Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the major causes of chronic liver disease among adolescents. However, epidemiological studies on MASLD in adolescents are still insufficient. In this study, we aim to investigate the global burden and the trend of MASLD in adolescents from 1990 to 2021.

The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of MASLD were calculated based on the Global Burden of Disease (GBD) 2021 study and stratified by sex, socio-demographic index (SDI), GBD regions, and countries. The temporal trends were examined using the average annual percentage change (AAPC) and joinpoint regression.

From 1990 to 2021, the global trends of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR) of MASLD show notable increase, and the male is significantly higher than the female in adolescents. According to the incidence and prevalence, nations with low SDI confront a higher burden of MASLD. Besides, the inequality of incidence and prevalence between different SDI regions have shrunk in 2021, but the inequality of DALYs and mortality are still exacerbated. Decomposition analysis revealed that population growth and epidemiological changes were the main reasons for the increase in the incidence of MASLD.

From 1990 to 2021, there is a significant upward trend in the incidence of MASLD among adolescents worldwide. Of particular note are male adolescents, East Asian regions, and groups living in high SDI countries.

Metabolic dysfunction associated steatotic liver disease (MASLD) is a universal hepatic disease, and many recent randomized clinical trials (RCTs) have explored whether hypoglycemic agents may be beneficial for its treatment. This study aimed to assess the relative effectiveness of each hypoglycemic agent for MASLD.

China National Knowledge Infrastructure（CNKI）, WanFang, Weipu, PubMed, Embase, The Cochrane Library, and Web of Science Core Collection were searched for RCTs on the efficacy of hypoglycemic agents in MASLD published up to December 31, 2024. All statistical analyses were performed using R version 4.3.3. The network meta-analysis was conducted using Bayesian statistical methods.

A total of 26 hypoglycemic agents for treating MASLD in 37 studies with 2406 participants were included. Empagliflozin was most effective in improving liver stiffness measurement (LSM), whereas liraglutide showed significant benefits in body weight, body mass index (BMI), and waist circumference. Both sodium-glucose co-transporter 2 (SGLT-2) inhibitors (e.g., empagliflozin) and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) improved liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), glucose metabolism (fasting plasma glucose [FPG], and homeostasis model assessment of insulin resistance [HOMA-IR]), and lipid profiles. Pioglitazone had limited benefits in these outcomes. Secondary outcomes such as inflammatory markers and fibrosis showed minimal changes.

Several hypoglycemic agents can improve laboratory and imaging indicators in adult patients with MASLD. Liraglutide is more effective than other agents, whereas empagliflozin emerged as the most effective for reducing LSM. However, different agents have different effects on the indicators; therefore, the relevant agents must be selected according to the specific patient condition.

This study aimed to investigate the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and NAFLD, as well as its relationship with hepatic steatosis and liver fibrosis, in a nationally representative sample of U.S. adults.

This cross-sectional study analyzed data from 3,529 participants from the National Health and Nutrition Examination Survey in 2017-2020. Multivariable logistic regression and subgroup analyses were used to assess the association between NHHR and NAFLD. Multivariate linear regression was employed to evaluate the relationship between NHHR and hepatic steatosis (controlled attenuation parameter) and liver fibrosis (liver stiffness measurement). Nonlinear relationships were explored through fitted smoothing curves and threshold effect analysis. Receiver operating curve (ROC) analysis was performed to compare the diagnostic performance of NHHR with body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC).

The study included 3,529 participants (mean age: 51.34 years, 95% CI: 49.97, 52.72), with 53.53% male. NHHR showed a significant positive association with NAFLD after adjusting for confounders (OR: 1.33, 95% CI: 1.24, 1.42). Subgroup analysis indicated a stronger association in females and individuals with normal weight. A nonlinear relationship was identified, with a significant positive association below an inflection point of 4 (OR: 1.52, 95% CI: 1.38, 1.68). NHHR was positively associated with hepatic steatosis but not with liver fibrosis. For NAFLD diagnosis, NHHR achieved an area under the curve (AUC) of 0.66, outperforming TC (AUC = 0.51) but indicating lower accuracy than BMI (AUC = 0.77) and HDL-C (AUC = 0.68).

NHHR is positively associated with NAFLD and hepatic steatosis in U.S. population, highlighting the important role of lipid control in the prevention and clinical management of NAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition with the potential to progress into liver cirrhosis or hepatocellular carcinoma, has become a significant global health concern due to its increasing prevalence alongside obesity and metabolic syndrome. Despite the promise of existing therapies such as thyroid hormone receptor-β (THR-β) agonists, PPAR agonists, FXR agonists, and GLP-1 receptor agonists, their effectiveness is limited by the complexity of the metabolic, inflammatory, and fibrotic pathways that drive MASLD progression, encompassing steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and reversible liver fibrosis. Recent advances in targeted therapeutics, including RNA interference (RNAi), mRNA-based gene therapies, monoclonal antibodies, proteolysis-targeting chimeras (PROTAC), peptide-based strategies, cell-based therapies such as CAR-modified immune cells and stem cells, and extracellular vesicle-based approaches, have emerged as promising interventions. Alongside these developments, innovative drug delivery systems are being actively researched to enhance the stability, precision, and therapeutic efficacy of these biotherapeutics. These delivery strategies aim to optimize biodistribution, improve target-specific action, and reduce systemic exposure, thus addressing critical limitations of existing treatment modalities. This review provides a comprehensive exploration of the underlying biological mechanisms of MASLD and evaluates the potential of these cutting-edge biotherapeutics in synergy with advanced delivery approaches to address unmet clinical needs. By integrating fundamental disease biology with translational advancements, it aims to highlight future directions for the development of effective, targeted treatments for MASLD and its associated complications.

Metabolic-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is an increasing global health challenge with substantial implications for metabolic and cardiovascular health (CVH). A recent study by Fu et al investigated the relationship between CVH metrics, specifically Life's Simple 7 and Life's Essential 8, and the prevalence of MAFLD. While this study offered important insights into the relationship between CVH and MAFLD, several methodological limitations, unaddressed confounding factors, and potential biases that could impact the interpretation of their findings should be considered. The study's cross-sectional nature restricted the ability to draw causal conclusions, and it did not fully account for potential confounding factors such as dietary habits, genetic predispositions, and medication use. Furthermore, relying on transient elastography to diagnose MAFLD introduces certain diagnostic limitations. Longitudinal study designs, advanced statistical modeling techniques, and diverse population groups should be utilized to strengthen future research. Exploring the mechanistic pathways that link CVH metrics to MAFLD through multi-omics approaches and interventional studies will be essential in formulating targeted prevention and treatment strategies. Structural equation modeling and machine learning techniques could provide a more refined analysis of these interrelated factors. Additionally, future research should employ longitudinal study designs and explore genetic and epigenetic influences to enhance our understanding of CVH and MAFLD interactions.

