Nonalcoholic fatty liver disease (NAFLD) is a significant global health burden. It comprises a broad pathological spectrum ranging from simple liver steatosis to steatohepatitis with variable degrees of fibrosis, and liver failure. Patients with NAFLD have an increased risk of liver-related and overall mortality. While the trials to assess the efficacy of the medications are ongoing, lifestyle modification is the first line of therapy recommended. The primary aim of this review paper is to synthesize literature related to current evidence-based lifestyle interventions for preventing and managing NAFLD. The review and synthesis of the literature reveal that personalized nutritional, exercise, and behavior change interventions are effective in managing NAFLD. Evidence suggests that there are several gaps in managing NAFLD. The gaps discussed in this paper include a lack of awareness of the disease, ineffective patient-provider communication, shortage of specialists, under-recognition of the disease, and liver health disparities. This paper highlights the evidence-based opportunities to overcome those gaps, such as utilizing comprehensive models of care, clinical care pathways, and clinical practice guidelines. Primary care physicians and endocrinologists, who are the first point of contact must utilize these opportunities for diagnosing and managing patients with NAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease, linked closely to metabolic syndrome and rising obesity rates. Affecting up to 37% of the global adult population, MASLD prevalence is exceptionally high among individuals of Hispanic descent, with genetic factors such as the PNPLA3 gene mutation playing a significant role. The subject of this review is the traditional Mesoamerican "milpa" diet, which includes unprocessed local crops like maize, beans, pumpkins, chili, and tomatoes and may represent a strategy to combat MASLD. Current treatment recommendations emphasize weight loss; a reduced intake of saturated fats, processed meats, and added sugars; and increased physical activity. The milpa diet, rich in protein, fiber, vitamins, and bioactive compounds, aligns with these recommendations and could potentially mitigate MASLD by preventing liver fat accumulation and fibrosis. This narrative review focuses on available preclinical and clinical studies adopting the milpa diet as a culturally relevant, nutritious, and sustainable dietary approach in preventing and treating MASLD. More clinical studies are needed to develop precise nutritional quantitative recommendations and guidelines.

Adherence to plant-based diets has significantly increased in popularity recently, with claims that they reduce the risk of non-communicable diseases. This study investigated whether high adherence to plant-based diets can reduce the risk of hepatic steatosis and fibrosis. In this study, 8516 participants from the Ravansar Noncommunicable Disease cohort completed a validated food frequency questionnaire (FFQ) to assess their plant-based diet scores. The study used the fatty liver index and fibrosis-4 index to predict hepatic steatosis and fibrosis. The plant-based diet index (PDI) was used to measure the overall quality of diets from healthy and unhealthy plant-derived foods and animal-derived foods. Associations were determined using binary logistic regression, considering potential confounders. Participants in the highest tertiles of plant-based diet scores had higher energy-adjusted intakes of fructose than those in the lowest tertiles (16.09 ± 12.11 vs. 26.65 ± 12; P-value < 0.001). In multivariable-adjusted models, participants in the highest tertile of PDI had lower odds of hepatic fibrosis than those in the lowest tertile (OR: 0.59; 95%CI: 0.43-0.81). There was no significant association between adherence to PDI and hepatic steatosis after adjustment for potential confounders (OR: 0.989; 95%CI 0.78 - 1.25). The odds of hepatic fibrosis decreased by 6% for each unit increase in healthy plant-based foods (OR: 0.94; 95%CI: 0.91-0.97). The odds of hepatic steatosis increased by 14% for each 1 SD increase in fructose intake (OR: 1.14; 95% CI: 1.02-1.28). This study highlights the potential benefits of high adherence to plant-based diets in reducing the risk of hepatic fibrosis, but high fructose content in some plant-based foods may have an unfavorable role in hepatic steatosis. These findings highlight the importance of selecting whole, fiber-rich plant foods and minimizing intake of fructose-dense products in plant-based diets to promote liver health. Therefore, selecting low-fructose food items in plant-based diets is recommended, though further research is needed to confirm these findings.

MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) is a growing global concern. Nutraceuticals offer an appealing approach by targeting key mechanisms, such as oxidative stress, inflammation, lipid metabolism, and insulin resistance. This narrative review examines the role of various nutraceuticals in MASLD treatment, including silymarin, vitamin E, omega-3, curcumin, berberine, and coenzyme Q10. Some of them show promising biochemical and metabolic changes, while others produce conflicting results due to relevant studies' design and endpoints. To bridge the gap between research and reality, we summarize the data, create an interpretation heatmap, and develop a practical supplement guide. Regardless of their potential, nutraceuticals should be viewed as add-ons to lifestyle interventions rather than standalone treatments. Future research should focus on well-designed, long-term studies to prove efficacy, dosing, and combination strategies for personalized MASLD management.

