The transition in terminology from fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) marks a considerable evolution in diagnostic standards. This new definition focuses on liver fat accumulation in the context of overweight/obesity, type 2 diabetes, or metabolic dysfunction, without requiring the exclusion of other concurrent liver diseases. The new definition also provides clear guidelines for defining alcohol consumption in relation to the disease. MASLD is currently acknowledged as the most widespread liver disorder globally, affecting ~25% of the population. Despite the extensive array of clinical trials conducted in recent years, the number of approved treatments for metabolic dysfunction-associated fatty liver disease is very limited. In the review critically evaluates the results of clinical trials of related drugs and assesses the future directions for drug development trials. The renaming of MASLD presents new challenges and opportunities for the design of clinical trials and the selection of target populations for drug development.

Manganese (Mn) is an essential nutrient that plays a crucial role in maintaining normal physiological functions of the human body. However, overexposure to Mn often leads to adverse health outcomes and contributes to the development of a variety of diseases. Several studies have explored the relationship between dietary Mn and metabolic dysfunction-associated steatotic liver disease (MASLD) risk. Two UK Biobank (UKB)-based studies suggested that Mn, as a key nutrient, may be associated with a reduced risk of MASLD. Another study found an association between the dietary antioxidant index and the onset of non-alcoholic fatty liver disease (NAFLD), highlighting the importance of nutritional factors (including Mn) in liver health. However, the relationship between dietary Mn intake and MASLD in the Chinese population remains unexplored, and further research is needed to elucidate its underlying mechanisms.

This prospective multi-cohort study had 1,137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort and 17,649 people from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort. We measured dietary intake using a validated and standardized food frequency questionnaire. Annual abdominal ultrasound was used to diagnose new-onset MASLD. We used multivariable Cox regression models to assess the relationship between dietary Mn intake and the risk of MASLD.

In the TCLSIH cohort, 3640 MASLD cases were observed with a follow-up time of 60,190 person-years. After taking into account possible confounding factors, the multivariable HRs (95% CIs) for MASLD across the quartiles of dietary Mn intake in males were 1.00 (reference), 1.08 (0.96-1.21), 1.12 (0.99-1.26), and 1.16 (1.02-1.31), with a P for trend = 0.02; for females, the HRs (95% CIs) for MASLD across the quartiles of dietary Mn intake were 1.00, 1.11 (0.95-1.31), 1.08 (0.91-1.28), and 0.97 (0.81-1.16), with a P for trend = 0.58. After adjustment for proteins, lipids, and carbohydrates, the HRs (95% CIs) for MASLD across the quartiles of dietary Mn intake in males were 1.00 (reference), 1.11 (0.97-1.26), 1.14 (1.00-1.31), and 1.16 (1.00-1.34), with a P for trend = 0.045. For females, the HRs (95% CIs) for MASLD across the quartiles of dietary Mn intake were 1.00 (reference), 1.08 (0.91-1.30), 1.06 (0.88-1.27), and 0.93 (0.76-1.13), with a P for trend = 0.39. In the GNHS cohort, 624 MASLD cases were observed with a follow-up time of 6454 person-years. After adjusting for relevant confounders, the HRs (95% CIs) for males comparing T3 versus T1 of dietary Mn intake were 1.04 (0.65-1.60); the HRs (95% CIs) for females comparing T3 versus T1 of dietary Mn intake were 1.00 (0.78-1.29).

In males, higher dietary Mn intake is associated with a higher incidence of MASLD.

Non-alcoholic fatty liver disease (NAFLD) is strongly linked with metabolic syndrome and atherosclerotic cardiovascular diseases (ASCVDs). This study aimed to assess the feasibility of using brachial-ankle pulse wave velocity (baPWV), a non-invasive technique, to monitor atherosclerosis (AS) in NAFLD patients and to evaluate the AS risk in various sub-populations of NAFLD patients.

A cross-sectional study was conducted with 4,844 participants, enrolled from January 1, 2019, to December 31, 2021, at the Physical Examination Center of Zhongnan Hospital of Wuhan University. Participants were aged 18 to 88 years. According to the main points of the ultrasonic diagnosis of NAFLD, the ultrasonic image report was made for the subjects. AS is defined as baPWV ≥ 1,400 cm/s. We used multiple logistic regression analysis to explore the relationship between NAFLD and AS, and multiple linear regression analysis to explore the correlation between NAFLD and baPWV by modeling. Subgroup analysis was performed based on age and gender to adjust for confounding bias and complete sensitivity analysis.

The prevalence of NAFLD was 38.3% in all participants, with 45.4% in men and 25.1% in women. Among the overall NAFLD population and male NAFLD patients, baPWV exceeded the diagnostic threshold for AS (1,419.70 ± 205.51, 1,429.71 ± 196.13) starting from the 45-55 age group. Through the analysis of the age-baPWV scatter plots and fitted lines, along with sensitivity analysis, it is recommended that male patients should start monitoring at 46 years old for AS using baPWV, while female patients should begin at 51 years old. NAFLD was associated with increased odds of AS (OR: 1.206, 95% CI [1.021-1.423], P = 0.027) after adjusting for confounders. NAFLD was independently positively correlated with baPWV (Model 2: β = 0.086, ΔR 2 = 0.006, P < 0.001; Model 3: β = 0.05, P < 0.001). This positive correlation was also observed in both males and females (male: Model 2: β = 0.081, ΔR 2 = 0.005, P < 0.001; Model 3: β = 0.052, P = 0.001; female: Model 2: β = 0.088, ΔR 2 = 0.006, P < 0.001; Model 3: β = 0.042, P = 0.02).

