Management Of Nonalcoholic Fatty Liver Disease Research Articles

Role of Circadian Clock on the Pathogenesis and Lifestyle Management in Non-Alcoholic Fatty Liver Disease

Several features of the modern lifestyle, such as weekly schedules or irregular daily eating patterns, have become major drivers of global health problems, including non-alcoholic fatty liver disease (NAFLD). Sleep is an essential component of human well-being, and it has been observed that when circadian rhythms are disrupted, or when sleep quality decreases, an individual's overall health may worsen. In addition, the discrepancy between the circadian and social clock, due to weekly work/study schedules, is called social jetlag and has also been associated with adverse metabolic profiles. Current management of NAFLD is based on dietary intake and physical activity, with circadian preferences and other environmental factors also needing to be taken into account. In this regard, dietary approaches based on chrononutrition, such as intermittent fasting or time-restricted feeding, have proven to be useful in realigning lifestyle behaviors with circadian biological rhythms. However, more studies are needed to apply these dietary strategies in the treatment of these patients. In this review, we focus on the impact of circadian rhythms and the role of sleep patterns on the pathogenesis and development of NAFLD, as well as the consideration of chrononutrition for the precision nutrition management of patients with NAFLD.

Does Non-Alcoholic Steatohepatitis Independently Increase the Risk of Venous Thromboembolism?

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Studies have shown a strong association between NASH (non-alcoholic steatohepatitis) cirrhosis and portal vein thrombosis (PVT). Data is scarce on the association of NASH and venous thromboembolism (VTE), with one such study predicting a 2.5-fold increased risk for VTE in comparison to other liver diseases in hospitalized patients. The mechanism is believed to be hepatocellular injury causing a chronic inflammatory state leading to unregulated activation of procoagulant factors. There is no prior analysis of the degree of steatosis and fibrosis (measured on transient elastography, commonly known as Fibroscan®) in NASH patients and its association with VTE. We performed an analysis to study the risk of unexplained VTE in patients with NASH. Methods: In our case-control study, we included patients with a documented diagnosis of NASH and excluded patients with inherited thrombophilia, hemoglobinopathy, malignancy, alcohol use disorder, autoimmune hepatitis, and primary biliary cirrhosis. Collected data included age, tobacco use, recreational drug use, medical history, and vibration-controlled transient elastography (VCTE) scores. Venous thromboembolism specific data included location, type of anticoagulant, need for hospital stay, and history of VTE recurrence. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate to severe) based on the controlled attenuation parameter (CAP) score. Fibrosis was classified based on the kilopascal(KPA) score and graded as F0-F1 (metavir stage), F2, F3, and F4(cirrhosis). Chi-square and Mann-Whitney U tests were used for qualitative and quantitative variable analysis, respectively. Furthermore, we computed logistic regression using VTE as a dependent variable. Results: A total of 415 patients were analyzed, and 386 met the inclusion criteria (Figure 1). Fifty-one patients were in the VTE group and 335 in the non-VTE group. Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group (p=0.014). Patients with VTE had a higher body mass index (31.14 kg/m² vs. 29.30 kg/m²) and a higher prevalence of diabetes mellitus (29.4% vs. 13.1%, p=0.002). The history of NASH was significantly higher in the VTE group (45.1% vs. 30.4%, p=0.037). Further, moderate to severe steatosis was significantly higher in the VTE group (66.7% vs. 47.2%, p=0.009). Similarly, the F2-F4 fibrosis grade had a higher prevalence of 58.8 % in the VTE group compared to 38.5% in the non-VTE group (p=0.006) (Table 1). On logistic regression, using VTE as a dependent variable, diabetes mellitus type II had an OR =1.702 (p = 0.015) and F2-F4 fibrosis grade had an OR = 2.5 (p=0.033). In the VTE group, 58.8% had deep vein thrombosis (DVT), 17.6 % had superficial venous thrombosis (SVT), 13.7 % had pulmonary embolism (PE), 5.9% had portal vein thrombosis, and embolic stroke (3.9%). The most common location of VTE was the lower extremity (56.9%), followed by the upper extremity (19.6%). Right-sided VTE (66.7%) was more common and a majority of patients (74.5%) required hospital admission with 2% requiring ICU admission. Concerning anticoagulation 64.71% of patients were on direct oral anticoagulants (DOAC), 25.5% were on warfarin, and 84.3% of patients continued indefinite anticoagulation. Discussion: Our analysis shows that NASH is an independent risk factor for VTE, especially DVT. Demographics including gender, tobacco use, alcohol consumption, and ethnicity, were equally distributed between the two groups. There is a statistically significant association between the incidence of VTE and moderate to severe steatosis and fibrosis. The current management strategy for NASH includes abstinence from alcohol and intense lifestyle modification to lose weight. Newer medications like glucagon-like peptides (semaglutide) and bariatric surgery are other recommended modalities for weight loss. All hospitalized patients should be considered for medical thromboprophylaxis, particularly in those with NASH, where a high index of suspicion for VTE should be maintained even in the presence of thromboprophylaxis. Additional studies are needed to analyze the risk of bleeding in this patient population who continue indefinite anticoagulation. Another area of interest would be to determine the reversibility of VTE risk with appropriate management of NAFLD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Indolepropionic Acid, a Gut Bacteria-Produced Tryptophan Metabolite and the Risk of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.

