At age 21, she died from accidental acute pancreatitis and subsequent liver failure and pulmonary hemorrhage. RESULTS: Rapid onset of obesity, hypoventilation, and hypothalamic disturbance appeared in childhood and was diagnosed as this syndrome. At age 17, liver cirrhosis due to NASH was diagnosed by liver biopsy, and at age 20, HCC was diagnosed by imaging. Transarterial chemoembolization and irradiation were performed, and the HCC was well controlled for a year. CONCLUSION: At age 21, she died from accidental acute pancreatitis, subsequent liver failure and pulmonary hemorrhage. Autopsy revealed that the HCC was mostly necrotized. This case was valuable not only for other ROHHAD(NET) syndrome cases, but also in improving our understanding of the natural history of NASH and HCC.
Asunto(s)
Autopsia , Carcinoma Hepatocelular , Enfermedades Hipotalámicas , Hipoventilación , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Femenino , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/terapia , Hipoventilación/etiología , Hipoventilación/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedades Hipotalámicas/complicaciones , Enfermedades Hipotalámicas/diagnóstico , Obesidad/complicaciones , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Resultado Fatal , Adulto Joven , Enfermedades del Sistema Nervioso Autónomo/etiología , SíndromeRESUMEN
BACKGROUND: Alcoholic steatohepatitis and nonalcoholic steatohepatitis-related liver cirrhosis (ASH/NASH-LC) are major causes of esophageal varices (EVs). However, the association between high visceral fat and exacerbation of EVs remains unclear. The aim of this study was to clarify the association of visceral fat and recurrence rate of EVs in ASH/NASH-LC and to identify independent predictors associated with recurrence. METHODS: We retrospectively evaluated data from 94 patients who underwent endoscopic injection sclerotherapy for EVs with ASH/NASH-LC. Using the receiver operating characteristic curve for the cut-off value of visceral fat index (VFI; 46.4 cm2/m2), we classified patients as having a high VFI (n = 53) or low VFI (n = 41). Propensity score matching was used to align for background factors, and the recurrence rate of EVs was compared between the two groups. Predictors associated with esophageal variceal recurrence were identified by multivariate analysis. The recurrence rate in patients with viral LC was also investigated. RESULTS: In the overall analysis, the recurrence rate was significantly higher in the high VFI group than in the low VFI group (P = 0.023). The recurrence rate was also higher in the high VFI group than in the low VFI group after propensity score matching, in which 19 patients were matched in each group (P = 0.048). VFI and Child-Pugh score were independently associated with recurrence. Recurrence rates were comparable between the two groups in viral LC patients. CONCLUSIONS: Worsening of variceal recurrence was observed in high visceral fat patients in ASH/NASH-LC but not in viral LC. Furthermore, high visceral fat was an independent predictor associated with variceal recurrence.
Asunto(s)
Várices Esofágicas y Gástricas , Grasa Intraabdominal , Cirrosis Hepática , Recurrencia , Humanos , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Cirrosis Hepática/complicaciones , Anciano , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Progresión de la EnfermedadRESUMEN
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters, including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV, are noninvasive markers of coronary microvascular circulation. The existing literature contains conflicting findings regarding these parameters in NAFLD patients. METHODS: A comprehensive systematic search was conducted on major electronic databases from inception until May 8, 2024, to identify relevant studies. We pooled the standardized mean differences (SMD) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at Pâ <â .05. RESULTS: Four studies with 1139 participants (226 with NAFLD and 913 as controls) were included. NAFLD was associated with a significantly lower CFRV (SMD: -0.77; 95% CI: -1.19, -0.36; Pâ <â .0002) and hyperemic DPFV (SMD: -0.73; 95% CI: -1.03, -0.44; Pâ <â .00001) than the controls. NAFLD demonstrated a statistically insignificant trend toward a reduction in baseline DPFV (SMD: -0.09; 95% CI: -0.38, 0.19; Pâ =â .52) compared to healthy controls. CONCLUSION: Patients with NAFLD are at a higher risk of coronary microvascular dysfunction, as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in patients with NAFLD provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions for impaired coronary flow reserve in subjects with NAFLD may lead to improvement in clinical outcomes.
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Enfermedad de la Arteria Coronaria , Enfermedad del Hígado Graso no Alcohólico , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Humanos , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/complicaciones , Circulación Coronaria/fisiología , Reserva del Flujo Fraccional Miocárdico/fisiología , Proyectos Piloto , Velocidad del Flujo Sanguíneo/fisiología , Microcirculación/fisiologíaRESUMEN
Type 2 diabetes mellitus (T2DM), often featuring hyperglycemia or insulin resistance, is a global health concern that is increasing in prevalence in the United States and worldwide. A common complication is metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of metabolic syndrome that is also rapidly increasing in prevalence. The majority of patients with T2DM will experience MASLD, and likewise, individuals with MASLD are at an increased risk for developing T2DM. These two disorders may act synergistically, in part due to increased lipotoxicity and inflammation within the liver, among other causes. However, the pathophysiological mechanisms by which this occurs are unclear, as is how the improvement of one disorder can ameliorate the other. This review aims to discuss the pathogenic interactions between T2D and MASLD, and will highlight novel therapeutic targets and ongoing clinical trials for the treatment of these diseases.
Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Animales , Síndrome Metabólico/metabolismo , Síndrome Metabólico/complicaciones , Resistencia a la Insulina , Hígado Graso/metabolismo , Hígado Graso/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: NASH is considered a contributor to atherosclerotic cardiovascular disease (ASCVD) risk; however, its contribution beyond traditional risk factors for CVD, particularly diabetes, is less clearly understood. This study aimed to quantify the cardiovascular-event risk associated with NASH, independent of diabetes status. METHODS: A cross-sectional analysis was conducted using the 2017-2020 NHANES pre-pandemic cycle. NASH was defined based on presence of steatosis without other causes of liver disease, and FibroScan+AST score from vibration-controlled transient elastography (VCTE). Significant fibrosis (stages F2-F4) was identified by liver stiffness measurement from VCTE. Predicted primary CV-event risk was estimated using both the Pooled Cohort Equations (PCE) and the Framingham Risk Score (FRS). NASH patients were matched with non-NASH controls on age, sex, race/ethnicity, and diabetes status. Weighted logistic regression was conducted, modeling elevated predicted CV risk (binary) as the dependent variable and indicators for NASH / fibrosis stages as independent variables. RESULTS: A sample of 125 NASH patients was matched with 2585 controls. NASH with significant fibrosis was associated with elevated predicted 10-year CV risk, although this association was only statistically significant in PCE analyses (odds ratio and 95% CI 2.34 [1.25, 4.36]). Analyses restricting to ages <65 years showed similar results, with associations of greater magnitude. CONCLUSION: Independent of diabetes, a significant association was observed between NASH with significant liver fibrosis and predicted primary CV-event risk in US adults, particularly for those <65. These findings suggest the importance of accounting for NASH and liver-fibrosis stage in predicting CV-event risk.
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Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Estados Unidos/epidemiología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Estudios de Casos y Controles , Anciano , Cirrosis Hepática/epidemiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). METHODS: Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. RESULTS: Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. CONCLUSIONS: This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD's adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.
Asunto(s)
Diabetes Mellitus Tipo 2 , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Disfunción Ventricular Izquierda , Función Ventricular Izquierda , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Anciano , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Volumen Sistólico , Adulto , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/etiología , Fenómenos BiomecánicosRESUMEN
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has significant genetic susceptibility. Adipocytokines play a crucial role in NAFLD development by participating in insulin resistance and hepatic steatosis. However, the association between adipocytokine pathway genes and NAFLD remains unclear. This study aims to explore the association of gene polymorphisms in the adipocytokine pathway and their interactions with NAFLD in obese children. METHODS: A case-control study was conducted, dividing obese children into NAFLD and control groups. Peripheral venous blood (2 mL) was collected from each participant for DNA extraction. A total of 14 single nucleotide polymorphisms (SNP) in the adipocytokine pathway were genotyped using multiplex PCR and high-throughput sequencing. Univariate and multivariate Logistic regression analyses were used to assess the association between SNP and NAFLD in obese children. Dominant models were used to analyze additive and multiplicative interactions via crossover analysis and Logistic regression. Generalized multifactor dimensionality reduction (GMDR) was used to detect gene-gene interactions among the 14 SNPs and their association with NAFLD in obese children. RESULTS: A total of 1 022 children were included, with 511 in the NAFLD group and 511 in the control group. After adjusting for age, gender, and BMI, multivariate Logistic regression showed that PPARG rs1801282 was associated with NAFLD in the obese children in 3 genetic models: heterozygote model (CG vs CC, OR=0.58, 95% CI 0.36 to 0.95, P=0.029), dominant model (GG+CG vs CC, OR=0.62, 95% CI 0.38 to 1.00, P=0.049), and overdominant model (CC+GG vs CG, OR=1.72, 95% CI 1.06 to 2.80, P=0.028). PRKAG2 rs12703159 was associated with NAFLD in 4 genetic models: heterozygous model (CT vs CC, OR=1.51, 95% CI 1.10 to 2.07, P=0.011), dominant model (CT+TT vs CC, OR=1.50, 95% CI 1.10 to 2.03, P=0.010), overdominant model (CC+TT vs CT, OR=0.67, 95% CI 0.49 to 0.92, P=0.012), and additive model (CC vs CT vs TT, OR=1.40, 95% CI 1.07 to 1.83, P=0.015). No significant multiplicative or additive interaction between PPARG rs1801282 and PRKAG2 rs12703159 was found in association with NAFLD. GMDR analysis, adjusted for age, gender, and BMI, revealed no statistically significant interactions among the 14 SNPs (all P>0.05). CONCLUSIONS: Mutations in PPARG rs1801282 and PRKAG2 rs12703159 are associated with NAFLD in obese children. However, no gene-gene interactions among the SNP are found to be associated with NAFLD in obese children.
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Adipoquinas , Predisposición Genética a la Enfermedad , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo de Nucleótido Simple , Humanos , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Niño , Estudios de Casos y Controles , Masculino , Femenino , Adipoquinas/genética , Adipoquinas/sangre , Obesidad/genética , Obesidad/complicaciones , PPAR gamma/genética , Adolescente , Obesidad Infantil/genética , Obesidad Infantil/complicacionesRESUMEN
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
BACKGROUND/AIMS: The relationship between neutrophil-to-lymphocyte ratio (NLR) and liver fibrosis in nonalcoholic fatty liver disease remains controversial. The aim of this study was to examine the association between NLR and liver fibrosis. MATERIALS AND METHODS: We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey. Vibration-controlled transient elastography was used to assess liver fibrosis and its severity. Neutrophil-to-lymphocyte ratio was calculated as the ratio of neutrophil count to lymphocyte count. RESULTS: This study included 1620 US adults with a mean age of 52.9 years, of which 53.3% were male. The obese population accounted for 62.5%, 68.5% had hypertension, 31.1% had diabetes, and 16% had significant liver fibrosis. After adjusting for all covariates, a positive correlation was observed between NLR and the severity of liver fibrosis (ß = 0.57, 95% CI = 0.22-0.92, P = .001), which remained stable across different subgroups. CONCLUSION: This study suggests that elevated NLR levels are positively correlated with the severity of liver fibrosis in patients with nonalcoholic fatty liver disease, and these results can be well generalized to the US adult population.
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Cirrosis Hepática , Linfocitos , Neutrófilos , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Índice de Severidad de la Enfermedad , Humanos , Masculino , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Femenino , Persona de Mediana Edad , Estudios Transversales , Cirrosis Hepática/sangre , Estados Unidos/epidemiología , Adulto , Recuento de Linfocitos , Recuento de Leucocitos , Diagnóstico por Imagen de Elasticidad , AncianoRESUMEN
BACKGROUND: Follistatin-like protein 1 (FSTL1) has been identified as a secreted glycoprotein that plays an important role in obesity. However, its role in children with metabolic-associated fatty liver disease (MAFLD) has not been investigated. This study aimed at characterizing the relationship between serum FSTL1 concentration and MAFLD in children with obesity. METHODS: A total of 121 subjects were recruited from the Second Affiliated Hospital of Xi'an Jiaotong University, including 45 obese children with MAFLD, 31 obese children without MAFLD, and 45 healthy controls. Anthropometric parameters, biochemical data were measured and circulating FSTL1 levels were detected by ELISA. RESULTS: The levels of FSTL1 in obese children with MAFLD were higher than that in obese children without MAFLD: 1.31 (0.35-2.29) ng/mL vs. 0.55 (0.36-1.38) ng/mL. Correlation analysis illustrated that FSTL1 was associated with nonesterified free fatty acid and leptin (r = 0.278, P < 0.05 and r = 0.572, P < 0.05, respectively). Binary logistic regression suggested that increased FSTL1 was a risk factor for MAFLD in children (OR = 1.105, 95% CI: 1.066-1.269, P < 0.05). CONCLUSIONS: Serum FSTL1 concentrations increase in obese children with MAFLD and may have the potential to be a risk factor for MAFLD in children with obesity.