NAFLD demonstrated an independent association with AS assessed via baPWV, an accessible non-invasive tool for early AS evaluation. Regular baPWV monitoring is recommended for NAFLD patients > 45 years, with males and females initiating surveillance at 46 and 51 years, respectively. Study limitations, including potential biases in NAFLD diagnosis, gender distribution imbalances, and confounding variable interdependencies, necessitate further stratified population analyses.

Background: Biological aging is considered a vital risk factor for age-related diseases, but its role in non-alcoholic fatty liver disease (NAFLD) remains uncertain. This study aimed to evaluate the associations of biological aging with NAFLD and the modified effect of genetic susceptibility. Methods: This study included 329,040 participants from the UK Biobank and 6783 participants from the Dongfeng-Tongji Cohort in China. We calculated the chronological age-adjusted biological age as a surrogate measure for biological aging. Accelerated aging was defined as biological age that exceeded chronological age. The association between biological aging and the risk of NAFLD was assessed in the two cohorts. Polygenic risk scores (PRSs) were used to determine genetic susceptibility for NAFLD in the UK Biobank and further analyze the interaction with biological aging. Results: In the UK Biobank, one year older in age-adjusted biological age increased prevalent NAFLD risk by 6%. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of NAFLD by accelerated aging were 1.35 (1.17, 1.56) and 1.69 (1.54, 1.85) compared to non-aging. In the Dongfeng-Tongji Cohort, biological aging was prospectively associated with NAFLD (accelerated aging: odds ratio (OR) (95% CI) = 1.18 (1.03, 1.36)). In the UK Biobank, high genetic risk was significantly associated with higher NAFLD risk compared to low genetic risk (HRs (95% CIs) = 1.65 (1.40, 1.95)). Analyses of joint effects showed that participants with high PRS and accelerated aging had the highest risk of NAFLD [2.66 (2.98, 3.57) and 2.06 (2.36, 3.96)]. However, biological aging was prospectively associated with NAFLD among participants regardless of genetic risk. There was no significant interaction between genetic risk and biological aging. Conclusions: Accelerated biological aging was associated with a higher risk of NAFLD independent of genetic susceptibility. Identifying populations with accelerated biological aging by the use of surrogate measures and timely intervention may be beneficial for the prevention of NAFLD.

The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity.

This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (β = -5.895; 95% CI: -10.014, -1.775).

Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Serum uric acid (SUA), a non-protein antioxidant, exerts anti-inflammatory and antioxidative stress effects. This study aimed to investigate the association between SUA levels and the risk of benign prostatic hyperplasia (BPH).

This cross-sectional study included 48 653 adult men who underwent health checkups at the Health Examination Center of the Affiliated Hospital of Yangzhou University in 2022. Data on demographics, clinical history and laboratory parameters were collected. Multivariable logistic regression models were used to analyse the relationship between SUA levels and BPH risk, with further exploration in different subgroups.

Logistic regression analysis revealed a significantly decreased risk of BPH among participants in the highest SUA quartile (Q4) compared with those in the lowest quartile (Q1) (fully adjusted OR=0.83, 95% CI: 0.78 to 0.90, p<0.0001). Subgroup analyses demonstrated that this inverse association was more pronounced in subgroups of age>60 years (Q4: OR=0.77, 95% CI: 0.68 to 0.87, p<0.0001), non-obesity (Q4: OR=0.81, 95% CI: 0.75 to 0.87, p<0.0001), without non-alcoholic fatty liver disease (NAFLD) (Q4: OR=0.81, 95% CI: 0.73 to 0.89, p<0.0001), hypertension (Q4: OR=0.81, 95% CI: 0.74 to 0.89, p<0.0001) and without diabetes (Q4: OR=0.84, 95% CI: 0.78 to 0.90, p<0.0001). Curve fitting revealed that higher SUA levels were associated with a lower risk of BPH even in the presence of increased BPH risk factors such as diabetes and hypertension.

This study demonstrates a significant inverse association between SUA levels and BPH risk, particularly in subgroups of older age, non-obesity, absence of NAFLD, hypertension and absence of diabetes. This suggests a potential protective role of SUA in BPH development, highlighting the potential value of maintaining SUA levels within a reasonable range for BPH prevention.

This study aimed to determine the relationship between occupational noise, shift work and non-alcoholic fatty liver disease (NAFLD) in male workers in the automobile manufacturing industry.

Cross-sectional study.

This study was carried out at the Guangzhou Twelfth People's Hospital using data from April to September 2022.

A total of 4672 eligible participants were included in the study.

Diagnosis of NAFLD was made using ultrasound. Noise was detected according to the Measurement of Physical Factors in the Workplace-Part 8: Noise. Environmental noise intensity was assessed using an EDGE personal noise dosimeter manufactured by CASELLA (UK). The working status of workers was investigated by questionnaire.

The OR of NAFLD was 1.39 (1.03, 1.88) in the cumulative noise exposure (CNE)≥95 group compared with CNE<85 group. Improved risk of NAFLD in workers with shift work compared with those without shift work (OR=1.35, 95% CI: 1.09, 1.68). As stratified analyses showed, the ORs of NAFLD prevalence related to occupational noise and shift work exposure appear to be increased in young workers. When both shift work and noise exposure work are present simultaneously, the synergy index between them was 0.47 (95% CI: 0.25, 0.89). Combined effects analysis revealed that the OR of NAFLD was 2.02 (95% CI: 1.34, 2.99) in CNE≥95 and cumulative length of night shifts work>2920 hours.

Occupational noise exposure may be an independent risk factor for NAFLD. It may synergistically affect disease when combined with night shift work, particularly among younger workers. These findings underscore the importance for companies to prioritise the management and training of younger workers, along with targeted occupational health education initiatives, as crucial measures for reducing the incidence of NAFLD.