Obesity presents a significant global health challenge due to its association with a range of systemic disorders. One such condition is metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), which has become the most common chronic liver disease worldwide. The prevalence of MASLD is closely linked to obesity, type 2 diabetes, and sedentary lifestyles, posing substantial risks for liver-related morbidity and extrahepatic complications such as cardiovascular and renal diseases. Despite recent advancements in pharmacological treatments, lifestyle modification remains the cornerstone of MASLD management. This review summarizes current evidence on lifestyle interventions, focusing on weight loss, dietary improvements, and increased physical activity. It also explores barriers to implementation, including socioeconomic factors, limited patient awareness, and stigma, while highlighting innovative strategies such as group-based programs, web-based interventions, and mobile technologies. As MASLD continues to rise globally, prioritizing lifestyle-based and scalable approaches will be critical to reducing its burden and improving patient outcomes.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

Metabolic-dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a highly prevalent metabolic disorder characterized by hepatic steatosis in conjunction with at least one cardiometabolic risk factor, such as obesity, type 2 diabetes, hypertension, or dyslipidemia. As global rates of obesity and metabolic syndrome continue to rise, MASLD is becoming a major public health concern, with projections indicating a substantial increase in prevalence over the coming decades. The disease spectrum ranges from simple steatosis to metabolic-dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma, contributing to significant morbidity and mortality worldwide. This review delves into the molecular mechanisms driving MASLD pathogenesis, including dysregulation of lipid metabolism, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota alterations. Recent advances in research have highlighted the role of genetic and epigenetic factors in disease progression, as well as novel therapeutic targets such as peroxisome proliferator-activated receptors (PPARs), fibroblast growth factors, and thyroid hormone receptor beta agonists. Given the multifaceted nature of MASLD, a multidisciplinary approach integrating early diagnosis, molecular insights, lifestyle interventions, and personalized therapies is critical. This review underscores the urgent need for continued research into innovative treatment strategies and precision medicine approaches to halt MASLD progression and improve patient outcomes.

Previous observational studies have not reached an agreement on the association between coffee consumption and risk of liver diseases. Also, none of these studies took sweetener added in coffee into consideration.

We aim to explore the associations of consumption of sweetened and unsweetened coffee with chronic liver disease (CLD) and liver-related events (LREs), and evaluate the degree to which sweetener added counteracted the effect of coffee.

We performed a longitudinal cohort study of 170,044 participants without liver diseases or cancer at baseline investigation (2006-2010) and followed until 2022. Consumption of coffee and sweetener was assessed by 24-h dietary recall questionnaire. Cox proportional hazards models and restricted cubic splines were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

During a median follow-up of 12.4 y, we identified 4152 incident of CLD and 853 LREs. Compared with nonconsumers, unsweetened coffee consumers of various amount had lower risk of CLD (HR: 0.75; 95% CI: 0.67, 0.83 for 1.5∼2.5 drinks/d) and LREs (HR: 0.60; 95% CI: 0.46, 0.80 for 2.5∼3.5 drinks/d) in the multivariable Cox models. U-shaped associations of unsweetened coffee with CLD and LREs were observed. The results for sweetened coffee were less consistent and conclusive in both CLD and LREs. We detected positive associations between sweetener and CLD and LREs. Compared with unsweetened coffee consumers, consumers of different amount of sugar added to coffee had higher risk of CLD in the multivariable Cox model. For artificial sweetener, a significant higher risk of CLD (HR: 1.61; 95% CI: 1.25, 2.05)and LREs (HR: 1.82; 95% CI: 1.11, 2.98) was only found in those who added ≥2 teaspoons/drink. We detected significant interaction between artificial sweetener and coffee intake on the risk of CLD (HR for product term: 0.76; 95% CI: 0.60, 0.96; P = 0.018; relative excess risk due to interaction: -0.32; 95% CI: -0.58, -0.06).

