Metabolic dysfunction-associated steatotic liver disease (MASLD) with onset in youth may be more consequential for adverse outcomes than that detected later in adulthood. Transaminitis in the general population is a marker of the prevalence of MASLD. There are no previous community-based studies in Indian youth assessing the prevalence of transaminitis. The purpose of this study was to find out the prevalence of transaminitis, MASLD and elevated Fibrosis-4 (FIB-4) index among young South Indian adults.

This was a cross-sectional study done over a period of 1 year from January 2022 among adults aged 18-30 years. Multistage sampling was used to recruit participants with body mass index (BMI) < 30 kg/m2 and without moderate to heavy alcohol consumption from four different sociogeographic regions. Detailed history, physical examination and investigations including liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), platelet count, and metabolic workup were carried out. FIB-4 index and Nonalcoholic fatty liver disease-liver fat score (NAFLD-LFS) were calculated. LFS ≥ -0.64 was used to rule in MASLD.

A total of 2373 (1170 males) participants with a mean age of 24 ± 3.5 years were included. Transaminitis (AST or ALT≥35 IU/L) was seen in 25.9% of the cohort. MASLD by NAFLD-LFS was present in 27.4% of the population. FIB-4 index ≥1.3 was found in 54 (2.27%) participants. Neck circumference and Trivandrum Medical College adiposity index were associated with transaminitis, MASLD, and elevated FIB-4. Blood pressure, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower among participants with transaminitis, but they were not different among those with elevated FIB-4 index. BMI and waist-hip ratio were not different among participants with and those without transaminitis or MASLD.

There is a high prevalence of transaminitis and MASLD in community-dwelling young adult Indians. We recommend screening all young adult Indians for MASLD and transaminitis.

The aim of this study is to analyze association between liver fibrosis with CVE, incident diabetes, and cirrhosis complications.

Historic cohort of biopsy-proven MASLD patients, divided into two groups: F0-F2 vs F3-F4 fibrosis. Baseline data included metabolic traits and liver function tests. Patients were contacted and scheduled for laboratory analysis and elastography. Endpoints were (a) CVE, defined as any of acute myocardial infarction, coronary stenting, ischemic cardiopathy, and stroke; (b) incident diabetes; (c) cirrhosis complications. Baseline data were collected at the time of liver biopsy, while follow-up data were recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables for each endpoint.

Study population included 220 patients with median age 53 years, and 145 were women; baseline fibrosis was F0-F2 in 165 patients and F3-F4 in 55 patients; median follow-up was 9.9 years. A higher percentage of F3-F4 patients had CVE (29.4%) than F0-F2 ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26-4.6; P  = 0.008). Incident diabetes occurred in 53.3% of F3-F4 and 20.2% of F0-F2 cohort (hazard ratio 3.04; 95% CI: 1.99-4.86; P  < 0.001); cirrhosis complications occurred in 9/55 F3-F4 patients and in 1/165 F0-F2 ones (hazard ratio 26.3; 95% CI: 3.3-208.3; P  = 0.002). Multivariate analysis confirmed liver fibrosis as an independent predictor of incident diabetes and cirrhosis complications. CVE were associated with baseline diabetes and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio.

In a cohort of 220 MASLD patients followed for 9.9 years, baseline F3-F4 was associated with incident diabetes and cirrhosis complications. AST/ALT ratio and diabetes were associated with CVE.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is associated with prevalent cardiovascular disease. More favorable cardiovascular health (CVH) profiles are associated with a lower prevalence of MASLD in cross-sectional studies. The relationship between long-term CVH patterns and MASLD prevalence in midlife remains unknown.

Participants (aged 18-30 years at baseline) of the CARDIA (Coronary Artery Risk Development in Young Adults) study who had individual CVH components measured at 7 examinations over 20 years and liver fat assessed by noncontrast computed tomography at year 25 follow-up were included. CVH score was defined using published American Heart Association definitions. Group-based trajectory modeling was used to identify CVH trajectories. MASLD was defined as liver attenuation of ≤51 Hounsfield units with at least 1 metabolic risk factor after excluding other causes of liver fat. Logistic regression was used to examine associations of CVH trajectory groups and MASLD prevalence. At baseline, 39% of 2529 participants had high and 5% had low CVH, respectively. MASLD prevalence at year 25 was 23% (n=587). Five distinct CVH trajectories were identified. Between the 2 groups that started at similar CVH scores, those whose CVH declined over time had a higher prevalence of MASLD at year 25 (7.0% in high-stable versus 23.0% high-decreasing; 24.4% in moderate-stable versus 35.7% in moderate-decreasing). Lower and decreasing trajectories were associated with higher year-25 MASLD prevalence compared with the high-stable trajectory.

