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Objectives: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses., Methods: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia., Results: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels., Conclusions: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aim: Hyperuricemia is associated with nonalcoholic fatty liver disease (NAFLD), whereas whether the association differed by hyperuricemia onset age remained unclear. This study sought to investigate the associations of hyperuricemia onset age with the risk of incident NAFLD across adulthood., Methods and Results: Based on Kailuan prospective cohort, our analysis comprised 3318 new-onset hyperuricemia cases from 2006 to 2015 and 3318 age- and sex-matched controls who were randomly selected from the general population. The risk of NAFLD across the onset age groups (<45, 45-54, 55-64, and ≥65 years) were compared using multivariable-adjusted Cox regression models. During a median follow-up of 6.78 years, 744 (22.42%) hyperuricemia participants and 586 (17.66%) normouricemia participants were diagnosed with incident NAFLD. After adjusted for potential confounders, the risk of NAFLD was gradually attenuated with each decade increase in hyperuricemia onset age. The adjusted hazard ratio (95% confidence interval) was 1.62 (1.33-1.97) for hyperuricemia onset age <45 years, 1.26 (1.01-1.57) for age of 45-54 years, 1.24 (1.00-1.59) for age of 55-64 years, and 1.19 (0.90-1.71) for age ≥65 years, respectively. The trend remained robust among the multiple sensitivity analyses., Conclusions: The relative risk of incident NAFLD differed across hyperuricemia onset age-group, and the association was more evident in those with a younger age of hyperuricemia onset, highlighting the importance of performing early strategies on the prevention of NAFLD., Competing Interests: Conflicts of interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: Accurate assessment of early non-alcoholic fatty liver disease (NAFLD) is important to reduce the possible complications. The purpose of the present study was to develop a simple algorithm for the screening of NAFLD in the Chinese population based on routine anthropometric data and laboratory tests., Study Design: This is a cross-sectional design., Methods: The subjects (1145) underwent routine physical examinations. The variables in the NAFLD index (NFI) were obtained by a stepwise multiple logistic regression analysis on 1000 bootstrap samples. The area under the receiver-operating characteristic (AUROC) was used to evaluate the accuracy of the NFI., Results: Multivariate analysis showed that body mass index, fasting blood glucose, ratio of alanine aminotransferase to aspartate aminotransferase, and triglyceride were included in the final equation. The AUROC of the NFI was 0.919 (95% confidence interval = 0.901-0.937). An NFI of <31.0 excluded the possibility of NAFLD with a sensitivity of 96.9%, and at a value of >36.0, the NFI could detect NAFLD with a specificity of 98.9%., Conclusions: NFI was a cost-effective NAFLD-screening model, which had a high accuracy for predicting NAFLD at early stages in the Chinese population., (Copyright © 2021. Published by Elsevier Ltd.)

Background & Aims: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD., Methods: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination., Results: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m 2 (IQR 23.8-28.1 kg/m 2 ). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained., Conclusions: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD., Lay Summary: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease., Competing Interests: Conflicts of interest The authors have declared no conflict of interest related to the study. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. Ilex hainanensis Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of I. hainanensis extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The aim of the study was to analyze the correlation between income and non-alcoholic fatty liver disease (NAFLD) in a Chinese population., Method: subjects were divided into three groups according to liver fat content (LFC). (1) normal: LFC < 9.15%, 197 cases; (2) low LFC: LFC 9.15-20%, 532 cases; and (3) high LFC: LFC > 20%, 201 cases. Participants' clinical and social background were collected, including a routine fasting test to assess the relevant indices. Intergroup differences were compared on 1-way ANOVA, to analyze the relation between income and each index on Pearson correlation, and independent factors for LFC were identified on binary logistic regression., Results: (1) In retired persons, prevalence of NAFLD was greater in females (81.2%) than males (75%), but fell with age: the highest prevalence was between 40 and 49 years of age (87.5%), and the lowest above 70 years (68%). (2) Income correlated positively with triglyceride and serum uric acid levels and LFC (P < 0.05) and negatively with alanine aminotransferase (P = 0.01). (3) As income increased from level I to V, prevalence of NAFLD increased progressively (P < 0.05). In the study, LFC was taken as the dependent variable, and the traditional NAFLD risk factors