Non-alcoholic fatty liver disease (NAFLD) affects more than a quarter of the global population and has become the world's number one chronic liver disease, seriously jeopardizing public life and health. Despite the new terminology of metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed, the mechanisms underlying the heterogeneity across BMI stratification in non-alcoholic fatty liver disease (NAFLD) remain unclear. The aim of this study was to reveal the differences in metabolic and fibrotic characteristics between lean (BMI < 23 kg/m2) and non-lean NAFLD in an Asian population.

The current study collected NAFLD patients from the physical examination population. Patients were divided into two groups by BMI to compare their clinical parameters, including lean (BMI < 23 kg/m2) and non-lean (BMI ≥ 23 kg/m2) and fibrosis subgroups (with a threshold of LSM = 8 kPa) and analyzed for risk factors by logistic regression models.

Of the 11,577 NAFLD patients who participated in the study, there were 916 lean and 10,661 non-lean. The non-lean group was younger than the lean group (median age 50 vs. 52 years, P < 0.001) and had a significantly higher prevalence of hypertension (28.0% vs. 18.3%), diabetes mellitus (10.1% vs. 6.1%), and liver fibrosis (9.1% vs. 5.1%) (all P < 0.001). Analysis of metabolic indexes showed that TyG, TyG-BMI, TG/HDL-C and APRI were higher in the non-lean group (all P < 0.001). Gender stratification revealed that ALT was significantly higher in the male non-lean group, while HDL-C was lower in the female non-lean group (1.35 vs. 1.47 mmol/L). Multiple regression suggested that the risk of fibrosis was independently associated with CAP values and fasting glucose, BMI, direct bilirubin, globulin, and age in the non-lean group, whereas the risk was mainly driven by GGT and ALP in the lean group.

Non-lean NAFLD patients showed more significant metabolic disturbances and risk of liver fibrosis. Although metabolic indicators (TyG, FIB-4) have limited predictive value for liver fibrosis, they are strongly associated with metabolic risk in MASLD.

The association of each of the recently classified steatotic liver diseases (SLDs), including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD), with new development of ischemic heart disease (IHD) remains unclear.

We investigated the associations of various SLDs with the development of IHD during a 10-year follow-up period in 13,815 Japanese individuals without a history of IHD (men/women 8,933/4,882; mean age 48 years) who underwent annual health checkups including an abdominal ultrasound examination. Among the participants, 4,639 (33.6%) subjects were diagnosed as having SLDs, and the proportions of subjects with MASLD, MetALD and ALD were 25.4%, 4.7% and 1.9%, respectively. During the follow-up period, 1,963 (16.2%; men/women 1,374 [17.2%]/589 [14.2%]) subjects had new development of IHD. Multivariable Cox proportional hazard model analysis after adjustment of age, sex, estimated glomerular filtration rate (eGFR), current smoking habit, diabetes, hypertension and dyslipidemia showed that the adjusted risk for new onset of IHD was significantly higher in subjects with MASLD (hazard ratio 1.20 [95% confidence interval 1.01-1.55]; P=0.042) than in those without SLD. Other SLDs were not selected as independent risk factors for the development of IHD.

The presence of MASLD, but not other SLDs, is an independent risk factor for new onset of IHD during a 10-year follow-up period.

Objective To evaluate the effect of pemafibrate (PEM) on metabolic dysfunction-associated steatotic liver disease (MASLD). Methods We retrospectively evaluated 43 patients with hyperlipidemia and MASLD to determine changes in clinical factors between the start of PEM treatment and 0.5 years later. Using FibroScan, 39 of 43 patients were evaluated for liver stiffness (LS; kPa) and controlled attenuation parameter (CAP; dB/m). None of the patients had decompensated cirrhosis. Results Thirty patients were women, the median age was 66 years old, the median fibrosis-4 (FIB-4) score was 2.52, the median LS was 8.05 kPa, and the median CAP was 280.5 dB/m at the start of PEM treatment. AST, ALT, ALP, γGTP, and triglyceride levels decreased 0.5 years after starting PEM treatment, but FIB-4, LS, and CAP values did not decrease. However, LS decreased in patients with a FIB-4 index ≥1.3 at the start of PEM treatment, whereas it did not change in patients with a FIB-4 index <1.3. Similarly, LS decreased in patients with a value ≥8 kPa at the start of treatment and did not change in those with <8 kPa. The decreased LS group had higher baseline ALT and LS levels and lower ALT levels during 0.5 years of follow-up than the increased LS group. Conclusion At the initiation of PEM treatment, the LS decreased in patients with MASLD complicated by hyperlipidemia and moderate LS (FIB-4>1.3 or LS >8 kPa). Although there is currently no approved treatment for MASLD, PEM may be a viable treatment option for MASLD with mild LS.

Background The controversy persists regarding whether the serum level of γ-glutamyltransferase (GGT), a marker of liver damage, is associated with hypertension irrespective of alcohol intake. Methods We investigated the relationship between the GGT level and new-onset hypertension during a 10-year follow-up period in Japanese individuals who underwent annual health examinations (n=28,990). After excluding subjects without systolic blood pressure and GGT data and those with hypertension at baseline, a total of 18,618 subjects (men/women: 11,262/7,356, mean age: 44 years) were enrolled. Results During the follow-up period, 2,753 men (24.4%) and 837 women (11.4%) developed hypertension. When the subjects were divided by quartiles of GGT at baseline (Q1-Q4), multivariable Cox proportional hazard model analyses after adjustment for age, sex, systolic blood pressure, body mass index, levels of uric acid, estimated glomerular filtration rate, family history of hypertension, habits of current smoking and alcohol drinking, and diagnosis of diabetes mellitus and dyslipidemia showed that hazard risks (HRs) for the development of hypertension were significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group. A significant interaction was observed between alcohol drinking habits and the GGT level at baseline for the development of hypertension (p=0.022), and adjusted HRs were similarly significant in alcohol infrequent drinkers (≤5 days/week). However, the GGT level was not significantly associated with the development of hypertension in frequent alcohol drinkers (≥6 days/week). Conclusions A high GGT level is an independent predictor of new-onset hypertension in infrequent alcohol drinkers but not in frequent drinkers.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease globally, with inflammation and nutrition playing key roles in its progression. The Advanced Lung Cancer Inflammation Index (ALI) is a novel biomarker reflecting nutritional and inflammatory status. This study aims to explore the association between ALI and the risk of liver fibrosis and prognosis in MAFLD patients.