Recently, the non-high-density to high-density lipoprotein cholesterol ratio (NHHR) has gained growing attention as an indicator for predicting diseases associated with lipid metabolism. Hepatic steatosis and fibrosis are tightly associated lipid metabolism. Our study aims to analyze the correlations among NHHR, hepatic steatosis, and fibrosis. This study analysed data from 14,578 adults in the US National Health and Nutrition Examination Survey (2005-2018). The degree of hepatic steatosis was measured through the Fatty Liver Index (FLI), while liver fibrosis severity was evaluated with the Fibrosis-4 (FIB-4) index. Multivariate linear regression assessed the association between NHHR and the FLI and FIB-4 score. Smooth curve describing the relationship between NHHR and FLI or FIB-4. Additionally, a two-part linear regression model adopted in order to more accurately account for the nonlinear relationship, with threshold effects estimated through its two components. To confirm the robustness of the findings, interaction tests and subgroup analyses were conducted. The multivariate logistic regression analysis demonstrated a significantly positive correlation of lnNHHR with FLI across all three models. In Model 3, the association was (β = 11.14, 95%CI:10.38,11.90). Curve fitting indicated a nonlinear relationship. The positive correlation between lnNHHR and FLI persists across gender, BMI, and physical activity groups. Nevertheless, a notable negative correlation between lnNHHR and FIB-4 was observed in all three models. In Model 3, the relationship between lnNHHR and FIB-4 was as follows: (β = -0.20; 95% CI: -0.22, -0.17). Curve fitting revealed a V-shaped relationship, with threshold effect analysis identifying a breakpoint at 1.51. Above this threshold, the relationship was found to be statistically insignificant (p-value = 0.424). Receiver operating characteristic (ROC) curve analysis demonstrated that NHHR exhibited better predictive performance for MASLD compared to non-HDL-C, HDL-C, and LDL-C/HDL-C. The current study's findings suggest that elevated levels of NHHR correlate with a greater risk of hepatic steatosis among adults in the U.S. Our findings imply that NHHR may be a valuable tool in improving MASLD prevention strategies in the general population.

Non-alcoholic fatty liver disease (NAFLD) is a common hepatic manifestation of metabolic syndrome affecting 20-30 % of the adult population worldwide. This disease, which includes simple steatosis and non-alcoholic steatohepatitis, poses a significant risk for cardiovascular and metabolic diseases. Lifestyle modifications are crucial in the treatment of NAFLD; however, patient adherence remains challenging. As there is no specific treatment, drug repositioning is being researched as an alternative strategy. Statins, which are known for their cholesterol-lowering effects, are considered potential interventions for NAFLD. This review aimed to present the current understanding of the effects of statins on liver physiology in the context of NAFLD. The pathophysiology of NAFLD includes steatosis, inflammation, and fibrosis, which are exacerbated by dyslipidemia and insulin resistance. Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, have pleiotropic effects beyond cholesterol-lowering and affect pathways related to inflammation, fibrogenesis, oxidative stress, and microcirculation. Although clinical guidelines support the use of statins for dyslipidemia in patients with NAFLD, more studies are needed to demonstrate their efficacy in liver disease. This comprehensive review serves as a foundation for future studies on the therapeutic potential of statins in NAFLD.

Liver dysfunctions during pregnancy can either be pregnancy-specific or preexisting in acute or chronic form. Data on the prevalence of abnormal liver functions and dyslipidemia during pregnancy in Bangladesh are scarce since these tests are not typically done in routine prenatal screening. This study aims to investigate the prevalence of elevated liver enzymes and dyslipidemia and associated risk factors in a cohort of pregnant women in Bangladesh. This cross-sectional study included 194 pregnant women participants from different trimesters. A standardized questionnaire was used to collect baseline, demographic, and lifestyle data. Blood samples were collected from each participant to measure biochemical parameters such as liver enzymes (ALT and GGT), lipid profile (TC, TG, HDL-C, and LDL-C), glucose, and creatinine levels in the serum. Logistic regression analysis was applied to identify factors associated with liver dysfunction and lipid profile abnormalities. The average age of the participants was 25 ± 5 years. Overall, the prevalence of preeclampsia was 12.4%. Among participants, 27% had increased ALT levels, most in their third trimester, while 11.8% had elevated GGT levels, mostly in early pregnancy. 83.8% of the study subjects had general dyslipidemia, with the highest prevalence in the second trimester and 5.2% had mixed dyslipidemia. Several factors were significantly associated with ALT elevation, such as preeclampsia, elevated blood pressure, low HDL-C levels, high parity number, having a higher number of children, hypertensive disorders during pregnancy and inadequate knowledge about pregnancy diet. On the other hand, advanced maternal age, high gravidity, and mixed dyslipidemia were associated with elevated GGT levels. Conversely, age, hypertensive disorders during pregnancy, preeclampsia, and diabetes were associated with dyslipidemia. In conclusion, elevated levels of liver enzymes and an abnormal lipid profile are common among pregnant women in Bangladesh. Various factors are linked to abnormal liver enzymes and dyslipidemia in these participants. Monitoring liver function and lipid levels, along with proper prenatal care, can help reduce the risk of maternal and neonatal mortality.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of liver disease ranging from hepatic fat accumulation to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma in the absence of excessive alcohol consumption. MASLD is characterized by substantial inter-individual variability in terms of severity and rate of progression, with a prevalence that is generally higher in men than in women. Steroids metabolism is characterized by sexual dimorphism and may have an impact on liver disease progression; indeed, several therapeutic strategies targeting hormone receptors are under phase 2/3 development. Despite the fact that the importance of sexual dimorphism in the setting of MASLD is well recognized, the underlying molecular mechanisms that can potentially drive the disease toward progression are not clear. The aim of this review is to delve into the crosstalk between sexual dimorphism and steroid hormone perturbation under nutritional and pharmacological intervention.