An intricate relationship between gut microbiota, diet, and the human body has recently been extensively investigated. Gut microbiota and gut-derived metabolites, especially, tryptophan derivatives, modulate metabolic and immune functions in health and disease. One of the tryptophan derivatives, indolepropionic acid (IPA), is increasingly being studied as a marker for the onset and development of metabolic disorders, including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). The IPA levels heavily depend on the diet, particularly dietary fiber, and show huge variations among individuals. We suggest that these variations could partially be explained using genetic variants known to be associated with specific diseases such as T2D. In this narrative review, we elaborate on the beneficial effects of IPA in the mitigation of T2D and NAFLD, and further study the putative interactions between IPA and well-known genetic variants (TCF7L2, FTO, and PPARG), known to be associated with the risk of T2D. We have investigated the long-term preventive value of IPA in the development of T2D in the Finnish prediabetic population and the correlation of IPA with phytosterols in obese individuals from an ongoing Kuopio obesity surgery study. The diversity in IPA-linked mechanisms affecting glucose metabolism and liver fibrosis makes it a unique small metabolite and a promising candidate for the reversal or management of metabolic disorders, mainly T2D and NAFLD.

Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non-alcoholic fatty liver disease.

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD. Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched. Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.

Chiliadenus iphionoides Reduces Body Weight and Improves Parameters Related to Hepatic Lipid and Glucose Metabolism in a High-Fat-Diet-Induced Mice Model of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has become an epidemic with increasing prevalence. Limited treatment options and poor adherence emphasize the urgent need for novel therapies for the treatment and/or prevention of NAFLD. Bioactive natural compounds found in medicinal plants are promising as novel therapeutic agents for NAFLD. Chiliadenus iphionoides, a medicinal plant with several health-promoting properties, is an encouraging candidate. The current study aimed to elucidate the metabolic effects of C. iphionoides consumption in a high-fat-diet (HFD)-induced model of NAFLD. Male C57BL/6J mice (n = 40, 7-8-week-old) were fed a HFD (60% fat) with/without 0.5 or 2.5 gr C. iphionoides for fifteen weeks. Diet supplementation with C. iphionoides significantly ameliorated HFD-induced weight gain. Likewise, liver and adipose tissue weights were profoundly lower in the C. iphionoides-fed groups. Reduced liver steatosis in those groups was corroborated by histology, plasma liver enzyme levels, and lipid profile, indicating improved liver function and lipid metabolism in addition to enhanced insulin sensitivity. The addition of C. iphionoides to an obesogeneic diet can beneficially alleviate metabolic alterations and may be a practicable strategy for the management of NAFLD.

Non-alcoholic fatty liver disease and cardiovascular pathology: features of patient management on a clinical example

Non-alcoholic fatty liver disease (NAFLD) is recognized as an interdisciplinary problem at the intersection of therapy, gastroenterology and endocrinology. In recent years, there has been a significant increase in interest in NAFLD as an accomplice of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). The article discusses the mechanisms of NAFLD in the development and progression of cardiovascular diseases depending on risk factors and comorbidity, including a clinical case. The proven clear association of NAFLD with obesity, DM 2, CVD suggests that these comorbid diseases are interdependent in their natural course. Pathogenetically substantiated management of NAFLD can positively influence the course of comorbid conditions. The role of ursodeoxycholic acid drugs in the treatment of NAFLD and the effect of this therapy on the course of associated diseases and conditions are discussed.