and income level (I-V) were taken as independent variables. Income emerged as an independent risk factor for NAFLD. Risk in group V was 1.964-fold higher than in group I., Conclusion: Prevalence of NAFLD was closely related to socio-economic level. Demographic risk factors include female gender, age 40-49 years, and monthly income > 5,000 RMB. Thus, if income is increased without improving educational level and health awareness, NAFLD prevalence will rise., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: This study aimed to explore and compare the effect of weight change, and waist circumference (WC) change, on the risk of nonalcoholic fatty liver disease (NAFLD) in individuals with metabolically healthy overweight or obesity (MHOW/O) and metabolically unhealthy overweight or obesity (MUOW/O) in a health check-up cohort in China., Methods: 5625 adults with overweight or obesity, and free from NAFLD at baseline were included. Metabolically healthy was defined as not having any components of metabolic syndrome. Weight/WC changes were calculated as the relative difference between the first and second visits of check-up. NAFLD was assessed based on abdominal ultrasound., Results: During a median follow-up of 2.1 (IQR: 1.1-4.3) years, 1849 participants developed NAFLD. In MHOW/O participants, the multivariable adjusted HRs (95 % CIs) for NAFLD in weight change ≤ -5.0 %, and - 4.9-- 1.0 % were 0.36 (0.23-0.59), 0.59 (0.43-0.80), respectively, compared to the weight stable group (-0.9% to 0.9 %). The corresponding HRs (95 % CIs) for the association between WC change (≤ 6.0 %, - 5.9 to -3.0 %) and NAFLD in MHOW/O participants were 0.41 (0.27-0.62), and 0.74 (0.54-1.01), respectively, compared to the WC stable group (-2.9-2.9 %). Similar patterns were observed in MUOW/O participants. A more marked gradient of cumulative incidence of NAFLD across weight/WC change categories was observed in MHOW/O than in MUOW/O individuals., Conclusions: A more evident association between weight/WC loss and risk of NAFLD was observed in MHOW/O than in MUOW/O individuals. Our findings indicate the practical significance of encouraging all individuals with overweight and obesity to achieve a clinically relevant level of weight/WC loss to prevent NAFLD, even among metabolic healthy groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Several studies have reported that apolipoprotein A5 (APOA5) is involved in the development of non-alcoholic fatty liver disease (NAFLD). However, no research has been performed regarding the association between APOA5 polymorphisms and the risk of NAFLD. This study aimed to explore the association between APOA5 gene polymorphisms and NAFLD in a Chinese Han population., Methods: Genotypes of the SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 in 232 NAFLD patients and 188 healthy controls were determined using polymerase chain reaction (PCR) analysis. Clinical characteristics were measured using biochemical methods., Results: The five single nucleotide polymorphisms (SNPs) (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 showed no significant association with NAFLD (P > 0.05). The rs10750097 with G allele showed a higher serum level of alkaline phosphatase (ALP) compared with C allele in overall series and NAFLD patients (P < 0.05). The rs1263173(A/A) carriers showed a higher level of glucose compared to the non-carriers in overall series (P < 0.05). The rs17120035(T/T) carriers showed a lower plasma TG level in overall series and NAFLD patients (P < 0.05), and the rs662799(G/G) carriers showed higher levels of plasma triglyceride (TG), ALP, and lower level of high-density lipoprotein (HDL) compared to non-carriers in NAFLD patients (P < 0.05). No significant difference were observed on the clinic parameters of APOA5 rs3135507(T/T) carriers in both group of overall series and NAFLD patients (P > 0.05)., Conclusions: The five SNPs (rs10750097, rs1263173, rs17120035, rs3135507 and rs662799) of APOA5 gene are not associated with the risk of NAFLD in the Chinese Han population. The genotypes of rs10750097(G/G), rs1263173(A/A), rs17120035(T/T), and rs662799(G/G) performed a significant effect on clinic characteristics in overall series and NAFLD patients, indicating that these polymorphisms may be associated with NAFLD., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Prospective cohort studies linking dietary patterns and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between dietary patterns and risk of NAFLD in a general Chinese adult population., Methods: This study included a total of 17,360 participants free from NAFLD at baseline. Dietary patterns at baseline were identified with factor analysis based on responses to a validated 100-item food frequency questionnaire. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between dietary patterns and risk of NAFLD., Results: During a median follow-up of 4.2 years, 4034 NAFLD cases were documented. Three main dietary patterns were extracted: sugar rich dietary pattern, vegetable rich dietary pattern, and animal food dietary pattern. After adjusting for age, sex, body mass index, smoking, alcohol, education, occupation, income, physical activity, total energy intake, personal and family history of disease, depressive symptoms, dietary supplement use, inflammation markers, and each other dietary pattern score, comparing the highest with the lowest quartiles of dietary pattern scores, the multivariable hazard ratios (95% confidence interval) of NAFLD were 1.11 (1.01, 1.23) for sugar rich dietary pattern, 0.96 (0.86, 1.07) for vegetable rich dietary pattern, and 1.22 (1.10, 1.36) for animal food dietary pattern. Further adjustment for waist circumference instead of body mass index provided similar results., Conclusion: Dietary patterns rich in animal foods or sugar were associated with a higher risk of NAFLD among Chinese adults, whereas a vegetable rich dietary pattern was not associated., Competing Interests: Conflict of interest None., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: The risk of metabolic disease in adulthood is not only attributed to an unhealthy lifestyle after birth but also to famine exposure during the foetal period. This systematic review and meta-analysis aimed to evaluate the effects of foetal exposure to famine as a risk factor for developing nonalcoholic fatty liver disease (NAFLD) in adulthood., Methods: Studies were retrieved from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to evaluate the effect of foetal exposure to famine on the risk of nonalcoholic fatty liver disease in adulthood., Results: Six studies involving 90,582 subjects were included in this meta-analysis. Foetal exposure to famine was associated with an increased risk of NAFLD(RR = 1.17, 95% CI: 1.08-1.27, P < 0.0001). Exposure to famine during the foetal period significantly increased the incidence of NAFLD in women (RR = 1.27, 95% CI: 1.16-1.40, P <0.00001), while similar results were not observed in the male subgroup (RR =0.99, 95% CI: 0.89-1.11, P = 0.88). Foetal exposure to famine was associated with the risk of mild NAFLD (RR = 1.17, 95% CI: 1.02-1.33, P = 0.02) and moderate to severe NAFLD (RR = 1.51, 95% CI: 1.16-1.98, P = 0.002)., Conclusions: Foetal exposure to famine is associated with an increased risk of NAFLD in adulthood. Women with NAFLD and moderate to severe NAFLD have a more robust association with foetal exposure to famine., Competing Interests: Conflict of interest The authors declare that the research was conducted without commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Numerous studies have shown that residential greenness positively correlates with enhanced health. Metabolic dysfunction-associated fatty liver disease (MAFLD) affects about a quarter of the population while lacking specific treatments. Given that the association between green space and MAFLD is still unknown, we explored the association between residential greenness and MAFLD as well as the potential mechanisms based on the baseline survey of the China Multi-Ethnic Cohort (CMEC)., Methods: Residential greenness was expressed as normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). MAFLD was assessed through hepatic steatosis, the presence of overweight/obesity, type 2 diabetes mellitus, and evidence of metabolic dysregulation. We used logistic regression to examine the association between NDVI/EVI and the prevalence of MAFLD. Moreover, we utilized causal mediation analyses to explore the role of physical activity and ambient particulate matters (PM 1 , PM 2.5 , and PM 10 ) on the association between residential greenness and MAFLD., Results: We included 72,368 participants from the CMEC and found that residential greenness was negatively associated with the prevalence of MAFLD. For an interquartile range (IQR) increase in NDVI 500 m and EVI 500 m , the odds ratio (OR) of MAFLD were 0.78 (95 %CI: 0.75, 0.81) and 0.81 (95 %CI: 0.78, 0.84), respectively. Greater association between residential greenness and MAFLD was observed among males. Air pollutants and physical activity could mediate a partial effect (8.5-22.9 %) of residential greenness on MAFLD., Conclusion: Higher residential greenness was associated with decreased risk of MAFLD. Moreover, the association was greater among males. The protective effects of residential greenness may be achieved by mitigating the hazardous effects of air pollutants and encouraging physical activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Wholegrain contributes a range of beneficial nutrients and is considered to play a role in the prevention of chronic diseases, but evidence of their influence on nonalcoholic fatty liver disease (NAFLD) is limited. We conducted this study to investigate the prospective association between daily wholegrain consumption and NAFLD in the general population., Methods: This prospective cohort study included a total of 14,968 (42.2% men) inhabitants living in Tianjin, China. Participants without a history of CVD, cancer, alcoholic fatty liver disease, other liver diseases, or NAFLD were followed up for 1-6 years with a median follow-up duration of 4.2 years. Wholegrain consumption was assessed using a validated self-administered food frequency questionnaire. NAFLD was diagnosed with the results of liver ultrasonography without significant alcohol consumption and other causes of liver disease. Cox proportional hazards regression models were used to estimate the association