The purpose of our study was to investigate the association between non-alcoholic fatty liver disease (NAFLD) and abdominal aortic aneurysms (AAA) progression using non-enhanced computed tomography (CT) and CT angiography (CTA).

Patients with AAA and age- and sex-matched healthy subjects who underwent abdominal CTA and non-enhanced CT examination between January 2015 and January 2023 from four hospitals were retrospectively analyzed. Patients with AAA were divided into progression (growth rate > 10 mL/year) and non-progression groups, as well as those with NAFLD and without NAFLD, based on abdominal CT results. The Kaplan-Meier and Cox regression were used to investigate the association between NAFLD and AAA progression.

A total of 151 patients with AAA (mean age: 69.1 ± 10.5 years old, 133 men) were included, among which 66 patients (43.7%) had NAFLD. During a median of 10.7 months (6.0-76.0 months), 57 patients (37.7%) had AAA progression. The prevalence of NAFLD was significantly higher in the AAA group compared to the control group (43.7% vs. 31.1%, p = 0.024). Multivariable regression analysis revealed that the NAFLD was independently associated with AAA progression (HR, 4.28; 95% CI, 2.20-8.31; p < 0.001). The area under curve of combined NAFLD and AAA maximal diameter was 0.857 for predicting AAA progression.

NAFLD on non-enhanced CT is an independent predictor of AAA progression. It can improve the diagnostic efficacy of predicting the progression of abdominal aortic aneurysms.

Not applicable. This research is a retrospective analysis.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a high prevalence. Recent data suggest that NAFLD may be an independent risk factor for cardiovascular disease (CVD). This study aimed to investigate the association between NAFLD and carotid high-risk plaque (HRP) as assessed by high-resolution magnetic resonance imaging (MRI), and to examine the diagnostic value of NAFLD.

A total of 125 patients with carotid plaques who underwent high-resolution MRI and unenhanced abdominal computed tomography (CT) examinations were included in this retrospective study. NAFLD was defined as a liver/spleen Hounsfield unit (HU) ratio <1.0 on a non-contrast CT scan. The criteria for defining HRP were at least one of the following features: fibrous cap rupture (FCR); a large lipid-rich necrotic core (LRNC) (occupying >40% of the wall area); or intraplaque hemorrhage (IPH). Univariable and multivariable logistic regression analyses were conducted to examined the association between HRP and NAFLD. The adjusted receiver operating characteristic (aROC) curve and the adjusted area under the curve (aAUC) with the 95% confidence interval (CI) were calculated for each model.

Compared with the patients without NAFLD, those with NAFLD had a higher prevalence of IPH, large LRNC, and FCR (all P<0.001). HRP was more commonly observed in the plaques of the NAFLD patients than the non-NAFLD patients (P<0.001). The multivariate analyses showed that NAFLD was an independent predictor of carotid HRP [odds ratio (OR) =12.06, 95% CI: 3.66-39.76, P<0.001]. The aROC curve analysis showed that NAFLD had an outstanding diagnostic ability (aAUC =0.95) in identifying HRP after adjusting for risk factors.

NAFLD is associated with carotid HRP as assessed by high-resolution MRI. CT-defined NAFLD may be a novel and robust predictor for identifying HRP.

Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global public health dilemma with wide-ranging social and economic implications. Diet and lifestyle modifications remain essential components of NAFLD management. The current study investigated the association between diet-related inflammation and NAFLD among 3110 Iranian adults participating in the Amol Cohort Study (AmolCS), employing the Structural Equation Modeling (SEM) approach.The inflammatory potential of the diet was quantified using an energy-adjusted dietary index (E-DII) score. Findings showed that in the total sample and separately in males, the E-DII score had a significant effect on NAFLD, with mediation through hypertension (βstandardized = 0.16, and 0.13, p < 0.001, respectively) and c-reactive protein (CRP) (βstandardized = 0.07, and 0.07, p < 0.001, respectively). In the total sample and separately in females, the E-DII score significantly affected NAFLD, with mediation through diabetes (βstandardized = 0.06, p < 0.001, and 0.07, p = 0.006, respectively). In full and both gender-specific models, dyslipidemia was a risk factor for NAFLD and partially mediated the effect of hypertension on NAFLD.The current study concluded a mediated association between dietary inflammation and NAFLD through hypertension, CRP, diabetes, and dyslipidemia, suggesting further longitudinal studies, especially in high-risk populations. These findings underscore the complex interplay between diet, inflammation, and NAFLD in Iranian adults.

Nonalcoholic fatty liver disease (NAFLD) encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol. Recently, traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver, among which Dendrobium nobile Lindl. powder has been affirmed by many doctors and patients to be effective. However, there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.

To survey the effect of combining Dendrobium nobile Lindl. powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.

Eighty patients with mild to moderate NAFLD participated in this retrospective study, classified into two groups: The observation group (n = 40) and the control group (n = 40). In November 2020 and November 2022, the study was conducted at People's Hospital of Chongqing Liang Jiang New Area. The control group received standard treatment, while the observation group received Dendrobium nobile Lindl. powder based on the control group. The study compared differences in traditional Chinese medicine clinical syndrome scores, liver fibrosis treatment, liver function indicators, lipid levels, and serum inflammatory factor levels before and after treatment, and we calculated the incidence of adverse reactions for both groups.

The total effective rate was 97.50% in the observation group and 72.5% in the control group. After 8 weeks of treatment, the main and secondary symptom scores remarkably decreased, especially in the observation group (P < 0.05), and there was a significant reduction in the serum levels of hyaluronic acid (HA), laminin (LN), human rocollagen III (PC III), and collagen type IV (CIV). The levels of HA, LN, PC III, and CIV were significantly lower in the observation group (P < 0.05). After 8 weeks, both groups indicated remarkable improvements in liver function and blood lipid levels, with the observation group having even lower levels (P < 0.05). Serum levels of interleukin-1β, tumor necrosis factor-α, and interleukin-8 also dropped significantly. The observation group had a lower rate of adverse reactions (5.00%) compared to the control group (22.50%).

Adding Dendrobium nobile Lindl. powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease. It also enhances hepatic function and lipid profile, ameliorates liver fibrosis indices, and lowers the risk of side effects. Consequently, this therapeutic protocol shows promise for clinical implementation and dissemination.