Pituitary stalk interruption syndrome (PSIS) is an infrequently occurring congenital condition, and there exists a dearth of systematic investigative work focusing on the clinical features and long-term outcomes in adult patients. Individuals who have reached adulthood with PSIS are at an increased risk of developing metabolic disorders, including metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction associated fatty liver disease (MAFLD), which are also one of the main factors for the poor prognosis of these patients. An analysis was conducted on the clinical data of adult PSIS patients who visited the endocrinology department of the First Medical Center of the People's Liberation Army General Hospital from January 2005 to August 2023. Patients were grouped based on their MAFLD and MS status, and the differences in clinical characteristics and risk factors between the groups were analyzed. Machine learning models were used to construct a prediction model for the occurrence of MAFLD in adult PSIS patients and to analyze high-risk predictors. Out of 136 PSIS adult patients, 93.3% were male. The prevalence of MAFLD was 55.5%, and MS was 22.3%. Patients with a history of growth hormone (GH) treatment were less likely to develop MAFLD (P = 0.032). MAFLD patients exhibited higher rates of hypertension, hyperuricemia, obesity, MS, and dyslipidemia. Multiple risk factors may contribute to MS, while no significant link was found between MS and hormone replacement. However, GH non-treatment may serve as the notable predictor of MAFLD in PSIS patients revealed by the Ridge regression model of machine learning model with the highest predictive performance of a mean area under the curve (AUC) of 0.82. The prevalence of MS and MAFLD is high among adult patients with PSIS. Multiple risk factors may contribute to these two diseases, and after constructing a predictive model, we found that MAFLD may be closely linked to the previous lack of GH treatment.

Whether the new standard of metabolic dysfunction-associated fatty liver disease (MAFLD) has more pronounced clinical and population screening diagnostic value than nonalcoholic fatty liver disease (NAFLD) is unclear. This study evaluated the utility of MAFLD and NAFLD for predicting major cardiovascular disease (CVD) risk.

A prospective cohort study approach was utilized to collect 19,399 study participants without CVD at baseline who completed follow-up from the Jinchang cohort platform during 2011-2017. According to clinical ultrasonic diagnosis results and disease diagnosis criteria, the baseline population was divided into MAFLD, NAFLD, Both-FLD and No-FLD groups. Based on the multifactorial Cox proportional risk model to analyze the relationship between three kinds of patients and CVD, the score prediction model of CVD was constructed with reference to the Framingham Risk Score (FRS) and the model was evaluated. Compared with No-FLD, the HRs and 95 % CIs for the risk of CVD development in patients with NAFLD, MAFLD, and Both-FLD were 1.54 (1.34-1.76), 1.57 (1.37-1.79), and 1.62 (1.41-1.87), in that order. The scoring model showed a range of 5.90%-84.59 % risk of CVD in the three groups. As the risk score increased, the risk of developing CVD gradually increased. Evaluation metrics of all three models in the training set and validation set showed that the models have good prediction efficacy.

In terms of CVD risk and prognosis, MAFLD had no advantage over NAFLD. However, Both-FLD was found to predict a higher risk of CVD and to have superior predictive efficacy.

Little is known about the associations of changes in drinking levels with the newly defined metabolic dysfunction-associated steatotic liver disease (MASLD). We therefore sought to estimate the associations between changes in drinking levels and MASLD in less developed regions of China.

This longitudinal study included 8727 participants from the China Multi-Ethnic Cohort (CMEC) in less developed regions, all participating in baseline and a follow-up survey. MASLD was defined as hepatic steatosis, along with the presence of at least one of five cardiometabolic risks, in addition to limiting excessive alcohol consumption. We applied the parametric g-formula to evaluate the association between changes in drinking levels and MASLD. We further estimated the association between changes in drinking levels and fibrosis scores (AST-to-platelet ratio and fibrosis-4 index) in patients with MASLD.

Compared with sustained non-drinking, sustained modest drinking was associated with a higher risk of MASLD (Mean Ratio (MR): 1.127 [95% CI: 1.040-1.242]). Compared to sustained non-drinking, the MR for those transitioning from non-drinking to modest drinking was 1.065 [95% CI: 0.983-1.169], while the MR for those changing from modest drinking to non-drinking was 1.059 [95% CI: 0.965, 1.173]. Non-invasive fibrosis scores tended to increase with modest drinking compared to sustained non-drinking.

In the less developed regions of China, sustained moderate drinking was associated with the risk of MASLD compared with sustained non-drinking. Increased drinking showed a trend towards a higher risk of MASLD. This study can inform drinking policies related to MASLD and liver fibrosis in less developed regions.

The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.

This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.

During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.

In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Over 30% of people worldwide suffer from metabolic dysfunction-associated steatotic liver disease (MASLD), a significant global health issue. Identifying and preventing high-risk individuals for MASLD early is crucial. The purpose of our study is to investigate the factors related to the development of MASLD and develop a risk prediction model for its occurrence.

The study included 5107 subjects, divided into training and validation groups in a 7:3 ratio using a random number table method. Collinearity diagnosis and Cox regression were used to identify factors associated with MASLD incidence, and a risk prediction model was created. The model's accuracy, reliability, and clinical applicability were assessed.

Our study indicated that male, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), serum uric acid to creatinine ratio (SUA/Cr) and white blood cell (WBC) were associated with MASLD incidence. The elements were determined to be crucial for creating a risk prediction model. The model showed strong discriminative potential with a C-index of 0.783 and the time-dependent AUCs of 0.781, 0.789, 0.814 and 0.796 for 1-4 years in the training group, and a C-index of 0.788 and the time-dependent AUCs of 0.798, 0.782, 0.787 and 0.825 for 1-4 years in validation. Calibration curves confirmed the model's accuracy, and decision curve analysis (DCA) validated its clinical utility.