between wholegrain consumption and NAFLD., Results: A total of 3505 (2171 men) first incident cases of NAFLD occurred during 53,303 person-years of follow-up (median follow-up of 4.2 years). After adjusting for several potential confounders and setting "almost never" as the control group, the multivariable hazard ratios (95% confidence intervals) of the NAFLD were 0.82 (0.73, 0.92) when they consuming ≤1 time/week, 0.78 (0.69, 0.88) when they consuming 2-6 time/week and 0.77 (0.66, 0.90) when they consuming ≥1 time/day (p for trend <0.001)., Conclusion: The results from our prospective study demonstrated that the higher consumption of wholegrain is associated with a decreased risk of NAFLD in Chinese adults., Competing Interests: Conflict of interest None of the authors had a conflict of interest to disclose., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: Metabolic dysfunction associated fatty liver disease (MAFLD) is the most common liver disease and dyslipidemia is commonly considered a prominent risk factor for MAFLD. This study was to investigate the association between the apolipoprotein B/A1 (apo B/A1) ratio and the risk of MAFLD based on new diagnostic criteria., Methods: We conducted a cross-sectional study on 3341 participants. Restricted cubic spline (RCS) analyses, logistic regression, Synergistic effects analyses and stratified analyses were used to evaluate the association between the apo B/A1 ratio and the risk of MAFLD., Results: The apo B/A1 ratio was nonlinearly related to the increased risk of MAFLD and the OR and 95% CI for the apo B/A1 95th percentile was 1.700 (1.004-2.879) compared with the 50th percentile. Each 1 SD increase in apo B/A1 ratio would increase the 1.313-fold risk of the risk of MAFLD in all participants and 1.46-fold risk in normolipidemic participants. Synergistic effects indicated elevated Apo B/A1 ratio and dyslipidemia collectively contributed to an increased risk of MAFLD [OR (95 %CI): 2.496(1.869-3.334)]., Conclusions: The apo B/A 1 ratio was a risk factor of the presence of MAFLD. Dyslipidemia and elevated the Apo B/A1 ratio can synergistically contributed to the risk of MAFLD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

At present, there is no consensus on the relationship between selenium (Se) exposure and human serum lipid metabolism. The etiological role of high-Se exposure in lipid markers, dyslipidemia, and nonalcoholic fatty liver (NAFLD) remains unclear. We used serum untargeted metabolomics analysis to evaluate whether high-Se exposure is cross-sectionally associated with lipid metabolism in adults from high-Se exposure area (n = 112) and control area (n = 101) in Hubei Province, China. An untargeted liquid chromatography/mass spectrometry (LC/MS)-based metabolomic analysis identified 144 differential pathways and yielded 204 differentially abundant metabolites, including 32 lipid metabolites associated with lipids profiles. To further explore the correlation between Se exposure and serum lipid metabolism, we measured serum levels of lipid profiles among all the people, including serum cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (APOB). The average serum Se level of the high-Se exposure group was 537.18 μg/L, significantly higher than 72.98 μg/L in the control group (p < 0.0001). The measurement levels of serum TG, LDL-C, HDL-C, and APOB in the high-Se exposure group were 1.03 (0.76, 1.34) mmol/L, 2.25 ± 0.48 mmol/L, 1.12 ± 0.24 mmol/L, and 0.77 ± 0.15 g/L, respectively, while the control group were 1.13 (0.84, 1.80) mmol/L, 2.56 ± 0.61 mmol/L, 1.02 ± 0.22 mmol/L, and 0.83 ± 0.16 g/L, respectively (all p values <0.05). Correlation analysis showed a significant negative correlation between serum Se and CHOL (r = -0.201, p < 0.01), serum Se is also associated with metabolomics markers, the negative correlation includes glyceric acid and ect., the positive correlation includes phosphorylcholine and ect. Our study suggests that high-Se exposure is negatively associated with serum lipid profiles and decreases the risk of high-TC and HDL-C dyslipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonalcoholic fatty liver disease (NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease (MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults., Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratified cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected., Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD (40.3%) was significantly higher than that of NAFLD (36.9%) (P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus (T2DM) (53.8%), impaired fasting glucose (35.7%) and impaired glucose tolerance (40.9%). High risk of advanced fibrosis based on fibrosis-4 was highly prevalent (14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481 (35.1%) fulfilled the diagnostic criteria for MAFLD and NAFLD (MAFLD+NAFLD+), 521 (5.2%) MAFLD+NAFLD-, and 181 (1.8%) MAFLD-NAFLD+. The MAFLD+NAFLD- group had more significant metabolic disorders than those in the MAFLD+NAFLD+ group (all P < 0.05). Among MAFLD-NAFLD+ subjects, 82.9% had metabolic disorders., Conclusions: The new definition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects., (Copyright © 2022. Published by Elsevier B.V.)

