No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Prevalence of and Risk Factors for Hepatic Steatosis in Northern Italy
Abstract
Background: Although hepatic steatosis is seen with increasing frequency in clinical practice, its prevalence and risk factors are unknown. Objective: To investigate the prevalence of and risk factors for hepatic steatosis, such as alcohol consumption and obesity. Design: Cross-sectional, observational study. Setting: Participants in the Dionysos Study. Patients: 257 participants assigned to one of four categories (67 controls, 66 obese persons, 69 heavy drinkers, and 55 obese heavy drinkers). Measurements: Ethanol intake, assessed by a validated questionnaire and expressed as daily (g/d) and lifetime (kg) consumption, and body mass, expressed as body mass index. Biochemical tests of liver and metabolic function and hepatic ultrasonography were done. Results: The prevalence of steatosis was increased in heavy drinkers (46.4% [95% Cl, 34% to 59%]) and obese persons (75.8% [CI, 63% to 85%]) compared with controls (16.4% [Cl, 8% to 25%]). Steatosis was found in 94.5% (Cl, 85% to 99%) of obese heavy drinkers. Compared with controls, the risk for steatosis was higher by 2.8-fold (Cl, 1.4-fold to 7.1-fold) in heavy drinkers, 4.6-fold (Cl, 2.5-fold to 11.0-fold) in obese persons, and 5.8-fold (Cl, 3.2-fold to 12.3-fold) in persons who were obese and drank heavily. In heavy drinkers, obesity increased the risk for steatosis by twofold (Cl, 1.5-fold to 3.0-fold) (P < 0.001), but heavy drinking was associated with only a 1.3-fold (Cl, 1.02-fold to 1.6-fold) increase in risk in obese persons (P = 0.0053). Elevated alanine aminotransferase and triglyceride levels are the most reliable markers of steatosis. Conclusions: Steatosis is frequently encountered in healthy persons and is almost always present in obese persons who drink more than 60 g of alcohol per day. Steatosis is more strongly associated with obesity than with heavy drinking, suggesting a greater role of overweight than alcohol consumption in accumulation of fat in the liver.
... 13.0% of patients with steatosis in our cohort had a lean BMI, lower than some other estimates of 16.7% and 25.3% 5,6 . Out of all lean patients, 13.0% had steatosis, slightly lower than estimates among nonobese patients from the Dionysos study, which was 16% 22 and slightly higher than others 6 . Differences in our results may come from our patient population and the method we used to detect steatosis, as some of the other studies used different ways of measuring hepatic steatosis on CT or other imaging techniques such as MRI and US. ...
... Using AI and non-invasive imaging would make it feasible to apply these techniques to a large cohort of patients. Although the number of individuals with lean steatosis in this study compared favorably with others in the literature 21,22 , it is acknowledged that there were comparatively fewer patients with lean steatosis compared to other groups such as overweight patients with or without steatosis. A potential future study combining data from multiple institutions may have even better statistical power for finding differences between groups. ...
The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m ² and hepatic steatosis with threshold SHAD ≥ − 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN . The cohort contained 8914 patients—lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.
... 26 26 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) 28 22 24 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) 20 (20)(21)(22)(23)(24)(25) CD4 to assess alcohol consumption in the past year. 11,12 AUDIT allows the quantification of alcohol intake as never, 1-2 standard drinks/day, 3-4 standard drinks/day or higher intake levels. ...
... 7,8 The synergistic interaction between the metabolic syndrome components and alcohol use is well established and increases the risk of severe liver disease. 35,36 The finding that the MetALD group had a higher rate of AF (9%) than MASLD (6%) lends support to that hypothesis. ...
Background
Metabolic dysfunction‐associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD.
Aims
To assess the effects of this new nomenclature on the prevalence and distribution of different SLD categories in people with HIV (PWH) and identified factors associated with MASLD and clinically significant fibrosis (CSF).
Methods
PWH were prospectively enrolled from 9 US centres and underwent clinical evaluation and vibration‐controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). SLD was defined as CAP ≥ 263 dB/m, CSF as LSM of ≥8 kPa, and advanced fibrosis (AF) as LSM ≥ 12 kPa. The prevalence of SLD, MASLD, metabolic dysfunction and alcohol‐associated liver disease (MetALD), ALD, cryptogenic (cSLD), CSF and AF were determined. Uni‐ and multivariate logistic regression models were used to assess factors associated with MASLD and CSF risk.
Results
Of 1065 participants, 74% were male, mean (SD) age 51.6 ± 11.9 years, 46% non‐Hispanic Black and 74% with undetectable HIV RNA. The prevalence of SLD was 52%, MASLD 39%, MetALD 10%, ALD 3%, CSF 15% and AF 4%. Only 0.6% had cSLD. Black race was protective whereas obesity, ALT and AST levels were associated with increased risk of MASLD and CSF in MASLD. HIV or antiretroviral therapy did not affect MASLD risk.
Conclusions
MASLD and MetALD are the dominant causes of SLD in PWH, affecting almost half. Application of the new nomenclature resulted in minimal change in the proportion of patients with MASLD who would have been diagnosed previously with NAFLD.
... Nonalcoholic fatty liver refers to fat accumulation (over 5%) in the liver cells due to alcohol consumption, hepatitis C, and drugs (1)(2)(3)(4)(5). NAFLD is classified into two groups, including nonalcoholic fatty liver and nonalcoholic steatohepatitis. ...
... The indications of biopsy conductance in NASH are: (1) in patients with an increased chance of disease progression, and biopsy should be repeated every five years in these patients; (2) high hepatic enzyme levels, which increases AST/ALT for three months (3,30); (3) metabolic syndrome, in which patients do not respond to the treatment for 6 months; (4) ruling out the other causes of chronic hepatic diseases (31, 32). ...
: Nonalcoholic fatty liver disease (NAFLD) refers to fat accumulation in hepatic cells due to alcohol consumption, hepatitis, and drugs. The prevalence of this disease has been reported at 20 - 50% in western and 12 - 13% in Latin countries. Patients who suffer from obesity, diabetes, and insulin resistance may be affected more than others. This disease is symptomless, and its paraclinical diagnosis is achievable by increasing the hepatic enzymes. Ultrasonography and fibroscan are some of the common diagnostic methods for this disease. The first treatment for this disease is weight loss and physical activities. Vitamin E can improve histopathological changes in terms of medications. While pioglitazone is an effective blood sugar-lowering drug, metformin has no role in treating diabetes or prediabetes.
... These alcohol intake thresholds, however, are impacted by factors such as liquor type, individual peculiarities, and the existence of metabolic risk factors. Surprisingly, individuals with metabolic risk factors tend to be more susceptible to hepatic steatosis compared to individuals who only consume alcohol (2). NAFLD, far from being a monolithic entity, manifests along a spectrum encompassing nonalcoholic fatty liver disease (NAFL), nonalcoholic steatohepatitis (NASH), and cirrhosis. ...
This literature review provides an in-depth analysis of nonalcoholic fatty liver disease (NAFLD), a common metabolic condition that affects a worldwide population. This review outlines the disease's scope, epidemiological trends, pathophysiology, noninvasive diagnostic criteria, and approaches. NAFLD presents as continuum of hepatic conditions ranging from mild steatosis to more serious illnesses such as nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. A combination of clinical examination, laboratory tests, and imaging methods are used to make a diagnosis, with a liver biopsy serving as the confirmed gold standard for both diagnosis and disease severity assessment. Because of the intricacy and multifaceted etiology of NAFLD, successful diagnosis, treatment, and prevention need a multidisciplinary approach.
... 71-42.49) of adults worldwide [1,13] and around 13% of children and adolescents [14]. This is linked to chronic liver disease, with its prevalence rising alongside obesity rates [15]. When left unmanaged, the disease will progress through various stages, such as steatosis, steatohepatitis, fibrosis/cirrhosis and hepatocellular carcinoma. ...