Moderate consumption of unsweetened coffee was associated with lower risk of CLD and LREs. Adding sweetener into coffee could bring additional risk of liver diseases in coffee consumers.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition affecting a broad population. This review aimed to identify and summarize the current evidence on bioactive-substance-based interventions for adults with MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD), covering publications from 2000 to 2023. Methods: A search was conducted across six databases (MEDLINE, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Food Science Source, and SPORTDiscus) for randomized controlled trials and other study types (e.g., prospective cohort studies and systematic reviews), reflecting the scoping nature of this review. The search was limited to studies in adults (>18 years old), with an intervention of interest and at least one comparator group. Results: A total of 4572 articles were retrieved, with 201 full-text articles screened for eligibility. Of these, 131 primary studies and 49 systematic reviews were included in the scoping review. The most studied bioactive substances were Curcumin (Turmeric) (n = 25), Silymarin (Milk Thistle) (n = 17), Resveratrol (n = 10), Coffee (n = 7), Green Tea (n = 5), and Berberine (n = 5 each). Moreover, 46 studies reported on 36 other bioactive substances with 2 or fewer articles each. Among the included systematic reviews, 13 focused on Curcumin, 12 on Coffee or Tea, 10 on bioactive substance combinations, 6 on Resveratrol, and 2 each on Silymarin and Artichoke Leaf. The included studies showed substantial heterogeneity in reported outcomes, which primarily focused on hepatic health, body weight, adverse events, glycemic control, blood lipids, and body composition. Conclusions: This scoping review highlights a range of bioactive substances used in the treatment of MASLD. While evidence is abundant for bioactive substances like Curcumin and Silymarin, further research and synthesis of findings is necessary to establish the clinical efficacy of all bioactive substances.

We investigated the possibility of caffeine supplementation for managing the inflammation, and hepatic function in cirrhotic patients.

In this randomized, double-blind, placebo-controlled trial, fifty patients with cirrhosis were randomly assigned to receive either caffeine supplement (400 mg), or placebo for eight weeks.

The results indicated a significant decrease in AST, platelets (P = 0.002), and PTT (P < 0.001), in the caffeine group compared to the placebo group. Also, caffeine supplementation resulted in a significant reduction in inflammatory biomarkers compared to placebo (p < 0.05). A significant improvement in liver indices including AST to platelet ratio index (APRI), (P < 0.001). Fibrosis 4 score (P < 0.001), and MELD score (P = 0.034)., was observed after 8 weeks caffeine supplementation.

The results of the present study indicated that daily supplementation of 400 mg caffeine in cirrhotic patients can significantly improve liver fibrosis and reduce inflammatory factors.The trial was registered at the Iranian Registry of Clinical Trials (Registration ID: IRCT20100524004010N34).

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

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

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a growing global health challenge requiring innovative approaches for effective management. This comprehensive review examines novel risk factors, including environmental pollutants like heavy metals, and underscores the complexity of personalized medicine tailored to individual patient profiles, influenced by gender and sex differences. Traditional treatments for MASLD, such as glucose- and lipid-lowering agents, show mixed results, highlighting the necessity for larger, long-term studies to establish safety and efficacy. Alternative therapies, including antioxidants, stem cells, and antiplatelets, although promising, demand extensive clinical trials for validation. This review highlights the importance of personalized medicine, considering individual variations and specific factors such as gender and sex, to optimize treatment responses. The shift from metabolic-associated fatty liver disease (MAFLD) to MASLD terminology underscores the metabolic components of the disease, aligning with the multiple-hit theory and highlighting the necessity for comprehensive risk factor management. Our vision advocates for an integrated approach to MASLD, encompassing extensive risk factor analysis and the development of safer, more effective treatments. Primary prevention and awareness initiatives are crucial in addressing the rising prevalence of MASLD. Future research must prioritize larger, long-term studies and personalized medicine principles to ensure the effective use of emerging therapies and technologies. The review underscores the need for continuous exploration and innovation, balancing the benefits and challenges of nanotechnology, to combat MASLD and improve patient outcomes comprehensively.

Metabolic dysfunction-associated steatotic liver disease (MASLD) originates from a homeostatic imbalance in hepatic lipid metabolism. Increased fat deposition in the liver of people suffering from MASLD predisposes them to develop further metabolic derangements, including diabetes mellitus, metabolic dysfunction-associated steatohepatitis (MASH), and other end-stage liver diseases. Unfortunately, only limited pharmacological therapies exist for MASLD to date. Autophagy, a cellular catabolic process, has emerged as a primary mechanism of lipid metabolism in mammalian hepatocytes. Furthermore, preclinical studies with autophagy modulators have shown promising results in resolving MASLD and mitigating its progress into deleterious liver pathologies. In this review, we discuss our current understanding of autophagy-mediated hepatic lipid metabolism, its therapeutic modulation for MASLD treatment, and current limitations and scope for clinical translation.

Coffee is one of the most widely consumed beverages in the world due to its unique aroma and psychostimulant effects, mainly due to the presence of caffeine. In recent years, experimental evidence has shown that the moderate consumption of coffee (3/4 cups per day) is safe and beneficial to human health, revealing protective effects against numerous chronic metabolic diseases such as diabetes, cardiovascular, neurodegenerative, and hepatic diseases. This review focuses on two of coffee's main bioactive compounds, i.e., caffeine and chlorogenic acids, and their effects on the progression of chronic liver diseases, demonstrating that regular coffee consumption correlates with a lower risk of the development and progression of non-alcoholic steatohepatitis, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. In particular, this review analyzes caffeine and chlorogenic acid from a pharmacological point of view and explores the molecular mechanism through which these compounds are responsible for the protective role of coffee. Both bioactive compounds, therefore, have antifibrotic effects on hepatic stellate cells and hepatocytes, induce a decrease in connective tissue growth factor, stimulate increased apoptosis with anti-cancer effects, and promote a major inhibition of focal adhesion kinase, actin, and protocollagen synthesis. In conclusion, coffee shows many beneficial effects, and experimental data in favor of coffee consumption in patients with liver diseases are encouraging, but further prospective studies are needed to demonstrate its preventive and therapeutic role in chronic liver diseases.