Achieving and maintaining high CVH scores starting in young adulthood lowers the risk of prevalent MASLD in midlife.

this investigation aimed to assess the correlation between the triglyceride glucose (TyG) index and its related indicators, as well as the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-c), with hepatic steatosis and liver fibrosis among middle-aged and elderly participants.

based on data from the 2017-2020 National Health and Nutrition Examination Survey, the study included adults of ages 40 years and older in the United States. To explore the correlation between TyG and its related indicators, as well as TG/HDL-c with hepatic steatosis and liver fibrosis, multiple regression models were employed. In addition, the receiver operating characteristic curves were used to further explore the diagnostic efficacy of these indicators in non-alcoholic fatty liver disease (NAFLD) and liver fibrosis.

following the adjustment for various possible covariates, TyG, triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), as well as TG/HDL-c were positively correlated with controlled attenuation parameter and NAFLD, with corresponding β coefficients of 17.90, 0.19, 0.20, and 1.57, alongside odds ratios of 2.10, 1.01, 1.01, and 1.15, respectively (all p < 0.05). The β coefficient for the association between TyG and liver stiffness measurement was -0.43 (p = 0.023). Notably, the area under the curve (AUC) of TyG-WC was the highest of all parameters, showing strong diagnostic potential for identifying NAFLD (AUC = 0.79) and liver fibrosis (AUC = 0.75).

this study reveals a significant positive correlation between TyG-WC and the prevalence of NAFLD in middle-aged and elderly people in the United States. These findings highlight that lowering TyG-WC levels may help reduce the incidence of NAFLD in middle-aged and older Americans.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) are the most prevalent causes of chronic liver disease worldwide. Both conditions have many pathophysiological mechanisms in common, such as altered lipid and bile acid metabolism, and share some similar clinical features. Furthermore, metabolic risk factors and alcohol often co-exist in the same individuals and have recently been shown to act synergistically to markedly increase the risk of liver disease. Given the high prevalence and impact of this interaction, steatotic liver disease due to the combination of metabolic dysfunction and moderate-to-high alcohol intake has been termed MetALD in the new steatotic liver disease nomenclature, attracting the interest of the scientific community. Subsequent studies have investigated the prevalence of MetALD, which ranges from 1.7% to 17% in cohorts of patients with steatotic liver disease, depending on the population setting and study design. A few cohort studies have also assessed the prognosis of this patient population, with preliminary data suggesting that MetALD is associated with an intermediate risk of liver fibrosis, decompensation and mortality among steatotic liver disease subtypes. In this review article, we examine the clinical evidence and the experimental models of MetALD and discuss the clinical implications of the term for early detection and management. We provide insight into the pathophysiological mechanisms of the synergistic effect of alcohol and metabolic risk factors, possible screening strategies, the use of biomarkers and emerging models of care, as well as potential therapeutic interventions with a special focus on medications for MASLD, highlighting the most promising drugs for patients with MetALD.

To study the associations of neighborhood socioeconomic disadvantage with 30-day mortality and readmission for common gastrointestinal conditions, adjusting for individual demographics, comorbidities, access to health-care resources, and treatment facility characteristics.

We analyzed a nationwide sample of United States Medicare beneficiaries hospitalized from 2017 to 2019 for common gastrointestinal diseases, grouped by diagnosis-related groups. We then estimated the association of neighborhood socioeconomic disadvantage, measured by the Area Deprivation Index, with 30-day mortality and readmission utilizing logistic regression models with restricted cubic splines. We performed multistep adjustments for individual socioeconomic status and demographics, medical comorbidities, access to inpatient and outpatient health-care resources, and hospital-level characteristics.

In total, 1,293,483 patients in the mortality cohort and 1,289,106 patients in the readmission cohort were included in analysis. The fully adjusted model demonstrated an association between neighborhood deprivation and 30-day mortality for patients with common gastrointestinal diseases, with the strongest associations for nonmalignant pancreatic disorders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.25-2.01), esophageal disorders (OR 1.50, 95% 1.02-2.21), gastrointestinal hemorrhage (OR 1.40, 95% CI 1.29-1.52), and biliary tract disorders (OR 1.40, 95% CI 1.16-1.69) in the most deprived groups. Neighborhood deprivation was not associated with 30-day readmission after full adjustment.

We describe an independent association between neighborhood deprivation and 30-day mortality for patients with common gastrointestinal diseases, which remains even after controlling for individual poverty, demographics and comorbidities, access to health-care resources, and characteristics of treating facilities.

This study aimed to determine the burden of suspected nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in a predominantly Hispanic patient population and explore the utility of the American Gastroenterological Association's NAFLD Clinical Care Pathway (CCP).

Electronic medical records (n = 223) were used to divide patients into risk groups based on the amount of metabolic risk factors they presented, diabetic status, or if they presented other liver diseases. Fribosis-4 (FIB-4) scores were used to determine the risk for advanced fibrosis.