Non-alcoholic fatty liver disease (NAFLD) is a metabolically stressed liver injury closely related to insulin resistance and genetic susceptibility and has become the leading chronic liver disease in China.

To analyze the effectiveness of five Chinese patent medicines used alone or in combination with western medications (WM) for NAFLD using Bayesian network meta-analysis.

Searches were conducted in Embase, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, and SinoMed for randomized controlled trials (RCTs) on Danning tablets, Huazhi Rougan granules, Dangfei Liganning capsules, Kezhi capsules, and Qianggan capsules, either alone or in combination with WM for NAFLD, up to January 10, 2024. This study was screened based on pre-designed inclusion and exclusion criteria, and the risk of bias was evaluated using the Cochrane ROB2 tool. The primary outcome was clinical efficacy rate, while secondary outcomes included levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglycerides (TG), and Low-density lipoprotein cholesterol (LDL-C). These data will be analyzed using WinBUGS 1.4.3 and then visualized using Stata 14.0 software.

A total of 77 RCTs involving 7770 patients were included. The results indicated that Huazhi Rougan granules combined with WM (OR = 0.13, 95 % CI 0.05 ∼ 0.26) had a SUCRA probability value of 81.7 %, ranked first in clinical efficacy and significantly improved blood lipids levels including TG, High-density Lipoprotein Cholesterol (HDL-C), and LDL-C, Total cholesterol (TC). For the Chinese patent medicines alone, Danning tablets led with a 75.3 % clinical efficacy rate. Huazhi Rougan granules significantly increased levels of ALT (96.2 %) and AST (MD = -14.48, 95 % CI -23.38 ∼ -5.32). Dangfei Liganning capsules demonstrated significant efficacy in improving TG (73.1 %) and TC (83 %) levels.

In the treatment of NAFLD, the combination of Huazhi Rougan granules and WM demonstrated significant clinical effectiveness and improvement in blood lipid profiles. For different outcome indicators, Danning tablets used alone showed the highest clinical efficacy, while significant improvement in liver function indicators was best achieved with Huazhi Rugan granules used alone.

The aim of this study was to evaluate the potential effects of administering mangaba powder on liver function and somatic, oxidative and lipid metabolism parameters in rats fed a high-fat diet. Prepared mangaba powder has important amounts of phenolic compounds, vitamin C, dietary fiber and oligosaccharides. A total of 32 adult Wistar rats were initially randomized into two groups for the biological assay: normal-fat (NF, n = 16) and high-fat (HF, n = 16) diets for 21 days. These rats were subsequently subdivided into four groups: NF (n = 8), HF (n = 8), normal-fat diet with mangaba powder administration (NFMG, n = 8) and high-fat diet with mangaba powder administration (HFMG, n = 8). The treatment with mangaba powder (400 mg/kg) lasted an additional 28 days. Compared to the HF rats, the HFMG rats showed an 8% reduction in the body mass index. Treatment with mangaba reduced the serum cholesterol by 18%, as well as the hepatic deposition of triacylglycerides by 26% and cholesterol by 25%, in addition to increasing bile acid synthesis by 77% in this organ. Mangaba powder consumption attenuated the degree of hepatic steatosis, reduced lipid peroxidation and increased the serum and hepatic antioxidant capacity in HFMG rats. These results show that the consumption of mangaba powder had lipid-lowering, hepatoprotective and antioxidant effects, especially in HFMG rats, which may be associated with an additive and synergistic action between the bioactive compounds present in the product.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing in prevalence, impacting over a third of the global population. The advanced form of MASLD, Metabolic dysfunction-associated steatohepatitis (MASH), is on track to become the number one indication for liver transplant. FDA-approved pharmacological agents are limited for MASH, despite over 400 ongoing clinical trials, with only a single drug (resmetirom) currently on the market. This is likely due to the heterogeneous nature of disease pathophysiology, which involves interactions between highly individualized genetic and environmental factors. To apply precision medicine approaches that overcome interpersonal variability, in-depth insights into interactions between genetics, nutrition, and the gut microbiome are needed, given that each have emerged as dynamic contributors to MASLD and MASH pathogenesis. Here, we discuss the associations and molecular underpinnings of several of these factors individually and outline their interactions in the context of both patient-based studies and preclinical animal model systems. Finally, we highlight gaps in knowledge that will require further investigation to aid in successfully implementing precision medicine to prevent and alleviate MASLD and MASH.

Background: Peripheral artery disease (PAD) is still the least studied and evaluated form in clinical practice among atherosclerotic pathologies, despite the increased mortality and comorbidities related to it. The relationship between steatotic liver disease and an increased risk of cardiovascular disease has been extensively documented. Methods: The purpose of this work is to perform a review of the evidence linking NAFLD or MASLD to PAD, and examine possible clinical scenarios that arise from this new terminology. Results: The new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) includes the presence of cardiometabolic risk factors and hepatic steatosis without any other underlying causes of hepatic steatosis; this terminology, coined in the hepatological field, could generate confusion, especially in the initial stages of its diffusion and among different medical specialists. Conclusions: Some recent data in the literature have strengthened the evidence of a pathological link between hepatic metabolic alteration (NAFLD or MAFLD) and PAD.

Dipeptidyl peptidase-4 inhibitors provide potent antidiabetic effects in patients with type 2 diabetes mellitus (T2DM), but their role in the presence of nonalcoholic fatty liver disease (NAFLD) is not well-known.

The aim of this clinical trial was to evaluate the effects of sitagliptin on the metabolic profile and liver test results in metformin-treated patients with T2DM and NAFLD.

This was a prospective, 12-week, single-center, comparative randomized clinical trial enrolling 66 adult patients with T2DM and NAFLD (diagnosed by ultrasound). Patients were randomly assigned to either metformin (2000 mg/d, n = 33) or sitagliptin + metformin (100 and 2000 mg/d, respectively, n = 33), administered orally. Certain metabolic parameters, that is, fasting blood sugar (FBS), glycosylated hemoglobin, triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol, vitamin D3 (vitD3), alkaline phosphatase, alanine aminotransferase (SGPT), and aspartate aminotransferase, were measured at baseline and after 12 weeks. Triglyceride-glucose (TG-G) index was also calculated.