The model may provide clinical physicians with a reliable method for identifying high-risk populations for MASLD and serve as a guide for developing prediction models for other diseases.

Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.

The effectiveness of established biomarkers for non-alcoholic fatty liver disease (NAFLD) within the updated framework of steatotic liver disease (SLD) remains uncertain. This cohort study examines the association of four metabolic biomarkers-retinol-binding protein 4 (RBP-4), fibroblast growth factor 21 (FGF-21), adiponectin, and osteocalcin-with SLD and its subtypes: metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction with alcohol-related liver disease (MetALD)/alcohol-related liver disease (ALD). Among 3,504 Chinese participants aged 55-70, 938 (26.8%) have developed SLD over 5 years, including 871 with MASLD and 67 with MetALD/ALD. The findings indicate that models incorporating RBP-4, FGF-21, adiponectin, and osteocalcin improve predictive accuracy for SLD beyond conventional models. Notably, adiponectin emerges as the most versatile marker, while elevated baseline levels of FGF-21 or RBP-4 indicate specific needs for metabolic or alcohol-related interventions, respectively, supporting tailored precision medicine strategies.

This narrative review explores the role of Medical Nutritional Therapy (MNT) in managing Metabolic-Associated Steatotic Liver Disease (MASLD), previously known as nonalcoholic fatty liver disease. It aims to examine the effectiveness of specific nutritional strategies in preventing and treating this obesity-linked liver disease.

Emerging evidence underscores the benefits of the Mediterranean diet, low-carbohydrate diets, and intermittent fasting in reducing liver fat, improving insulin sensitivity, and mitigating inflammation. Supplementing with vitamin E, omega-3 fatty acids, and silymarin can potentially reduce liver fibrosis and promote liver health. MNT is a key intervention for MASLD management, emphasizing dietary patterns, caloric restriction, and nutraceutical supplementation. Integrating these strategies with lifestyle modifications, including regular physical activity, offers a comprehensive approach to improving metabolic and liver outcomes in patients with MASLD. Further research is needed to refine and personalize these therapeutic interventions.

Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored.

A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease.

A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease.

Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/significant fibrosis according to race/ethnicity.

A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry.

The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.05 (95% confidence interval [CI], 1.36 to 3.09) and 1.48 (95% CI, 1.04 to 2.09) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70 per 1-standard deviation in subcutaneous fat volume), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order.

Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

Hyperuricemia is associated with nonalcoholic fatty liver disease (NAFLD), whereas whether the association differed by hyperuricemia onset age remained unclear. This study sought to investigate the associations of hyperuricemia onset age with the risk of incident NAFLD across adulthood.

Based on Kailuan prospective cohort, our analysis comprised 3318 new-onset hyperuricemia cases from 2006 to 2015 and 3318 age- and sex-matched controls who were randomly selected from the general population. The risk of NAFLD across the onset age groups (<45, 45-54, 55-64, and ≥65 years) were compared using multivariable-adjusted Cox regression models. During a median follow-up of 6.78 years, 744 (22.42%) hyperuricemia participants and 586 (17.66%) normouricemia participants were diagnosed with incident NAFLD. After adjusted for potential confounders, the risk of NAFLD was gradually attenuated with each decade increase in hyperuricemia onset age. The adjusted hazard ratio (95% confidence interval) was 1.62 (1.33-1.97) for hyperuricemia onset age <45 years, 1.26 (1.01-1.57) for age of 45-54 years, 1.24 (1.00-1.59) for age of 55-64 years, and 1.19 (0.90-1.71) for age ≥65 years, respectively. The trend remained robust among the multiple sensitivity analyses.

The relative risk of incident NAFLD differed across hyperuricemia onset age-group, and the association was more evident in those with a younger age of hyperuricemia onset, highlighting the importance of performing early strategies on the prevention of NAFLD.

To examine the associations of healthy lifestyles with risk of all-cause and cause-specific mortality among adults with metabolic dysfunction-associated steatotic liver disease (MASLD), and whether the association was mediated by systemic immune-inflammatory biomarkers (SIIBs).

The study included 10,347 subjects with MASLD, who were enrolled in the Dongfeng-Tongji cohort study. The healthy lifestyles referred to non-smoking, being physically active (≥7.5 metabolic equivalents-hours/week), low-risk alcohol consumption (1-14 g/day for women and 1-28 g/day for men), and optimal sleep duration (≥6 to ≤8 h/day). Cox proportional hazard models were used to examine the relationship between each lifestyle and SIIBs with the risk of all-cause and cause-specific mortality. A mediation analysis was conducted to investigate the role of SIIBs on the association between healthy lifestyles and mortality.

There were 418 MASLD subjects dead till the follow-up of 2018, including 259 deaths from cardiovascular disease (CVD). Compared to MASLD participants with 0-1 healthy lifestyle score (HLS), those with 3-4 HLS had the lowest risk of all-cause mortality [hazard ratio (HR), 0.46; 95% CI, (0.36-0.60)], and CVD mortality [HR (95%CI), 0.41 (0.29-0.58)]. Mediation analyses indicated that SIIBs mediated the association between healthy lifestyles and mortality, with proportions ranging from 2.5% to 6.1%.

These findings suggest that adherence to healthy lifestyles can significantly reduce mortality for MASLD patients, and the decreased SIIBs may partially explain the protection mechanism of healthy lifestyles.