Background: Epidemiologic studies consistently find associations between whole-grain intake and reduced risk of obesity and related metabolic diseases, yet data on the potential of whole grains to prevent fatty liver diseases are scarce., Objectives: To examine whether plasma 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, is associated with nonalcoholic fatty liver disease (NAFLD)., Methods: This case-control study of Chinese adults enrolled 940 NAFLD cases and 940 age- and sex-matched non-NAFLD controls (mean age: 55.2 y; 65% males). NAFLD diagnosis was defined as individuals whose hepatic ultrasound disclosed hepatic steatosis at any stage, after the exclusion of alcohol abuse and other liver diseases. Fasting plasma DHPPA concentration was measured by LC-MS/MS. Multivariate adjusted ORs and 95% CIs were estimated to assess the association between plasma DHPPA and NAFLD using conditional logistic regression., Results: Plasma concentration of DHPPA was significantly lower in patients with NAFLD compared with controls (median: 9.86 nmol/L compared with 10.9 nmol/L, P = 0.002). In multivariable logistic regression models, the ORs (95% CIs) for NAFLD across increasing tertiles of plasma DHPPA were 1 (reference), 0.76 (0.54, 1.05), and 0.65 (0.45, 0.93), respectively (P-trend = 0.026). In addition, the inverse associations persisted in subgroups stratified by sex, age, BMI, abdominal adiposity, smoking status, physical activity, diabetes, hypertension, and hyperlipidemia., Conclusions: These results indicate that increased plasma DHPPA concentration is associated with lower risk of NAFLD in Chinese adults, independently of well-known risk factors. Our finding provides evidence to support health benefits of whole-grain consumption on NAFLD. This trial was registered at clinicaltrials.gov as NCT03845868., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background & Aims: Accumulating animal studies have demonstrated the harmful contribution of ambient air pollution (AP) to metabolic dysfunction-associated fatty liver disease (MAFLD), but corresponding epidemiological evidence is limited. We examined the associations between long-term AP exposure and MAFLD prevalence in a Chinese population., Methods: We conducted a cross-sectional study of 90,086 participants recruited in China from 2018 to 2019. MAFLD was assessed based on radiologically diagnosed hepatic steatosis and the presence of overweight/obese status, diabetes mellitus, or metabolic dysregulation. Residence-specific levels of air pollutants, including particulate matter with aerodynamic diameters of ≤1 μm (PM 1 ), ≤2.5 μm (PM 2.5 ), and ≤10 μm (PM 10 ), and nitrogen dioxide (NO 2 ), were estimated by validated spatiotemporal models. We used logistic regression models to examine the AP-MAFLD associations and further evaluated potential effect modifications by demographics, lifestyle, central obesity, and diabetes status., Results: Increased exposure levels to all 4 air pollutants were significantly associated with increased odds of MAFLD, with odds ratios (ORs) of 1.13 (95% CI 1.10-1.17), 1.29 (1.25-1.34), 1.11 (1.09-1.14), and 1.15 (1.12-1.17) for each 10 μg/m 3 increase in PM 1 , PM 2.5 , PM 10 , and NO 2 , respectively. Further stratified analyses revealed that individuals who are male, alcohol drinkers, and current and previous smokers, those who consume a high-fat diet, and those with central obesity experience more significant adverse effects from AP exposure than other individuals., Conclusions: This study provides evidence that long-term exposure to ambient PM 1 , PM 2.5 , PM 10 , and NO 2 may increase the odds of MAFLD in the real world. These effects may be exacerbated by unhealthy lifestyle habits and central obesity., Lay Summary: We conducted an epidemiological study on the potential effect of ambient air pollution on the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in approximately 90 thousand adults in China. We found that long-term exposure to ambient air pollution may increase the odds of MAFLD, especially in individuals who are male, smokers, and alcohol drinkers, those who consume a high-fat diet, and those with central obesity., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD)., Methods: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance., Results: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m 2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes., Conclusions: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients., (Copyright © 2021. Published by Elsevier B.V.)