Most patients (83.8%) were considered at risk for NAFLD based on CCP criteria, and about a third of patients (33.2%) were found to be at indeterminate (n = 60; 26.9%) or high risk (n = 14; 6.3%) for advanced fibrosis. Most indeterminate-risk patients (78.3%) were not referred for liver imaging.

This study demonstrates the potential of the CCP as a corrective tool that could help to better identify and screen patients at risk for NAFLD.

The association between socioeconomic factors and disease severity is not well studied in people living with metabolic dysfunction-associated steatotic liver disease (MASLD). We thus examined if socioeconomic factors influence the presence of, or risk for future, major adverse liver outcomes (MALOs) in people living with MASLD.

We conducted a register-based cohort study that included all individuals with a MASLD diagnosis between 1987 and 2020 in Sweden. Logistic and Cox regression were used to examine the association between socioeconomic factors (country of birth, educational level, and marital status) and the presence of MALOs before or upon MASLD diagnosis or during follow-up, respectively.

In total, 14 026 people living with MASLD were identified, among whom the median age was 55 years, 50% were male and 775 (5.5%) had MALOs before or upon diagnosis. The adjusted odds ratio (aOR) for pre-existing MALOs was higher in divorced (aOR = 1.29, 95% confidence interval [CI] = 1.06-1.57) compared to married individuals. The aOR for pre-existing MALOs was lower among those with >12 years of education (aOR = .76, 95% CI = .62-.93) compared to individuals with an education level of 10-12 years. During a 5.2-year median follow-up, several socioeconomic factors were associated with increased rates of developing MALOs in a crude model; however, none were independently associated with incident MALOs after adjustment for confounders.

Socioeconomic factors were associated with somewhat higher odds for prevalent, but not incident, MALOs in people living with MASLD, after adjustments. This suggests primarily that risk factors for fibrosis progression are differently distributed across socioeconomic subgroups.

Although prior observational studies have suggested that patients with non-alcohol fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis.

Utilizing summary-level data from multiple large-scale genome-wide association studies (GWAS) in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting (IVW) method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods was applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC.

The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC (Beta: 0.01, 95% CI: -0.02 to 0.03, P = 0.74). Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (OR: 1.00, 95% CI: 0.96 to 1.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC.

Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.

Liver fibrosis is associated with increased cardiovascular disease (CVD) risk and mortality. However, it is unknown how these risks compare in those with pre-diabetes (pre-DM) or diabetes (DM). We examined the association of FIB-4 levels, an indicator of liver fibrosis, with CVD risk and mortality according to DM status.

Prospective, longitudinal cohort study.

We examined 13,326 U.S. adults (6.7 % with DM) with FIB-4 measures classified as low (<1.30), intermediate (1.30- < 2.67), high (2.67- < 3.25), and very high (≥3.25). National Death Index linkage provided mortality status for CVD, liver-related, and all causes over 17.5 years.

We calculated 10-year ASCVD risk in persons without known ASCVD. Cox regression examined the relation of FIB-4 with mortality by DM status.

High/very high FIB-4 levels were greater in those with (2.2 %) vs. without (0.4 %) DM (p < 0.0001). Higher FIB-4 scores and DM were associated with greater estimated ASCVD risks (p < 0.0001); 44.5 % of those at high /very high FIB-4 levels had ≥20 % estimated ASCVD risk. CVD mortality hazard ratios (HRs) (95 % CI) associated with high/very high FIB-4 in those with pre-DM and DM were 8.76 (3.66-20.95), and 0.89 (0.22-3.53), respectively, and for total mortality were 5.46 (3.16-9.43), and 2.07 (0.90-4.74), respectively, which were attenuated after adjustment.

Our findings indicate the need for increased efforts to identify those at risk of liver fibrosis in adults with pre-DM or DM to prevent CVD and total mortality.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. Endothelial dysfunction (EnD) constitutes the main driver in the progression of atherosclerosis and coronary artery disease (CAD). Several pathophysiological alterations and molecular mechanisms are involved in the development of EnD in patients with NAFLD. Our aim is to examine the association of NAFLD and CAD with the parallel assessment of EnD, discussing the pathophysiological mechanisms and the genetic background that underpin this relationship. This review delves into the management of the condition, exploring potential clinical implications and available medical treatment options to facilitate the deployment of optimal treatment strategies for these patients.

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.

Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function. Non-pharmacological interventions included diet (caloric restriction or lipid enrichment), bariatric surgery and physical activity. Caloric restriction in humans achieving a mean weight loss of 3% only reduces muscle fat. Lipid-enriched diet increases liver fat in human with no impact on muscle fat, except sphingomyelin-enriched diet which reduces both lipid contents exclusively in pre-clinical studies. Bariatric surgery, hybrid training (resistance exercise and electric stimulation) or whole-body vibration in human decrease both liver and muscle fat. Physical activity impacts both phenotypes by reducing local and systemic inflammation, enhancing insulin sensitivity and modulating the expression of key mediators of the muscle-liver-adipose tissue axis. The combination of diet and physical activity acts synergistically in liver, muscle and white adipose tissue, and further decrease muscle and liver fat. Several pharmacological interventions (patchouli alcohol, KBP-089, 2,4-dinitrophenol methyl ether, adipoRon and atglistatin) and food supplementation (vitamin D or resveratrol) improve liver and muscle phenotypes in pre-clinical studies by increasing fatty acid oxidation and anti-inflammatory properties. These interventions are effective in reducing myosteatosis in MASLD while addressing the liver disease itself. This review supports that disturbances in inter-organ crosstalk are key pathophysiological mechanisms involved in MASLD and myosteatosis pathogenesis. Focusing on the skeletal muscle might offer new therapeutic strategies to treat MASLD by modulating the interactions between liver and muscles.

The systemic inflammation response index (SIRI) is associated with various diseases with inflammatory components, but its relationship with the progression of hepatic fibrosis and survival outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study was designed to investigate the potential associations between the SIRI and advanced hepatic fibrosis (AHF) as well as between the SIRI and long-term outcomes in individuals with MASLD.

A prospective cohort study was conducted using data gathered from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Weighted binary logistic regression, the Cox proportional hazards model, and time-dependent receiver operating characteristic (ROC) analyses were employed to assess the relationships among the SIRI, AHF, and mortality in patients with MASLD. Our study included a total of 5126 patients with MASLD. A higher SIRI was significantly associated with increased odds of AHF (OR 1.55, 95% CI 1.22, 1.96). According to the survival analyses, a higher SIRI was associated with greater all-cause (HR 1.19, 95% CI 1.15, 1.22) and cardiovascular mortality (HR 1.25, 95% CI 1.19, 1.32) after adjustment. The time-dependent ROC analysis indicated that the SIRI had a modest predictive value for discriminating MASLD individuals at higher versus lower mortality risk over 3-year, 5-year, and 10-year follow-up.

The SIRI is a promising tool for identifying MASLD individuals at risk of progressing to AHF and for predicting mortality outcomes.

liver stiffness measurement, assessed by vibration-controlled transient elastography, has been recognized as a powerful tool for liver fibrosis assessment. The potential of liver stiffness measurement to predict clinically relevant outcomes in fatty liver disease has received considerable attention. This study aimed to investigate the prediction of liver-related events in metabolic dysfunction-associated steatotic liver disease patients by liver stiffness measurement value on transient elastography.

the electronic databases including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov until 6 September 2023 were systematically searched. The hazard ratios adjusted for confounders were extracted and pooled by random-effects model analysis.

a total of 20,587 individuals from seven studies were included. The pooled hazard ratios (HRs) were 18.65 (95 % CI: 9.95-34.95, p < 0.01, I2 = 0 %) in the stratification analysis of the highest versus lowest liver stiffness measurement categories. In 1-kPa analysis, the risk of liver-related events was increased with 1 kPa increment (HR 1.05, 95 % CI: 1.03-1.07, p < 0.01, I2 = 74.47 %).

metabolic dysfunction-associated steatotic liver disease patients with high liver stiffness measurement values were at an increased risk of liver-related events. Liver stiffness measurement can be used as a prognostic tool to achieve risk stratification in fatty liver patients.

The aim of this study was to assess the role of elevated serum ferritin levels in the onset, pathological progression and prognosis of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease has been rapidly increasing worldwide. Despite extensive research on the pathogenesis of nonalcoholic fatty liver disease, a lack of sufficient clinical research on the relationship between nonalcoholic fatty liver disease and serum ferritin levels remains.

We analysed 968 patients with type 2 diabetes mellitus who underwent liver ultrasound examination and had their serum ferritin levels measured. The presence of nonalcoholic fatty liver disease and advanced liver fibrosis was determined through abdominal ultrasound examination and the nonalcoholic fatty liver disease fibrosis score.

Compared to that in the non-nonalcoholic fatty liver disease group, the presence of hyperferritinemia was significantly more common in the nonalcoholic fatty liver disease group (83.3 vs. 56.3%, p=0.005). When patients with nonalcoholic fatty liver disease were stratified by the nonalcoholic fatty liver disease fibrosis score, those with advanced liver fibrosis exhibited a higher prevalence of hyperferritinemia (56.3, 78.9, and 88.9% for none, simple steatosis, and advanced fibrosis, respectively; p for trend=0.002). In multivariate logistic regression, liver fibrosis was independently associated with hyperferritinemia (odds ratio [OR] 1.45; 95% confidence interval [CI] 1.18-2.02; p=0.014), and this association remained significant in male patients after adjusting for other risk factors (OR 2.66; 95% CI 1.43-5.48; p=0.026).