The prevalence and incidence of NAFLD is rising due to the obesity pandemic, caused by the widespread availability of ultra-processed foods and the decrease of physical activity. Factors such as socioeconomic status (SES), ethnicity and geographical location are associated with NAFLD, with lower SES correlating with higher incidence, particularly in regions like America or Europe. Beside the quality of food, the quantity also plays a crucial role. The World Health Organization (WHO) recommends a Mediterranean diet with a balanced energy intake. Since no hard medical treatment is available for NAFLD, lifestyle adjustments are key. Patient empowerment by providing relevant information and co-ownership of the therapy will increase the implementation rate and enhance the quality of medical follow-up and medication adherence, as studies report a good adherence to medication among patients who are well-aware of the severity of their disease. Regarding sustainability, patients with NAFLD have a high load of ambulatory follow-up, which, since the COVID-19 pandemic, can be partially provided by teleconsulting. Both patients’ lifestyle modifications and healthcare practitioners’ therapeutical strategy can decrease the carbon footprint.
... Liver disease remains a significant global burden with regard to mortality rates and associated costs. The disease's high morbidity and mortality levels contribute to its continued impact on global health [1]. It is becoming a major concern in terms of global public health. ...
The global burden of liver disease is enormous, which highlights the need for effective hepatoprotective agents. It was reported that allicin exhibits protective effects against a range of diseases. In this study, we further evaluated allicin’s effect and mechanism in acute hepatic injury. Liver injury in mice was induced by intraperitoneal injection with 1% CCl4 (10 mL/kg/day). When the first dose was given, CCl4 was given immediately after administration of different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day), and then different doses of allicin (40, 20, and 10 mg/kg/day) as well as compound glycyrrhizin (CGI, 80 mg/kg/day) were administrated every 12 h. The animals were dissected 24 h after the first administration. The findings demonstrated a significant inhibition of CCl4-induced acute liver injury following allicin treatment. This inhibition was evidenced by notable reductions in serum levels of transaminases, specifically aspartate transaminase, along with mitigated histological damage to the liver. In this protective process, allicin plays the role of reducing the amounts or the expression levels of proinflammatory cytokines, IL-1β, IL-6. Furthermore, allicin recovered the activities of the antioxidant enzyme catalase (CAT) and reduced the production of malondialdehyde (MDA) in a dose-dependent manner, and also reduced liver Caspase 3, Caspase 8, and BAX to inhibit liver cell apoptosis. Further analysis showed that the administration of allicin inhibited the increased protein levels of Nuclear factor-erythroid 2-related factor 2 (Nrf2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), which is related to inflammation and oxidative stress. The in vitro study of the LPS-induced RAW264.7 inflammatory cell model confirmed that allicin can inhibit important inflammation-related factors and alleviate inflammation. This research firstly clarified that allicin has a significant protective effect on CCl4-induced liver injury via inhibiting the inflammatory response and hepatocyte apoptosis, alleviating oxidative stress associated with the progress of liver damage, highlighting the potential of allicin as a hepatoprotective agent.
... Endocrines 2024, 5 167 NASH progression links metabolic dysfunctions such as insulin resistance, obesity, and dyslipidemia, which exacerbate liver damage [8,9]. Central to these disorders is insulin resistance, a hallmark of metabolic syndrome intricately linked to NASH pathogenesis [10]. ...
Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet.
... Among the numerous adverse consequences of obesity, an important correlation has been established between its degree and the incidence and severity of MAFLD. In fact, obesity has been found to increase the likelihood of developing MAFLD by 4.6 times (22). The natural course of MAFLD indicates that fibrosis manifests in around 32-37% of patients within 3-6 years, and approximately 12% of patients tend to progress to cirrhosis over 8-10 years (23). ...
Introduction
Roux-en-Y gastric bypass surgery can effectively improve steatosis, necroinflammatory activity, and hepatic fibrosis in individuals diagnosed with morbid obesity or nonalcoholic steatohepatitis (NASH). Common methods such as body mass index (BMI) to evaluate the postoperative effect of clinical bariatric surgery cannot differentiate subcutaneous fats from visceral fats and muscles. Several Quantitative ultrasound (QUS)–based approaches have been developed to quantify hepatic steatosis. QUS techniques (tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI)) from radio frequency (RF) data analysis as a means for the detection and grading of hepatic steatosis has been posited as an objective and noninvasive approach. The implementation and standardization of QUS techniques (TAI, TSI) in assessing hepatic steatosis quantitatively after bariatric surgery is of high-priority. Our study is aimed to assess hepatic steatosis with QUS techniques (TAI, TSI) in morbidly obese individuals before and after bariatric surgery, and to compare with anthropometric measurements, laboratory assessments and other imaging methods.
Methods and analysis
The present investigation, a self-discipline examination of navigational capacity devoid of visual cues, is designed as a single-site, forward-looking evaluation of efficacy with the imprimatur of the institutional review board. The duration of the study has been provisionally determined to span from 1 January 2023 through 31 December 2025. Our cohort shall encompass one hundred participants, who was scheduled to undergo Roux-en-Y gastric bypass (RYGB) at Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All patients will undergo anthropometric measurements, blood-based biochemical analyses, ultrasonic examination and magnetic resonance imaging proton density fat fraction (MRI-PDFF). The primary endpoint is the analysis of evaluating the efficacy of QUS techniques assessing hepatic steatosis compared to other methods before and after bariatric surgery.
Results
Prior to the fomal study, we recruited 21 obese Chinese participants who received ultrasonic examination (TAI, TSI) and MRI-PDFF. AC-TAI showed moderate correlations with MRI-PDFF (adjusted r = 0.632; P < 0.05). For MRI-PDFF ≥10%, SC-TSI showed moderate correlations with MRI-PDFF (adjusted r = 0.677; P < 0.05).
Conclusion
Our pre-experiment results signified that using QUS techniques for postoperative evaluation of bariatric surgery is promising. QUS techniques will be signed a widespread availability, real-time functionality, and low-cost approach for assessing hepatic steatosis before and after bariatric surgery in obese individuals, thus is capable for subsequent scale-up liver fat quantification.
Ethics and dissemination
The present research endeavor has been bestowed with the imprimatur of the Ethics Committee of the Hospital, as indicated by its Approval Number: 2023-KY-015. In due course, upon completion of the study, we intend to disseminate our findings by publishing them in a suitable academic journal, thereby facilitating their widespread utilization.
Registration
The trial is duly registered with the Chinese Clinical Trial Registry, and with a unique Trial Registration Number, ChiCTR2300069892, approved on March 28, 2023.
... Metabolic-associated fatty liver disease (MAFLD) refers to a range of conditions that are characterised by hepatic fat accumulation [1] and is the leading cause of chronic liver disease, affecting 25% of the global population [2]. MAFLD is strongly associated with obesity; it affects 75% of patients with a body mass index (BMI) > 30 kg/m 2 compared to 16% of individuals with a normal BMI [3]. MAFLD ranges from simple steatosis, which is the intrahepatic accumulation of lipids, to its more serious stage, metabolic-associated steatohepatitis (MASH), which manifests as steatosis concurrent with inflammation, oxidative stress, and fibrosis in the liver [4]. ...
Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance (p < 0.001) and hepatic expression of markers of inflammation (p < 0.001), oxidative stress (p < 0.05), and fibrosis (p < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.
... El diagnóstico de NAFLD requiere la exclusión tanto de causas secundarias de hepatopatía, como la exclusión de un consumo de alcohol mayor de 30 g para hombres y de 20 g para mujeres 5 . Consumos de alcohol superiores a estos límites indican enfermedad hepática alcohólica; pero pese a no tener un consumo superior a los límites marcados, ingestas menores pueden predisponer a padecer NAFLD si presentara factores de riesgo metabólicos 6 . De esta forma, deben descartarse otras causas de enfermedades concurrentes 7 (Tabla 1). ...