Background: Although preserved egg is a traditional Chinese delicacy widely consumed in China and Southeast Asian countries, whether habitual preserved egg consumption is associated with nonalcoholic fatty liver disease (NAFLD) remains unknown., Objectives: This study aimed to examine the association between preserved egg consumption and risk of NAFLD in a cohort of Chinese adults., Methods: This prospective cohort study included 15,883 participants aged 19-88 y (58% women) from the TCLSIH (Tianjin Chronic Low-grade Systemic Inflammation and Health) cohort study who were free of liver diseases, cancer, and cardiovascular disease at baseline. Preserved egg consumption was assessed using an FFQ at baseline. NAFLD was diagnosed by transabdominal sonography during an annual health examination. Multivariable Cox proportional hazards regression models were used to calculate HRs and 95% CIs across categories of preserved egg consumption., Results: During 56,002 person-years of follow-up, 3683 first incident cases of NAFLD were recorded. After adjustment for sociodemographic characteristics, lifestyle risk factors, total energy intake, egg intake, and eating patterns, the multivariable HRs (95% CIs) of incident NAFLD according to categories of preserved egg consumption were 1.00 (reference) for never, 1.05 (0.98, 1.14) for <1 time/wk, 1.09 (0.96, 1.24) for 1 time/wk, and 1.26 (1.09, 1.46) for ≥2 times/wk (P-trend < 0.01). The results were robust to a series of sensitivity analyses., Conclusions: Habitual preserved egg consumption is associated with a modestly higher risk of NAFLD among the Chinese adult population. The mechanism underlying this association warrants further research.This trial was registered at www.umin.ac.jp/ctr/ as UMIN000027174., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background and Aims: Several susceptibility gene variants predisposing to nonalcoholic fatty liver disease (NAFLD) have been identified in chronic kidney disease (CKD). Evidence supports that 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13) rs72613567 plays a role in NAFLD development by affecting lipid homeostasis. Since lipid droplets may accumulate in the kidneys and contribute to renal injury, we investigated the association between the HSD17B13 rs72613567 variant and markers of renal function/injury in NAFLD., Methods and Results: We measured estimated glomerular filtration rate (eGFR), urinary/serum neutrophil gelatinase-associated lipocalin (NGAL), and urinary albumin-to-creatinine ratio (u-ACR) in individuals with biopsy-proven NAFLD. Multivariable regression analyses were undertaken to examine the associations between the HSD17B13 rs72613567 variant and markers of renal function/injury. Individuals were stratified by HSD17B13 rs72613567 genotypes into -/-, A/- and A/A groups. HSD17B13 rs72613567 genotypes were not significantly associated with eGFR and urinary/serum NGAL levels. Conversely, the prevalence of abnormal albuminuria in the A/- + A/A group was lower than in the -/- group (4.92% vs. 19.35%, p = 0.001). Additionally, the mean u-ACR levels were lower among carriers of the A/- or A/A genotypes with coexisting hypertension or diabetes, than among those with the -/- genotype. The risk of abnormal albuminuria (adjusted-odds ratio 0.16, p = 0.001) remained significantly lower in the A/- + A/A group after adjustment for established renal risk factors and histologic severity of NAFLD., Conclusion: HSD17B13 rs72613567: A allele is associated with a lower risk of having abnormal albuminuria, but not with lower eGFR or urinary/serum NGAL levels, in patients with biopsy-proven NAFLD., Competing Interests: Declaration of competing interest All authors do not have nothing to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Results of in vitro and in vivo studies showed that green leafy vegetables (GLV) could attenuate liver steatosis. However, little is known regarding the association between GLV intake and nonalcoholic fatty liver disease (NAFLD) in human. We examined the association of GLV intake with NAFLD in a large-scale adult population., Methods and Results: This cross-sectional study investigated 26,891 adults in China who participated in health examinations from 2013 to 2017. Newly diagnosed NAFLD was detected by liver ultrasonography. Dietary intake was assessed by using a validated and standardized food frequency questionnaire. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) across categories of GLV intake. After adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the OR (95% CI) for comparing the highest vs. lowest GLV intake categories (≥7 times/week vs. almost never) was 0.72 (0.59, 0.90) (P < 0.0001). In addition, a linear inverse association was demonstrated between GLV intake and NAFLD in women (P for trend = 0.04), but ORs for any intake category did not reach significance. Stratified analyses suggested a potential effect modification by obesity status; the ORs (95% CIs) for comparing the highest vs. lowest GLV intake categories was 0.72 (0.54, 0.97) in normal/overweight individuals and 1.04 (0.65, 1.65) in obese individuals (P-interaction < 0.0001)., Conclusion: This large population-based study shows that high GLV intake is inversely associated with NAFLD, particularly in women and non-obese participants., Competing Interests: Declaration of competing interest None., (Copyright © 2021. Published by Elsevier B.V.)