All biochemical variables decreased by a greater extent in the sitagliptin + metformin group than in the metformin group, with differences in FBS (P = 0.030), TC (P = 0.017), TG (P = 0.008), SGPT (P = 0.018), and vitD3 (P = 0.001) reaching statistical significance. Furthermore, the mean reduction of the TG-G index was significantly greater in the sitagliptin + metformin group than in the metformin group (0.67 vs 0.21, respectively; P = 0.017).

Sitagliptin + metformin therapy led to significantly greater improvements in FBS, TC, TG, SGPT, vitD3, and TG-G compared with the metformin monotherapy group. Other biomarkers also decreased more in the sitagliptin + metformin group than in the metformin group, but these differences did not reach statistical significance. The present findings should be interpreted with caution, although they suggest certain metabolic benefits after sitagliptin addition in metformin-treated patients with T2DM and NAFLD. Further studies are required to elucidate these effects and provide strong evidence for safe conclusions.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome and increased cardiovascular risk. Resmetirom, a novel liver-directed selective thyroid hormone receptor-β (THR-β) agonist, has shown promise in addressing both hepatic and systemic lipid metabolism. This systematic review and meta-analysis aimed to evaluate the efficacy of resmetirom in improving cholesterol levels in NASH patients. A systematic literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, and ClinicalTrials.gov, identifying three randomized controlled trials for inclusion. The meta-analysis revealed that resmetirom significantly reduced low-density lipoprotein cholesterol (LDL-C) levels compared to placebo (MD: -23.62; 95% CI: -37.32 to -9.93; p < 0.001). Similarly, triglyceride (TG) levels showed a significant reduction in the resmetirom group (MD: -33.86; 95% CI: -47.79 to -19.92; p < 0.001). Importantly, there was no significant difference in the risk of serious adverse events between resmetirom and placebo groups (RR: 1.09; 95% CI: 0.73 to 1.63; p = 0.67). These findings suggest that resmetirom effectively improves lipid profiles in NASH patients without compromising safety. However, the analysis was limited by the small number of studies, all from the same research group, and high heterogeneity in results. Future research should include more diverse studies, longer follow-up periods, and cost-effectiveness evaluations. Despite these limitations, resmetirom shows promise as a potential treatment for managing dyslipidemia and cardiovascular risk in NASH patients, potentially influencing future treatment guidelines for both liver and cardiovascular health in this population.

Excessive caloric intake and obesity due to high-fat (HFD) and high-disaccharide (HDD) diets have been recognized as major contributing factors to dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effect of HFD and HDD without excessive caloric intake is obscure. The aim of the study was to evaluate the effect of physiological caloric intake delivered through HFD and HDD on liver and lipid profiles. The study was performed on 6-week-old male and female (50/50%) Sprague Dawley rats, receiving either a standard (controls, n = 16), HFD (n = 14) or HDD (n = 14) chow. All groups received the same, standard daily calorie rations, titrated weekly to the age of growing rats, for 12 weeks. A panel of metabolic in vivo measurement were performed, followed by histological, biochemical and molecular biology assays on tissues harvested from sacrificed rats. There was no significant difference between the groups in body weight. In contrast to controls, HFD and HDD groups showed metabolic dysfunction-associated steatohepatitis (MASH) characterized by liver steatosis, inflammation, ballooning of hepatocytes and fibrosis. These changes were more pronounced in the HFD than in the HDD group. The HFD group showed significantly higher serum LDL than controls or HDD rats. Furthermore, the HFD group had higher liver protein levels of low-density lipoprotein receptor (LDLR) but lower plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) than the controls or HDD group. There were no differences between sexes in evaluated parameters. The excessive caloric intake and obesity are not prerequisites for the development of MASH and dyslipidemia in rats. The liver changes induced by the HFD and HDD diets exhibit differences in severity, as well as in the expression patterns of LDLR and PCSK9. Notably, these effects are independent of the sex of the rats.

Previously published studies have shown that women with type 2 diabetes have a higher risk of atherosclerotic cardiovascular disease than men with type 2 diabetes. The exact reason for this is not yet known. The association between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes appears to be bidirectional, meaning that the onset of one may increase the risk of the onset and progression of the other. Dyslipidemia is common in both diseases. Our aim was therefore to investigate whether there is a sex difference in the pathogenesis and management of dyslipidemia in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction. While the majority of published studies to date have found no difference between men and women in statin treatment, some studies have shown reduced effectiveness in women compared to men. Statin treatment is under-prescribed for both type 2 diabetics and patients with dysfunction-associated steatotic liver disease. No sex differences were found for ezetimibe treatment. However, to the best of our knowledge, no such study was found for fibrate treatment. Conflicting results on the efficacy of newer cholesterol-lowering PCSK9 inhibitors have been reported in women and men. Results from two real-world studies suggest that up-titration of statin dose improves the efficacy of PCSK9 inhibitors in women. Bempedoic acid treatment has been shown to be effective and safe in patients with type 2 diabetes and more effective in lipid lowering in women compared to men, based on phase 3 results published to date. Further research is needed to clarify whether the sex difference in dyslipidemia management shown in some studies plays a role in the risk of ASCVD in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction.

Non-alcoholic fatty acid disease (NAFLD) is caused by a build-up of fat in the liver, inducing local inflammation and fibrosis. We evaluated the effects of probiotic lactic acid-generating bacteria (LAB) derived from a traditional fermented beverage in a mouse model of NAFLD. The LAB isolated from this traditional Korean beverage were screened using the human hepatic cell line HepG2, and Lactocaseibacillus paracasei HY7207 (HY7207), which was the most effective inhibitor of fat accumulation, was selected for further study. HY7207 showed stable productivity in industrial-scale culture. Whole-genome sequencing of HY7207 revealed that the genome was 2.88 Mbp long, with 46.43% GC contents and 2778 predicted protein-coding DNA sequences (CDSs). HY7207 reduced the expression of lipogenesis and hepatic apoptosis-related genes in HepG2 cells treated with palmitic acid. Furthermore, the administration of 109 CFU/kg/day of HY7207 for 8 weeks to mice fed an NAFLD-inducing diet improved their physiologic and serum biochemical parameters and ameliorated their hepatic steatosis. In addition, HY7207 reduced the hepatic expression of genes important for lipogenesis (Srebp1c, Fasn, C/ebpa, Pparg, and Acaca), inflammation (Tnf, Il1b, and Ccl2), and fibrosis (Col1a1, Tgfb1, and Timp1). Finally, HY7207 affected the expression of the apoptosis-related genes Bax (encoding Bcl2 associated X, an apoptosis regulator) and Bcl2 (encoding B-cell lymphoma protein 2) in the liver. These data suggest that HY7207 consumption ameliorates NAFLD in mice through effects on liver steatosis, inflammation, fibrosis, and hepatic apoptosis. Thus, L. paracasei HY7207 may be suitable for use as a functional food supplement for patients with NAFLD.