Identifying nonalcoholic fatty liver disease patients at a risk of developing nonalcoholic steatohepatitis and advanced fibrosis is crucial for implementing timely interventions and improving patient outcomes. This study highlights the potential utility of serum ferritin levels as a serum biomarker for identifying nonalcoholic steatohepatitis patients and those at a risk of late-stage fibrosis, particularly in male patients with nonalcoholic fatty liver disease.

Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD.

We performed a cohort study using the data of the1999-2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value).

We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10-5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status.

Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.

Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population.

We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively.

We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years.

The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.

We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.

19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05).

People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Observational studies have identified an inverse association between education and non-alcoholic fatty liver disease (NAFLD). However, it is not possible to establish causality for this relationship.

To gain more insight into the causal nature of the relationship between education and NAFLD.

We performed two-sample Mendelian randomization (MR) analyses using summary-level, large-scale datasets to study the association of genetically predicted educational attainment (n = 1271 genetic instruments, obtained from 1,131,881 participants) with risk of NAFLD (i.e., liver fat [n = 32,858 participants] and electronic health record (EHR)-based NAFLD [n = 778,614 participants]). In sensitivity analyses, educational attainment was replaced by three education-related traits (i.e., genetically predicted cognition, math ability and highest math).

Inverse-variance weighted method showed a statistically significant association between genetically predicted educational attainment and liver fat (beta: -0.251, 95%CI: -0.305; -0.198) and EHR-based NAFLD (OR: 0.609, 95%CI: 0.547; 0.677). MR-Egger regression did not show statistically significant intercepts. Similar findings were obtained when other MR tests were used or when educational attainment was replaced by education-related traits.

This study suggests a causal, protective effect of higher education on NAFLD risk. Societal interventions targeted at people with low education are needed to alleviate the burden of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels.

Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression.

A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively.

The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM).

Nationwide population based study.

Longitudinal cohort study in Korea.

7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years.

The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death.

Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM.

NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of multisystemic complications, including muscle changes such as sarcopenia and myosteatosis that can reciprocally affect liver function. We conducted a systematic review to highlight innovative assessment tools, pathophysiological mechanisms and metabolic consequences related to myosteatosis in MASLD, based on original articles screened from PUBMED, EMBASE and COCHRANE databases. Forty-six original manuscripts (14 pre-clinical and 32 clinical studies) were included. Microscopy (8/14) and tissue lipid extraction (8/14) are the two main assessment techniques used to measure muscle lipid content in pre-clinical studies. In clinical studies, imaging is the most used assessment tool and included CT (14/32), MRI (12/32) and ultrasound (4/32). Assessed muscles varied across studies but mainly included paravertebral (4/14 in pre-clinical; 13/32 in clinical studies) and lower limb muscles (10/14 in preclinical; 13/32 in clinical studies). Myosteatosis is already highly prevalent in non-cirrhotic stages of MASLD and correlates with disease activity when using muscle density assessed by CT. Numerous pathophysiological mechanisms were found and included: high-fat and high-fructose diet, dysregulation in fatty acid transport and ketogenesis, endocrine disorders and impaired microRNA122 pathway signalling. In this review we also uncover several potential consequences of myosteatosis in MASLD, such as insulin resistance, MASLD progression from steatosis to metabolic steatohepatitis and loss of muscle strength. In conclusion, data on myosteatosis in MASLD are already available. Screening for myosteatosis could be highly relevant in the context of MASLD, considering its correlation with MASLD activity as well as its related consequences.

Fuzi-Gancao herb couple is one of the most common herb couples involved in the TCM formula, which was used for the treatment of chronic diseases. The herb couple has a hepatoprotective effect. However, its main components and therapeutic mechanism are not yet clear. This study aims to elucidate the therapeutic effect and mechanism of the Fuzi-Gancao herb couple on NAFLD from animal experiments, network pharmacology, and molecular docking.

60 Male C57BL/6 mice (20 g ± 2 g) were randomly divided into six groups including the blank group (n=10) and NALFD group (n=50). The mice of the NALFD group were fed with a high-fat diet for 20 weeks to establish the NAFLD model and the NALFD mice were randomly divided into five groups including positive group (berberine), model group and F-G groups with three dosages (0.257, 0.514, 0.771 g/kg) (n=10). After 10 weeks of administration, the serum was collected for the analysis of ALT, AST, LDL-c, HDL-c, and TC, and liver tissues were collected for pathological analysis. The TCMAS database was used to collect the main components and targets of the Fuzi-Gancao herb couple. The GeneCards database was used to collect NAFLD-related targets, and the key targets were obtained by intersecting with herbal targets. The diseasecomponent- target relationship diagram was constructed by Cytoscape 3.9.1. The obtained key targets were imported into the String database to obtain the PPI network, and imported into the DAVID database for KEGG pathway analysis and GO analysis. Finally, the key targets and key gene proteins were imported into Discovery Studio 2019 for molecular docking verification.