Chlorogenic acid (CGA) is a natural polyphenol found in coffee, tea, vegetables, and fruits. It exhibits strong antioxidant activity and possesses several other biological properties, including anti-inflammatory effects, antimicrobial activity, and insulin-sensitizing properties. Moreover, it may improve lipid and glucose metabolism. This review summarizes the available information on the therapeutic effect of CGA in metabolic dysfunction-associated steatotic liver disease (MASLD). As the literature search engine, the browsers in the PubMed, Scopus, Web of Science databases, and ClinicalTrials.gov register were used. Animal trials and clinical studies suggest that CGA has promising therapeutic potential in treating MASLD and hepatic steatosis. Its mechanisms of action include antioxidant, anti-inflammatory, and anti-apoptotic effects via the activation of the Nrf2 signaling pathway and the inhibition of the TLR4/NF-κB signaling cascade. Furthermore, the alleviation of liver disease by CGA also involves other important molecules such as AMPK and important physiological processes such as the intestinal barrier and gut microbiota. Nevertheless, the specific target cell and key molecule to which CGA is directed remain unidentified and require further study.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disorder, affecting approximately 25 % of the population. Coffee-drinking obese smokers exhibit lower body weights and decreased NAFLD rates, but the reasons behind this remain unclear. Additionally, the effect of nicotine, the main component of tobacco, on the development of NAFLD is still controversial. Our study aimed to explore the possible reasons that drinking coffee could alleviate NAFLD and gain weight and identify the real role of nicotine in NAFLD of obese smokers. A NAFLD model in mice was induced by administering nicotine and a high-fat diet (HFD). We recorded changes in body weight and daily food intake, measured the weights of the liver and visceral fat, and observed liver and adipose tissue histopathology. Lipid levels, liver function, liver malondialdehyde (MDA), superoxide dismutase (SOD), serum inflammatory cytokine levels and the expression of hepatic genes involved in lipid metabolism were determined. Our results demonstrated that nicotine exacerbated the development of NAFLD and caffeine had a hepatoprotective effect on NAFLD. The administration of caffeine could ameliorate nicotine-plus-HFD-induced NAFLD by reducing lipid accumulation, regulating hepatic lipid metabolism, alleviating oxidative stress, attenuating inflammatory response and restoring hepatic functions. These results might explain why obese smokers with high coffee consumption exhibit the lower incidence rate of NAFLD and tend to be leaner. It is essential to emphasise that the detrimental impact of smoking on health is multifaceted. Smoking cessation remains the sole practical and effective strategy for averting the tobacco-related complications and reducing the risk of mortality.

The pursuit of studying this subject is driven by the urgency to address the increasing global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) and its profound health implications. NAFLD represents a significant public health concern due to its association with metabolic disorders, cardiovascular complications, and the potential progression to more severe conditions like non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Liver estrogen signaling is important for maintaining liver function, and loss of estrogens increases the likelihood of NAFLD in postmenopausal women. Understanding the multifaceted mechanisms underlying NAFLD pathogenesis, its varied treatment strategies, and their effectiveness is crucial for devising comprehensive and targeted interventions. By unraveling the intricate interplay between genetics, lifestyle, hormonal regulation, and gut microbiota, we can unlock insights into risk stratification, early detection, and personalized therapeutic approaches. Furthermore, investigating the emerging pharmaceutical interventions and dietary modifications offers the potential to revolutionize disease management. This review reinforces the role of collaboration in refining NAFLD comprehension, unveiling novel therapeutic pathways, and ultimately improving patient outcomes for this intricate hepatic condition.