This cross-sectional study analyzed NHANES data from the 1999-2018 on adult participants in the US. Weighted logistic regression assessed the association between ALI and liver fibrosis risk. Mortality outcomes, including all-cause, cardiovascular disease (CVD), and cancer mortality, analyzed using weighted Kaplan-Meier and Cox proportional hazards models. Restricted cubic splines (RCS) and threshold effect analyses were uesd to explore non-linear relationships. Receiver operating characteristic (ROC) curve evaluated the prognostic value of ALI, and stratified analyses examined subgroup differences.

A total of 6,858 MAFLD patients (mean age 51.38 ± 17.22 years, 54% male) were included. A non-linear relationship was found between ALI and liver fibrosis risk, with a threshold at 5.68, beyond which the risk increased significantly (OR = 2.35, 95% CI: 1.89-2.95). Stronger associations were observed in subgroups with central obesity and prediabetes (P for interaction < 0.05). ALI was inversely associated with all-cause mortality (HR = 0.64, 95% CI: 0.56-0.72) and CVD mortality (HR = 0.57, 95% CI: 0.46-0.65), but not cancer mortality. RCS analysis showed an L-shaped non-linear relationship with all-cause mortality (threshold at 5.36) and a linear relationship with CVD mortality. Low HDL cholesterol and excessive alcohol consumption influenced the association between ALI and all-cause mortality (P for interaction < 0.05). ALI demonstrated the highest predictive accuracy for CVD mortality.

ALI is associated with an increased risk of liver fibrosis and reduced all-cause and CVD mortality, highlighting its potential value in assessing MAFLD prognosis, particularly CVD-related mortality.

Non-alcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated fatty liver disease (MAFLD), can also manifest in patients classified as non-MAFLD who do not meet MAFLD criteria. The involvement of cortisol and thyroid hormones may play a role in the pathogenesis of FLD by modifying the metabolism of specific lipoproteins, particularly apolipoprotein M (Apo M). This study investigated cortisol and thyroid hormones levels and Apo M gene expression in white blood cells (WBCs) of individuals with MAFLD, non-MAFLD, and healthy controls.

The serum and WBCs of the study subjects were collected from patients with FLD (n=99) including 58 MAFLD and 41 non-MAFLD and healthy individuals (n=23). To investigate the gene expression of Apo M and thyroid and cortisol hormones, qRT-PCR and ELISA methods were used, respectively.

The Apo M gene expression was significantly lower in FLD patients, both non-MAFLD, and MAFLD patients compared to the control group (p<0.05). Total T4 and TSH hormone levels in the MAFLD patients were significantly decreased and increased compared to the control group, respectively (p<0.05). The cortisol level was significantly elevated in the FLD and MAFLD patients compared to the control group (p<0.01).

Alterations in Apo M gene expression also cortisol and thyroid hormones levels in non-MAFLD patients were milder than MAFLD patients when compared to the control. Also, likely Apo M may be involved in FLD pathogenesis.

Objective Metabolic-associated fatty liver disease (MAFLD) has only recently been proposed; therefore, the characteristics of patients with autoimmune hepatitis (AIH) and MAFLD remain unclear. This study evaluated the effect of MAFLD on AIH patients with AIH. Methods We reevaluated the Japanese Nationwide Survey of AIH in 2018, which involved a survey of patients diagnosed with AIH between 2014 and 2017. We categorized patients with AIH according to the presence or absence of MAFLD and compared the clinical characteristics between the two groups. Results A total of 427 patients (77 men and 350 women) were included in this study. The overall prevalence of MAFLD was 10.5%. Compared to AIH patients without MAFLD, AIH patients with MAFLD had the following characteristics at the time of the AIH diagnosis: (1) a higher body mass index, (2) a higher prevalence of hypertension, (3) mild elevation of hepatobiliary enzymes and total bilirubin, and (4) histologically progressive fibrosis. However, the levels of hepatobiliary enzymes and total bilirubin after treatment were significantly higher in AIH patients with MAFLD than in those without MAFLD. Conclusion AIH patients with MAFLD had characteristics different from those of AIH patients without MAFLD. These findings could help increase our understanding of patients with AIH with MAFLD.

Utilizing the National Health and Nutrition Examination Survey (NHANES) dataset to investigate the relationship between dietary quality, as assessed by the Healthy Eating Index-2015 (HEI-2015), and the prevalence of metabolic associated fatty liver disease (MAFLD) among adults in the United States, our analysis revealed that an increased dietary quality was significantly correlated with a reduced risk of MAFLD in the American population.

The NHANES dataset, encompassing the years 2017-2018 and comprising 3,557 participants, was incorporated into our analytical framework. Weighted multivariate linear regression model was performed to assess the linear relationship between the HEI-2015 and MAFLD. Dietary intake data were derived from two 24-h dietary recall interviews conducted as part of NHANES.

Following multivariable adjustment, the weighted multivariable linear regression models demonstrated a negative correlation between the HEI-2015 total scores and the risk of MAFLD. The weighted logistic regression models revealed that each unit of increased HEI-2015 total value was associated with a 1.2% (95% CI: 0.9%, 1.5%; P < 0.001) decrease in the risk of f MAFLD. Upon categorization of the HEI-2015 scores into quartiles, the odds ratios (ORs) for the association between the risk of MAFLD and the quartile scores of HEI-2015, in comparison to the baseline quartile, were 0.945 (95% CI: 0.852-1.047; P = 0.279), 0.834 (95% CI: 0.750-0.927; P < 0.001), and 0.723 (95% CI: 0.646-0.811; P < 0.001), respectively. When participants were stratified by age and sex, subgroup analyses showed a similar trend. This pattern was also evident in the smooth curve fitting (SCF) and weighted generalized additive model (GAM).

Elevated dietary quality, as assessed by the total and component food scores of the HEI-2015, was significantly correlated with a diminished risk of MAFLD among participants in the NHANES survey featured in this investigation.