A pesar de que la acumulación de grasa en el hígado es común, la mayoría de las personas con NAFLD no experimenta síntomas, pero un subconjunto desarrolla una forma más grave de la enfermedad conocida como esteatohepatitis no alcohólica (NASH). Existen varios sistemas de clasificación utilizados en la práctica clínica. La clasificación más comúnmente utilizada es la del American Association for the Study of Liver Diseases (AASLD), que se basa en la histología hepática y divide la enfermedad en cuatro estadios: esteatosis simple, NASH sin fibrosis, NASH con fibrosis y cirrosis. Comienza con el acumulo de grasa en el hígado que puede progresar a una inflamación crónica (NASH), fibrosis y, finalmente, cirrosis, insuficiencia hepática y cáncer de hígado. Varios estudios experimentales han demostrado que los hígados esteatósicos presentan un riesgo del 25 % de progresar por sí mismos a NASH con y sin fibrosis. Este riesgo se ve sustancialmente aumentado por la concomitancia de factores de riesgo metabólicos. La diabetes, el aumento de peso, la hipertensión, la menopausia y los polimorfismos genéticos son los principales factores de riesgo para la progresión de la NAFLD. Un tercio de los pacientes con esteatosis simple y NASH, presenta progresión de la fibrosis, pero un 20 % aproximado presenta regresión de la misma. La fibrosis hepática es el único predictor mayor independiente de mortalidad.
... Consumption of alcohol is not uncommon in individuals with MASLD, and it also seems to increase the risk of incident steatosis in individuals with presumed MASLD [47,48] , with an almost direct dose-response relationship between alcohol consumption and hepatic steatosis [49] . As mentioned, the gold standard for excluding patients with excessive alcohol consumption (i.e., disqualifying them from a MASLD diagnosis) is self-reported alcohol consumption. ...
Hepatic steatosis is caused by exaggerated hepatic lipid accumulation and is a common histological and radiological finding. Non-alcoholic fatty liver disease (NAFLD), or metabolic dysfunction associated steatotic liver disease (MASLD), is highly associated with metabolic syndrome and represents the most common cause of hepatic steatosis. However, since several comorbidities, lifestyle factors, and drugs can cause hepatic steatosis, MASLD is, to some extent, a diagnosis of exclusion. Nevertheless, initiatives have been taken to encompass positive (instead of negative) criteria for diagnosis - such as the presence of cardiometabolic risk factors together with hepatic steatosis. Nonetheless, before confirming a patient with MASLD, it is essential to map and evaluate other causes of fatty liver disease or steatotic liver disease. Several causes of hepatic steatosis have been identified in studies; however, the study cohorts are scarce and often anecdotal. Additionally, many studies have shown correlation without proving causation, and many are retrospective without reporting relevant patient characteristics and comorbidities - making it difficult to draw conclusions regarding the underlying etiology or present comorbidity of hepatic steatosis. In this narrative review, we aimed to identify and summarize present studies evaluating the impact of the most common and often suggested causes of hepatic steatosis.
... In this setting, intracellular activation of interferon regulatory factor 3 (IRF3) [149] and stimulation of interferon gene protein (STING) triggers TANK-binding kinase (TBK) and activates mitochondrial apoptotic mechanisms in hepatocytes. This phenomenon will lead to a wound-healing response, and a marked fibrotic response will be developed, progressing to cirrhosis in the most severe cases [145,150,151]. ...
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and its incidence has been increasing in recent years because of the high prevalence of obesity and metabolic syndrome in the Western population. Alcohol-related liver disease (ArLD) is the most common cause of cirrhosis and constitutes the leading cause of cirrhosis-related deaths worldwide. Both NAFLD and ArLD constitute well-known causes of liver damage, with some similarities in their pathophysiology. For this reason, they can lead to the progression of liver disease, being responsible for a high proportion of liver-related events and liver-related deaths. Whether ArLD impacts the prognosis and progression of liver damage in patients with NAFLD is still a matter of debate. Nowadays, the synergistic deleterious effect of obesity and diabetes is clearly established in patients with ArLD and heavy alcohol consumption. However, it is still unknown whether low to moderate amounts of alcohol are good or bad for liver health. The measurement and identification of the possible synergistic deleterious effect of alcohol consumption in the assessment of patients with NAFLD is crucial for clinicians, since early intervention, advising abstinence and controlling cardiovascular risk factors would improve the prognosis of patients with both comorbidities. This article seeks to perform a comprehensive review of the pathophysiology of both disorders and measure the impact of alcohol consumption in patients with NAFLD.
... Patients with fatty liver disease frequently exhibit metabolic syndrome characteristics, such as overweight, insulin resistance, and atherogenic dyslipidemia that are characterized by elevated plasma triglyceride concentrations. Research indicates that the prevalence of NAFLD among obese patients is as high as 80%, compared to 16% in individuals with a normal body mass index and no metabolic risk factors [18,19]. Dyslipidemia in patients with FLD is primarily characterized by hypertriglyceridemia due to large very-low-density lipoprotein particles, increased levels of small and dense low-density lipoprotein particles, and reduced high-density cholesterol levels [20,21]. ...
Background:
Fatty liver disease (FLD) is an important risk factor for liver cancer and cardiovascular disease and can lead to significant social and economic burden. However, there is currently no nationwide epidemiological survey for FLD in China, making early FLD screening crucial for the Chinese population. Unfortunately, liver biopsy and abdominal ultrasound, the preferred methods for FLD diagnosis, are not practical for primary medical institutions. Therefore, the aim of this study was to develop machine learning (ML) models for screening individuals at high risk of FLD, and to provide a new perspective on early FLD diagnosis.
Methods:
This study included a total of 30,574 individuals between the ages of 18 and 70 who completed abdominal ultrasound and the related clinical examinations. Among them, 3474 individuals were diagnosed with FLD by abdominal ultrasound. We used 11 indicators to build eight classification models to predict FLD. The model prediction ability was evaluated by the area under the curve, sensitivity, specificity, positive predictive value, negative predictive value, and kappa value. Feature importance analysis was assessed by Shapley value or root mean square error loss after permutations.
Results:
Among the eight ML models, the prediction accuracy of the extreme gradient boosting (XGBoost) model was highest at 89.77%. By feature importance analysis, we found that the body mass index, triglyceride, and alanine aminotransferase play important roles in FLD prediction.
Conclusion:
XGBoost improves the efficiency and cost of large-scale FLD screening.
... Furthermore, obesity is strongly linked with respiratory symptoms and diseases, including exertional dyspnea, obstructive sleep apnea syndrome (OSAS), obesity hypoventilation syndrome (OHS), chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism, and aspiration pneumonia [7]. On the other hand, obesity and its related conditions, especially type 2 diabetes and hypertriglyceridemia, are major contributors to the current epidemic of Non-Alcoholic Fatty Liver Disease (NAFLD) [8]. Non-Alcoholic Steatohepatitis (NASH) is the accumulation of fat in hepatocytes which causes inflammation, cell death, and fibrous scarring resulting in the disruption of the normal hepatic architecture and hepatic dysfunction. ...
Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients’ individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.
... NAFLD is among the most common liver diseases and is the most common cause of chronic liver disease. NAFLD reported a prevalence as high as 80% in obese patients in comparison to 16% in those reporting a normal BMI and without metabolic risk factors [218][219][220]. The most defining feature of NAFLD is steatosis. ...