Aim: This study used urinary caffeine and its metabolites to evaluate their relationships with liver steatosis and advanced liver fibrosis. Methods: A total of 2068 adult participants with required data were filtered from the 2009-2014 National Health and Nutrition Examination Survey (NHANES) cycles. Non-invasive scores were applied to define liver steatosis and advanced liver fibrosis. Logistic regression models, weighted quantile sum (WQS) regression models, quantile-based g-computation (QG-Comp) models, and restricted cubic spline (RCS) regression models were used to assess the associations of urinary caffeine and its metabolites with liver steatosis and advanced liver fibrosis. A series of additional analyses were conducted to examine the subgroup-specific differences and test the robustness of the observed results. Results: The major caffeine metabolite mixture and most individual caffeine metabolites were found to be negatively associated with the risk of advanced liver fibrosis with subgroup-specific variations. Only 7-MX consistently showed a negative association with liver steatosis in all analyses, while no association was observed between the major caffeine metabolite mixture and liver steatosis. Conclusion: The major caffeine metabolite mixture and most individual urinary caffeine metabolites exhibited inverse associations with advanced liver fibrosis with subgroup differences. Further prospective and experimental studies are urgently needed to verify our results and further identify the possible mechanisms.

Weight loss achieved through a combination of healthy eating patterns that encompass the principles of the Mediterranean diet and regular physical activity is the most evidence-based treatment for nonalcoholic fatty liver disease. Although other types of diets have demonstrated efficacy in liver fat reduction, the Mediterranean diet confers additional cardiometabolic benefits. Macronutrient composition, food choices, and timing of eating can be tailored to individual preferences, culture, and financial circumstances; however, recommended healthy eating patterns are characterized by minimally processed or unprocessed foods (vegetables, legumes, nuts and seeds, fruits, whole grains, and unprocessed meats and fish) that are low in sugar, refined carbohydrates, and saturated fat and high in fiber, polyphenols, vitamins, minerals, and healthy fats. Physical activity can independently improve steatosis, prevent fibrosis and cirrhosis, and reduce mortality.

A variety of observational studies have demonstrated that coffee, likely acting through caffeine, improves health outcomes in patients with chronic liver disease. The primary pharmacologic role of caffeine is to act as an inhibitor of adenosine receptors. Because key liver cells express adenosine receptors linked to liver injury, regeneration, and fibrosis, it is plausible that the biological effects of coffee are explained by effects of caffeine on adenosinergic signaling in the liver. This review is designed to help the reader make sense of that hypothesis, highlighting key observations in the literature that support or dispute it.

Although coffee has a potential hepatoprotective effect, evidence of the relationship between coffee consumption and metabolic dysfunction-associated steatotic liver disease (MASLD) remains conflicting. There is limited evidence regarding the most appropriate coffee intake to prevent advanced liver fibrosis (ALF) in patients with MASLD. We investigated the effect of coffee consumption on MASLD and ALF among 5266 participants without MASLD and 1326 with MASLD but without ALF. Participants were grouped by coffee intake: non-consumers, >0 and <1 cups/day, ≥1 and <2 cups/day, and ≥2 cups/day. Over a median follow-up of 11.6 years for MASLD and 15.7 years for ALF, coffee consumption did not significantly affect the incidence of MASLD, with 2298 new cases observed. However, a notable inverse association was found with ALF risk in patients with MASLD among those consuming coffee ≥2 cups/day (adjusted HR 0.57, 95% CI: 0.37-0.90, p = 0.014), especially among those consuming coffee ≥2 and <3 cups/day (adjusted HR 0.51, 95% CI: 0.30-0.89, p = 0.018). This suggests a potential hepatoprotective effect of coffee, especially in preventing the progression of liver fibrosis in patients with MASLD. These findings propose that coffee consumption could be a simple and effective approach to mitigate the risk of ALF in individuals with MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD.

A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria.

Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment.

A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10%. NAFLD can be progressive and is associated with increased mortality from cardiovascular disease, extrahepatic cancers and liver complications. Despite these numerous adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat. Physical activity at a level where one can talk but not sing is also recommended, including leisure-time activities and structured exercise. Avoidance of smoking and alcohol is also recommended. Policy-makers, community and school leaders need to work together to make their environments healthy by developing walkable and safe spaces with food stores stocked with culturally appropriate and healthy food items at affordable prices as well as providing age-appropriate and safe play areas in both schools and neighbourhoods.

Metabolic-associated Fatty Liver Disease is one of the outstanding challenges in gastroenterology. The increasing incidence of the disease is undoubtedly connected with the ongoing obesity pandemic. The lack of specific symptoms in the early phases and the grave complications of the disease require an active approach to prompt diagnosis and treatment. Therapeutic lifestyle changes should be introduced in a great majority of patients; but, in many cases, the adherence is not satisfactory. There is a great need for an effective pharmacological therapy for Metabolic-Associated Fatty Liver Disease, especially before the onset of steatohepatitis. Currently, there are no specific recommendations on the selection of drugs to treat liver steatosis and prevent patients from progression toward more advanced stages (steatohepatitis, cirrhosis, and cancer). Therefore, in this Review, we provide data on the clinical efficacy of therapeutic interventions that might improve the course of Metabolic-Associated Fatty Liver Disease. These include the drugs used in the treatment of obesity and hyperlipidemias, as well as affecting the gut microbiota and endocrine system, and other experimental approaches, including functional foods. Finally, we provide advice on the selection of drugs for patients with concomitant Metabolic-Associated Fatty Liver Disease.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Epidemiological evidence has shown an association between coffee consumption and reduced risk for chronic liver diseases, including metabolic-dysfunction-associated liver disease (MALFD). Lipotoxicity is a key cause of hepatocyte injury during MAFLD. The coffee component caffeine is known to modulate adenosine receptor signaling via the antagonism of adenosine receptors. The involvement of these receptors in the prevention of hepatic lipotoxicity has not yet been explored. The aim of this study was to explore whether caffeine protects against palmitate-induced lipotoxicity by modulating adenosine receptor signaling.

Primary hepatocytes were isolated from male rats. Hepatocytes were treated with palmitate with or without caffeine or 1,7DMX. Lipotoxicity was verified using Sytox viability staining and mitochondrial JC-10 staining. PKA activation was verified by Western blotting. Selective (ant)agonists of A1AR (DPCPX and CPA, respectively) and A2AR (istradefyline and regadenoson, respectively), the AMPK inhibitor compound C, and the Protein Kinase A (PKA) inhibitor Rp8CTP were used. Lipid accumulation was verified by ORO and BODIPY 453/50 staining.

Caffeine and its metabolite 1,7DMX prevented palmitate-induced toxicity in hepatocytes. The A1AR antagonist DPCPX also prevented lipotoxicity, whereas both the inhibition of PKA and the A1AR agonist CPA (partially) abolished the protective effect. Caffeine and DPCPX increased lipid droplet formation only in palmitate-treated hepatocytes and decreased mitochondrial ROS production.

The protective effect of caffeine against palmitate lipotoxicity was shown to be dependent on A1AR receptor and PKA activation. Antagonism of A1AR also protects against lipotoxicity. Targeting A1AR receptor may be a potential therapeutic intervention with which to treat MAFLD.

For many years, we have faced the complications of viral hepatitis and alcohol-related liver diseases such as cirrhosis, decompensation, portal hypertension, and hepatocellular carcinoma (HCC). Recently, we have seen a dynamic change in the field of hepatology. With the significant achievements in eradicating the hepatitis C virus by direct-acting antiviral agents and the rising epidemic of obesity, diabetes mellitus, and metabolic syndrome, there is a paradigm shift in the leading cause of liver cirrhosis and cancer to nonalcoholic fatty liver disease (NAFLD). Current data highlight the rapidly rising incidence of NAFLD-related HCC worldwide and expose the unseen part of the iceberg. In this review, we aim to update knowledge about the pathogenesis of NAFLD-induced HCC, surveillance difficulties, and promising disease markers. Molecular biomarkers, for example, may become a promising cornerstone for risk-stratified surveillance, early detection, and treatment selection for NAFLD-related HCC. Physicians can offer personalized and tailor-made clinical decisions for this unique patient subgroup.

In metabolic (dysfunction)-associated fatty liver disease (MAFLD), activation of inflammatory processes marks the transition of simple steatosis to steatohepatitis, which can further evolve to advanced fibrosis or hepatocellular carcinoma. Under the stress of chronic overnutrition, the innate immune system orchestrates hepatic inflammation through pattern recognition receptors (PRRs). Cytosolic PRRs that include NOD-like receptors (NLRs) are crucial for inducing inflammatory processes in the liver.

A literature search was performed with Medline (PubMed), Google Scholar and Scopus electronic databases till January 2023, using relevant keywords to extract studies describing the role of NLRs in the pathogenesis of MAFLD.

Several NLRs operate through the formation of inflammasomes, which are multimolecular complexes that generate pro-inflammatory cytokines and induce pyroptotic cell death. A multitude of pharmacological agents target NLRs and improve several aspects of MAFLD. In this review, we discuss the current concepts related to the role of NLRs in the pathogenesis of MAFLD and its complications. We also discuss the latest research on MAFLD therapeutics functioning through NLRs.

NLRs play a significant role in the pathogenesis of MAFLD and its consequences, especially through generation of inflammasomes, such as NLRP3 inflammasomes. Lifestyle changes (exercise, coffee consumption) and therapeutic agents (GLP-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, obeticholic acid) improve MAFLD and its complications partly through blockade of NLRP3 inflammasome activation. New studies are required to explore these inflammatory pathways fully for the treatment of MAFLD.

In the current review, we focused on identifying aliment compounds and micronutrients, as well as addressed promising bioactive nutrients that may interfere with NAFLD advance and ultimately affect this disease progress. In this regard, we targeted: 1. Potential bioactive nutrients that may interfere with NAFLD, specifically dark chocolate, cocoa butter, and peanut butter which may be involved in decreasing cholesterol concentrations. 2. The role of sweeteners used in coffee and other frequent beverages; in this sense, stevia has proven to be adequate for improving carbohydrate metabolism, liver steatosis, and liver fibrosis. 3. Additional compounds were shown to exert a beneficial action on NAFLD, namely glutathione, soy lecithin, silymarin, Aquamin, and cannabinoids which were shown to lower the serum concentration of triglycerides. 4. The effects of micronutrients, especially vitamins, on NAFLD. Even if most studies demonstrate the beneficial role of vitamins in this pathology, there are exceptions. 5. We provide information regarding the modulation of the activity of some enzymes related to NAFLD and their effect on this disease. We conclude that NAFLD can be prevented or improved by different factors through their involvement in the signaling, genetic, and biochemical pathways that underlie NAFLD. Therefore, exposing this vast knowledge to the public is particularly important.

Non-alcoholic fatty liver disease (NAFLD), one of the most common causes of liver disease, is an increasingly common cause of hepatocellular carcinoma (HCC). Several demographic, clinical, and genetic factors contribute to HCC risk in NAFLD patients, which may inform risk stratification scores. Proven efficacious approaches to primary prevention approach in patients with non-viral liver disease remain an area of need. Semi-annual surveillance is associated with improved early tumor detection and reduced HCC-related mortality; however, patients with NAFLD have several challenges to effective surveillance, including under-recognition of at-risk patients, low surveillance utilization in clinical practice, and lower sensitivity of current tools for early-stage HCC detection. Treatment decisions are best made in a multidisciplinary fashion and are informed by several factors including tumor burden, liver dysfunction, performance status, and patient preferences. Although patients with NAFLD often have larger tumor burden and increased comorbidities compared to counterparts, they can achieve similar post-treatment survival with careful patient selection. Therefore, surgical therapies continue to provide a curative treatment option for patients diagnosed at an early stage. Although there has been debate about the efficacy of immune checkpoint inhibitors in patients with NAFLD, current data are insufficient to change treatment selection based on liver disease etiology.

Lifestyle modification is the primary intervention to control NAFLD progression, but despite evidence-based effectiveness it is difficult to distinguish the benefits of nutrition from physical activity and the optimal diet composition is not established. Macronutrients as saturated fatty acids, sugars and animal proteins are harmful in NAFLD and the Mediterranean Diet reducing sugar, red meat and refined carbohydrates and increasing unsaturated-fatty-acids was reported to be beneficial. However one size cannot fit all since NAFLD is a multifaceted syndrome encompassing many diseases of unknown etiologies, different clinical severity and outcomes. Studies of the intestinal metagenome, provided new insights into the physio-pathological interplay between intestinal microbiota and NAFLD. How much the microbiota heterogeneity can influence response to diet remains unknown. New knowledge indicates that AI guided personalized nutrition based on clinic-pathologic and genetic data combined with pre/post nutritional intervention gut metagenomics/metabolomics will be part of the future management of NAFLD.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of premature death worldwide. Inflammation and its biomarkers, like C-reactive protein (CRP), among the risk factors, such as hypertension, lipid disorders, and diabetes, may be also responsible for the residual cardiovascular disease (CVD) risk. Modern lipid-lowering treatment with statins, ezetimibe, PCSK9 inhibitors, or bempedoic acid does not fully protect against inflammation. The recommendations of the International Lipid Expert Panel (ILEP) indicate selected nutraceuticals with anti-inflammatory properties. Diet may have a significant impact on inflammation. Especially interesting in the context of inflammation is the consumption of coffee and tea. These drinks in many observational studies significantly reduced cardiovascular risk and mortality. The question is whether the anti-inflammatory effects of these drinks contribute significantly to the observed clinical effects. Thus, in this narrative review, we primarily discuss the anti-inflammatory properties of consuming tea and coffee. Based on a comprehensive analysis of the studies and their meta-analyses, inconsistent results were obtained, which makes it impossible to conclusively state how clinically significant the potential anti-inflammatory properties of black and green tea and coffee are. A number of confounding factors can cause the inconsistency of the available results. Consumption of tea and coffee appears to increase adiponectin concentrations, decrease reactive oxygen species, decrease low density lipoprotein (LDL) cholesterol concentrations (effect of green tea, etc.). Despite the still uncertain anti-inflammatory effect of tea and coffee, we recommend their consumption as a part of the healthy diet.

Fatty liver disease is a common condition caused by excess fat in the liver. It consists of two types: Alcoholic Fatty Liver Disease, also called alcoholic steatohepatitis, and Non-Alcoholic Fatty Liver Disease (NAFLD). As per epidemiological studies, fatty liver encompasses 9% to 32% of the general population in India and affects overweight people.

An Optimized Support Vector Machine with Support Vector Regression model is proposed to evaluate the volume of liver fat by image analysis (LFA-OSVM-SVR).

The input computed tomography (CT) liver images are collected from the Chennai liver foundation and Liver Segmentation (LiTS) datasets. Here, input datasets are pre-processed using Gaussian smoothing filter and bypass filter to reduce noise and improve image intensity. The proposed U-Net method is used to perform the liver segmentation. The Optimized Support Vector Machine is used to classify the liver images as fatty liver image and normal images. The support vector regression (SVR) is utilized for analyzing the fat in percentage.

The LFA-OSVM-SVR model effectively analyzed the liver fat from CT scan images. The proposed approach is activated in python and its efficiency is analyzed under certain performance metrics.

The proposed LFA-OSVM-SVR method attains 33.4%, 28.3%, 25.7% improved accuracy with 55%, 47.7%, 32.6% lower error rate for fatty image classification and 30%, 21%, 19.5% improved accuracy with 57.9%, 46.5%, 31.76% lower error rate for normal image classificationthan compared to existing methods such as Convolutional Neural Network (CNN) with Fractional Differential Enhancement (FDE) (CNN-FDE), Fully Convolutional Networks (FCN) and Non-negative Matrix Factorization (NMF) (FCN-NMF), and Deep Learning with Fully Convolutional Networks (FCN) (DL-FCN).

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC-MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by Fibroscan^® assessment of fibrosis. No associations were found between self-reported coffee intake and NAFLD parameters; however, total urine caffeine metabolites, defined as Σ_caffeine (caffeine + paraxanthine + theophylline), and adjusted for fat-free body mass, were significantly higher for subjects with no liver fibrosis than for those with fibrosis. Total non-caffeine metabolites, defined as Σ_ncm (trigonelline + caffeic acid + p-coumaric acid), showed a significant negative association with the FLI. Multiple regression analyses for overweight/obese T2D subjects (n = 89) showed that both Σ_caffeine and Σ_ncm were negatively associated with the FLI, after adjusting for age, sex, Hb_A1c, ethanol intake and glomerular filtration rate. The theophylline fraction of Σ_caffeine was significantly increased with both fibrosis and the FLI, possibly reflecting elevated CYP2E1 activity-a hallmark of NAFLD worsening. Thus, for overweight/obese T2D patients, higher intake of both caffeine and non-caffeine coffee components is associated with less severe NAFLD. Caffeine metabolites represent novel markers of NAFLD progression.

Oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the "acidic pathway" of cholesterol metabolism. Previously, we demonstrated that an inability to upregulate CYP7B1 in the setting of insulin resistance leads to the accumulation of cholesterol metabolites such as (25R)26-hydroxycholesterol (26HC) that initiate and promote hepatocyte injury; followed by an inflammatory response. The current study demonstrates that dietary coffee improves insulin resistance and restores Cyp7b1 levels in a well-characterized Western diet (WD)-induced nonalcoholic fatty liver disease (NAFLD) mouse model. Ingestion of a WD containing caffeinated (regular) coffee or decaffeinated coffee markedly reduced the serum ALT level and improved insulin resistance. Cyp7b1 mRNA and protein levels were preserved at normal levels in mice fed the coffee containing WD. Additionally, coffee led to upregulated steroid sulfotransferase 2b1 (Sult2b1) mRNA expression. In accordance with the response in these oxysterol metabolic genes, hepatocellular 26HC levels were maintained at physiologically low levels. Moreover, the current study provided evidence that hepatic Cyp7b1 and Sult2b1 responses to insulin signaling can be mediated through a transcriptional factor, hepatocyte nuclear factor (HNF)-4α. We conclude coffee achieves its beneficial effects through the modulation of insulin resistance. Both decaffeinated and caffeinated coffee had beneficial effects, demonstrating caffeine is not fundamental to this effect. The effects of coffee feeding on the insulin-HNF4α-Cyp7b1 signaling pathway, whose dysregulation initiates and contributes to the onset and progression of NASH as triggered by insulin resistance, offer mechanistic insight into approaches for the treatment of NAFLD.NEW & NOTEWORTHY This study demonstrated dietary coffee prevented the accumulation of hepatic oxysterols by maintaining Cyp7b1/Sult2b1 expression in a diet-induced NAFLD mice model. Lowering liver oxysterols markedly reduced inflammation in the coffee-ingested mice. Caffeine is not fundamental to this effect. In addition, this study showed Cyp7b1/Sult2b1 responses to insulin signaling can be mediated through a transcriptional factor, HNF4α. The insulin-HNF4α-Cyp7b1/Sult2b1 signaling pathway, which directly correlates to the onset of NASH triggered by insulin resistance, offers insight into approaches for NAFLD treatment.