S1348 Patterns of GI Specialty Referral for Primary Care Patients With Nonalcoholic Fatty Liver Disease

Introduction: Early specialist intervention for patients with significant fibrosis from nonalcoholic fatty liver disease (NAFLD) is important in preventing related morbidity and mortality. For patients with evidence of hepatic steatosis, we aim to determine what proportion received gastroenterology (GI) referral, the reason for referral, and the severity of fibrosis between groups. Methods: This retrospective study of electronic health record data from 2012-2018 included patients with (i) radiographic reports of liver steatosis (abdominal ultrasound, CT, or MRI) and (ii) no competing, non-NAFLD chronic liver disease diagnoses. Referral to GI any time after imaging was the primary outcome. Chart review was conducted to determine if a patient was referred and the reason for the referral. Fibrosis-4 Index (FIB-4) scores were calculated and categorized by advanced fibrosis risk. Statistical analysis was performed with Student t-tests and Chi-square tests using SAS. Results: The cohort included 652 patients with a mean age of 55 (SD ± 14) years. Of included patients, 64% were female and 36% identified as Black. One in four patients received a formal diagnosis of NAFLD. FIB-4 scores were high-risk for advanced fibrosis in 12% of patients, indeterminate-risk for 31% of patients, and low-risk for 57% of patients. Overall, 46% of patients received a GI referral, with 32% of these referrals being for colonoscopy. A larger portion of referred patients (33%) received a diagnosis of NAFLD during the study period compared to those not referred (19%, p< 0.001). Of patients referred for non-colonoscopy reasons, only 15% of referral orders mentioned steatosis. When fatty liver disease was mentioned at referral, a larger proportion of patients received a formal NAFLD diagnosis compared to all other non-colonoscopy referrals (80% vs. 26%, p< 0.001). There was no difference in the proportion of high-risk FIB-4 scores between patients with and without a GI referral (p=0.95). Conclusion: Appropriate GI referral for NAFLD management remains a concern, even so NAFLD is predicted to be the leading indication for liver transplantation within the next 10 years. Our data suggests hepatic steatosis is infrequently recognized as a notable finding on abdominal imaging and did not prompt excessive GI referral. Use of FIB-4 scoring has been shown to reduce unnecessary referral and improve detection of advanced fibrosis, though FIB-4 scoring did not influence referral likelihood in this cohort.

Probiotics suppress nonalcoholic steatohepatitis and carcinogenesis progression in hepatocyte-specific PTEN knockout mice

Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice.

Ultrasound-Based Hepatic Elastography in Non-Alcoholic Fatty Liver Disease: Focus on Patients with Type 2 Diabetes.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is the hepatic expression of metabolic syndrome. The development of non-invasive methods for the diagnosis of hepatic steatosis and advanced fibrosis in high-risk patients, especially those with type 2 diabetes mellitus, is highly needed to replace the invasive method of liver biopsy. Elastographic methods can bring significant added value to screening and diagnostic procedures for NAFLD in patients with diabetes, thus contributing to improved NAFLD management. Pharmacological development and forthcoming therapeutic measures that address NAFLD should also be based on new, non-invasive, and reliable tools that assess NAFLD in at-risk patients and be able to properly guide treatment in individuals with both diabetes and NAFLD. This is the first review aiming to outline and discuss recent studies on ultrasound-based hepatic elastography, focusing on NAFLD assessment in patients with diabetes.

Real-world evidence on non-invasive tests and associated cut-offs used to assess fibrosis in routine clinical practice

Non-invasive tests (NITs) offer a practical solution for advanced fibrosis identification in non-alcoholic fatty liver disease (NAFLD). Despite increasing implementation, their use is not standardised, which can lead to inconsistent interpretation and risk stratification. We aimed to assess the types of NITs and the corresponding cut-offs used in a range of healthcare settings. A survey was distributed to a convenience sample of liver health experts who participated in a global NAFLD consensus statement. Respondents provided information on the NITs used in their clinic with the corresponding cut-offs and those used in established care pathways in their areas. There were 35 respondents from 24 countries, 89% of whom practised in tertiary level settings. A total of 14 different NITs were used, and each respondent reported using at least one (median= 3). Of the respondents, 80% reported using FIB-4 and liver stiffness by vibration-controlled transient elastography (Fibroscan®), followed by the NAFLD fibrosis score (49%). For FIB-4, 71% of respondents used a low cut-off of <1.3 (range <1.0 to <1.45) and 21% reported using age-specific cut-offs. For Fibroscan®, 21% of respondents used a single liver stiffness cut-off: 8kPa in 50%, while the rest used 7.2kPa, 7.8kPa and 8.7kPa. Among the 63% of respondents who used lower and upper liver stiffness cut-offs, there were variations in both values (<5 to <10kPa and >7.5 to >20kPa, respectively). The cut-offs used for the same NITs for NAFLD risk stratification vary between clinicians. As cut-offs impact test performance, these findings underscore the heterogeneity in risk-assessment and support the importance of establishing consistent guidelines on the standardised use of NITs in NAFLD management. Owing to the high prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population it is important to identify those who have more advanced stages of liver fibrosis, so that they can be properly treated. Non-invasive tests (NITs) provide a practical way to assess fibrosis risk in patients. However, we found that the cut-offs used for the same NITs vary between clinicians. As cut-offs impact test performance, these findings highlight the importance of establishing consistent guidelines on the standardised use of NITs to optimise clinical management of NAFLD.

Gut microbiota-mitochondrial inter-talk in non-alcoholic fatty liver disease.

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD), which is a progressive disease, has exerted huge a healthcare burden worldwide. New investigations have suggested that the gut microbiota closely participates in the progression of NAFLD through the gut–liver axis or gut–brain–liver axis. The composition of the microbiota can be altered by multiple factors, primarily dietary style, nutritional supplements, or exercise. Recent evidence has revealed that gut microbiota is involved in mitochondrial biogenesis and energy metabolism in the liver by regulating crucial transcription factors, enzymes, or genes. Moreover, microbiota metabolites can also affect mitochondrial oxidative stress function and swallow formation, subsequently controlling the inflammatory response and regulating the levels of inflammatory cytokines, which are the predominant regulators of NAFLD. This review focuses on the changes in the composition of the gut microbiota and metabolites as well as the cross-talk between gut microbiota and mitochondrial function. We thus aim to comprehensively explore the potential mechanisms of gut microbiota in NAFLD and potential therapeutic strategies targeting NAFLD management.

Lifestyle Intervention for Patients with Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial Based on the Theory of Planned Behavior.

Introduction Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, accounting for about 25% and 33% of the world's adult population and Iranians, respectively. There is currently no effective therapeutic agent available for the treatment of NAFLD. However, lifestyle modifications aimed at weight loss have been introduced as a cornerstone of NAFLD management. The aim of the present study was to evaluate the effect of educational intervention on lifestyle and anthropometric indices in patients with NAFLD. Methods The randomized controlled clinical trial was performed on 87 overweight or obese patients with NAFLD, including intervention (n = 42) and control (n = 45) groups. The intervention received 8 training sessions based on theory of planned behavior (TPB), while the control groups received nutritional and physical activity recommendations from their internal specialist and nutritionist. Analyses were carried out based on data collected from TPB constructs and anthropometric indices (weight, body mass index (BMI), waist size, and waist-hip ratio (WHR)) at three stages (before intervention and two and 12 weeks after the intervention), as well as data obtained from liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), and ultrasound-based grading of NAFLD at two stages (before and 12 weeks after the intervention). Results After the intervention, a significant difference was found between the intervention and control groups, resulting in the increased mean scores of TPB constructs, decreased liver enzymes, and decreased degree of NAFLD ultrasound. In addition, the intervention group experienced more activity and healthy diet as compared with the control group. Anthropometric indices showed only a significant decrease in BMI in the intervention group (p < 0.05). Conclusions TPB-based training, as compared with traditional training, is a more effective and cost-effective strategy for altering nutritional behavior and physical activity of patients with NAFLD.

Which is the optimal antiobesity agent for patients with nonalcoholic fatty liver disease?

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM.

Daily Intake of Smallanthus sonchifolius (Yacon) Roots Reduces the Progression of Non-alcoholic Fatty Liver in Rats Fed a High Fructose Diet.

High-fructose diet is associated with an increased risk of dyslipidemia, metabolic syndrome, and the development of non-alcoholic fatty liver disease (NAFLD) through chronic inflammation. The present study aimed to elucidate the potential benefit of daily consumption of Smallanthus sonchifolius (yacon) roots, rich in fructooligosaccharides (FOS), on the progression to liver fibrosis, in a rat model of NAFLD induced by a high-fructose diet. Male Wistar rats were fed a standard diet (CD, n= 6) or a standard diet plus 10% fructose solution (FD; n= 18). After 20weeks, FD rats were randomly separated into the following groups (n= 6, each): FD; FD treated with yacon flour (340mg FOS/body weight; FD + Y) and FD treated with fenofibrate (30mg/kg body weight; FD + F), for 16weeks. Daily intake of yacon flour significantly reduced body weight gain, plasma lipid levels, transaminase activities, and improved systemic insulin response in FD rats. In the liver, yacon treatment decreased fructose-induced steatosis and inflammation, and reduced total collagen deposition (64%). Also, yacon decreased TGF-β1 mRNA expression (78%), followed by decreased nuclear localization of p-Smad2/3 in liver tissue. Yacon significantly reduced the expression of α-smooth muscle actin (α-SMA), Col1α1, and Col3α1 mRNAs (85, 44, and 47%, respectively), inhibiting the activation of resident hepatic stellate cells (HSCs). These results suggested that yacon roots have the potential to ameliorate liver damage caused by long-term consumption of a high-fructose diet, being a promising nutritional strategy in NAFLD management.

Management of NAFLD in primary care settings.

Non-alcoholic fatty liver disease (NAFLD) affects at least 25% of the general population and is an increasingly important cause of cirrhosis and hepatocellular carcinoma. Although it is the research focus of the hepatology field, it is clear that primary care physicians are seeing the majority of NAFLD patients and are in a pivotal position to provide quality care. In this article, we review the role of primary care in the management of NAFLD. NAFLD is common in patients with diabetes, obesity and other metabolic risk factors. Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. Simple fibrosis scores have high negative predictive values in excluding advanced liver fibrosis and future liver-related events and can be used in primary care as initial evaluation. An abnormal result should be followed by subsequent workup or specialist referral. Primary care is the ideal setting to institute multidisciplinary care, especially the involvement of dietitians and physical activity trainers in lifestyle intervention, as well as initiating the discussion of bariatric surgery in patients with severe obesity. Although specific drug treatment for steatohepatitis would require a more precise diagnosis, metabolic drugs that improve both steatohepatitis and cardiovascular outcomes (e.g. glucagon-like peptide-1 receptor agonists) may be considered in patients with NAFLD.

Nonalcoholic fatty liver disease in relation to the remission and progression along the glycemic continuum.

BackgroundThe study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum.MethodsThis prospective cohort study was performed among the general population in 2010–2015. NAFLD was defined as ultrasound‐detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition.ResultsDuring a median follow‐up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60–7.07]) and lower likelihood of diabetes remission (0.48 [0.30–0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32–0.80]) and increased the probability of prediabetes remission (2.67 [1.49–4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes.ConclusionsPresence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver‐specific subgroups of diabetes to tailor early intervention.

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

Simple SummaryNon-alcoholic fatty liver disease (NAFLD) is an unmet medical need due to its increasingly high incidence, severe clinical consequences, and the absence of feasible diagnostic tools and effective drugs. This review summarizes the preclinical and clinical data on adipokines, cytokine-like hormones secreted by adipose tissue, and NAFLD. The aim is to establish the potential of adipokines as diagnostic and prognostic biomarkers, as well as their potential as therapeutic targets for NAFLD. The limitations of current research are also discussed, and future perspectives are outlined.Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and the leading indication for liver transplantation in the future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, and chronic kidney disease. Aggravating the socio-economic impact of this complex pathology, routinely feasible diagnostic methodologies and effective drugs for NAFLD management are unavailable. The pathophysiology of NAFLD, recently defined as metabolic associated fatty liver disease (MAFLD), is correlated with abnormal adipose tissue–liver axis communication because obesity-associated white adipose tissue (WAT) inflammation and metabolic dysfunction prompt hepatic insulin resistance (IR), lipid accumulation (steatosis), non-alcoholic steatohepatitis (NASH), and fibrosis. Accumulating evidence links adipokines, cytokine-like hormones secreted by adipose tissue that have immunometabolic activity, with NAFLD pathogenesis and progression; however, much uncertainty still exists. Here, the current knowledge on the roles of leptin, adiponectin, ghrelin, resistin, retinol-binding protein 4 (RBP4), visfatin, chemerin, and adipocyte fatty-acid-binding protein (AFABP) in NAFLD, taken from preclinical to clinical studies, is overviewed. The effect of therapeutic interventions on adipokines’ circulating levels are also covered. Finally, future directions to address the potential of adipokines as therapeutic targets and disease biomarkers for NAFLD are discussed.

Plant-derived bioactive compounds regulate the NLRP3 inflammasome to treat NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by abnormal accumulation of hepatic fat and inflammatory response with complex pathogenesis. Over activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the secretion of interleukin (IL)-1β and IL-18, induces pyroptosis, and promotes the release of a large number of pro-inflammatory proteins. All of which contribute to the development of NAFLD. There is a great deal of evidence indicating that plant-derived active ingredients are effective and safe for NAFLD management. This review aims to summarize the research progress of 31 active plant-derived components (terpenoids, flavonoids, alkaloids, and phenols) that alleviate lipid deposition, inflammation, and pyroptosis by acting on the NLRP3 inflammasome studied in both in vitro and in vivo NAFLD models. These studies confirmed that the NLRP3 inflammasome and its related genes play a key role in NAFLD amelioration, providing a starting point for further study on the correlation of plant-derived compounds treatment with the NLRP3 inflammasome and NAFLD.

Complete alcohol abstinence increases the risk of NAFLD but not severity. A population analysis with transient elastography

Background & Aims As the global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise, ubiquity of alcohol use has also prompted discussion regarding the potential interactions between the two. This study aims to examine the effects of modest alcohol consumption on the prevalence and complications of NAFLD in a multi-ethnic population. Methods This study analyses the 2017–2018 cycles of NHANES that examined liver fibrosis and steatosis with vibration controlled transient elastography. A coarsened exact matching was conducted to reduce confounding. Logistic regression was done with a multivariate model to assess the relationship between alcohol consumption (modest drinkers and non-drinkers) and risk of NAFLD and its complications. Results 2,067 individuals were found to have NAFLD and 284 NAFLD patients had a total history of alcohol abstinence. After coarsened exact matching, the prevalence of NAFLD was 49% (CI: 0.41 − 0.58) in non-drinkers and 33% (CI: 0.26 − 0.41) in modest drinkers. Non-drinkers had twice the odds of NAFLD compared to modest drinkers (OR: 1.99, CI: 1.22 − 3.22, p<.01) after adjustment for confounders. There were no significant differences in the odds of significant fibrosis, advance fibrosis, cirrhosis, cardiovascular disease and stroke between non-drinkers and modest drinkers. The odds of malignancy in non-drinkers were almost significantly less than modest drinkers (OR: 0.28, CI:0.08 − 1.02, p=.053). Conclusion Interestingly, modest alcohol consumption is associated with decreased odds of NAFLD. Further investigations are required to examine the relationship between alcohol consumption and NAFLD and subsequently the potential impact on NAFLD management.

Preparedness of Residents to Manage Pediatric Nonalcoholic Fatty Liver Disease: A National Survey.

Non-Alcoholic Fatty Liver Disease (NAFLD) is reported to be the most common chronic pediatric liver disease. Little information is available on the adherence of residents in-training to the published guidelines for the evaluation and management of pediatric NAFLD.The goals of this study are: (i) to assess the consistency of screening and evaluation for NAFLD in obese and overweight children at continuity clinics by upper level residents, and (ii) to determine the residents' extent of training, knowledge, comfort and competence levels in NAFLD care. An electronic survey developed using REDCap was emailed to accredited Pediatric Residency Programs in the United States. Program directors and coordinators were requested to forward the survey to their upper level pediatric and medicine/pediatrics residents. Statistical analysis of responses (n= 399) was performed. More than 88% of residents reported to be exposed to obese and overweight children, representing at least 25% of the patients encountered in clinics. Regardless of their training level, they inconsistently screened for (>60%), initiated evaluation of, or provided counseling on NAFLD in these patients, not following the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Over 80% of residents perceived to have received inadequate training resulting in insufficient knowledge on NAFLD, which they identified as their biggest barrier (25.7%). There was minimal statistically significant difference in the survey findings between training levels (PGY-2 vs PGY-3/4). Educational interventions should be implemented by pediatric residency programs to enhance educational core curricula for the early detection and initiation of management of NAFLD, an emerging public health problem.