Cardiovascular disease (CVD) is a leading cause of death in women and risk of development is greatly increased following menopause. Menopause occurs over several years and is associated with hormonal changes, including a reduction in estradiol and an increase in follicle-stimulating hormone. This hormonal shift may result in an increased risk of developing abdominal adiposity, insulin resistance, dyslipidemia, vascular dysfunction, hypertension, type 2 diabetes mellitus (T2DM), metabolic dysfunction-associated fatty liver disease (MAFLD), and metabolic syndrome (MetS). Furthermore, with the onset of menopause, there is an increase in oxidative stress that is associated with impaired vascular function, inflammation, and thrombosis, further increasing the risk of CVD development. Despite the harmful consequences of the menopause transition being well known, women in premenopausal, perimenopausal, and postmenopausal stages are unlikely to be enrolled in research studies. Therefore, investigations on the prevention and treatment of cardiovascular and metabolic disease in middle-aged women are still relatively limited. Whilst lifestyle interventions are associated with reduced CVD risk in this population sample, the evidence still remains inconclusive. Therefore, it is important to explore the effectiveness of early intervention and potential therapeutic approaches to maintain cellular redox balance, preserve endothelium, and reduce inflammation. Glycine, N-acetylcysteine, and L-theanine are amino acids with potential antioxidant and anti-inflammatory activity and are identified as therapeutic interventions in the management of age-related and metabolic diseases. The benefits of the intake of these amino acids for improving factors associated with cardiovascular health are discussed in this review. Future studies using these amino acids are warranted to investigate their effect on maintaining the vascular health and cardiovascular outcomes of postmenopausal women.

Introduction Although metabolic dysfunction-associated fatty liver disease (MAFLD) is becoming more common in individuals with hepatocellular carcinoma (HCC), it is still unknown how this condition relates to postoperative complications of HCC. While hepatitis B/C virus (HBV/HCV) infection and alcohol use are primary risk factors, MAFLD has emerged as a significant contributor to HCC incidence. Understanding the prognostic impact of MAFLD on HCC outcomes, particularly post-radical resection, is essential. Objective This study aims to evaluate the prognostic significance of MAFLD on postoperative outcomes in HCC patients, following radical hepatectomy, with a focus on gender-specific mortality differences. Methodology A retrospective cohort study was conducted at Pakistan Navy Station Shifa Hospital, Bahria University Medical and Dental College, Karachi, Pakistan. Consecutive HCC patients who underwent radical resection between May 2023 and April 2024 were included. MAFLD was diagnosed based on hepatic steatosis and metabolic dysfunction criteria. Data on demographics, clinical features, and outcomes were collected from electronic medical records. The primary outcome was overall survival (OS), and the secondary outcomes included recurrence-free survival (RFS). Statistical analyses involved multivariate Cox regression and Kaplan-Meier survival curves using IBM SPSS Statistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, NY, USA). Results MAFLD patients exhibited higher median body mass index (BMI) (25.3 kg/m² vs. 23.5 kg/m², p < 0.001), increased prevalence of type 2 diabetes mellitus (33.0% vs. 12.0%, p = 0.019), greater metabolic dysregulation (63.0% vs. 17.0%, p < 0.001), and elevated alanine aminotransferase (ALT) levels (38.0 IU/L vs. 32.0 IU/L, p = 0.045) compared to non-MAFLD patients. While OS and RFS rates were marginally better in the MAFLD group, differences were not statistically significant (p > 0.05). Notably, MAFLD significantly increased mortality in female HCC patients, but not in males. Significant predictors of progression included Child-Pugh grade B, tumour size, and microvascular invasion. Conclusion MAFLD does not significantly impact OS or RFS following radical resection of HCC. However, MAFLD is associated with increased mortality in female patients, highlighting the need for gender-specific monitoring and management strategies in MAFLD-related HCC cases. Further large-scale studies are required to confirm these findings and elucidate the underlying mechanisms.

The circadian system plays a crucial role in regulating metabolic homeostasis at both systemic and tissue levels by synchronizing the central and peripheral clocks with exogenous time cues, known as zeitgebers (such as the light/dark cycle). Our body's behavioral rhythms, including sleep-wake cycles and feeding-fasting patterns, align with these extrinsic time cues. The body cannot effectively rest and repair itself when circadian rhythms are frequently disrupted. In many shift workers, the internal rhythms fail to fully synchronize with the end and start times of their shifts. Additionally, exposure to artificial light at night (LAN), irregular eating patterns, and sleep deprivation contribute to circadian disruption and misalignment. Shift work and jet lag disrupt the normal circadian rhythm of liver activity, resulting in a condition known as "circadian disruption". This disturbance adversely affects the metabolism and homeostasis of the liver, contributing to excessive fat accumulation and abnormal liver function. Additionally, extended working hours, such as prolonged night shifts, may worsen the progression of non-alcoholic fatty liver disease (NAFLD) toward non-alcoholic steatohepatitis (NASH) and increase disease severity. Studies have demonstrated a positive correlation between night shift work (NSW) and elevated liver enzymes, indicative of hepatic metabolic dysfunction, potentially increasing the risk of hepatocellular carcinoma (HCC) related to NAFLD. This review consolidates research findings on circadian disruption caused by NSW, late chronotype, jet lag, and social jet lag, drawing insights from studies involving both humans and animal models that investigate the effects of these factors on circadian rhythms in liver metabolism.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a major global health concern due to its association with increased mortality. While previous studies have indicated a link between NAFLD and mortality, variations in risk factors such as age, sex, and disease severity warrant a comprehensive meta-analysis to clarify these associations. This meta-analysis aimed to evaluate the overall cardiovascular disease (CVD) mortality risk associated with NAFLD, considering various subgroups defined by age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. A systematic search of eight studies was conducted to assess the hazard ratios (HRs) for all-cause and CVD mortality associated with NAFLD. Heterogeneity among studies was evaluated using the I² statistic, and subgroup analyses were performed based on participant age, sex, disease severity, presence of cirrhosis or fibrosis, study quality, and follow-up duration. NAFLD was significantly associated with an increased risk of all-cause mortality (HR = 1.34, 95% CI: 1.17-1.54, I² = 80.0%). Subgroup analyses revealed that individuals aged ≥50 years (HR = 1.50, 95% CI: 1.31-1.73) and males (HR = 1.43, 95% CI: 1.29-1.59) had a higher mortality risk. Patients with nonalcoholic steatohepatitis (NASH) showed a significant association with both overall (HR = 1.37, 95% CI: 1.14-1.65) and CVD mortality (HR = 1.56, 95% CI: 1.25-1.97). The presence of cirrhosis or fibrosis further elevated the risk of mortality (HR = 3.22, 95% CI: 2.40-4.33). However, NAFLD was not significantly associated with CVD mortality in the overall analysis (HR = 1.13, 95% CI: 0.92-1.38). Heterogeneity was high across most subgroups, indicating varying effects based on study characteristics. NAFLD is significantly associated with increased all-cause mortality, particularly in older individuals, males, and those with NASH or cirrhosis/fibrosis. The association with CVD mortality was not significant in the overall analysis but was evident in specific subgroups. These findings underscore the importance of early detection and tailored management of NAFLD to mitigate its impact on mortality. Further research is needed to elucidate the mechanisms linking NAFLD with adverse health outcomes and to develop effective interventions.