Previous studies have shown a positive correlation between the non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol(non-HDLc/HDLc ratio) and metabolism-associated steatohepatitis (MASLD), suggesting it is a superior predictor of MASLD.The aim of this study is to assess the predictive value of the non-HDLc/HDLc ratio for MASLD.

In this study, we retrospectively analyzed data from 4,498 adult patients at the Health Management Centre of Guangdong Provincial Hospital of Integrative Medicine, regardless of gender, and the diagnostic criteria for MASLD were derived from guidelines. We used univariate and multivariate logistic regression to verify the relationship between the non-HDLc/HDLc ratio and MASLD and assessed the stability of the results through interaction tests. ROC curve analysis was then employed to compare the diagnostic efficacy of several lipid indices, including the non-HDLc/HDLc ratio, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), and the composite lipid profile in diagnosing MASLD.

These data suggested that non-HDLc/HDLc, LDL-C, TG, and TC were positively correlated with MASLD, while HDL-C was inversely correlated, even after adjusting for confounders such as gender, age, body mass index, ALT, AST, uric acid, blood glucose, and hypertension. Among them, non-HDLc/HDLc ratio(OR: 2.709, 95% CI: 2.316-3.169, p < 0.001), LDL-C (OR: 1.294, 95% CI: 1.125-1.489, p < 0.001), TG (OR: 2.854, 95% CI: 2.473-3.293, p < 0.001), TC (OR: 1.242, 95% CI: 1.122-1.374, p < 0.001), and HDL-C (OR: 0.074, 95% CI: 0.044-0.123, p < 0.001) were identified. The interaction results showed that gender did not affect lipid levels in MASLD (p > 0.05). ROC analysis confirmed the validity of the non-HDL cholesterol/HDL cholesterol ratio in predicting MASLD incidence, with an AUC of 0.801. Moreover, the composite lipid indices demonstrated greater predictive power for MASLD compared to individual indices (AUC: 0.857), and validation set results were consistent with those of the training set.

The present study revealed that the non-HDLc/HDLc ratio was positively correlated with the development of MASLD, and the ratio was also effective in predicting MASLD.

Metabolic dysfunction-associated fatty liver disease (MASLD) is a common liver and health issue associated with heightened cardiovascular disease (CVD) risk, with Cytokeratin 18 (CK-18) as a marker of liver injury across the MASLD to cirrhosis spectrum. Autoantibodies against apolipoprotein A-1 (AAA-1s) predict increased CVD risk, promoting atherosclerosis and liver steatosis in apoE-/- mice, though their impact on liver inflammation and fibrosis remains unclear. This study examined AAA-1s' impact on low-grade inflammation, liver steatosis, and fibrosis using a MASLD mouse model exposed to AAA-1s passive immunization (PI). Ten-week-old male C57BL/6J mice under a high-fat diet underwent PI with AAA-1s or control antibodies for ten days. Compared to controls, AAA-1-immunized mice showed higher plasma CK-18 (5.3 vs. 2.1 pg/mL, p = 0.031), IL-6 (13 vs. 6.9 pg/mL, p = 0.035), IL-10 (27.3 vs. 9.8 pg/mL, p = 0.007), TNF-α (32.1 vs. 24.2 pg/mL, p = 0.032), and liver steatosis (93.4% vs. 73.8%, p = 0.007). Transcriptomic analyses revealed hepatic upregulation of pro-fibrotic mRNAs in AAA-1-recipient mice, though histological changes were absent. In conclusion, short-term AAA-1 PI exacerbated liver steatosis, inflammation, and pro-fibrotic gene expression, suggesting that AAA-1s may play a role in MASLD progression. Further research with prolonged AAA-1 exposure is warranted to clarify their potential role in liver fibrosis and associated complications.

The prospective study aimed to investigate the long-term associated risks of cirrhosis and hepatocellular carcinoma (HCC) across various subtypes of steatotic liver disease (SLD).

We enrolled 332,175 adults who participated in a health screening program between 1997 and 2013. Participants were categorized into various subtypes, including metabolic dysfunction-associated SLD (MASLD), MASLD with excessive alcohol consumption (MetALD), and alcohol-related liver disease (ALD), based on ultrasonography findings, alcohol consumption patterns, and cardiometabolic risk factors. We used computerized data linkage with nationwide registries from 1997 to 2019 to ascertain the incidence of cirrhosis and HCC.

After a median follow-up of 16 years, 4,458 cases of cirrhosis and 1,392 cases of HCC occurred in the entire cohort, resulting in an incidence rate of 86.1 and 26.8 per 100,000 person-years, respectively. The ALD group exhibited the highest incidence rate for cirrhosis and HCC, followed by MetALD, MASLD, and non-SLD groups. The multivariate adjusted hazard ratios for HCC were 1.92 (95% confidence interval [CI] 1.51-2.44), 2.91 (95% CI 2.11-4.03), and 2.59 (95% CI 1.93-3.48) for MASLD, MetALD, and ALD, respectively, when compared with non-SLD without cardiometabolic risk factors. The pattern of the associated risk of cirrhosis was similar to that of HCC (all P value <0.001). The associated risk of cirrhosis for ALD increased to 4.74 (95% CI 4.08-5.52) when using non-SLD without cardiometabolic risk factors as a reference.

This study highlights elevated risks of cirrhosis and HCC across various subtypes of SLD compared with non-SLD, emphasizing the importance of behavioral modifications for early prevention.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most recent definition for steatotic liver disease associated with metabolic syndrome. The results of recent metabolic and observational studies suggest a potential beneficial effect of food-derived flavonoids in some chronic diseases, including MASLD. The study aims to evaluate the protective role of diet flavonoids in subjects with and without MASLD belonging to a cohort living in the South of Italy.