Nicotine usage by mothers throughout pregnancy has been observed to relate to numerous deleterious effects in children, especially relating to obesity. Children who have prenatally been exposed to nicotine tend to have lower birth weights, with an elevated risk of becoming overweight throughout development and into their adolescent and adult life. There are numerous theories as to how this occurs: catch-up growth theory, thrifty phenotype theory, neurotransmitter or endocrine imbalances theory, and a more recent examination on the genetic factors relating to obesity risk. In addition to the negative effect on bodyweight and BMI, individuals with obesity may also suffer from numerous comorbidities involving metabolic disease. These may include type 1 and 2 diabetes, high cholesterol levels, and liver disease. Predisposition for obesity with nicotine usage may also be associated with genetic risk alleles for obesity, such as the DRD2 A1 variant. This is important for prenatally nicotine-exposed individuals as an opportunity to provide early prevention and intervention of obesity-related risks.
Background
Nonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The present study aimed to investigate the prevalence, characteristics, and risk factors of NAFLD in the Mashhad Persian Cohort Study population.
Method
The present population-based cross-sectional study included all PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences (POCM), Mashhad, Iran by census sampling method. Eligible participants were divided into two groups due to their NAFLD condition (NAFLD positive or NAFLD negative). All enrolled participants were evaluated based on their clinical aspects, anthropometric measures, laboratory tests, and ultrasound features. Statistical analysis was conducted using SPSS software version 16 (SPSS Inc., Chicago, USA –version 16). A P-value less than 0.05 was considered as the significance level.
Results
A total of 1198 individuals were included in the study, of which 638 (53.3%) were male and the rest were female. The mean age of the participants was 46.89 ± 8.98 years. A total of 246 patients (20.53%) were NAFLD positive, of which 122 (49.59%) were in grade 1, 112 (45.52%) were in grade 2, and 12 (4.87%) were in grade 3. The prevalence of fatty liver was significantly higher in males than in females (p < 0.001). There were significant differences between NAFLD positive and NAFLD negative participants in terms of having a history of hypertension (P = 0.044), body mass index (P < 0.001), body fat percentage (P = 0.001), waist circumference (P < 0.001), liver craniocaudal length (P = 0.012), fasting blood sugar (FBS) (P = 0.047), aspartate aminotransferase (AST) (P = 0.007), and alanine aminotransferase (ALT) (P = 0.001). Further analysis revealed a strong significant association between BMI, previous history of hypertension, higher levels of serum ALT, and NAFLD (P < 0.05).
Conclusion
It can be concluded that ultrasound findings accompanied by laboratory AST and ALT level enzymes could be a cost-benefit approach for NAFLD early diagnosis. The craniocaudal size of the liver could be a beneficent marker for estimating the severity of the disease; however, more studies are recommended to evaluate this variable for future practice against the issue.
У роботі аналізуються причини та механізми розвитку запалення в тканинах органів людини при ожирінні (жировій дистрофії). Показано, що відкладання нейтральних жирів (тригліцеридів) в клітинах призводить до механічного пошкодження їх органел, в першу чергу мембран лізосом, з виходом гідролітичних (протеолітичних) ферментів в цитоплазму, розвитком некрозу клітин та запалення в мезенхімі.
Background
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) showed great value in treating nonalcoholic fatty liver disease (NAFLD). We aimed to compare the effectiveness of long-acting and short-acting GLP-1RAs on improving body weight and related metabolic parameters in patients with type 2 diabetes (T2DM) as a reference for the treatment of NAFLD with T2DM.
Methods
We searched eligible randomized controlled trials (RCTs) in PubMed, Embase, Cochrane and web of science database until August 2023. The risk of bias of included RCTs were assessed by the Risk Assessment of Cochrane Review items. We mainly drew forest plots to compare the effects of long and short acting GLP-1 RAs using RevMan 5.4.
Results
Twelve RCTs involving 2751 patients were included in our meta-analysis. Compared with short-acting GLP-1 RAs, the long-acting group was better in body weight (P < .00001, MD = −0.65, 95% confidence interval [CI] [−0.90, −0.40], I² = 20%), and the same results in glycosylated hemoglobin (HbA1c) (P < .00001, MD = −0.43, 95% CI [−0.54, −0.33], I² = 55%) and fasting plasma glucose (FPG) (P < .00001, MD = −0.77, 95% CI [−1.01, −0.52], I² =70%). For the lipid parameters, long-acting drugs lowered cholesterol (TC) (P = .02, SMD = −0.19, 95% CI [−0.35, −0.03], I² =57%) and low-density lipoprotein (LDL) (P = .02, SMD = −0.17, 95% CI [−0.33, −0.02], I² =51%) more significantly compared with short-acting drugs. But treatment differences were not significant in triglycerides (TG) (P = .40, SMD = −0.05, 95% CI [−0.15, −0.06], I² = 0%), and high-density lipoprotein (HDL) (P = .85, SMD = −0.01, 95% CI [−0.11, −0.09], I² = 0%).
Conclusion
Long-acting GLP-1RAs may be more promise than short-acting GLP-1RAs in improving weight and related metabolic parameters.
Introduction:
Increasingly, research groups have been studying the association of serum vitamin D and metabolic health indicators, especially in patients with obesity. We compared the serum 25-hydroxy Vitamin D [25(OH)D] concentrations in children and adolescents who had obesity and hepatosteatosis with children and adolescents who had obesity without hepatosteatosis, and investigate the relationship between serum 25(OH)D concentrations and severity of hepatosteatosis. We also aimed to assess the effect of vitamin D treatment after 6 months on hepatosteatosis and liver biochemistry.
Methods:
One hundred thirty-three patients with obesity (body mass index (BMI) > +2 standard deviations (SD) for their age and gender) and vitamin D deficiency [serum 25(OH)D < 12 ng/ml] were recruited. Anthropometric measurements, biochemical parameters [serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25(OH)D, glucose and insulin concentrations] and ultrasonographic findings of hepatosteatosis were recorded before and six months after Vitamin D treatment. Chi-square, Student's t tests and multivariate analysis were performed.
Results:
Grade 1, 2 and 3 hepatosteatosis at baseline was present in 51 (38.4%) , 43 (32.3%) and 10 (7.5%) subjects respectively. Mean (± SD) serum 25(OH)D concentrations were significantly lower in those with hepatosteatosis (8.4 ± 2.4 ng/ml) compared with those without hepatosteatosis (9.9 ± 2.4 ng/ml, P < 0.005). Multivariable logistic regression analysis showed serum 25(OH)D concentration was the independent predictor for hepatosteatosis (P < 0.005), whereas age, sex, weight SD, BMI SD and HOMA-IR were not (P > 0.05). There was no significant difference in BMI SD, HOMA-IR and liver enzymes between subjects with and without hepatosteatosis (P > 0.05). Despite improvement in serum 25(OH)D concentrations at 6 months post-treatment (34.7 ± 10.6 ng/ml vs. 8.7 ± 2.4 ng/ml; p < 0.0001), there was no significant difference in the proportion of patients with different severity of hepatosteatosis as compared to before treatment (p = 0.88).
Conclusion:
Serum 25(OH)D concentrations were lower in children and adolescents with obesity and hepatic steatosis as compared to those without hepatic steatosis, with an inverse association between the severity of hepatosteatosis and serum 25(OH)D concentrations. Vitamin D treatment in children and adolescents with obesity and hypovitaminosis D did not improve severity of hepatic steatosis on ultrasonography at 6 months.