The lack of therapeutics along with complex pathophysiology made non-alcoholic fatty liver disease (NAFLD) a research hotspot. Studies showed that the deficiency of Vitamin D plays a vital role in NAFLD pathogenesis. While several research studies focused on vitamin D supplementation in NAFLD, there is still a need to understand the regulatory mechanism of direct vitamin D receptor activation in NAFLD. In the present study, we explored the role of direct Vitamin D receptor activation using paricalcitol in choline-deficient high-fat diet-induced NAFLD rat liver and its modulation on protein acetylation. Our results showed that paricalcitol administration significantly reduced the fat accumulation in HepG2 cells and the liver of NAFLD rats. Paricalcitol attenuated the elevated serum level of alanine transaminase, aspartate transaminase, insulin, low-density lipoprotein, triglyceride, and increased high-density lipoprotein in NAFLD rats. Paricalcitol significantly decreased the increased total protein acetylation by enhancing the SIRT1 and SIRT3 expression in NAFLD liver. Further, the study revealed that paricalcitol reduced the acetylation of NFκB and FOXO3a in NAFLD liver along with a decrease in the mRNA expression of IL1β, NFκB, TNFα, and increased catalase and MnSOD. Moreover, total antioxidant activity, glutathione, and catalase were also elevated, whereas lipid peroxidation, myeloperoxidase, and reactive oxygen species levels were significantly decreased in the liver of NAFLD after paricalcitol administration. The study concludes that the downregulation of SIRT1 and SIRT3 in NAFLD liver was associated with an increased acetylated NFκB and FOXO3a. Paricalcitol effectively reversed hepatic inflammation and oxidative stress in NAFLD rats through transcriptional regulation of NFκB and FOXO3a, respectively, by inhibiting their acetylation.

To update information about the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis. This review emphasizes the potential mechanisms linking MASLD with atherosclerosis and the possible causal relationships between these conditions.

An increased risk of cardiovascular disease is related to MASLD. Several molecular, cellular, and metabolic mechanisms have been described to explain the development of atherothrombosis in MASLD patients. These include atherogenic dyslipidemia, low-grade vascular inflammation, endothelial dysfunction, foam cell formation, proliferation of vascular smooth muscle cells, insulin resistance, gut microbiota dysbiosis, activation of renin-angiotensin and sympathetic nervous systems, hypercoagulability, and decreased fibrinolysis. Also, there is recent evidence suggesting an association between genetically driven liver fat and coronary heart disease mediated by the causal effect of apoB-containing lipoproteins. Several meta-analyses and systematic reviews have reported a strong association between MASLD and cardiovascular outcomes. MASLD is an important and independent risk factor for atherosclerosis development. Multiple mechanisms may be involved in this association. Further research is required to establish a causal association between MASLD and atherosclerosis.

The association between traditional lipid parameters and non-alcoholic fatty liver disease (NAFLD) has been extensively discussed. This study aims to evaluate and compare the lipoprotein combine index (LCI) and traditional lipid parameters [total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] to identify NAFLD.

The analysis included 14,251 participants from the NAfld in the Gifu Area, Longitudinal Analysis (NAGALA). Logistic regression models were employed to calculate standardized odds ratios (ORs) and 95% confidence intervals (CIs) for assessing and comparing the association of LCI and traditional lipid parameters with NAFLD. Additionally, receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC) for LCI and traditional lipid parameters in identifying NAFLD.

After adjusting for various confounders, we found that LCI was positively associated with NAFLD (OR=2.25, 95% CI 1.92-2.63), and this association was stronger than that of traditional lipid parameters [OR: TC1.23, TG1.73 LDL-C1.10]. Further subgroup analyses revealed that the association of LCI with NAFLD was stronger than other traditional lipid parameters in all subgroups, including men and women, overweight/obese [body mass index (BMI)≥25 kg/m2] and non-obese (BMI<25 kg/m2), and older (age≥45 years) and younger (age<45 years) participants. Additionally, ROC analysis indicated that LCI (AUC=0.8118) had significantly higher accuracy (All DeLong P<0.05) in identifying NAFLD compared to traditional lipid parameters (AUC: TC0.6309; TG0.7969; LDL-C0.6941); HDL-C0.7587). Sensitivity analysis further confirmed the robustness of the study findings.

This study revealed for the first time a positive correlation between LCI and NAFLD. Compared to traditional lipid parameters, LCI has a higher correlation with NAFLD. Additionally, further ROC analysis demonstrated that LCI had higher accuracy in identifying NAFLD compared to traditional lipid parameters, suggesting that LCI may be a better marker for NAFLD identification than traditional lipid parameters.

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is closely associated with insulin resistance, glucose and lipid metabolism disorders. Patients with PCOS have a significantly higher risk of non-alcoholic fatty liver disease and are associated with hyperandrogenemia (HA). However, the exact mechanism by which HA exacerbates hepatic steatosis in PCOS has not yet been fully elucidated. This work aims to investigate the effects and underlying mechanisms of androgens on hepatic triglyceride (TG) metabolism in rats with PCOS.

Twenty-four female Sprague-Dawley rats were randomly divided into four groups (6 rats/group): control, high-fat diet (HFD), PCOS, and PCOS + flutamide (Flu). Changes in the estrous cycle, liver and ovarian tissue sections, serum total testosterone, serum and liver biochemical indicators, and key enzymes involved in TG metabolism were studied.

Hepatocyte steatosis and TG accumulation were more evident in the PCOS group than in the control and HFD groups. The PCOS group showed apparent increases in the levels of serum alanine aminotransferase, aspartate aminotransferase, TG, free fatty acid, fasting insulin, and homeostasis model assessment of insulin resistance. Hepatic VLDL and apoB-100 levels decreased in the PCOS group. After Flu was administered to block the actions of androgens, the above abnormalities had been improved. The expression of MTTP was greatly decreased in the PCOS group and significantly increased after Flu administration.