The study cohort comprised 1297 participants assessed in the NUTRIHEP cohort (2015-2018), divided into two groups, based on presence or absence of MASLD.

The results indicated statistically significant flavonoid consumption, showing a protective role against MASLD, at an optimal concentration of 165 mg/day, with an OR value of 0.63, (p = 0.001, 95% C.I.: 0.47; 0.83 t). The OR remained almost unchanged when the intake increased from 165 mg per day to 185 mg per day.

In conclusion, our study results show a protective role of flavonoids against MASLD. Consuming only 165 mg of flavonoids daily can activate this protective function, reducing the risk of MASLD.

This study estimated the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) according to cardiometabolic risk factors. The long-term impacts of MASLD on all-cause and cardiometabolic-specific mortality were evaluated.

We enrolled 343 816 adults aged ≥30 years who participated in a health screening program from 1997 through 2013. MASLD was identified on the basis of abdominal ultrasonography and metabolic profiles. The participants were further categorized by liver enzyme elevation. Baseline cardiometabolic comorbidities were classified on the basis of self-reported medication use and clinical seromarkers. All-cause and cardiometabolic-specific deaths were determined through computerized data linkage with nationwide death certifications until December 31, 2020.

The overall prevalence of MASLD was 36.4%. Among patients with MASLD, 35.9% had abnormal liver enzyme levels. Compared with patients without MASLD, abnormal liver enzymes were positively associated with cardiometabolic comorbidities in patients with MASLD (Pfor trend < 0.001). After follow-up, patients with MASLD had a 9%-29% higher risk of all-cause, cardiovascular-related, or diabetes-related mortality. In the groups with MASLD and elevated and normal liver enzyme levels, the multivariate-adjusted hazard ratios for cardiovascular deaths were 1.14 (1.05-1.25) and 1.10 (1.03-1.17), respectively, and those for diabetes deaths were 1.42 (1.05-1.93) and 1.24 (0.98-1.57), respectively, compared with those in the non-MASLD group (Pfor trend < 0.001).

Individuals with MASLD and elevated liver enzyme levels exhibited significantly higher risks of all-cause and cardiometabolic deaths and should be monitored and given consultation on cardiometabolic modifications.

In clinical practice, there are few effective biomarkers for identifying non-alcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the diagnostic value of γ-glutamyl transpeptidase to platelet ratio (GPR) combined with triglyceride (TG) in NAFLD.

A total of 14,415 individuals participated in the annual physical examination. Multivariate logistic regression analysis was conducted to investigate the exposure factors associated with NAFLD. Spearman's analysis was performed to assess the correlation among the exposure factors of NAFLD. Furthermore, the diagnostic efficacy of the combination of GPR and TG in NAFLD was analyzed using the receiver operating characteristic curve (ROC).

The results of the multivariate logistic regression analysis showed that BMI (OR = 1.619), Systolic Blood Pressure (SBP) (OR = 1.014), Diastolic Blood Pressure (DBP) (OR = 1.028), GPR (OR = 12.809), and TG (OR = 2.936) were all risk factors for NAFLD, while HDL-C (OR = 0.215) was a protective factor. Spearman correlation analysis revealed significant positive correlations between GPR and SBP, DBP, BMI, TG (p < 0.01), but a negative correlation between GPR and HDL-C (p < 0.01). TG was only positively correlated with GPR (p < 0.001). ROC curve analysis demonstrated that the area under the curve (AUC) of GPR combined with TG for diagnosis of NAFLD was 0.855 (95 % CI: 0.819-0.891), sensitivity was 83.45 % and specificity was 73.56 %.

This study indicated that high levels of GPR and TG were risk factors for NAFLD and demonstrated good clinical value in diagnosing NAFLD.

We aimed to investigate the correlation and to explore which MAFLD subtypes have the greatest influence on progression of arterial stiffness risk.

Using data from a health examination-based cohort, a total of 12,129 participants who underwent two repeated health examinations that included brachial-ankle pulse wave velocity (baPWV) from 2012 to 2020 were enrolled. Participants were separated into non-MAFLD, overweight/obese (OW-MAFLD), lean/normal weight (lean-MAFLD) and diabetes (DM-MAFLD) groups. Among the participants with a median follow-up of 2.17 years, 4511 (37.2%) participants had MAFLD at baseline, among which 3954 (87.7%), 123 (2.7%), and 434 (9.6%) were OW-, lean- and DM-MAFLD, respectively. Analyses using linear regression models confirmed that compared with the non-MAFLD group, the elevated baPWV change rates (cm/s/year) were 12.87 (8.81-16.94), 25.33 (7.84-42.83) and 38.49 (27.88-49.10) in OW, lean and DM-MAFLD, respectively, while the increased change proportions (%) were 1.53 (1.10-1.95), 3.56 (1.72-5.40) and 3.94 (2.82-5.05), respectively. Similar patterns were observed when these two baPWV parameters were transformed in the form of the greatest increase using Cox proportional hazards model analyses. Furthermore, the risk of arterial stiffness progression across MAFLD subtypes presented a significant, gradient, inverse relationship in the order of DM-, lean-, OW with metabolic abnormalities (MA)-, and OW without MA-MAFLD.

MAFLD, especially DM-MAFLD and lean-MAFLD, was significantly associated with arterial stiffness progression, providing evidence that stratification screening and surveillance strategies for CVD risk have important clinical implications.

A splice variant in HSD17B13 gene is demonstrated to protect against nonalcoholic fatty liver disease (NAFLD), and mitigate the effect of Patatin-like phospholipase domain-containing 3 (PNPLA3-I148M). It is being explored as a putative drug target and in polygenic risk scores. Based on whole exome sequencing (WES) in our cohort of biopsy proven NAFLD and limited data on the variant in our ethnicity, we sought to explore its role.