The cardiometabolic index (CMI) is an emerging and effective indicator for predicting the presence of metabolic-associated fatty liver disease (MAFLD). This study aims to investigate the relationship between CMI and MAFLD using data from NHANES 2017-2020. In this cross-sectional study, a total of 3,749 subjects were included. The study conducted a thorough analysis of CMI with three multivariate logistic regression models, subgroup analyses, and restricted cubic splines (RCS) were utilized. Using multifactorial logistic regression as the primary method of analysis, we found that a higher CMI was also significantly associated with an increased risk of MAFLD (OR = 1.45, 95% CI (1.05-2.01)). This result was further visualized by the RCS curve: There was a non-linear positive correlation between CMI and MAFLD incidence (the turning point is CMI = 0.4554). These findings were strongly reinforced by subsequent subgroup and sensitivity analyses. There is a robust positive relationship between the CMI and the risk of MAFLD, providing valuable clinical benefits for early detection and screening of MAFLD. It is important to highlight the presence of a non-linear association between CMI and MAFLD, with an inflection point identified at CMI = 0.4554.

The current study aimed to evaluate the serum levels of nitric oxide (NO) and adropin in males with non-alcoholic fatty liver disease (NAFLD) induced erectile dysfunction (ED) and NAFLD patients without ED and controls. The current study selected 165 participants from the hepatology department from November 2021 to November 2022. The patients were either suffering from NAFLD with normal liver functions or non-alcoholic steatohepatitis with abnormal liver functions. They were diagnosed by abdominal ultrasonography. Participants were evaluated using the validated Arabic version of the International Index of Erectile Function (ArIIEF-5), the Arabic form of the Generalized Anxiety Disorder-7 (GAD-7) questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Noteworthy, there were significant positive correlations between ArIIEF-5 score, NO, adropin and total testosterone (r = 0.380, p = 0.001; r = 0.507, p =  < 0.001; r = 0.246, p = 0.038, respectively). Meanwhile, there were significant negative correlations between ArIIEF-5 score, creatinine, duration of the disease and scores of GAD-7 and PHQ-9 (r = -0.656, p =  < 0.001; r = -0.368, p = 0.002; r = -0.663, p =  < 0.001; r = -0.248, p = 0.037, respectively). Finally, a linear regression analysis revealed that GAD-7, creatinine, and adropin were the only strong independent predictors of ArIIEF-5, as the 95% confidence interval in the form of upper and lower bounds was -0.349, -0.843, p < 0.001, -6.507, -18.402, p < 0.001, 0.476, 0.117, and p 0.002, respectively. Impaired NO and adropin levels play a potential role in the development of ED in patients with NAFLD.

Metabolic-associated fatty liver disease and liver fibrosis are intimately linked to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Transient elastography (TE) and point shear wave elastography (pSWE) were used to measure liver stiffness in patients who met the ultrasound criteria for steatotic liver diseases (SLD). This study compared two methods for estimating liver stiffness in patients with SLD, which in turn correlated with liver fibrosis.

Ultrasound B-mode imaging was used to identify SLD. In total, 250 MAFLD patients were recruited. Patient characteristics, laboratory investigations, and liver stiffness measurements using TE and pSWE were assessed on the same day.

In the study, 56.0% of the patients were male, with a mean age of 41.5 ± 10.7 years. The correlation between TE and pSWE was significant (Spearman's r = 0.867*, p < 0.001). The Bland-Altman Plot analysis confirmed this, with 97.5% of variations in LSM falling within 95% agreement ranges. Cohen's κ was used to assess the agreement between TE and pSWE fibrosis stages, showing almost perfect agreement (83.5% kappa agreement) and a strong association between pSWE and TE in the assessment fibrosis stages.

In patients with MAFLD, TE, and SWE are reliable methods for measuring liver stiffness and can be used as non-invasive screening tools for the assessment of fibrosis in SLD.

Nonalcoholic fatty liver disease (NAFLD) is expanding as a global health problem with approximately 25% of the world's population affected by it. Dietary modification is one of the most important strategies for preventing NAFLD. The association between nutrient density and the Healthy Eating Index 2015 (HEI2015) with NAFLD demonstrates that nutrient density is an independent predictor of NAFLD in Iranian adults [fully adjusted model: OR (95% CI)tertile3vs.1: 0.68 (0.54-0.85), P for trend = 0.001]. However, a favorable association between NAFDL and diet quality (HEI 2015) is more pronounced in participants with abdominal obesity [fully adjusted model: OR (95% CI)tertile3vs.1: 0.63 (0.41-0.98), P for trend = 0.03]. Based on the gender-stratified path analysis, diet quality indirectly through Waist-to-Height Ratio (WHtR), C-reactive protein (CRP), and metabolic syndrome in women, and men through WHtR, hemoglobin A1c (HBA1c), CRP, and metabolic syndrome affects NAFLD. Nutrient density directly and indirectly in women through WHtR, CRP, and metabolic syndrome, and in men indirectly through WHtR, hemoglobin A1c, and metabolic syndrome negatively affect NAFLD. Hence, in these subjects; we can provide early dietary intervention and education to prevent progression to NAFLD.

Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan.

This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire.

A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD.

Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.

The occurrence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. The link between serum remnant cholesterol (RC) to high-density lipoprotein cholesterol (HDL-C) ratio and NAFLD remains unclear. Therefore, we sought to clarify the relationship between the RC/HDL-C ratio and the NAFLD.

Data for our cross-sectional study came from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) with 2,269 participants. Associations between RC/HDL-C levels and the prevalence of NAFLD and hepatic fibrosis were evaluated using adjusted multivariate logistic regression analyses. A generalized additive model examined the non-linear relationship between RC/HDL-C and the probability of developing NAFLD.

Among 2,269 participants, 893 (39.36%) were diagnosed with NAFLD. In each of the three models, RC/HDL-C and NAFLD had a strong positive statistical relationship: model 1 (OR = 9.294, 95%CI: 6.785, 12.731), model 2 (OR = 7.450, 95%CI: 5.401, 10.278), and model 3 (OR = 2.734, 95%CI: 1.895, 3.944). In addition, the subgroup analysis by gender and BMI suggested that RC/HDL-C showed a positive correlation with NAFLD. The RC/HDL-C ratio was positively correlated with the degree of liver steatosis. There was an inverted U-shaped connection between the prevalence of NAFLD and RC/HDL-C, with an inflection point of 0.619 for all participants and 0.690 for men. Receiver operating characteristic (ROC) analysis showed that the predictive value of RC/HDL-C for NAFLD (area under the curve: 0.7139; 95%CI: 0.6923, 0.7354; P < 0.001), was better than traditional lipid parameters.

Increased RC/HDL-C levels are independently associated with an increased risk of NAFLD and the severity of liver steatosis in the American population. In addition, the RC/HDL-C ratio can be used as a simple and effective non-invasive biomarker to identify individuals with a high risk of NAFLD.

Ultrasonography is a noninvasive and widely accessible modality in clinical practice. Recently, ultrasonography has been used to evaluate tissue stiffness; the two representative techniques are transient elastography (FibroScan®) and shear wave elastography. These modalities are now generally used for the assessment of liver fibrosis, the prediction of hepatocarcinogenesis, and determining prognosis. In addition, shear wave elastography is available, not only for the liver but also for various other organs, including the breast and brain. In the breast and brain, shear wave elastography distinguishes malignant lesions from benign ones. Moreover, shear wave elastography can be useful for differentiating between ischemic and hemorrhagic strokes. This review summarizes the recent progress in transient elastography and shear wave elastography of the liver and introduces the advantages of ultrasonographic assessment of tissue stiffness in various organs, including the breast, brain, kidney, heart, thyroid, pancreas, muscle, and bone.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important entity in patients with type-2 diabetes (T2D). Exploring the prevalence and related factors of MASLD is vital toward developing effective methods of diagnosis and treatment. The objective of this study was to determine the prevalence of MASLD in persons with obesity and T2D.

This cross-sectional study was conducted at a private healthcare facility (Medicell Clinics) in Karachi, Pakistan, reviewing records from January to December 2022. Persons of either gender aged 18 or above with a diagnosis of T2D and/or obesity were analyzed.

Of a total of 646 persons, 430 (66.6%) were females. The mean age was 48.58 ± 13.88 years, ranging between 18 and 85 years. T2D was noted in 351 (54.3%) patients, while obesity was observed in 593 (91.8%) persons, 396 (61.3%) had MASLD. Persons having MASLD had significantly higher body mass index (31.16 ± 5.13 vs 28.14 ± 4.76 kg/m2, p < 0.001). Likewise, obesity was significantly associated with MASLD (94.9 vs 86.8%, p < 0.001). The odds ratios (OR) and 95% confidence intervals (CIs) are reported in multivariate logistic regression table. Persons with T2DM (OR = 1.519, p = 0.009), and obesity (OR = 2.651, p = 0.001) showed significantly increased odds of having MASLD. The analysis revealed that individuals in the age-group of 18-40 (OR = 1.627, p = 0.014) had increased odds of having MASLD.

The prevalence of MASLD was very high in persons with T2D, and obesity. Type-2 diabetes with or without obesity, or the other way around, significantly increases the risk of MASLD. Therefore, these persons should be screened for MASLD to improve clinical outcomes in the affected people.

Latif S, Ahsan T. Prevalence of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) in Persons with Obesity and Type 2 Diabetes Mellitus: A Cross-sectional Study. Euroasian J Hepato-Gastroenterol 2024;14(2):129-133.

There is an international consensus among experts advocating for the classification of fatty liver disease as a metabolic condition. However, some authors have raised concerns that this metabolic-centric framing may result in the underdiagnosis of metabolicdysfunction-associated steatotic liver disease (MASLD) in lean individuals. The present study was carried out with the objective of describing metabolic characteristics in MASLD and the prevalence of lean MASLD in the general population.

We carried out a hospital-based cross-sectional study. A pre-tested proforma was used to collect data on socio-demographic factors, lifestyle factors, and medical history. Transient elastography and blood investigations were carried out in all patients. The identification of independent predictors for MASLD and liver fibrosis was carried out using multivariable logistic regression. A test of interaction was conducted for studying effect modification in the association of diabetes and MASLD by subgroups of body mass index (BMI).

A total of 1,243 participants were interviewed and screened for MASLD. The overall prevalence of MASLD was 43.7% (n = 543), with the prevalence of lean MASLD being 4.3% (n = 53). The prevalence of MASLD in lean vs non-lean subjects differed (21.3 vs 66.7%, p < 0.001). Of the total MASLD cases, lean MASLD constituted 9.7% of cases. The association of diabetes and MASLD did not differ in subgroups by BMI. The test for interaction to detect effect modification was not statistically significant (p = 0.673).

The results support laying emphasis on metabolic dysfunction as a key criterion when defining fatty liver disease. The findings emphasize the shared metabolic underpinnings between lean and non-lean MASLD and advocate for inclusive approaches in diagnosis, management, and public health initiatives.

Prasad M, Bhardwaj N, Gupta E, et al. Prevalence and Predictors for Lean Fatty Liver Disease in General Population Attending a COVID-19 Vaccination Center in a Tertiary Care Hospital in India. Euroasian J Hepato-Gastroenterol 2024;14(2):145-150.

Fat accumulation in the liver is affecting 38% of the global population. It can also occur in normal-weight individuals, termed lean non-alcoholic fatty liver disease (NAFLD). This study examines Asian and Western body mass index (BMI) criteria, as well as metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) diagnostic guidelines, in lean fatty liver cases within a healthcare setting.

This study was cross-sectional included 111 lean patients diagnosed with NAFLD using either ultrasound or VCTE from January 2023 to March 2024. Anthropometric, laboratory and non-invasive liver fibrosis evaluation parameters were used. The study assessed clinical characteristics and metabolic risk factors of patients with BMI ≤ 23 kg/m2 and BMI between 23 and ≤ 25 kg/m2 using MASLD and MAFLD diagnostic criteria.

The cohort included NAFLD patients with a mean age of 43.3 years (±13.2 years). Of the participants, 33% were diagnosed through ultrasonography, whereas 67% diagnosis were made via Fibro scan. Majority were male 92 (83%), while females were 19 (17%) of the entire group. The lean NAFLD criteria for Asia and the West were satisfied by 43 (39%) persons with a BMI ≤ 23 kg/m2 and 68 (61%) individuals with a BMI between 23 and ≤ 25 kg/m2, respectively. The average body mass index (BMI) was 23.0 ± 1.5 kg/m2. Diabetes was observed in 16%, hypertension 11%, and ischemic heart disease in 2%. Out of the total individuals, 92 satisfied the MASLD-MAFLD criteria, whereas 18 did not qualify the MAFLD criteria for diagnosis and were classed as MASLD-Alone. Elevated triglycerides, insulin resistance (HOMA-IR ≥ 2), and three or more cardiometabolic risk factors (CMRF) were significant in the MASLD-MAFLD group compared to the MASLD-Alone group (p < 0.05). Comparing BMI criteria, no significant differences were found in terms of fibrosis between the Western and Asian lean NAFLD BMI criteria's (p = 0.243).

Lean NAFLD is a major global health concern. Applying non-Asian BMI criteria (BMI ≤ 25 kg/m2) for lean Asians improves early detection and intervention for at-risk individuals. Accurate use of MAFLD and MASLD criteria is essential to prevent confusion in diagnosing lean NAFLD. Further multicenter investigations with larger sample numbers are required to corroborate these results in our community.

Nazir S, Abbas Z, Gazder DP, et al. Characterizing Nonalcoholic Fatty Liver Disease (NAFLD) in Lean Individuals at a Tertiary Care Hospital: A Cross-sectional Study. Euroasian J Hepato-Gastroenterol 2024;14(2):198-204.

Non-alcoholic fatty liver disease (NAFLD) was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol. Alcoholic liver disease (ALD) has many similarities to NAFLD in both pathogenesis and histology. This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity. Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease. This new term, however, has the disadvantage of the use of terms that may be perceived as derogatory. The terms fatty and non-alcoholic have negative connotations in many cultures. In addition, non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis. Recently, an international collaborative effort, with participants from 56 countries, after a global consultation process, recommended to change the nomenclature to steatotic liver disease -including metabolic dysfunction- associated steatotic liver disease, metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD. The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis, prognosis and treatment.

Limited research has been conducted to quantitatively assess the impact of systemic inflammation in metabolic dysfunction-associated fatty liver disease (MAFLD) and sub-clinical carotid atherosclerosis (SCAS). The systemic immune-inflammation index (SII), which integrates inflammatory cells, has emerged as a reliable measure of local immune response and systemic inflammation Therefore, this study aims to assess the mediating role of SII in the association between MAFLD and SCAS in type 2 diabetes mellitus (T2DM).

This study prospectively recruited 830 participants with T2DM from two centers. Unenhanced abdominal CT scans were conducted to evaluate MAFLD, while B-mode carotid ultrasonography was performed to assess SCAS. Weighted binomial logistic regression analysis and restricted cubic splines (RCS) analyses were employed to analyze the association between the SII and the risk of MAFLD and SCAS. Mediation analysis was further carried out to explore the potential mediating effect of the SII on the association between MAFLD and SCAS.

The prevalence of both MAFLD and SCAS significantly increased as the SII quartiles increased (P<0.05). MAFLD emerged as an independent factor for SCAS risk across three adjusted models, exhibiting odds ratios of 2.15 (95%CI: 1.31-3.53, P < 0.001). Additionally, increased SII quartiles and Ln (SII) displayed positive associations with the risk of MAFLD and SCAS (P < 0.05). Furthermore, a significant dose-response relationship was observed (P for trend <0.001). The RCS analyses revealed a linear correlation of Ln (SII) with SCAS and MAFLD risk (P for nonlinearity<0.05). Importantly, SII and ln (SII) acted as the mediators in the association between MAFLD and SCAS following adjustments for shared risk factors, demonstrating a proportion-mediated effect of 7.8% and 10.9%.

SII was independently correlated with MAFLD and SCAS risk, while also acting as a mediator in the relationship between MAFLD and SCAS.

Life's essential' 8 (LE8) is a newly updated cardiovascular health (CVH) metrics from the American Heart Association, with close relevance to metabolism. Our objective is to explore the association between LE8 scores and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis in American adults.

This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, encompassing adults aged 20 years or older. Validated non-invasive scoring systems were employed to define liver steatosis and advanced liver fibrosis. Multivariable logistic regression and smooth curve fitting techniques were applied to evaluate the associations. All analyses were adjusted for the survey' complex design parameters and accounted for sample weights.

A total of 11,820 participants were included. A higher LE8 score was found to be inversely associated with the incidence of MAFLD and advanced liver fibrosis, with odds ratios (OR) of 0.64 (95% CI: 0.57-0.71) for MAFLD and 0.75 (95% CI: 0.61-0.92) for advanced liver fibrosis per 1 standard deviation (SD) increase in LE8 score. Similar patterns were found in the relationship between health behaviors/factors score and incidence of MAFLD and advanced liver fibrosis. In subgroup analyses, the interaction test showed that age, education level, marital status, CVD, hypertension and diabetes had a significant impact on the association between LE8 score and MAFLD (all P for interaction < 0.05). Among male, elderly, wealthy, other race, CVD, diabetes and depression participants, the correlation between LE8 score and advanced liver fibrosis was not statistically significant (P > 0.05). Younger participants exhibited a more pronounced negative association between the CVH metric and both MAFLD and advanced life fibrosis.

LE8 and its subscales score were inversely associated with the presence of MAFLD and advanced liver fibrosis in non-linear patterns. Optimal LE8 score may significantly reduce the risk of liver steatosis and fibrosis.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/d. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is an overlooked and undetected pathology, which affects more than 32% of adults worldwide. NAFLD is becoming more common in Western industrialised countries, particularly in patients with central obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Although NAFLD has traditionally been interpreted as a liver disease with a high risk of liver-related complications, NAFLD is an underappreciated and independent risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Treatment options to counteract both the progression and development of cardiovascular disease and NAFLD include lifestyle interventions, such as weight loss, increased physical activity and dietary modification, and optimal medical therapy of comorbid conditions; nevertheless, further studies are needed to define optimal treatment strategies for the prevention of both hepatic and cardiovascular complications of NAFLD.

Obesity is a heterogeneous condition which results from complex interactions among sex/gender, sociocultural, environmental, and biological factors. Obesity is more prevalent in women in most developed countries, and several clinical and psychological obesity complications show sex-specific patterns. Females differ regarding fat distribution, with males tending to store more visceral fat, which is highly correlated to increased cardiovascular risk. Although women are more likely to be diagnosed with obesity and appear more motivated to lose weight, as confirmed by their greater representation in clinical trials, males show better outcomes in terms of body weight and intra-abdominal fat loss and improvements in the metabolic risk profile. However, only a few relatively recent studies have investigated gender differences in obesity, and sex/gender is rarely considered in the assessment and management of the disease. This review summarizes the evidence of gender differences in obesity prevalence, contributing factors, clinical complications, and psychological challenges. In addition, we explored gender differences in response to obesity treatments in the specific context of new anti-obesity drugs.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions globally in parallel to the rising prevalence of obesity. Despite its significant burden, there is no approved pharmacotherapy specifically tailored for this disease. Many potential drug candidates for MAFLD have encountered setbacks in clinical trials, due to safety concerns or/and insufficient therapeutic efficacy. Nonetheless, several investigational drugs that mimic the actions of endogenous metabolic hormones, including thyroid hormone receptor β (THRβ) agonists, fibroblast growth factor 21 (FGF21) analogues, and glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed promising therapeutic efficacy and excellent safety profiles. Among them, resmetirom, a liver-targeted THRβ-selective agonist, has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis (MASH), the advanced form of MAFLD, and liver fibrosis in phase-3 clinical trials. These hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis, inflammation and fibrosis, but also improve metabolic profiles. Furthermore, these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects, suggesting their combined therapies may yield synergistic therapeutic benefits. Further in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies, enabling precision management of MAFLD and its associated comorbidities.

There has been an exponential increase in the global prevalence of fatty liver disease in recent years in association with the obesity pandemic worldwide. 'Metabolic dysfunction-associated fatty liver disease', the new terminology adopted by an international panel of experts in 2020 to largely replace the old term 'non-alcoholic fatty liver disease', has now been accepted by most hepatologists and diabetologists across the globe. The term metabolic dysfunction-associated fatty liver disease was created to better reflect the metabolicand liver-specific manifestations and complications of fatty liver disease. It is important to disseminate our current understanding of this enigmatic disease among the global scientific fraternity. Recent publications, including articles from the latest issue of Endocrinology & Metabolism Clinics of North America, are attempting to fill this knowledge gap.

Artificial intelligence (AI) in medicine is transforming healthcare by automating system tasks, assisting in diagnostics, predicting patient outcomes and personalising patient care, founded on the ability to analyse vast datasets. In paediatric endocrinology, AI has been developed for diabetes, for insulin dose adjustment, detection of hypoglycaemia and retinopathy screening; bone age assessment and thyroid nodule screening; the identification of growth disorders; the diagnosis of precocious puberty; and the use of facial recognition algorithms in conditions such as Cushing syndrome, acromegaly, congenital adrenal hyperplasia and Turner syndrome. AI can also predict those most at risk from childhood obesity by stratifying future interventions to modify lifestyle. AI will facilitate personalised healthcare by integrating data from 'omics' analysis, lifestyle tracking, medical history, laboratory and imaging, therapy response and treatment adherence from multiple sources. As data acquisition and processing becomes fundamental, data privacy and protecting children's health data is crucial. Minimising algorithmic bias generated by AI analysis for rare conditions seen in paediatric endocrinology is an important determinant of AI validity in clinical practice. AI cannot create the patient-doctor relationship or assess the wider holistic determinants of care. Children have individual needs and vulnerabilities and are considered in the context of family relationships and dynamics. Importantly, whilst AI provides value through augmenting efficiency and accuracy, it must not be used to replace clinical skills.

Since the results of previous observational studies on the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and pancreatic cancer were still controversial and inconsistent, we performed a systematic evaluation and meta-analysis of cohort studies to assess any potential association.

We conducted a systematic search of PubMed, Embase, and Web of Science databases from the database's inception up to November 30, 2023. For summary purposes, hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models, and subgroup and sensitivity analyses were performed as well. The Egger's test and Begg's test were utilized to detect the publication bias.

This meta-analysis included nine cohort studies with a total of 10,428,926 participants. The meta-analysis demonstrated an increased risk of pancreatic cancer in those with MASLD (HR = 1.32, 95% CI: 1.10-1.59, P = 0.003) with moderate heterogeneity (I2 = 54%, P = 0.03). Subsequent subgroup analyses revealed that the pooled HRs remained significantly unchanged, irrespective of the study area, nomenclature of fatty liver disease, and sample size. The results of the sensitivity analyses remained unchanged. No evidence of publication bias was found.

This meta-analysis indicated that MASLD was associated with a higher risk of pancreatic cancer. To further strengthen the association, future prospective cohort studies should take into account different ethnic groups, diagnostic methods of fatty liver, the severity of MASLD, and potential confounding factors, as well as explore the potential mechanisms of pancreatic cancer development in MASLD patients.

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023489137.

Depressive symptoms are frequently observed in patients with Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a prevalent metabolic disorder that affects many individuals. It is not yet clear whether there is an association between serum chromium levels and depression.

The purpose of this research was to explore the association between serum chromium level and the manifestation of depression among patients with MAFLD.

The selection of 1837 patients diagnosed with MAFLD was based on data obtained from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database in this research. The Patient Health Questionnaire-9 (PHQ-9) was employed to evaluate the severity of depression. The researchers utilized logistic regression models that were weighted for multiple variables to investigate the association between depression and serum chromium levels.

In our study, we found that 8.98% of US adults with MAFLD were suffering from depression at the time of evaluation. In the logistic regression model, serum chromium levels showed an inverse association with depression (OR=0.82, 95%CI: 0.69-0.96; p=0.016), this relationship remained after adjusting for fully confounding factors (OR=0.83, 95%CI: 0.71-0.97; p=0.021), subgroup analyses showed that the association between serum chromium levels and depression existed in relatively high-prevalence of depression groups.

Patients diagnosed with MAFLD have a greater likelihood of experiencing depression, whereas individuals with higher levels of serum chromium are less likely to suffer from depression, and this association persists even after adjusting for other factors. These findings indicate supplementing chromium may be a viable treatment for their depressive symptoms.

Over the last years non-alcoholic fatty liver disease (NAFLD) has grown into the most common chronic liver disease globally, affecting 17-38% of the general population and 50-75% of patients with obesity and/or type 2 diabetes mellitus (T2DM). NAFLD encompasses a spectrum of chronic liver diseases, ranging from simple steatosis (non-alcoholic fatty liver, NAFL) and non-alcoholic steatohepatitis (NASH; or metabolic dysfunction-associated steatohepatitis, MASH) to fibrosis and cirrhosis with liver failure or/and hepatocellular carcinoma. Due to its increasing prevalence and associated morbidity and mortality, the disease-related and broader socioeconomic burden of NAFLD is substantial. Of note, currently there is no globally approved pharmacotherapy for NAFLD. Similar to NAFLD, osteoporosis constitutes also a silent disease, until an osteoporotic fracture occurs, which poses a markedly significant disease and socioeconomic burden. Increasing emerging data have recently highlighted links between NAFLD and osteoporosis, linking the pathogenesis of NAFLD with the process of bone remodeling. However, clinical studies are still limited demonstrating this associative relationship, while more evidence is needed towards discovering potential causative links. Since these two chronic diseases frequently co-exist, there are data suggesting that anti-osteoporosis treatments may affect NAFLD progression by impacting on its pathogenetic mechanisms. In the present review, we present on overview of the current understanding of the liver-bone cross talk and summarize the experimental and clinical evidence correlating NAFLD and osteoporosis, focusing on the possible effects of anti-osteoporotic drugs on NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear.

Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant.

A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]).

Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

The relationships between heavy metals and fatty liver, especially the threshold values, have not been fully elucidated. The objective of this research was to further investigate the correlation between blood heavy metal exposures and the risk of Metabolic dysfunction Associated Fatty Liver Disease (MAFLD) in adults.

Laboratory data on blood metal exposure levels were obtained from National Health and Nutrition Examination Survey (NHANES) data for the period 2015 to 2020 for a cross-sectional study in adults. Associations between blood levels of common heavy metals and the risk of MAFLD in adults were analyzed using multifactorial logistic regression and ranked for heavy metal importance using a random forest model. Finally, thresholds for important heavy metals were calculated using piecewise linear regression model.

In a multifactorial logistic regression model, we found that elevated levels of selenium (Se) and manganese (Mn) blood exposure were strongly associated with the risk of MAFLD in adults. The random forest model importance ranking also found that Se and Mn blood exposure levels were in the top two positions of importance for the risk of disease in adults. The restricted cubic spline suggested a non-linear relationship between Se and Mn blood exposure and adult risk of disease. The OR (95% CI) for MAFLD prevalence was 3.936 (2.631-5.887) for every 1 unit increase in Log Mn until serum Mn levels rose to the turning point (Log Mn = 1.10, Mn = 12.61 μg/L). This correlation was not significant (p > 0.05) after serum Mn levels rose to the turning point. A similar phenomenon was observed for serum Se levels, with a turning point of (Log Se = 2.30, Se = 199.55 μg/L).

Blood heavy metals, especially Se and Mn, are significantly associated with MAFLD in adults. They have a non-linear relationship with a clear threshold.

With the increasing incidence of diabetes worldwide, patients diagnosed with diabetes has been getting younger. Previous studies have shown that high remnant cholesterol (RC) level leads to an increased risk of cardiovascular disease events. However, the relationship between RC levels and newly diagnosed early-onset type 2 diabetes mellitus (T2DM) is unknown. This study aimed to explore the association between RC and newly diagnosed early-onset T2DM.

A total of 606 patients newly diagnosed with early-onset T2DM and 619 gender-matched subjects with normal blood glucose levels were retrospectively enrolled in this study. All T2DM patients showed onset age of 18-40 years. Binary logistic regression analysis was performed to analyze independent risk factors and receiver operating characteristic (ROC) analysis was used to explore the predictive value of RC and other unconventional lipids. Moreover, the correlation between RC and insulin resistance in patients with newly diagnosed early-onset T2DM was also examined with binary logistic regression analysis and Spearman correlation analysis.

Increased RC level was an independent risk factor for early-onset T2DM (p < .05). The area under the curve on ROC analysis of RC was 0.805, 95% confidence interval (CI) was 0.781 ~ 0.826, sensitivity was 82.18% and specificity was 66.24%, which showed higher predictive value than those of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and total cholesterol (TC)/HDL-C ratio. Cutoff value of RC was 0.32 mmol/L. Level of RC in early-onset T2DM patients with moderate or severe insulin resistance was significantly higher than that in patients with mild insulin resistance (p < .0001). No difference in RC levels was found between patients with moderate and severe insulin resistance (p > .05). RC was still correlated with insulin resistance after adjusting the conventional lipid parameters (TG, TC, HDL-C, and low-density lipoprotein cholesterol) using partial correlation analysis.

RC level was higher in patients with early-onset T2DM and was correlated to the degree of insulin resistance as well. Patients aged 18-40 years with RC >0.32 mmol/L showed an increased risk of developing T2DM.

Objective To assess the prevalence and clinical correlates of non-alcoholic fatty liver disease (NAFLD) identified by computed tomography (CT) in the general population compared with ultrasonography (US). Methods Four hundred and fifty-eight subjects who received health checkups at Meijo Hospital in 2021 and underwent CT within a year of US in the past decade were analyzed. The mean age was 52.3±10.1 years old, and 304 were men. Results NAFLD was diagnosed in 20.3% by CT and in 40.4% by the US. The NAFLD prevalence in men was considerably greater in subjects 40-59 years old than in those ≤39 years old and in those ≥60 years old by both CT and US. The NAFLD prevalence in women was substantially higher in the subjects 50-59 years old than in those ≤49 years old or those ≥60 years old on US, while no significant differences were observed on CT. The abdominal circumference, hemoglobin value, high-density lipoprotein cholesterol level, albumin level, and diabetes mellitus were independent predictors of NAFLD diagnosed by CT. The body mass index, abdominal circumference, and triglyceride level were independent predictors of NAFLD diagnosed by the US. Conclusion NAFLD was found in 20.3% of CT cases and 40.4% of US cases among recipients of health checkups. An "inverted U curve" in which the NAFLD prevalence rose with age and dropped in late adulthood was reported. NAFLD was associated with obesity, the lipid profile, diabetes mellitus, hemoglobin values, and albumin levels. Our research is the first in the world to compare the NAFLD prevalence in the general population simultaneously by CT and US.

Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) has become a global epidemic, and air pollution has been identified as a potential risk factor. This study aims to investigate the non-linear relationship between ambient air pollution and MASLD prevalence.

In this cross-sectional study, participants undergoing health checkups were assessed for three-year average air pollution exposure. MASLD diagnosis required hepatic steatosis with at least 1 out of 5 cardiometabolic criteria. A stepwise approach combining data visualization and regression modeling was used to determine the most appropriate link function between each of the six air pollutants and MASLD. A covariate-adjusted six-pollutant model was constructed accordingly.

A total of 131,592 participants were included, with 40.6% met the criteria of MASLD. "Threshold link function," "interaction link function," and "restricted cubic spline (RCS) link functions" best-fitted associations between MASLD and PM2.5, PM10/CO, and O3 /SO2/NO2, respectively. In the six-pollutant model, significant positive associations were observed when pollutant concentrations were over: 34.64 µg/m3 for PM2.5, 57.93 µg/m3 for PM10, 56 µg/m3 for O3, below 643.6 µg/m3 for CO, and within 33 and 48 µg/m3 for NO2. The six-pollutant model using these best-fitted link functions demonstrated superior model fitting compared to exposure-categorized model or linear link function model assuming proportionality of odds.

Non-linear associations were found between air pollutants and MASLD prevalence. PM2.5, PM10, O3, CO, and NO2 exhibited positive associations with MASLD in specific concentration ranges, highlighting the need to consider non-linear relationships in assessing the impact of air pollution on MASLD.