Hepatic steatosis in PCOS rats was correlated with HA. Androgens may exacerbate hepatic TG accumulation by downregulating MTTP expression in PCOS.

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC-TOF-MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.

The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis.

The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-β, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied.

To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC.

Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-β genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver, often related to obesity and insulin resistance, which can lead to inflammation and scarring of the liver tissue. While efforts have been made to develop effective treatments for NAFLD, the need for pharmaceutical interventions remains unmet. Large clinical trials investigating the association between statin use and NAFLD are scarce, leading to contradictory results. Statins play a crucial role in cholesterol synthesis in the liver. Several studies have demonstrated that statins possess anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. These properties make statins potentially useful in preventing the progression of NAFLD from simple steatosis to more severe forms like non-alcoholic steatohepatitis (NASH) and fibrosis. The results indicate that statin use is associated with a lower prevalence of NASH and fibrosis and may have a preventive effect on NAFLD.

This study examined the preventative effects of esculeogenin A (ESGA), a newly discovered glycan from tomato, on liver damage and hepatic steatosis in high-fat-diet (HFD)-fed male rats. The animals were divided into six groups (each of eight rats): a control group fed a normal diet, control + ESGA (200 mg/kg), HFD, and HFD + ESAG in 3 doses (50, 100, and 200 mg/kg). Feeding and treatments were conducted for 12 weeks. Treatment with ESGA did not affect gains in the body or fat weight nor increases in fasting glucose, insulin, and HOMA-IR or serum levels of free fatty acids (FFAs), tumor-necrosis factor-α, and interleukin-6 (IL-6). On the contrary, it significantly reduced the serum levels of gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total triglycerides (TGs), cholesterol (CHOL), and low-density lipoprotein cholesterol (LDL-c) in the HFD-fed rats. In addition, it improved the liver structure, attenuating the increase in fat vacuoles; reduced levels of TGs and CHOL, and the mRNA levels of SREBP1 and acetyl CoA carboxylase (ACC); and upregulated the mRNA levels of proliferator-activated receptor α (PPARα) and carnitine palmitoyltransferase I (CPT I) in HFD-fed rats. These effects were concomitant with increases in the mRNA, cytoplasmic, and nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and heme oxygenase-1 (HO); a reduction in the nuclear activity of nuclear factor-kappa beta (NF-κB); and inhibition of the activity of nuclear factor kappa B kinase subunit beta (IKKβ). All of these effects were dose-dependent effects in which a normal liver structure and normal levels of all measured parameters were seen in HFD + ESGA (200 mg/kg)-treated rats. In conclusion, ESGA prevents NAFLD in HFD-fed rats by attenuating hyperlipidemia, hepatic steatosis, oxidative stress, and inflammation by acting locally on Nrf2, NF-κB, SREBP1, and PPARα transcription factors.

This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene, and β-pinene from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables in this cross-sectional study. Continuous lipid variables included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), residual cholesterol (RC), and apolipoprotein B (Apo B). Binary lipid variables (elevated TC, ≥5.18 mmol/L; lowered HDL-C, <1.04 mmol/L in men, and <1.30 mmol/L in women; elevated non-HDL-C, ≥4.2 mmol/L; elevated TG, ≥1.7 mmol/L; elevated LDL-C, ≥3.37 mmol/L; elevated RC, ≥1.0 mmol/L; and elevated Apo B, ≥1.3 g/L) suggest dyslipidemia. The relationships between the mixture of serum terpenes with lipid variables were investigated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The study for TC, HDL-C, and non-HDL-C included a total of 1,528 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 714 participants. The mean age of the overall participants was 47.69 years, and 48.77% were male. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. WQS regression and BKMR analysis revealed that the mixture of serum terpenes was linked with the prevalence of dyslipidemia. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global epidemic intricately linked to the rising tide of obesity and metabolic syndrome. This comprehensive review delves into the complex web of relationships between NAFLD, liver fibrosis, and subclinical atherosclerosis, shedding light on their interplay, shared risk factors, and clinical implications. NAFLD encompasses a spectrum of liver conditions, from the benign non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), characterized by inflammation and hepatocellular injury. Central to the discussion is the insidious development of liver fibrosis, the ominous harbinger of progressive liver damage, cirrhosis, and hepatocellular carcinoma. The increasing prevalence of NAFLD, now affecting a quarter of the global population, poses a significant public health challenge. Its association with obesity, insulin resistance, and metabolic syndrome highlights the multifactorial nature of this disease. However, NAFLD's repercussions extend beyond the liver. This review unveils a potent connection between NAFLD and subclinical atherosclerosis, the early precursor to cardiovascular disease. Individuals with NAFLD face an elevated risk of atherosclerosis, even without traditional cardiovascular risk factors. The intricate link between these two conditions is illuminated through shared pathophysiological pathways, including systemic inflammation, insulin resistance, and dyslipidemia. Understanding the interplay between liver fibrosis and subclinical atherosclerosis has profound clinical implications. Patients with advanced fibrosis or cirrhosis are not only at risk of liver-related complications but also of cardiovascular events. This necessitates a holistic approach to patient care, with lifestyle modifications and pharmacological interventions simultaneously managing both conditions. Physicians must prioritize early detection and collaborate across disciplines to provide comprehensive care. Looking ahead, the future holds promising avenues of research. Emerging areas include genetics and precision medicine, microbiome research, and epigenetics, which may unveil new therapeutic targets. Innovations in diagnostics and therapeutics, such as non-invasive biomarkers and combination therapies, offer hope for more effective management. Long-term outcomes and survivorship research will provide insights into the lasting impact of interventions. In conclusion, this review underscores the imperative of addressing liver fibrosis and atherosclerosis in the context of NAFLD. It is a call to action for healthcare professionals, researchers, and policymakers to work collaboratively, promote early detection, and advance our understanding of these interconnected conditions. By doing so, we can enhance patient outcomes and chart a course toward a healthier future for those grappling with NAFLD and its intricate web of consequences.