This is a cross-sectional study that recruited 1,020 individuals with ultrasound/biopsy-confirmed NAFLD and matched controls. Liver enzymes and lipid profiles were estimated (Beckman coulter LX750/DXH800); WES was performed in NAFLD patients and controls (Illumina; HiSeqX); HSD17B13-A-INS/I148M-PNPLA3 variants were genotyped (sequencing/qR T-PCR); HSD17B13 protein expression was estimated (immunohistochemistry); the Student's t-test/Mann-Whitney U/Chi-square test and odds ratio (95% confidence interval) were used.

There was no significant difference (Odds ratio = 0.76; 95% CI -0.57 to 1.03; P = 0.76) in the frequency of the rs72613567-A-INS between controls and patients (17.8% vs. 14.4%). No difference in the ALT (Alanine transaminase; 72.24 ± 65.13 vs. 73.70 ± 60.06; P = 0.51) and AST levels (Aspartate aminotransferase; 60.72 ± 55.59 vs. 61.63 ± 60.33; P = 0.91) between HSD17B13-wild and variant carriers were noted. Significantly elevated liver enzymes were seen in PNPLA3-148-variant/HSD17B13-wild compared with PNPLA3-148-variant/HSD17B13-variant (90.44 ± 59.0 vs. 112.32 ± 61.78; P = 0.02). No difference in steatosis (P = 0.51) between HSD17B13-wild and variant carriers was noted. No other variants in the intron-exon boundaries were identified. Although, protein expression differences were noted between wild and variant carriers, no difference in the extent of steatosis was seen.

Our study reports lack of association of the splice variant with reduced risk of NAFLD, and mitigating the effect of PNPLA3 variant. Ethnicity-based validation must be carried out before including it in assessing protection against NAFLD.

Various lifestyle factors including smoking, alcohol, physical activity, sedentary behavior, diet quality, sleep behavior, and overweight have been related to metabolic dysfunction-associated steatotic liver disease (MASLD); however, their joint impact on risk of MASLD is not well known. We prospectively investigated the association between a combination of lifestyle factors and risk of MASLD.

This prospective cohort study included 13,303 participants (mean age: 39.1 ± 11.3 years, female: 60.1%) in China. A novel healthy lifestyle score was created combining seven healthy factors: not smoking, no alcohol intake, regular physical activity, short sedentary time, healthy diet, healthy sleep, and healthy weight. Incident MASLD cases were ascertained annually by liver ultrasound and cardiometabolic risk factors. Multivariable Cox proportional hazards regression models were used to estimate the association of healthy lifestyle score with risk of MASLD.

Within 48,036 person-years of follow-up, 2823 participants developed MASLD. After adjusting for age, sex, education, occupation, household income, personal and family history of disease, and total energy intake, compared with participants with 0-2 healthy lifestyle factors, the multivariable hazard ratios (95% confidence interval) of MASLD were 0.81 (0.73, 0.89), 0.67 (0.61, 0.75), and 0.55 (0.49, 0.62) for healthy lifestyle score of 3, 4, and 5-7, respectively (P for trend <0.0001). Such associations were consistent across subgroup and sensitivity analyses.

Our results indicate that a higher healthy lifestyle score is associated with a lower risk of MASLD.

We aimed to explore the associations of baseline and cumulative cardiovascular health with nonalcoholic fatty liver disease (NAFLD) development and regression using the new Life's Essential 8 score.

From a health screening database, participants who underwent at least 4 health examinations between 2012 and 2022 were recruited and categorized into two cohorts: (a) the NAFLD development cohort with no history of NAFLD prior to Exam 4 and (b) the NAFLD regression cohort with diagnosed NAFLD prior to Exam 4. The LE8 score was calculated from each component. The outcomes were defined as newly incident NAFLD or regression of existing NAFLD from Exam 4 to the end of follow-up.

In the NAFLD development cohort, of 21,844 participants, 3,510 experienced incident NAFLD over a median follow-up of 2.3 years. Compared with the lowest quartile of cumulative LE8, individuals in the highest quartile conferred statistically significant 76% lower odds (hazard ratio [HR] 0.24, 95% confidence interval [CI], 0.21-0.28) of NAFLD incidence, and corresponding values for baseline LE8 were 42% (HR 0.58, 95% CI 0.53-0.65). In the NAFLD regression cohort, of 6,566 participants, 469 experienced NAFLD regression over a median follow-up of 2.4 years. Subjects with the highest quartile of cumulative LE8 had 2.03-fold (95% CI, 1.51-2.74) higher odds of NAFLD regression, and corresponding values for baseline LE8 were 1.61-fold (95% CI, 1.24-2.10).

Cumulative ideal cardiovascular health exposure is associated with reduced NAFLD development and increased NAFLD regression. Improving and preserving health behaviors and factors should be emphasized as an important part of NAFLD prevention and intervention strategies.

The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known.

A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019.

In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively.

These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.

According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to explore the associations of the TyG index with CKD among adults with MAFLD.

In this retrospective observational cohort study, data from 11,860 participants who underwent a minimum of three health assessments between 2008 and 2015 were retrospectively collected. Participants were followed up until the final medical visit or health examination. CKD refers to an eGFR < 60 mL/min per 1·73 m2 or the occurrence of two or more incidents of proteinuria.