In this study, H-E staining indicated the pathological changes of liver tissue in Fuzi- Gancao groups were significantly improved, and the levels of AST, ALT, TC, HDL-c, and LDL-c in serum of Fuzi-Gancao groups decreased in a dose-dependent manner, compared with the model group. 103 active components and 299 targets in the Fuzi-Gancao herb couple were confirmed in the TCMSP database and 2062 disease targets in NAFLD were obtained. 142 key targets and 167 signal pathways were screened, such as the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. The main bioactive ingredients of Fuzi-Gancao herb couple in the treatment of NAFLD are quercetin, kaempferol, naringenin, inermine, (R)-norcoclaurine, isorhamnetin, ignavine, 2,7-Dideacetyl-2,7- dibenzoyl-taxayunnanine F, glycyrol mainly involving IL6, AKT1, TNF, TP53, IL1B, VEGFA and other core targets. Molecular docking analysis indicated that there is a good affinity between the key components and the key targets.

This study preliminarily explained the main components and mechanism of the Fuzi- Gancao herb couple in the treatment of NAFLD and provided an idea for subsequent research.

To evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular outcomes, including angina, coronary artery disease (CAD), coronary artery calcification (CAC), myocardial infarction (MI), and calcified coronary plaques.

A comprehensive search of databases, including PubMed, EMBASE, and Cochrane Library, was conducted up to January 2023. Studies were included investigating the relationship between NAFLD and cardiovascular outcomes in adult populations. Exclusion criteria were studies on animals, pediatric populations, and those not published in English. Two reviewers assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models.

The meta-analysis included 32 studies with a total of 5,610,990 participants. NAFLD demonstrated significant associations with increased risks of angina (Relative Risk (RR): 1.45, 95% CI: 1.17, 1.79), CAD (RR: 1.21, 95% CI: 1.07, 1.38), CAC >0 (RR: 1.39, 95% CI: 1.15, 1.69), and calcified coronary plaques (RR: 1.55, 95% CI: 1.05, 2.27). However, no significant association was found between NAFLD and CAC >100 (RR: 1.16, 95% CI: 0.97, 1.38) or MI (RR: 1.70, 95% CI: 0.16, 18.32).

The meta-analysis demonstrated a significant association between NAFLD and cardiovascular outcomes independent of conventional cardiovascular disease (CVD) risk factors. These findings emphasize the importance of prevention, early detection, and proper management of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after the exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD).

Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD.

A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n = 104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD.

A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 adults and contributes to advanced liver injury and cardiometabolic disease. While recent evidence points to involvement of the brain in NAFLD, the downstream neural circuits and neuronal molecular mechanisms involved in this response, remain unclear. Here, we investigated the role of a unique forebrain-hypothalamic circuit in NAFLD.

Chemogenetic activation and inhibition of circumventricular subfornical organ (SFO) neurons that project to the paraventricular nucleus of the hypothalamus (PVN; SFO→PVN) in mice were used to study the role of SFO→PVN signaling in NAFLD. Novel scanning electron microscopy techniques, histological approaches, molecular biology techniques, and viral methodologies were further used to delineate the role of endoplasmic reticulum (ER) stress within this circuit in driving NAFLD.

In lean animals, acute chemogenetic activation of SFO→PVN neurons was sufficient to cause hepatic steatosis in a liver sympathetic nerve dependent manner. Conversely, inhibition of this forebrain-hypothalamic circuit rescued obesity-associated NAFLD. Furthermore, dietary NAFLD is associated with marked ER ultrastructural alterations and ER stress in the PVN, which was blunted following reductions in excitatory signaling from the SFO. Finally, selective inhibition of PVN ER stress reduced hepatic steatosis during obesity.

Collectively, these findings characterize a previously unrecognized forebrain-hypothalamic-ER stress circuit that is involved in hepatic steatosis, which may point to future therapeutic strategies for NAFLD.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and obesity is worldwide on the rise. Body roundness index (BRI), as a newly developed anthropometric indicator, has been recently reported to identify obesity. However, it is still unclear whether BRI is associated with the prevalence of NAFLD.

Data were from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. NAFLD was diagnosed based on hepatic steatosis defined by CAP values ≥274 dB/m. Multivariable logistic regression analysis was performed to detect the association between BRI and the odds of NAFLD. Subgroup analysis stratified by age, gender, BMI, and race was further conducted. To explore the potential ability of BRI in predicting NAFLD, the area under the curve (AUC) of BRI was calculated by receiver operating characteristic (ROC) analysis.