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Biomarcadores , Proteínas Relacionadas con la Folistatina , Enfermedad del Hígado Graso no Alcohólico , Obesidad Infantil , Humanos , Proteínas Relacionadas con la Folistatina/sangre , Masculino , Femenino , Niño , Obesidad Infantil/sangre , Obesidad Infantil/complicaciones , Estudios de Casos y Controles , Biomarcadores/sangre , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Pronóstico , Adolescente , Estudios de Seguimiento , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Liver fatty acid-binding protein (LFABP) controls hepatocyte lipid metabolism and can be a biomarker in liver diseases. We compared the correlation of LFABP levels with liver histology in viral hepatitis and nonalcoholic fatty liver disease (NAFLD) and investigated the utility of serum LFABP as a biomarker for liver damage. MATERIALS AND METHODS: We included 142 patients (60 chronic viral hepatitis B [CHB], 35 chronic viral hepatitis C [CHC], 47 NAFLD) and 40 healthy controls. LFABP levels were determined in all participants, and a liver biopsy was performed on patients. The nonalcoholic steatohepatitis (NASH) activity score (NAS), hepatosteatosis, liver inflammation, and fibrosis were evaluated for NAFLD patients. Ishak's histological scores were used for viral hepatitis. The correlation between LFABP levels and histologic scores was assessed in each group. RESULTS: Serum LFABP levels in CHB, CHC, NAFLD, and control groups were 2.2, 3.5, 7.6, and 2.1 ng/mL, respectively. LFABP levels were significantly higher in the NAFLD group compared to the control, CHC, and CHB groups. LFABP was significantly higher in the NASH group than in nonalcoholic steatohepatitis, 8 ng/mL and 5.4 ng/mL, respectively (P = .001). In the NAFLD group, LFABP levels showed a moderate positive correlation with NAS score (r = 0.58, P <.001), ballooning degeneration (r = 0.67, P <.001), and lobular inflammation (r = 0.62, P <.001). A logistic regression study showed that the level of LFABP was predictive of NASH independent of age, gender, homeostasis model of IR, body mass index, aspartate aminotransferase, and alanine aminotransferase (OR = 1.869, P = .01). CONCLUSION: LFABP specifically correlates with liver histology in NAFLD compared to viral hepatitis. Additionally, it can distinguish NASH from simple steatosis. LFABP may be a valuable biomarker for hepatocyte injury in NASH.
Asunto(s)
Biomarcadores , Proteínas de Unión a Ácidos Grasos , Hepatitis C Crónica , Hígado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Biomarcadores/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Proteínas de Unión a Ácidos Grasos/sangre , Hígado/patología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/sangre , Estudios de Casos y Controles , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/sangre , Biopsia , Índice de Severidad de la EnfermedadRESUMEN
This awareness study aimed to determine the ultrasound (US) examination rates in relation to US-confirmed metabolic dysfunction-associated fatty liver disease (MAFLD) diagnosis in internal medicine outpatients with type 2 diabetes (T2D) across Türkiye. A total of 6283 T2D patients were included in this multicenter retrospective cohort study conducted at 17 internal medicine clinics across Türkiye. The presence and indications for US performed within the last 3 years were recorded along with US-confirmed MAFLD rates, laboratory findings on the day of US, and referral rates. Fibrosis-4 (FIB-4) index was calculated to estimate the risk of advanced liver fibrosis (FIB-4 index ≥ 1.3). Overall, 1731 (27.6%) of 6283 patients had US examination, which revealed MAFLD diagnosis in 69.9% of cases. In addition, 24.4% of patients with US-confirmed MAFLD were at risk of advanced fibrosis (FIB-4 index ≥ 1.3), and the referral rate was 15.5%. In conclusion, our findings emphasize an insufficient MAFLD awareness among clinicians and the likelihood of most of T2D patients to be at risk of living with an unknown status regarding their MAFLD and advanced fibrosis risk.
Asunto(s)
Diabetes Mellitus Tipo 2 , Medicina Interna , Cirrosis Hepática , Ultrasonografía , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/etiología , Turquía/epidemiología , Anciano , Enfermedad del Hígado Graso no Alcohólico/complicaciones , AdultoRESUMEN
OBJECTIVE: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD). METHODS: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model. RESULTS: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; Pâ <â 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; Pâ <â 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; Pâ <â 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect. CONCLUSION: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.
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Aterosclerosis , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Incidencia , Aterosclerosis/epidemiología , Factores de Riesgo , Anciano , Diabetes Mellitus/epidemiología , Modelos de Riesgos Proporcionales , Análisis de Mediación , Medición de Riesgo , Modelos Logísticos , AdultoRESUMEN
The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Here, we develop a mouse model (Streptozotocin with high-fat diet, STZ + HFD) that gradually develops fatty liver, metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. The hepatic transcriptomic features of STZ + HFD mice closely reflect those of patients with obesity accompanying type 2 diabetes mellitus, MASH, and MASLD-related HCC. Dietary changes and tirzepatide administration alleviate MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ + HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients is successfully established.
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Carcinoma Hepatocelular , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Masculino , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Ratones , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Humanos , Hígado/metabolismo , Hígado/patología , Hígado Graso/metabolismo , Hígado Graso/patología , Estreptozocina , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Transcriptoma , Obesidad/metabolismo , Obesidad/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with a paucity of available information about its impact on female sexual dysfunction (FSD). AIM: We aimed to study the association between NAFLD and FSD in Egyptian premenopausal women. METHODS: Sexually active married premenopausal women who visited our NAFLD outpatient screening clinic (2019 to 2022) were divided into NAFLD and non-NAFLD (control) groups based on liver ultrasound and fatty liver index data. All participants completed the Arabic Female Sexual Function Index (ArFSFI) questionnaire. The resulting data were used to calculate the domains and total scores. FSD is then graded as follows: no FSD (≥28.2), minimal (21.7-28.1), mild (14.5-21.6), moderate (7.3-14.4), and severe (≤7.2). OUTCOMES: We determined the proportions of patients and controls for whom ArFSFI scores indicated dissatisfaction with their sexual lives. RESULTS: Of 995 women participants whose FSFI scores were available, NAFLD was detected in 487 (48.9%) and absent in 508 (51.1%). The two groups were comparable in age, socioeconomic level, residence, and history of female genital cutting. The NAFLD patients had significantly much lower mean scores for the sexual arousal, lubrication, orgasm, satisfaction, and pain domains of the FSFI (P < .001 for all), while no statistical difference was noticed in the desire domain for NAFLD patients compared with the controls. NAFLD women had significantly lower mean total FSFI scores than the controls (mean [SD] 16.7 [6.8] vs 21.7 [5.1], respectively; P < .001) with higher rates of FSD (98.5% vs 82.1%; P < .001, respectively). Most NAFLD women had higher FSD grades than controls (%): no FSD (1.5, 17.9), minimal (20.6, 51.8), mild (42.5, 38.8), moderate (26.2, 9.4), and severe (10.7, none), respectively. CLINICAL IMPLICATIONS: Given the high prevalence of FSD in patients with NAFLD, greater attention to FSF could improve the quality of life in patients with NAFLD. STRENGTHS AND LIMITATIONS: This study was limited by the lack of testing of sex hormones and some other important factors that were not tested (eg, age, socioeconomic level, residence, and female genital cutting), as these characteristics were previously matched. Strengths of the study include the large study size, to our knowledge the largest to date to investigate the possible link between FSD and NAFLD in premenopausal women, together with the inclusion of the detailed version of the validated ArFSFI. CONCLUSIONS: In Egyptian premenopausal women, NAFLD could harm their sexual function.
Asunto(s)
Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Premenopausia , Disfunciones Sexuales Fisiológicas , Humanos , Femenino , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Egipto/epidemiología , Adulto , Síndrome Metabólico/epidemiología , Premenopausia/fisiología , Disfunciones Sexuales Fisiológicas/epidemiología , Encuestas y Cuestionarios , Disfunciones Sexuales Psicológicas/epidemiología , Persona de Mediana Edad , Estudios de Casos y ControlesRESUMEN
On March 14, 2024, after more than 25 years of intense research and a long series of failures, the Food and Drug Administration approved resmetirom as first drug for the treatment of non-alcoholic steatohepatitis (NASH) with fibrosis (now Metabolic-Associated Steatotic Liver Disease - MASLD). The present review covers this difficult process, finally providing a drug to complement lifestyle intervention, that has long been the sole approved therapeutic intervention. However, the availability of a drug shown to reduce disease progression in advanced stages of diseases opens a series of questions that deserve even more intense research. How to continue ongoing trials? How to generate an appropriate use of resmetirom in the community, limiting treatment according to predefined criteria and according to individual risk assessment? How to guarantee that both hepatic and non-hepatic comorbidities are appropriately targeted? How to define cost-effective strategies that might prevent the generation of unacceptable differences within the population, given the high costs of novel drugs and the extremely high numbers of candidates to treatment? Only a close surveillance of drug use in the real world, generated by insurance databases and national healthcare system registries, might provide adequate answers to these compelling questions.