Within a median 10·02-year follow-up period, 2005 (16·9%) participants reported developing CKD. Multivariate Cox regression models indicated a noticeable correlation between the TyG index and CKD incidence (HR per unit increase, 1.19; 95% CI: 1.09-1.29) and between the TyG index and CKD incidence (HR per SD increase, 1.12; 95% CI: 1.06-1.18). The CKD incidence increased by 1.8 times in participants in the highest TyG index quartile relative to patients in the lowest quartile of the TyG index quartile (HR 1·18, 95% CI: 1.01-1.38, P = 0.007). According to subgroup analysis, an elevated TyG index is likely to become more harmful to participants younger than 60 years (P for interaction = 0.035).

An elevated TyG index may increase CKD incidence among MAFLD adults, particularly among younger people. Early intervention may help reduce the incidence of CKD.

Non-alcoholic fatty liver disease (NAFLD) and alcohol-associated fatty liver disease (ALD) are the most common chronic liver diseases. Hepatic steatosis is an early histological subtype of both NAFLD and ALD. Excessive alcohol consumption is widely known to lead to hepatic steatosis and subsequent liver damage. However, reported findings concerning the association between moderate alcohol consumption and hepatic steatosis remain inconsistent. Notably, alcohol consumption as a modifiable lifestyle behavior is likely to change over time, but most previous studies covered alcohol intake only once at baseline. These inconsistent findings from existing studies do not inform decision-making concerning policies and clinical guidelines, which are of greater interest to health policymakers and clinician-scientists. Additionally, recommendations on the types of alcoholic beverages are not available. Usually, assessing the effects of two or more hypothetical alcohol consumption interventions on hepatic steatosis provides answers to questions concerning the population risk of hepatic steatosis if everyone changes from heavy drinking to abstinence, or if everyone keeps on drinking moderately, or if everyone of the drinking population switches from red wine to beer? Thus, we simulated a target trial to estimate the effects of several hypothetical interventions, including changes in the amount of alcohol consumption or the types of alcoholic beverages consumed, on hepatic steatosis using longitudinal data, to inform decisions about alcohol-related policymaking and clinical care.

This longitudinal study included 12687 participants from the UK Biobank (UKB), all of whom participated in both baseline and repeat surveys. We excluded participants with missing data related to components of alcohol consumption and fatty liver index (FLI) in the baseline and the repeat surveys, as well as those who had reported liver diseases or cancer at the baseline survey. We used FLI as an outcome indicator and divided the participants into non-, moderate, and heavy drinkers. The surrogate marker FLI has been endorsed by many international organizations' guidelines, such as the European Association for the Study of the Liver. The calculation of FLI was based on laboratory and anthropometric data, including triglyceride, gamma-glutamyl transferase, body mass index, and waist circumference. Participants responded to questions about the types of alcoholic beverages, which were defined in 5 categories, including red wine, white wine/fortified wine/champagne, beer or cider, spirits, and mixed liqueurs, along with the average weekly or monthly amounts of alcohol consumed. Alcohol consumption was defined as pure alcohol consumed per week and was calculated according to the amount of alcoholic beverages consumed per week and the average ethanol content by volume in each alcoholic beverage. Participants were categorized as non-drinkers, moderate drinkers, and heavy drinkers according to the amount of their alcohol consumption. Moderate drinking was defined as consuming no more than 210 g of alcohol per week for men and 140 g of alcohol per week for women. We defined the following hypothetical interventions for the amount of alcohol consumed: sustaining a certain level of alcohol consumption from baseline to the repeat survey (e.g., none to none, moderate to moderate, heavy to heavy) and changing from one alcohol consumption level to another (e.g., none to moderate, moderate to heavy). The hypothetical interventions for the types of alcoholic beverages were defined in a similar way to those for the amount of alcohol consumed (e.g., red wine to red wine, red wine to beer/cider). We applied the parametric g-formula to estimate the effect of each hypothetical alcohol consumption intervention on the FLI. To implement the parametric g-formula, we first modeled the probability of time-varying confounders and FLI conditional on covariates. We then used these conditional probabilities to estimate the FLI value if the alcohol consumption level of each participant was under a specific hypothetical intervention. The confidence interval was obtained by 200 bootstrap samples.

For the alcohol consumption from baseline to the repeat surveys, 6.65% of the participants were sustained non-drinkers, 63.68% were sustained moderate drinkers, and 14.74% were sustained heavy drinkers, while 8.39% changed from heavy drinking to moderate drinking. Regarding the types of alcoholic beverages from baseline to the repeat surveys, 27.06% of the drinkers sustained their intake of red wine. Whatever the baseline alcohol consumption level, the hypothetical interventions for increasing alcohol consumption from the baseline alcohol consumption were associated with a higher FLI than that of the sustained baseline alcohol consumption level. When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to moderate drinking, the mean ratio of FLI was 1.027 (95% confidence interval [CI]: 0.997-1.057). When comparing sustained non-drinking with the hypothetical intervention of changing from non-drinking to heavy drinking, the mean ratio of FLI was 1.075 (95% CI: 1.042-1.108). When comparing sustained heavy drinking with the hypothetical intervention of changing from heavy drinking to moderate drinking, the mean ratio of FLI was 0.953 (95% CI: 0.938-0.968). The hypothetical intervention of changing to red wine in the UKB was associated with lower FLI levels, compared with sustained consumption of other types of alcoholic beverages. For example, when comparing sustaining spirits with the hypothetical intervention of changing from spirits to red wine, the mean ratio of FLI was 0.981 (95% CI: 0.948-1.014).

Regardless of the current level of alcohol consumption, interventions that increase alcohol consumption could raise the risk of hepatic steatosis in Western populations. The findings of this study could inform the formulation of future practice guidelines and health policies. If quitting drinking is challenging, red wine may be a better option than other types of alcoholic beverages in Western populations.

The relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature.

This retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis.

The incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively (p < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively (p < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10-3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis (p < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group.

The prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD.