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The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, affecting up to 30% of the population, with approximately 20% of cases occurring in non-obese individuals. The recent shift to the term metabolic dysfunction-associated steatosis liver disease (MASLD) highlights the disease's heterogeneity. However, there are no well-established animal models replicating non-obese NAFLD (NO-NAFLD). This study aimed to evaluate the relevance of the high-fat diet (HFD) combined with the propylthiouracil (PTU)-induced rat model in mimicking the histopathology and pathophysiology of NO-NAFLD. We first analyzed metabolic and clinical parameters between NO-NAFLD patients (Average BMI = 21.96 kg/m2) and obese NAFLD patients (Average BMI = 29.7 kg/m2). NO-NAFLD patients exhibited significantly higher levels of carnitines, phospholipids, and triglycerides. In the animal model, we examined serum lipid profiles, liver inflammation, histology, and transcriptomics. Hepatic steatosis in the HFD+PTU model at week 4 was comparable to that of the HFD model at week 8. The HFD+PTU model showed higher levels of carnitines, phospholipids, and triglycerides, supporting its relevance for NO-NAFLD. Additionally, the downregulation of lipid synthesis-related genes indicated differences in lipid accumulation between the two models. Overall, the HFD+PTU-induced rat model is a promising tool for studying the molecular mechanisms of NO-NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aim: Dietary characteristics associated with non‐alcoholic fatty liver disease (NAFLD) and metabolic dysfunction‐associated steatotic liver disease (MASLD) in non‐obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status. Methods: We performed a cross‐sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35–74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty‐liver‐related dietary characteristics were assessed using a self‐administered questionnaire. Results: For non‐obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non‐obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable‐adjusted stepwise logistic regression analysis indicated that, in males, both non‐obese NAFLD and non‐obese MASLD were significantly and negatively associated with "often eat sesame/nuts", and positively associated with "often eat noodles/rice bowl" and "often eat evening meal" (P < 0.05). For non‐obese women, both NAFLD and MASLD were significantly and positively associated with "often eat sweet buns/bread with fillings" (P < 0.05). Adjusted analyses showed that all dietary characteristics were not significantly associated with the risk of NAFLD/MASLD in obese men and women. Conclusion: This cross‐sectional study indicates the existence of sex and obesity differences in the association of NAFLD and MASLD with dietary characteristics. Our findings suggest that some dietary characteristics are associated with NAFLD and MASLD prevalence in non‐obese Japanese participants. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Dietary characteristics associated with non‐alcoholic fatty liver disease (NAFLD) and metabolic dysfunction‐associated steatotic liver disease (MASLD) in non‐obese patients remain to be elucidated. This study examined the association of NAFLD and MASLD with dietary characteristics according to obesity status. Methods We performed a cross‐sectional study of 15 135 participants (n = 7568 men and 7567 women) aged 35–74 years using data of annual health checks between 2008 and 2020. Obesity was defined as BMI ≥ 25 kg/m2. Diagnosis of fatty liver was based on abdominal ultrasonography. Fatty‐liver‐related dietary characteristics were assessed using a self‐administered questionnaire. Results For non‐obese participants, NAFLD was found in 31.0% of men and 19.4% of women. Non‐obese MASLD was found in 27.6% of men and 18.1% of women. Multivariable‐adjusted stepwise logistic regression analysis indicated that, in males, both non‐obese NAFLD and non‐obese MASLD were significantly and negatively associated with “often eat sesame/nuts”, and positively associated with “often eat noodles/rice bowl” and “often eat evening meal” (P

The incidence of non-obese non-alcoholic fatty liver disease (NAFLD), characterized by the presence of a fatty liver in individuals with a normal body mass index, is on the rise globally. Effective management strategies, including lifestyle interventions such as diet and exercise therapy, are urgently needed to address this growing public health concern. The aim of this study was to investigate the association between non-obese NAFLD, dietary habits, and physical activity levels. By elucidating these relationships, this research may contribute to the development of evidence-based recommendations for the management of non-obese NAFLD. The study had a single-center retrospective cross-sectional design and compared clinical data and dietary and physical activity habits between patients with and without non-obese NAFLD. Logistic regression analysis was utilized to investigate the relationship between food intake frequency and the development of NAFLD. Among the 455 patients who visited the clinic during the study period, 169 were selected for analysis, including 74 with non-obese NAFLD and 95 without NAFLD. The non-obese NAFLD group showed a less-frequent consumption of fish and fish products as well as olive oil and canola/rapeseed oil, while they showed more frequent consumption of pastries and cake, snack foods and fried sweets, candy and caramels, salty foods, and pickles compared to the non-NAFLD group. Logistic regression analysis revealed that NAFLD was significantly associated with the consumption of fish, fish products, and pickles at least four times a week. The physical activity level was lower and the exercise frequency was lower in patients with non-obese NAFLD compared to those without NAFLD. The results of this study suggest that a low consumption of fish and fish products and high consumption of pickles may be associated with a higher risk of non-obese NAFLD. Moreover, dietary habits and physical activity status should be taken into consideration for the management of patients with non-obese NAFLD. It is important to develop effective management strategies, such as dietary and exercise interventions, to prevent and treat NAFLD in this patient population. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide yet predicting non-obese NAFLD is challenging. Thus, this study investigates the potential of regional fat percentages obtained by dual-energy X-ray absorptiometry (DXA) in accurately assessing NAFLD risk. Using the United States National Health and Nutrition Examination Survey (NHANES) 2011–2018, multivariate logistic regression and marginal analysis were conducted according to quartiles of regional fat percentages, stratified by gender. A total of 23,752 individuals were analysed. Males generally showed a larger increase in marginal probabilities of NAFLD development than females, except in head fat, which had the highest predictive probabilities of non-obese NAFLD in females (13.81%, 95%CI: 10.82–16.79) but the lowest in males (21.89%, 95%CI: 20.12–23.60). Increased percent of trunk fat was the strongest predictor of both non-obese (OR: 46.61, 95%CI: 33.55–64.76, p < 0.001) and obese NAFLD (OR: 2.93, 95%CI: 2.07–4.15, p < 0.001), whereas raised percent gynoid and leg fat were the weakest predictors. Ectopic fat deposits are increased in patients with non-obese NAFLD, with greater increases in truncal fat over gynoid fat. As increased fat deposits in all body regions can increase odds of NAFLD, therapeutic intervention to decrease ectopic fat, particularly truncal fat, may decrease NAFLD risk. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, affecting approximately 25% of the world's population. Recently, because of the sedentary lifestyle and overnutrition resulting from urbanisation, the burden of NAFLD has rapidly increased in many Asian countries. Currently, the prevalence of NAFLD in Asia is approximately 30%, as is the case in many Western countries. In Asia, the prevalence and presentation of NAFLD vary widely across regions because of the substantial diversity in race, socioeconomic status and living environment. Furthermore, the dual aetiology of fatty liver, particularly with viral hepatitis in Asia, makes it complex and challenging to manage. Because Asians are likely to have central adiposity and insulin resistance, approximately 7%-20% of non-obese Asians with body mass indexes of less than 25 kg/m² are estimated to have NAFLD. Accumulating evidence indicates that NAFLD is associated with various extrahepatic comorbidities such as cardiovascular disease, chronic kidney disease, malignancy, in addition to liver-specific complications. Therefore, NAFLD should be managed as a multisystem disease in conjunction with metabolic syndrome. Lifestyle modification remains the basis of NAFLD management, but few patients can achieve adequate weight loss and maintain it long term. While various pharmacological agents are in phase 3 trials for steatohepatitis, Asian patients are underrepresented in most trials. This article reviews the epidemiological trends, clinical features, optimal assessment and current management practices for NAFLD in Asia. [ABSTRACT FROM AUTHOR]

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017–2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0–15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1–7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7–8.5), and truncal fat (100-unit increase ORadjusted = 1.07, 95% CI: 1.04–1.10) were associated with higher odds of non-obese NAFLD. Meanwhile, low physical activity (ORadjusted = 2.9, 95% CI 1.2–7.1) was also positively associated with non-obese NAFLD. Non-obese NAFLD is prevalent in the US and is highly associated with metabolic conditions and syndrome. Our results support the importance of considering racial/ethnic differences when investigating NAFLD in a clinical setting. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, affecting approximately 25% of the world's population. Recently, because of the sedentary lifestyle and overnutrition resulting from urbanisation, the burden of NAFLD has rapidly increased in many Asian countries. Currently, the prevalence of NAFLD in Asia is approximately 30%, as is the case in many Western countries. In Asia, the prevalence and presentation of NAFLD vary widely across regions because of the substantial diversity in race, socioeconomic status and living environment. Furthermore, the dual aetiology of fatty liver, particularly with viral hepatitis in Asia, makes it complex and challenging to manage. Because Asians are likely to have central adiposity and insulin resistance, approximately 7%‐20% of non‐obese Asians with body mass indexes of less than 25 kg/m2 are estimated to have NAFLD. Accumulating evidence indicates that NAFLD is associated with various extrahepatic comorbidities such as cardiovascular disease, chronic kidney disease, malignancy, in addition to liver‐specific complications. Therefore, NAFLD should be managed as a multisystem disease in conjunction with metabolic syndrome. Lifestyle modification remains the basis of NAFLD management, but few patients can achieve adequate weight loss and maintain it long term. While various pharmacological agents are in phase 3 trials for steatohepatitis, Asian patients are underrepresented in most trials. This article reviews the epidemiological trends, clinical features, optimal assessment and current management practices for NAFLD in Asia. [ABSTRACT FROM AUTHOR]

Abstract Background Although nonalcoholic fatty liver disease (NAFLD) is commonly seen in metabolic abnormalities patients, NAFLD is also occurred in the non-obese individuals. The ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) is considered as a predictive factor of NAFLD. However, it is still difficult to confirm the correlation of TG/HDL-C ratio with NAFLD among non-obese Chinese people with normal blood lipid levels. In our study, it is aimed to analyze the correlation of TG/HDL-C ratio with NAFLD among non-obese Chinese population without dyslipidemia. Methods In the retrospective cohort study, 9838 non-obese subjects who were free of NAFLD were enrolled. NAFLD was diagnosed by ultrasonography. Results During the median follow-up period of 2.9 years, cumulative incidence of NAFLD in non-obesity individuals was 8.69% among the overall population; meanwhile, its incidence was gradually enhanced across the quartiles of TG/HDL-C ratio (0.61, 1.28, 2.55 and 4.25% respectively). Then the multivariate factors were adjusted. The multivariate cox regression analysis results showed that the hazard ratio of NAFLD in higher quartiles (Q2-Q4) was 2.10 (1.33–3.32), 3.11 (2.03–4.75) and 3.40 (2.24–5.17), respectively. Besides, the area under receiver operator characteristic curve (AUC) of TG/HDL-C ratio in the male was 0.70 (0.68–0.72) and 0.72 (0.70–0.75) in the female. The final values were dramatically larger than the other lipid index. Conclusion There is an independent relationship between TG/HDL-C and NAFLD among non-obese Chinese population without dyslipidemia, and TG/HDL-C may be used as a better predictor for NAFLD.

Background and Aim: Gut microbiota composition is associated with the pathogenesis of non‐alcoholic fatty liver disease. However, the association between gut microbiota composition and non‐alcoholic fatty liver disease in non‐obese patients remains unclear. We compared clinical parameters and gut microbiota profiles of healthy controls and non‐obese and obese patients with non‐alcoholic fatty liver disease. Methods: We examined the clinical parameters and gut microbiota profiles by 16S rRNA sequences and short‐chain fatty acid levels in fecal samples from 51 non‐obese patients with non‐alcoholic fatty liver disease (body mass index <25 kg/m2) and 51 obese patients with non‐alcoholic fatty liver disease (body mass index ≥30 kg/m2) who underwent pathological examination and 87 controls at five hospitals in Japan. Results: Although no significant differences between the non‐obese and other groups were observed in alpha diversity, a significant difference was found in beta diversity. We observed a significant decrease in serum alanine aminotransferase levels, Eubacterium population, and butyric acid levels in non‐obese patients with non‐alcoholic fatty liver disease compared with those in obese patients with non‐alcoholic fatty liver disease. A significant negative correlation was found between the stage of hepatic fibrosis and Eubacterium abundance in non‐obese patients with non‐alcoholic fatty liver disease. Conclusions: The decrease in the abundance of Eubacterium that produces butyric acid may play an important role in the development of non‐alcoholic fatty liver disease in non‐obese individuals. This study was registered at the University Hospital Medical Information Network clinical trial registration system (UMIN000020917). [ABSTRACT FROM AUTHOR]

Aim: The underlying mechanism of non‐obese non‐alcoholic fatty liver disease (NAFLD) has not been fully elucidated. We classified patients with NAFLD by sex and body mass index and compared their clinical features to clarify the background pathophysiology of non‐obese NAFLD. Methods: A total of 404 patients with NAFLD were divided according to their body mass index (<25 [non‐obese], 25 to <30 [obese], and ≥30 [severe obese]), and were further compared with 253 patients without obesity and NAFLD (non‐NAFLD). Results: The proportion of the individuals with non‐obese NAFLD was 25.7% in men and 27.6% in women. The male and female non‐obese NAFLD groups had lower skeletal muscle mass and muscle strength than the obese NAFLD groups. The visceral fat area, although low, was ≥100 cm2 in 59.3% of men and 43.8% of women. An increase in liver fat accumulation, hepatic fibrosis, homeostasis model assessment of insulin resistance, and leptin levels was modest in the non‐obese NAFLD group compared with a marked increase in the obese NAFLD groups. The muscle mass of the non‐obese NAFLD group was similar to that of the non‐NAFLD group, but muscle steatosis was particularly common among women. Multivariate analysis revealed that the factors contributing to increased liver fat accumulation in the non‐obese NAFLD group were visceral fat area, HbA1c, myostatin, and leptin. Conclusions: In patients with non‐obese NAFLD, a sex difference was observed in the clinical features. In addition to increased visceral fat, decreased muscle mass and muscle strength, muscle atrophy (presarcopenia), and impaired glucose tolerance were considered to be important pathophysiological factors. [ABSTRACT FROM AUTHOR]

Background Non-alcoholic fatty liver disease (NAFLD), one of the leading causes of end-stage liver disease, is known to be associated with obesity. However, only a few studies in the United States (US) have described non-obese NAFLD, most of which were on the outpatient population. Aim We aimed to investigate the proportion of hospitalizations in the US with a diagnosis code that included NAFLD in the non-obese population. Methods We analyzed adult discharges from the Nationwide Inpatient Sample with a diagnosis of NAFLD from January 2010 to December 2014. We created two groups: obese (overweight or obese) and non-obese (normal or underweight) groups. Basic demographic and clinical characteristics were compared using the chi-square test and Student's t-test . Results A total of 194,787 hospitalizations with NAFLD were identified over the five-year period. It was observed that the prevalence of non-obese NAFLD hospitalizations increased yearly. Non-obese NAFLD hospitalizations had a higher mean age (57.5 vs 51.5 years, p < 0.0001) and a higher proportion of males (43.3% vs 36.1%, p < 0.0001) than obese NAFLD hospitalizations. With univariate analysis, non-obese NAFLD hospitalizations had lower odds of hypertension (OR 0.74, p < 0.0001), diabetes mellitus (OR 0.65, p < 0.0001). Non-obese hospitalizations had higher odds of cirrhosis (OR 1.30, p < 0.001) and decompensated cirrhosis (OR 1.30, p < 0.001) after adjusting for age, sex, race, diabetes mellitus, and dyslipidemia. Hospitalizations with non-obese NAFLD had higher odds of death (OR 1.49, p < 0.001) after adjusting for age, gender, race, co-morbidities, cirrhosis, and liver decompensation. Conclusion There is a continued rise in the proportion of non-obese NAFLD among hospitalizations in the US. Non-obese NAFLD hospitalizations were less likely to have hypertension and diabetes, but more likely to have decompensated liver disease. Further studies are needed to better characterize these patients to enable early detection, treatment, and reduction in complications of liver disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Oladunjoye et al.)