Dyslipidemia has been linked metabolic-associated fatty liver disease (MAFLD). Several genes and transcription factors involved in lipid metabolism can increase susceptibility to MAFLD. Multiple parallel 'hits' have been proposed for developing hepatic steatosis, NASH, and MAFLD, including insulin resistance and subsequent free fatty acid excess, de novo lipogenesis, and excessive hepatic triglyceride and cholesterol deposition in the liver. This lead to defective beta-oxidation in the mitochondria and VLDL export and increased inflammation. Given the significant cardiovascular risk, dyslipidemia associated with MAFLD should be managed by lifestyle changes and lipid-lowering agents such as statins, fenofibrate, and omega-3 fatty acids, with judicious use of insulin-sensitizing agents, and adequate control of dysglycemia.

This prospective longitudinal study aims to evaluate and compare the incidence of prediabetes/diabetes among women stratified at the baseline postpartum visit according to the prior GDM and NAFLD status.

Of the 309 women with baseline postpartum assessment at a median of 16 months following the index delivery, 200 (64.7%) [GDM: 137 (68.5%), normoglycaemia: 63 (31.5%)] were available for the follow-up analysis (performed at median of 54 months following the index delivery) and were participants for this study. We obtained relevant demographic, medical and obstetric details and performed a 75 g OGTT with glucose estimation at 0 and 120 min. NAFLD status was defined by ultrasonography at the baseline visit. Participants were divided into four groups: no NAFLD and no prior GDM (group 1), NAFLD but no prior GDM (group 2), prior GDM but no NAFLD (group 3), and NAFLD and prior GDM (group 4).

The mean age of study participants (n = 200) was 32.2 ± 5.1 years, and the mean interval between the two visits was 34.8 ± 5.5 months. A total of 74 (37%) women had progression to prediabetes/diabetes [incidence rate of 12.8/100 woman-years]. The incidence rates (per 100 woman-years) were 8.6, 8.9, 13.4 and 15.3 in groups 1, 2, 3 and 4, respectively. The adjusted hazard ratio for incident (new-onset) prediabetes/diabetes in group 4 (reference: group 1) was 1.99 (95% CI 0.80, 4.96, P = 0.140). Among women with baseline NAFLD (irrespective of GDM status), the risk of incident prediabetes/diabetes increased with an increase in the duration of follow-up (3.03-fold higher per year of follow-up, P = 0.029) and was significantly higher in women who were not employed (6.43, 95% CI 1.74, 23.7, P = 0.005) and in women with GDM requiring insulin/metformin during pregnancy (4.46, 95% CI 1.27, 15.64, P = 0.019).

NAFLD and GDM increased the risk for glycaemic deterioration in young Indian women. Future studies should focus on evaluating the effectiveness of lifestyle and behavioural interventions in such high-risk women.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease. Fucoxanthin, a red-orange marine carotenoid, is found in natural marine seaweeds with high antioxidant activity and several other remarkable biological features. The aim of this review is to gather evidence of the positive benefits of fucoxanthin on NAFLD. Fucoxanthin provides an extensive list of physiological and biological properties, such as hepatoprotective, anti-obesity, anti-tumor, and anti-diabetes properties, in addition to antioxidant and anti-inflammatory properties. This review focuses on published research on the preventative effects of fucoxanthin on NAFLD from the perspective of human clinical trials, animal experiments in vivo, and in vitro cell investigations. Using a variety of experimental designs, including treatment dosage, experiment model, and experimental periods, the positive effects of fucoxanthin were demonstrated. Fucoxanthin's biological activities were outlined, with an emphasis on its therapeutic efficacy in NAFLD. Fucoxanthin showed beneficial effects in modulating lipid metabolism, lipogenesis, fatty acid oxidation, adipogenesis, and oxidative stress on NAFLD. A deeper comprehension of NAFLD pathogenesis is essential for the development of novel and effective therapeutic strategies.

The epidemic prevalence of non-alcoholic fatty liver disease (NAFLD), despite extensive research in the field, underlines the importance of focusing on personalized therapeutic approaches. However, nutrigenetic effects on NAFLD are poorly investigated. To this end, we aimed to explore potential gene-dietary pattern interactions in a NAFLD case-control study. The disease was diagnosed with liver ultrasound and blood collection was performed after an overnight fast. Adherence to four a posteriori, data-driven, dietary patterns was used to investigate interactions with PNPLA3-rs738409, TM6SF2-rs58542926, MBOAT7-rs641738, and GCKR-rs738409 in disease and related traits. IBM SPSS Statistics/v21.0 and Plink/v1.07 were used for statistical analyses. The sample consisted of 351 Caucasian individuals. PNPLA3-rs738409 was positively associated with disease odds (OR = 1.575, p = 0.012) and GCKR-rs738409 with lnC-reactive protein (CRP) (beta = 0.098, p = 0.003) and Fatty Liver Index (FLI) levels (beta = 5.011, p = 0.007). The protective effect of a "Prudent" dietary pattern on serum triglyceride (TG) levels in this sample was significantly modified by TM6SF2-rs58542926 (pinteraction = 0.007). TM6SF2-rs58542926 carriers may not benefit from a diet rich in unsaturated fatty acids and carbohydrates in regard to TG levels, a commonly elevated feature in NAFLD patients.

Gut microbiota imbalances lead to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is primarily accompanied by hepatic steatosis. Hydroxyphenyl propionic acids (HPP) have shown great potential in inhibiting lipid accumulation but their protective effects concerning NAFLD and intestinal microbiota have remained unclear. In this paper, we investigated the efficacies of 3-HPP and 4-HPP on hepatic steatosis and gut flora in mice fed a high-fat diet (HFD). We found that 3-HPP and 4-HPP administration decreased body weight and liver index, ameliorated dyslipidemia, and alleviated hepatic steatosis. Furthermore, 3-HPP and 4-HPP enhanced the multiformity of gut microbiota; improved the relative abundance of GCA-900066575, unidentified_Lachnospiraceae, and Lachnospiraceae_UCG-006 at genus level; increased concentration of acetic acid, propionic acid and butanoic acid in faeces; and reduced systemic endotoxin levels in NAFLD mice. Moreover, 4-HPP upregulated the relative abundance of genera Rikenella and downregulated the relative abundance of Faecalibaculum. Furthermore, 3-HPP and 4-HPP regulated lipid metabolism and ameliorated gut dysbiosis in NAFLD mice and 4-HPP was more effective than 3-HPP.