MicroRNA-29a (miR-29a) is a well characterized fibro-inflammatory molecule and its aberrant expression is linked to a variety of pathological liver conditions. The long-term effects of a high-fat diet (HFD) in combination with different levels of EtOH consumption on miR-29a expression and liver pathobiology are unknown. Mice at 8 weeks of age were divided into five groups (calorie-matched diet plus water (CMD) as a control group, HFD plus water (HFD) as a liver disease group, HFD plus 2% EtOH (HFD + 2% E), HFD + 10% E, and HFD + 20% E as intervention groups) and fed for 4, 13, 26, or 39 weeks. At each time point, analyses were performed for liver weight/body weight (BW) ratio, AST/ALT ratio, as well as liver histology assessments, which included inflammation, estimated fat deposition, lipid area, and fibrosis. Hepatic miR-29a was measured and correlations with phenotypic traits were determined. Four-week feeding produced no differences between the groups on all collected phenotypic traits or miR-29a expression, while significant effects were observed after 13 weeks, with EtOH concentration-specific induction of miR-29a. A turning point for most of the collected traits was apparent at 26 weeks, and miR-29a was significantly down-regulated with increasing liver injury. Overall, miR-29a up-regulation was associated with a lower liver/BW ratio, fat deposition, inflammation, and fibrosis, suggesting a protective role of miR-29a against liver disease progression. A HFD plus increasing concentrations of EtOH produces progressive adverse effects on the liver, with no evidence of beneficial effects of low-dose EtOH consumption. Moreover, miR-29a up-regulation is associated with less severe liver injury.
Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach.
The most prevalent chronic liver disease is nonalcoholic fatty liver disease (NAFLD), being associated with the epidemics of obesity and metabolic syndrome (MetS). The prognosis of NAFLD varies; however, it can be relatively predicted based on the presence or absence of histological liver injury. The NAFLD spectrum includes simple steatosis, also known as nonalcoholic fatty liver (NAFL); steatosis with necro-inflammatory changes, known as nonalcoholic steatohepatitis (NASH); NASH-related cirrhosis; and hepatocellular cancer. The most significant histological predictor of hepatic and non-hepatic related mortality, according to recently available data, is liver fibrosis rather than NASH per se. Several risk factors were found to influence the progression of NAFLD including MetS and its components, as well as genetics and environmental factors. Beyond the liver, where cardiovascular disease and cancer are two additional significant mortality causes, NAFLD is crucial for overall survival.KeywordsNonalcoholic fatty liver disease (NAFLD)Metabolic dysfunction-associated fatty liver disease (MAFLD)Natural historyHepatic fibrosisLiver cirrhosis
Nonalcoholic fatty liver disease (NAFLD) is a major health problem, representing one of the most common chronic liver diseases worldwide with an increasing prevalence, concomitant with the rise in the prevalence of obesity and diabetes mellitus. Presence of another concomitant liver disease can have synergistic and bidirectional implications aggravating the progression of steatohepatitis to advanced liver fibrosis and hepatocellular carcinoma.Other causes of hereditary/autoimmune liver and metabolic diseases, HCV infection, and drugs may underlie, mimic, or aggravate NAFLD, and these are described in this chapter.NAFLD and alcoholic liver disease are complex multifactorial disorders that share a number of pathophysiologic and clinical characteristics that very often coincide. The major drivers of ALD and NAFLD are the damaging effects of excess alcohol consumption and insulin resistance secondary to metabolic syndrome and obesity, respectively. However, the distinction between the two entities is often difficult.Diagnosing the presence of a dual etiology of liver disease in the subgroup of patients with NAFLD should lead to a multidisciplinary approach for targeted therapy as well as prophylactic measures.KeywordsSteatosisFatty liverFibrosisMultidisciplinary approach
The prevalence of obesity and metabolic consequences, including non-alcoholic fatty liver disease (NAFLD) has become a global health problem. Obesity has an important impact on chronic liver disease even beyond NAFLD, as it accelerates the progression of alcohol liver disease. Conversely, even moderate alcohol use can affect NAFLD disease severity. Weight loss is the gold standard treatment but adherence to lifestyle changes is very low in the clinical setting. Bariatric surgery can improve metabolic components and cause long-term weight loss. Therefore, bariatric surgery could serve as an attractive treatment option for NAFLD patients. A pitfall is the use of alcohol after bariatric surgery. This short review integrates data about the influence of obesity and alcohol on liver function and the role of bariatric surgery.
Background:
Obstructive sleep apnea (OSA) is closely associated with non-alcoholic fatty liver disease (NAFLD). The current definition of NAFLD cannot exclude the involvement of alcohol consumption in the development of fatty liver disease (FLD), but alcohol can aggravate OSA and participate in steatosis. There is limited evidence on the relationship between OSA and alcohol and its effect on FLD severity.
Objective:
To determine the effect of OSA on FLD severity based on ordinal responses, and its relationship with alcohol consumption, in order to develop strategies for the prevention and treatment of FLD.
Methods:
Patients with chief complaints of "snoring" who underwent polysomnography and abdominal ultrasound between January 2015 and October 2022 were selected. A total of 325 cases were divided into three groups according to abdominal ultrasound results: no FLD (n = 66), mild FLD (n = 116), and moderately severe FLD (n = 143) group. Patients were also categorized into alcoholic and nonalcoholic groups. Univariate analysis was used to examine the correlation between OSA and FLD severity. Multivariate ordinal logistic regression analysis was further used to identify the determinants of FLD severity and differences between the alcoholic and nonalcoholic groups.
Results:
A higher proportion of moderately severe FLD was observed in the group with an apnea/hypopnea index (AHI) > 30 compared to the AHI<15 group in all participants and in the nonalcoholic population (all p < 0.05). There was no significant difference among these groups in the alcoholic population. Ordinal logistic regression analysis found that in all participants, age [OR = 0.966(0.947-0.986)], BMI [OR = 1.293 (1.205-1.394)], diabetes mellitus [OR = 1.932(1.132-3.343)], hyperlipidemia [OR = 2.432(1.355-4.464)], severe OSA [OR = 2.36(1.315-4.259)] (all p < 0.05) were the independent risk factors for more severe FLD. However, different risk factors applied according to alcohol consumption. In addition to age and BMI, the independent risk factors for the alcoholic group also included diabetes mellitus [OR = 3.323(1.494-7.834)] while in the non-alcoholic group risk factors included hyperlipidemia [OR = 4.094(1.639-11.137)], and severe OSA[OR = 2.956(1.334-6.664)] (all p < 0.05).
Conclusion:
Severe OSA is an independent determinant for developing more severe NAFLD in nonalcoholic population, and alcohol consumption may obscure the effect of OSA on the progression of FLD.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which can progress from simple steatosis to advanced cirrhosis and hepatocellular carcinoma. Clinical diagnosis of NAFLD is crucial in the early stages of the disease. The main aim of this study was to apply machine learning (ML) methods to identify significant classifiers of NAFLD using body composition and anthropometric variables. A cross-sectional study was carried out among 513 individuals aged 13 years old or above in Iran. Anthropometric and body composition measurements were performed manually using body composition analyzer InBody 270. Hepatic steatosis and fibrosis were determined using a Fibroscan. ML methods including k-Nearest Neighbor (kNN), Support Vector Machine (SVM), Radial Basis Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN), Adaboost and Naïve Bayes were examined for model performance and to identify anthropometric and body composition predictors of fatty liver disease. RF generated the most accurate model for fatty liver (presence of any stage), steatosis stages and fibrosis stages with 82%, 52% and 57% accuracy, respectively. Abdomen circumference, waist circumference, chest circumference, trunk fat and body mass index were among the most important variables contributing to fatty liver disease. ML-based prediction of NAFLD using anthropometric and body composition data can assist clinicians in decision making. ML-based systems provide opportunities for NAFLD screening and early diagnosis, especially in population-level and remote areas.
Although the association of nonalcoholic fatty liver disease (NAFLD) with obesity or sarcopenia is known, few studies have investigated the combined effect of various body composition parameters on the risk of NAFLD. Thus, the aim of this study was to evaluate effects of interactions between various body composition parameters, including obesity, visceral adiposity, and sarcopenia, on NAFLD. Data of subjects who underwent health checkups between 2010 and December 2020 were retrospectively analyzed. Body composition parameters including appendicular skeletal muscle mass (ASM) and visceral adiposity were assessed using bioelectrical impedance analysis. Sarcopenia was defined as ASM/weight beyond two standard deviations below the gender-specific mean for healthy young adults. NAFLD was diagnosed using hepatic ultrasonography. Interaction analyses, including relative excess risk due to interaction (RERI), synergy index (SI), and attributable proportion due to interaction (AP), were performed. Among a total of 17,540 subjects (mean age: 46.7 years, 49.4% males), the prevalence of NAFLD was 35.9%. The odds ratio (OR) of interaction between obesity and visceral adiposity affecting NAFLD was 9.14 (95% CI: 8.29–10.07). The RERI was 2.63 (95% CI: 1.71–3.55), SI was 1.48 (95% CI: 1.29–1.69) and AP was 29%. The OR of interaction between obesity and sarcopenia affecting NAFLD was 8.46 (95% CI: 7.01–10.21). The RERI was 2.21 (95% CI: 0.51–3.90). SI was 1.42(95% CI: 1.11–1.82) and AP was 26%. The OR of interaction between sarcopenia and visceral adiposity affecting NAFLD was 7.25 (95% CI: 6.04–8.71), however, there was no significant additive interaction with RERI = 0.87 (95% CI: −0.76 to 2.51). Obesity, visceral adiposity, and sarcopenia were found to be positively associated with NAFLD. Obesity, visceral adiposity, and sarcopenia were found to have additive interaction effects on NAFLD.
Background and aims:
NAFLD is one of the fast-growing health problems that affects up to 25% of people worldwide. Numerous miRNAs have been clarified as important regulators of liver pathophysiology, including NAFLD. Thus, we investigated the expression of the MiRNA-34a and MiRNA-192 as diagnostic markers for NAFLD.
Patients and methods:
Blood samples were collected from NAFLD cases and healthy controls. The expression profile of both studied miRNAs was detected via real-time PCR analysis.
Results:
The present study showed that both studied miRNAs were upregulated in NAFLD patients compared to controls. Interestingly, miRNA-34a and MiRNA-192 are upregulated in NAFLD patients with early fibrosis compared to controls [with a fold change of 4.02 ± 11.49 (P = 0.05) and 18.43 ± 47.8 (P = 0.017), respectively]. However, miRNA-34a is downregulated in NAFLD patients with advanced fibrosis compared to controls, with fold expression of 0.65 ± 1.17 (P = 0.831). The area under the receiver operating characteristics (AUROC) for miRNA-34a and miRNA-192 were 0.790 and 0.643, respectively; furthermore, the sensitivities and specificities were 76.7%, 100% for miRNA-34a and 63.3%, and 93.3% for miRNA-192 (P < 0.05). Additionally, MiRNA34a was positively correlated with hypertension and fasting blood sugar, and it also was negatively correlated with hemoglobin level and total leucocyte count (P < 0.05).
Conclusion:
The results obtained indicated that both studied miRNAs could potentially be used as diagnostic biomarkers for the early stage of liver fibrosis in NAFLD cases. Also, miRNA-34a was positively correlated with metabolic disorders associated with NAFLD such as hypertension and diabetes. However, their expression showed no association with advanced fibrosis. Thus, larger cohorts are necessitated to certify the utility of serum MiRNA-34a and MiRNA-192 in monitoring the deterioration of NAFLD.
Background:
Adipose tissue thermogenic activities use fatty acids from lipolysis for heat generation. Therefore, a tight coupling between lipolysis and thermogenesis is physiologically imperative in maintaining not only body temperature but also lipids homeostasis. Adipose tissue dysfunction contributes to alcoholic liver disease (ALD). Here, studies were conducted to examine how alcohol intake affects adipose tissue thermogenic activities and whether altered adipose tissue thermogenesis contributes to ALD.
Methods:
Both the Lieber-DeCarli and the NIAAA mouse models of ALD were used. Denervation surgery in epididymal fat pads was performed. CL316,243, a selective β3-adrenoceptor agonist, SR59230A, a selective β3 adrenoceptor (ADRB3) antagonist, and rapamycin, a selective mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, were administrated through i.p. injection. Adipocyte-specific Prdm16 knockout mice were subjected to alcohol-containing diet chronically.
Results:
Chronic alcohol consumption, which enhances adipose tissue lipolysis, inhibits thermogenic activities of beige adipocytes in inguinal white adipose tissue (WAT), leading to an uncoupling status between lipolysis and thermogenesis in WAT at both basal and ADRB3 stimulation states. CL316,243 administration exacerbates liver pathologies of ALD. Alcohol intake inhibits mTORC1 activities in WAT. In mice, mTORC1 inhibition by rapamycin inhibits the thermogenesis of iWAT, whereas enhancing WAT lipolysis. Further investigations using adipocyte-specific Prdm16 knockout mice revealed that functional deficiency of beige adipocytes aggravates liver pathologies of ALD, suggesting that the inhibitory effect of alcohol on WAT browning/thermogenesis contributes to ALD pathogenesis.
Conclusion:
Chronic alcohol consumption induces an "uncoupling status" between lipolysis and browning/thermogenesis in WAT by inhibiting mTORC1 activation. Diminished WAT browning/thermogenesis, concomitant with enhanced lipolysis, contributes to ALD pathogenesis.
Background:
Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear.
Methods:
Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed.
Results:
A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05; 95%CI 1.94-2.16) and diabetes (OR 4.68; 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78; 95%CI 0.62-0.97). In patients with HSI>36, being female (OR 7.33; 95%CI 1.34-40), age (OR 1.22; 95%CI 1.11-1.34), body mass index (OR 1.35; 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk.
Conclusion:
NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.
Population-based data regarding the prognostic implication of gamma-glutamyl transferase (GGT) have been inconsistent. We examined the association of GGT with all-cause and disease-specific mortality. Using the Korean nationwide database, we included 9,687,066 subjects without viral hepatitis or cirrhosis who underwent a health examination in 2009. Subjects were classified into three groups by sex-specific tertile of serum GGT levels. The underlying causes of death were classified by 10th Revision of the International Classification of Diseases codes. During the median follow-up period of 8.3 years, 460,699 deaths were identified. All-cause mortality increased as serum GGT levels became higher (hazard ratio [HR], 95% confidence interval [CI] 1.05, 1.04–1.05 in the middle tertile, and 1.33, 1.32–1.34 in the high tertile) compared to the low tertile of serum GGT levels. Similar trends were observed for cardiovascular disease (CVD) (HR, 95% CI 1.07, 1.05–1.09 in the middle tertile, 1.29, 1.26–1.31 in the high tertile), cancer (HR, 95% CI 1.08, 1.07–1.10 in the middle tertile, 1.38, 1.36–1.39 in the high tertile), respiratory disease (HR, 95% CI 1.10, 1.08–1.13 in the middle tertile, 1.39, 1.35–1.43 in the high tertile), and liver disease mortality (HR, 95% CI 1.74, 1.66–1.83 in the middle tertile, 6.73, 6.46–7.01 in the high tertile). Regardless of smoking, alcohol consumption and history of previous CVD and cancer, a higher serum GGT levels were associated with a higher risk of mortality. Serum GGT levels may be useful for risk assessment of all-cause and disease-specific mortality in general population.
Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014–2020) who were classified according to their body mass index (BMI) as normal (BMI < 25 kg/m2, n = 38), overweight (25 ≤ BMI < 30 kg/m2, n = 68), and obese (BMI ≥ 30 kg/m2, n = 57). VCTE and MRE detected fibrosis of stages ≥ 2, ≥ 3, and 4 with an area under the receiver operating curve (AUROC) of 0.83–0.94 (VCTE) and 0.85–0.95 (MRE) in all groups, without considerable differences. MRI-PDFF detected steatosis of grades ≥ 2 and 3 with high AUROC in all groups (0.81–1.00). CAP’s diagnostic ability (0.63–0.95) was lower than that of MRI-PDFF and decreased with increasing BMI compared to MRI-PDFF. VCTE and MRE similarly accurately assess fibrosis, although MRI-PDFF is more accurate than CAP in detecting steatosis in overweight and obese patients with NAFLD.