Among the 4467 study participants, 1718 (38.5%) were diagnosed with NAFLD. Compared to the non-NAFLD group, participants with NAFLD had a higher level of BRI. The positive associations between BRI and NAFLD were detected in all three models (mode 1: OR = 1.71, 95% CI: 1.65-1.78, p < 0.0001; mode 2: OR = 1.78, 95% CI: 1.71-1.86, p < 0.0001; mode3: OR = 1.23, 95% CI: 1.11-1.35, p < 0.0001). The positive association steadily existed in different subgroups after stratified by age, gender, and BMI. Moreover, the non-linear association between BRI and NAFLD was detected, presenting inverted U-shaped curves. Furthermore, BRI had a high predictive value (AUC = 0.807) in identifying NAFLD.

BRI was positively associated with the prevalence of NAFLD among individuals in America, regardless of age, gender, and BMI. Besides, BRI presented a high ability for identifying NAFLD.

Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients.

Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995-2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related).

The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5-3.5% and 4.3-7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022).

Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.

Several studies have identified that three SAMM50 polymorphisms (rs2073082, rs738491, rs3761472) are associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). However, the clinical significance of the SAMM50 SNP in relation to NAFLD remains largely unknown. Therefore, we conducted a clinical study and SNP-SNP interaction analysis to further elucidate the effect of the SAMM50 SNP on the progression of NAFLD in the elderly.

A total of 1053 patients over the age of 65 years were recruited. Liver fat and fibrosis were detected by abdominal ultrasound or FibroScan, respectively. Genomic DNA was extracted and then genotyped by Fluidigm 96.96 Dynamic Array. Multivariable logistic regression was used to evaluate the association between NAFLD and SNP. SNP-SNP interactions were analyzed using generalized multivariate dimensionality reduction (GMDR).

The risk of NAFLD was substantially higher in people who carried SAMM50-rs2073082 G and -rs738491 T alleles (OR, 1.962; 95% CI, 1.448-2.659; p < 0.001; OR, 1.532; 95% CI, 1.246-1.884; p = 0.021, respectively) compared to noncarriers. Carriers of the rs738491 T and rs3761472 G alleles in the cohort showed a significant increase in liver stiffness measurements (LSM). The combination of the three SNPs showed the highest predictive power for NAFLD. The rs2073082 G allele, rs738491 T allele and rs3761472 G carriers had a two-fold higher risk of NAFLD compared to noncarriers.

Our research has demonstrated a strong correlation between the genetic polymorphism of SAMM50 and NAFLD in the elderly, which will contribute to a better understanding of the impact of age and genetics on this condition. Additionally, this study provides a potential predictive model for the early clinical warning of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition. In the United States (US), the prevalence of NAFLD in men is higher than that in women. This study aimed to evaluate sex differences in long-term all-cause and cardiovascular (CV) outcomes in patients with NAFLD.

We collected data from participants aged ≥18 years from the National Health and Nutrition Examination Surveys, 2000-2014, which included seven continuous 2-year surveys. A US Fatty Liver Index score of ≥30 was used to define NAFLD. We used a weighted Cox proportional hazards model to compare sex differences in overall and CV mortality. The all-cause and CV mortality rates were obtained from the National Center for Health Statistics. From the selected 2627 participants with NAFLD, 65.4% were males. Men had a significantly higher all-cause mortality than women (12.4% vs. 7.7%; p = 0.005), and the risk of CV death was higher in women with NAFLD aged ≤60 years (adjusted hazard ratio 0.214, 95% confidence interval 0.053-0.869, p = 0.031). Men with a body mass index >30 kg/m² and diabetes showed a higher risk of all-cause mortality. Sex differences in CV events were not apparent in the patients aged >60 years.

Male sex was associated with all-cause mortality in all the age groups. However, CV death is influenced by age, with a higher risk in young and middle-aged women and no apparent difference in older patients.

The leading cause of death in patients with nonalcoholic fatty liver disease (NAFLD) is cardiovascular disease (CVD). However, the mechanisms are unknown. Mice deficient in hepatocyte proliferator-activated receptor-α (PPARα) (PparaHepKO) exhibit hepatic steatosis on a regular chow diet, making them prone to manifesting NAFLD. We hypothesized that the PparaHepKO mice might be predisposed to poorer cardiovascular phenotypes due to increased liver fat content. Therefore, we used PparaHepKO and littermate control mice fed a regular chow diet to avoid complications with a high-fat diet, such as insulin resistance and increased adiposity. After 30 wk on a standard diet, male PparaHepKO mice exhibited elevated hepatic fat content compared with littermates as measured by Echo MRI (11.95 ± 1.4 vs. 3.74 ± 1.4%, P < 0.05), hepatic triglycerides (1.4 ± 0.10 vs. 0.3 ± 0.01 mM, P < 0.05), and Oil Red O staining, despite body weight, fasting blood glucose, and insulin levels being the same as controls. The PparaHepKO mice also displayed elevated mean arterial blood pressure (121 ± 4 vs. 108 ± 2 mmHg, P < 0.05), impaired diastolic function, cardiac remodeling, and enhanced vascular stiffness. To determine mechanisms controlling the increase in stiffness in the aorta, we used state-of-the-art PamGene technology to measure kinase activity in this tissue. Our data suggest that the loss of hepatic PPARα induces alterations in the aortas that reduce the kinase activity of tropomyosin receptor kinases and p70S6K kinase, which might contribute to the pathogenesis of NAFLD-induced CVD. These data indicate that hepatic PPARα protects the cardiovascular system through some as-of-yet undefined mechanism.

NAFLD is increasingly common among young people. Whether NAFLD carries a more benign course in younger adults is not known. We aimed to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression across age groups.

We conducted a retrospective study of adults with NAFLD seen within Michigan Medicine, a tertiary care center, between 2010 and 2021. NAFLD was defined by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases. Cirrhosis was determined by validated International Classification of Diseases-9/10 codes or imaging. Fine-Gray competing risk models were generated, with incident cirrhosis and liver-related events (LREs) as the primary outcomes and death without cirrhosis or LREs as a competing risk. The primary predictor was the age category.

We included 31,505 patients with NAFLD, with 8,252 aged 18 to younger than 40, 15,035 aged 40 to younger than 60, and 8,218 aged 60 years or older years at diagnosis. Compared with older patients, young adults more often had obesity, higher ALT, and high-risk PNPLA3 alleles, and fewer had prevalent cirrhosis, hypertension, hyperlipidemia, and diabetes. The 10-year risk of incident cirrhosis was similar between ages (3.4% in age 18 to <40 vs 3.7% in age 40 to <60 vs 4.7% in age ≥60; p = 0.058). Predictors of LREs were advancing age and diabetes, with a significantly higher 10-year risk of LREs in the oldest age group (0.2% in age 18 to <40 vs 0.7% in age 40 to <60 vs 1.1% in age ≥60; p = 0.008).

While the baseline prevalence of cirrhosis was higher among older adults, the rate of NAFLD progression to cirrhosis was similar in young and older adults. Older patients were more likely to have LREs.

In this study, we aimed to analyze the proteomics of the liver in rabbits on a high cholesterol diet (HCD). We randomly divided New Zealand white rabbits into the normal diet group and the HCD group. We established the atherosclerosis model and measured plasma cholesterol and triglycerides. The model was successfully established using ultrasound examination and histopathological staining of the intima of aorta and liver of the two groups of rabbits. The differential proteins in the rabbit liver were analyzed using Tandem Mass Tags proteomic analysis technology. Finally, we used western blot to verify the reliability of proteomics. The results showed that compared with the control group, the serum lipid levels of rats in the HCD group was significantly increased, and the pathological sections showed the formation of atherosclerotic plaques in the aorta, inflammation, and adipose lesions in the liver. Proteomic analysis of the liver revealed 149 differences in HCD-expressed protein, which is mainly involved in inflammation and regulation of lipid and sugar metabolism. In addition, we verified differentially expressed liver proteins in the HCD group using western blot. We found that HCD caused lipid accumulation, abnormal glucose metabolism, and inflammatory response in the liver.

Background and aim: Diagnosing nonalcoholic steatohepatitis (NASH) is challenging. This study intended to explore the diagnostic value of multiple technical acoustic measurements in the diagnosis of NASH, and to establish a diagnostic model combining technical acoustic measurements with clinical parameters to improve the diagnostic efficacy of NASH. Methods: We consecutively enrolled 75 patients with clinically suspected nonalcoholic fatty liver disease (NAFLD) who underwent percutaneous liver biopsy in our hospital from June 2020 to December 2021. All cases underwent multiple advanced acoustic measurements for liver such as shear wave dispersion (SWD), shear wave speed (SWS), attenuation imaging (ATI), normalized local variance (NLV), and liver-kidney intensity ratio (Ratio) examination before liver biopsies. A nomogram prediction model combining the technical acoustic measurements and clinical parameters was established and the model is proposed to improve the diagnostic performance of NASH. Results: A total of 75 cases were included in this study. The classification of pathological grade for NASH was as follows: normal liver, (n = 15, 20%), nonalcoholic fatty liver (NAFL), (n = 44, 58.7%), and NASH, (n = 16, 21.3%). There were statistically significant differences in SWS (p = 0.002), acoustic coefficient (AC) (p = 0.018), NLV (p = 0.033), age (p = 0.013) and fasting blood glucose (Glu) (p = 0.049) between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH, and the calibration curves showed good calibrations in both training and validation sets. The AUCs of the combined nomogram model for the training set and validation set were 0.8597 and 0.7794, respectively. Conclusion: There were statistically significant differences in SWS, AC, NLV, age and Glu between NASH and non-NASH. A nomogram model which includes SWS, AC, NLV, age and Glu was built to predict NASH. The predictive model has a higher diagnostic performance than a single factor model in the diagnosis of NASH and has good clinical application prospects.