Quantitative magnetic resonance imaging (MRI) techniques are emerging as non-invasive alternatives to biopsy for assessment of diffuse liver diseases of iron overload, steatosis and fibrosis. For testing and validating the accuracy of these techniques, phantoms are often used as stand-ins to human tissue to mimic diffuse liver pathologies. However, currently, there is no standardization in the preparation of MRI-based liver phantoms for mimicking iron overload, steatosis, fibrosis or a combination of these pathologies as various sizes and types of materials are used to mimic the same liver disease. Liver phantoms that mimic specific MR features of diffuse liver diseases observed in vivo are important for testing and calibrating new MRI techniques and for evaluating signal models to accurately quantify these features. In this study, we review the liver morphology associated with these diffuse diseases, discuss the quantitative MR techniques for assessing these liver pathologies, and comprehensively examine published liver phantom studies and discuss their benefits and limitations.
Fatty liver disease (steatosis) is considered a risk factor in donor liver transplantation (LT). Macrosteatosis (>50%) is associated with primary graft dysfunction and may reduce long-term recipient survival.
Objective: to identify predictors of macrovesicular steatosis (>50%) by analyzing donor characteristics.
Materials and methods. The retrospective study included 525 potential liver donors between January 1, 2019 and December 31, 2020. Clinical and morphological characteristics of donors were studied using logistic regression and receiver operating characteristic (ROC) analysis. Threshold values of parameters demonstrating statistical significance in multivariate analysis as predictors of >50% hepatic steatosis were obtained by ROC analysis based on calculation of the optimal cutoff point.
Results. Diabetes mellitus (DM), cause of donor’s death (traumatic brain injury), alanine transaminase (ALT) >90 units/L and aspartate transaminase (AST) >110 units/L were predictors of >50% steatosis, revealed by time-zero biopsy in the donor. Almost identical sensitivity and specificity indicators were determined in ROC analysis for liver enzymes – ALT and AST – which were 69.1 and 80.6; 72.2 and 81.1, respectively. Given the obtained values, we can say that with elevated levels of liver enzymes in the donor’s blood, there is a high degree of probability of liver parenchymal damage, but low sensitivity indicates possible multifactoriality of liver damage, and fatty liver disease may be one of the factors, but there may also be no damage to the liver parenchyma. At the same time, the rather high specificity revealed in ROC analysis for liver enzymes is a reliable sign of the absence of fatty liver disease at enzyme values less than the threshold.
Conclusion. The thresholds established for ALT and AST and their corresponding levels of sensitivity and specificity indicate that these parameters have a relatively low predictive level in the context of the presence of severe fatty liver disease in a donor. This allows, nevertheless, to use models built on their basis as screening models in the primary evaluation of liver donors.
Background:
Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults.
Methods:
This cross-sectional study included data from 33,216 Spanish adult workers (18-65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression.
Results:
The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3-28.5%) for men and 6.8% (95% CI 6.4-7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses.
Conclusions:
Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.
Background: The polymorphism associated with liver fat content, which is well-known as PNPLA3 rs738409 (Patatin-like phospholipase domain-containing protein 3), is one of the critical subjects widely investigated in the literature regarding the prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide. The present research aimed to study the bioinformatics investigations of this polymorphism together with the in vitro analyses among patients with NAFLD. Materials and Methods: In this case-control study, after performing bioinformatics analysis, the laboratory examination was performed in several steps. Genomic DNA was extracted from the blood of 53 NAFLD patients and 107 subjects with normal liver ultrasounds. PNPLA3 rs738409 was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The laboratory test results, including fasting blood sugar, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase were collected from medical records. Finally, statistical analysis was performed using SPSS software, version 18.0. Results: The frequency of the G allele was 56% and 36% among patients and in the control group, respectively. The frequency of genotypes was 35.8% and 47.7% (CC), 17% and 31.8% (CG), 47.2% and 20.6% (GG) in patients and control groups, respectively. The adjusted odds ratios for PNPLA3 rs738409 C>G were 3.0 (95% confidence interval [CI]: 1.28-6.98, P=.011) and 0.68 (95% CI: 0.25- 1.83, P = .44) for GG and CG genotypes, respectively. Conclusion: The findings showed the association between the GG genotype and the presence of NAFLD. Furthermore, the bioinformatics findings suggested the probable risk of the disease incidence regarding the change of hydropathic characteristics resulting from the amino acid substitution.
The growing obesity epidemic in the US poses a threat to individuals and the healthcare system beyond the immediate impacts evidenced by the association of obesity with multiple comorbidities. This chapter explores the pathogenesis of obesity, focusing on the effect of chronic low-grade inflammation in individuals with obesity. Given this underlying inflammatory state, obesity can both directly cause certain gastrointestinal diseases but also predispose to other gastrointestinal dysfunction through changes in immune regulatory processes. Interventions to reduce the burden of obesity include further discussion of medical and nonmedical management.
Non-alcoholic fatty liver disease (NAFLD) is an important health threat that is strongly linked to components of metabolic syndrome, particularly the low-grade inflammatory changes. Significantly, several of the available anti-diabetic drug classes demonstrate a considerable anti-inflammatory effect, and hence might be of benefit for NAFLD patients. In this study, we used a rat model of diet-induced NAFLD to examine the potential effect of metformin, pioglitazone, dapagliflozin and their combinations on NAFLD manifestations. Rats were fed an atherogenic diet containing 1.25 % cholesterol, 0.5 % cholic acid and 60 % cocoa butter for 6 weeks causing a number of metabolic and hepatic alterations including insulin resistance, dyslipidemia, systemic inflammation, increased hepatic oxidative stress and lipid peroxidation, hepatic steatosis, lobular inflammation, as well as increased markers of liver inflammation and hepatocyte apoptosis. Drug treatment, which started at the third week of NAFLD induction and continued for three weeks, not only ameliorated the observed metabolic impairment, but also functional and structural manifestations of NAFLD. Specifically, anti-diabetic drug treatment reversed markers of systemic and hepatic inflammation, oxidative stress, hepatic fibrosis, and hepatocyte apoptosis. Our findings propose that anti-diabetic drugs with a potential anti-inflammatory effect can ameliorate the manifestations of NAFLD, and thus might provide a therapeutic option for such a condition that is closely associated with metabolic diseases. The detailed pharmacology of these classes in aspects linked to the observed impact on NAFLD requires to be further investigated and translated into clinical studies for tailored therapy specifically targeting NAFLD.
Nonalcoholic fatty liver disease (NAFLD) is entering a new era in terms of diagnosis and conceptualization. The term NAFLD is considered to not reflect current knowledge. Metabolic dysfunction-associated fatty liver disease (MAFLD) has been suggested as a more appropriate overarching term by experts in this field. Regarding NAFLD progression, most patients die from non-liver-related diseases, even patients with advanced fibrosis. Liver biopsy is essential for the diagnosis of nonalcoholic steatohepatitis (NASH); it is the only procedure that reliably differentiates NAFLD from NASH. Recently, various noninvasive methods for diagnosing steatosis and fibrosis have been developed. Ultrasound attenuation measurements and proton density fat fraction with magnetic resonance imaging (MRI) have been developed as imaging tools for predicting steatosis. Fibrosis-4 index and NAFLD fibrosis score are complex scores for predicting fibrosis in patients with NAFLD. In addition, elastography based on ultrasound and MRI has been developed as an imaging tool for predicting fibrosis. There is a strong correlation between values from various real-time shear wave elastography devices and transient elastography, which is the gold standard for ultrasound-based measurements of liver stiffness. In conclusion, NAFLD is at a turning point in terms of its conceptualization, terminology, and diagnostics. It is now time to reconfirm the role of ultrasonography for the assessment of NAFLD.
Studies characterizing Nonalcoholic Fatty Liver Disease (NAFLD) are limited in Oman. This study aims to assess the prevalence of NAFLD in obese Omani patients and find its relationship with other obesity-related medical conditions. Fifty-five adult obese patients were evaluated via medical history, clinical examination, and laboratory tests. Patients with any possible risk of liver injury were excluded. Diagnosis of NAFLD relied on ultrasonography criteria. Data were entered and analyzed in SPSS (version 22). The prevalence of NAFLD was calculated using frequency and percentages. Out of the total patient population, 37 (67.3%) have had NAFLD. Most of the patients (81%) were below 50 years of age. Systolic hypertension was present in 45.9%, while diastolic hypertension was present in 43.2%. AST and ALT levels were significantly increased (p<0.001) in most patients; 81.1% and 73%, respectively. Fasting blood sugar (FBS) and glycosylated hemoglobin (HbA1c) levels were higher in NAFLD patients (p<0.01). Mean levels of LDL, uric acid, and total cholesterol were significantly higher in the NAFLD patients (p<0.01). In conclusion, NAFLD and related metabolic complications are prevalent in obese Omani individuals. Keywords. NAFLD, Obesity, Oman
Non-alcoholic fatty liver disease (NAFLD) is common, affecting approximately 25% of the general population. The evidence base for the investigation and management of NAFLD is large and growing, but there is currently little practical guidance to support development of services and delivery of care. To address this, we produced a series of evidence-based quality standard recommendations for the management of NAFLD, with the aim of improving patient care. A multidisciplinary group of experts from the British Association for the Study of the Liver and British Society of Gastroenterology NAFLD Special Interest Group produced the recommendations, which cover: management of people with, or at risk of, NAFLD before the gastroenterology or liver clinic; assessment and investigations in secondary care; and management in secondary care. The quality of evidence for each recommendation was evaluated by the Grading of Recommendation Assessment, Development and Evaluation tool. An anonymous modified Delphi voting process was conducted individually by each member of the group to assess the level of agreement with each statement. Statements were included when agreement was 80% or greater. From the final list of statements, a smaller number of auditable key performance indicators were selected to allow services to benchmark their practice. It is hoped that services will review their practice against our recommendations and key performance indicators and institute service development where needed to improve the care of patients with NAFLD.
This article reviews hepatic fibrosis‐associated histopathology of aged cadavers (mean age 82 years). A study of 68 livers identified steatosis in 35.5%, central vein fibrosis in 49.2%, perisinusoidal fibrosis in 63.2%, portal tract fibrosis in 47.7%, septa formation in 44.1%, bridging fibrosis in 30.8%, and cirrhosis in 4.4% of the samples as well as one hepatocellular carcinoma and six metastatic tumors. Other studies have revealed that collagens I, III, IV, V, and VI and fibronectin constitute the matrices of fibrous central veins, perisinusoidal space, portal tracts, and septa. Elastin is rich in portal tracts and fibrous septa but absent from the perisinusoidal space. Hepatic stellate cells are ubiquitous in the liver parenchyma while myofibroblasts localize in fibrotic foci. Factor VIII‐related antigen expression signals sinusoidal to systemic vascular endothelium transformation while collagen IV and laminin codistribution indicates formation of perisinusoidal membranes. Their coincidence reflects focalized capillarization of sinusoids in the aged liver. In response to fibrogenesis, hepatic progenitor cells residing in the canal of Hering in the periportal parenchyma undergo expansion and migration deep into the lobule. Concomitantly, intermediate hepatocyte‐like cells increase in advanced fibrosis stages, which is possibly related to hepatic regeneration. Metabolic zonation of glutamine synthetase expands from the perivenous to non‐perivenous parenchyma in fibrosis progression but its expression is lost in cirrhosis, while cytochrome P‐4502E1 expression is maintained in centrilobular and midlobular zones in fibrosis progression and expressed in cirrhosis. Hence, cadaveric livers provide a platform for further investigation of hepatic histopathologies associated with the aging liver.
With the current epidemic of obesity worldwide, the prevalence of various obesity-related diseases is constantly increasing. Obesity remains the strongest phenotypic risk factor in both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD). In OSA, intermittent hypoxia-reoxygenation and sleep fragmentation, as a result of recurrent episodes of upper airway obstruction during sleep, may give rise to a plethora of metabolic derangements downstream. Intermittent hypoxia (IH) is postulated to be an important mechanistic trigger for potential systemic impact on organs or tissues in OSA, and has served as a useful experimental model for seeking evidence for downstream effects of OSA. This narrative review focuses on the clinical association between OSA and NAFLD, and the role of IH in the progression of NAFLD in lean and diet-induced obese animal models. Understanding the roles of obesity and IH on NAFLD would advance our limited knowledge on the potential health consequences of OSA, a disease which is afflicting more and more people globally, and also in devising effective therapeutic strategies for this progressively common liver condition.
Polysaccharides are the important active constituents of Radix Puerariae thomsonii. Numerous studies have shown that polysaccharides can regulate gut microbiota, repair intestinal barrier, and affect the microbiota-intestine-liver axis, thereby showing therapeutic effects on metabolic disorders. In this study, Radix Puerariae thomsonii polysaccharide (RPP) was extracted from Radix Puerariae thomsonii. The average Mw of RPP was determined to be 1.09 × 10⁵ Da and the monosaccharide composition showed it consisted of glucose. The effects and underlying mechanisms of RPP on fatty liver were studied using C57/BL6J mice induced by alcohol and high-fat diet. The results showed that the oral supplementation of RPP could alleviate alcohol and high-fat diet-induced hepatic injury and steatosis. RPP also promoted intestinal barrier integrity and reduced inflammation through NF-κB signaling pathway. RPP could ameliorate the lipid peroxidation by AMPK/NADPH oxidase signaling pathway. Additionally, these improvements might be related to the enrichment of intestinal bacteria Parabacteroides (promote intestinal barrier integrity) and Prevotellaceae UCG 001 (activation of AMPK signaling pathway). These results demonstrated that RPP could improve inflammation and lipid peroxidation in the alcohol and high-fat diet mouse by restoring the intestinal barrier integrity and regulating the gut microbiota. This suggested that RPP was a potential food supplement for the treatment of fatty liver disease.
Background:
Long working hours are known to account for approximately one-third of the total expected work-related diseases, and much interest and research on long working hours have recently been conducted. Additionally, as the prevalence of prediabetes and the high-risk group for diabetes are increasing worldwide, interest in prediabetes is also rising. However, few studies have addressed the development of type 2 diabetes and long working hours in prediabetes. Therefore, the aim of this longitudinal study was to evaluate the relationship between long working hours and the development of diabetes in prediabetes.
Methods:
We included 14,258 prediabetes participants with hemoglobinA1c (HbA1c) level of 5.7 to 6.4 in the Kangbuk Samsung Cohort Study. According to a self-reported questionnaire, we evaluated weekly working hours, which were categorized into 35-40, 41-52, and > 52 hours. Development of diabetes was defined as an HbA1c level ≥ 6.5%. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the development of diabetes were estimated using Cox proportional hazards analyses with weekly working 35-40 hours as the reference.
Results:
During a median follow-up of 3.0 years, 776 participants developed diabetes (incidence density, 1.66 per 100 person-years). Multivariable-adjusted HRs of development of diabetes for weekly working > 52 hours compared with working 35-40 hours were 2.00 (95% CI: 1.50-2.67). In subgroup analyses by age (< 40 years old, ≥ 40 years old), sex (men, women), and household income (< 6 million KRW, ≥ 6 million KRW), consistent and significant positive associations were observed in all groups.
Conclusions:
In our large-scale longitudinal study, long working hours increases the risk of developing diabetes in prediabetes patients.
ResearchGate has not been able to resolve any references for this publication.