The phytochemical investigations on the fruits of Kadsura coccinea led to the isolation of six undescribed dibenzocyclooctadiene lignans named kadcolignans B-G, together with eleven previously described analogues. The structures of these compounds were established by spectroscopic methods including NMR, HRESIMS, and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity by measuring the levels of triglyceride (TG), total cholesterol (TC), and reactive oxygen species (ROS) in FFA-induced HepG2 cells. As a result, compounds 4, 5, 9, 13, and 15 showed potent inhibitory effects on hepatocyte lipid accumulation at a concentration of 100 μM. Our research not only broadens the understanding on the chemical composition of K. coccinea but also provides experimental and theoretical evidences supporting the fruit's active ingredients in alleviating nonalcoholic fatty liver disease (NAFLD)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Epidemiological evidence for the association of soft drink consumption with nonalcoholic fatty liver disease (NAFLD) is inconsistent, and such association has not been prospectively examined in the general adult population., Objectives: We aimed to investigate the prospective association between soft drink consumption and the risk of NAFLD in a Chinese adult population., Methods: This prospective cohort study investigated 14,845 participants [mean age: 39.3 y; 6203 (41.8%) men] who were free of liver disease, cardiovascular disease, and cancer at baseline. Soft drink consumption (mainly sugar-containing carbonated beverages) was measured at baseline using a validated FFQ. NAFLD was diagnosed based on abdominal ultrasound without significant alcohol consumption and other causes of liver disease. Hepatic steatosis index (HSI) was calculated based on sex, BMI, and blood transaminase levels. Cox proportional hazards regression models were used to examine the association of soft drink consumption with incident NAFLD., Results: A total of 2888 first-incident cases of NAFLD occurred during 42,048 person-years of follow-up (median follow-up: 4.2 y). After adjusting for demographic characteristics, lifestyle factors, dietary intake, and inflammatory markers, the multivariable HRs (95% CIs) for incident NAFLD were 1.00 (reference) for <1 serving/wk, 1.18 (1.03, 1.34) for 1 serving/wk, 1.23 (1.08, 1.40) for 2-3 servings/wk, and 1.47 (1.25, 1.73) for ≥4 servings/wk, respectively (P for trend < 0.0001). Further sensitivity analysis showed that the corresponding multivariable HRs (95% CIs) for incident HSI-defined NAFLD were 1.00 (reference), 0.96 (0.70, 1.31), 1.16 (0.83, 1.62), and 1.59 (1.07, 2.37), respectively (P for trend < 0.0001)., Conclusions: The results from our prospective study indicate that soft drink consumption is associated with an increased risk of NAFLD in Chinese adults. This study was registered at UMIN Clinical Trials Registry as UMIN000027174., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background and Aims: Emerging evidence suggests that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are decreased in patients with imaging-defined nonalcoholic fatty liver disease (NAFLD), but no data are currently available on the association between plasma NT-proBNP levels and the histological severity of NAFLD., Methods and Results: We enrolled 351 (73.5% men) consecutive adult patients with biopsy-proven NAFLD without a prior history of cardiovascular disease (CVD). Plasma NT-proBNP levels were measured using a commercially available immunochemical system (VITROS® 5600, Johnson, New Jersey). Fifty-three percent of these subjects had nonalcoholic steatohepatitis (NASH). After stratification of patients by plasma NT-proBNP tertiles; compared to those in the 1st tertile (NT-proBNP ≤16 pg/ml), the odds ratio for NASH was 0.52 (95% CI 0.29-0.95) in patients in the 2nd tertile (NT-proBNP of 17-33 pg/ml) and 0.49 (95% CI 0.26-0.93) in those in the 3rd tertile (NT-proBNP ≥34 pg/ml) of plasma NT-proBNP levels, even after adjustment for age, sex, body mass index, homeostasis model assessment (HOMA)-estimated insulin resistance, pre-existing diabetes, hypertension, and dyslipidemia., Conclusion: In subjects with biopsy-proven NAFLD without known CVD, this cross-sectional study shows for the first time, that lower plasma NT-proBNP levels are strongly associated with a higher prevalence of NASH., Competing Interests: Declaration of Competing Interest All authors do not have conflicts of interest to disclose., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Animal studies have shown that soy protein and isoflavones can increase antioxidant capacity and improve insulin resistance, and thus ameliorate nonalcoholic fatty liver disease (NAFLD). However, only limited epidemiological studies have examined the association of soy food intake with NAFLD., Objectives: We investigated the association between soy food intake and NAFLD in a Chinese cohort., Methods: A total of 24,622 participants aged 20-90 y were included in the study. Diet information was collected using a validated 100-item FFQ. NAFLD was defined as having fatty liver diagnosed by ultrasonography and excluding men and women who consumed >210 g alcohol/wk and >140 g/wk, respectively. Logistic regression analysis was used to assess the association of soy food intake with NAFLD., Results: After adjustment for potential confounders, and taking those with <1 time/wk soy food intake as the reference group, the ORs for NAFLD across soy food intake frequency were 0.94 (95% CI: 0.83, 1.07) for 1 time/wk, 0.88 (95% CI: 0.78, 0.99) for 2-3 times/wk, and 0.75 (95% CI: 0.65, 0.87) for ≥4 times/wk (P-trend <0.0001). The results were similar when participants were categorized by the energy-adjusted soy food intake (grams per 1000 kilocalories) quartiles (OR = 0.80; 95% CI: 0.71, 0.91; comparing extreme quartiles)., Conclusions: Higher soy food intake was associated with a lower prevalence of NAFLD in Chinese adults. Further prospective studies and randomized clinical trials are necessary to confirm if soy food intake is inversely related to the risk of NAFLD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: It is unclear whether low muscle mass and low muscle strength are independently or jointly associated with nonalcoholic fatty liver disease (NAFLD). Hence, the aim of the present study was to investigate the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity., Methods: A total of 5132 participants aged 18-80 years were recruited in this cross-sectional study. NAFLD was diagnosed using ultrasound. Muscle mass was evaluated using skeletal muscle mass index and muscle strength was evaluated using weight-adjusted hand grip strength. Sarcopenia was defined as the presence of both low muscle mass and low muscle strength. Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Multivariate logistic regression models were used to explore the associations of NAFLD with low muscle mass, low muscle strength, sarcopenia, and sarcopenic obesity., Results: Low muscle mass and low muscle strength were positively and independently associated with NAFLD (mass: odds ratio [OR], 2.57; 95% confidence interval [CI], 2.03-3.25; strength: OR, 1.47; 95% CI, 1.21-1.80). Compared with low muscle mass or low muscle strength alone, sarcopenia was associated with a higher risk of NAFLD (OR, 3.91; 95% CI, 2.90-5.28). Whether obesity was defined by body mass index (BMI) or waist circumference (WC), sarcopenic obesity was associated with a higher risk of NAFLD (BMI: OR, 10.42; 95% CI, 7.14-15.22; WC: OR, 11.64; 95% CI, 8.22-16.48) than sarcopenia or obesity alone., Conclusions: Low muscle mass and low muscle strength were positively and independently associated with NAFLD. When both were presented in the sarcopenic state, the risk of NAFLD was higher, and a concurrence of sarcopenia and obesity showed the highest risk of NAFLD., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Study Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common cause of chronic liver disease worldwide. Diet plays a critical role in the prevention and treatment of MAFLD. Our hypothesis was that the intake of some macronutrients, vitamins, or mineral elements is associated with MAFLD., Patients and Methods: Patients with MAFLD can be diagnosed based on the evidence of hepatic steatosis and if they meet any of the three additional criteria of overweight/obesity, diabetes mellitus, or metabolic dysregulation. Diets were recorded using photographs and diaries of meals for seven consecutive days. The consumed dietary composition was compared with the recommended intake according to the China Food Composition Tables (Standard Edition) version 2019 and the Chinese Dietary Reference Intakes version 2013, and its association with MAFLD was assessed by logistical regression analyses., Results: A total of 229 MAFLD patients and 148 healthy controls were included in this study. MAFLD patients, compared with that by non-MAFLD participants, consumed more polyunsaturated fatty acids (PUFAs) (p < 0.001), vitamin E (p < 0.001), and iron (p = 0.008). The intake of PUFAs (OR = 1.070, 95 % CI: 1.017-1.127, p = 0.009) and vitamin E (OR = 1.100, 95 % CI: 1.018-1.190, p = 0.016) was positively associated with MAFLD. In addition, the percentages of individuals who consumed PUFAs (p = 0.006), vitamin E (p < 0.001), or iron (p = 0.046) above the recommended intake were higher among the individuals with MAFLD. Daily intake of PUFAs > 11 % (OR = 2.328, 95 % CI: 1.290-4.201, p = 0.005) and vitamin E > 14 mg (OR = 2.189, 95 % CI: 1.153-4.158, p = 0.017) was positively correlated with MAFLD., Conclusions: Patients with MAFLD consumed more PUFAs, vitamin E, and iron in their daily diet. Excessive consumption of PUFAs and vitamin E might be independent risk factors for the incidence of MAFLD., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background & Aims: Fibroblast growth factor 21 (FGF21), a hormone predominantly secreted by the liver, has been shown to be positively associated with the severity of non-alcoholic fatty liver disease (NAFLD) in cross-sectional studies. We investigated the prospective association of FGF21 with NAFLD development in a 3-year prospective study involving a population-based cohort comprising 808 Chinese subjects., Methods: Serum FGF21 levels at baseline and follow-up were measured using an enzyme-linked immunosorbent assay. Independent predictors of NAFLD development were identified using multiple logistic regressions. The predicting accuracy of the models was evaluated using area under the receiver-operating characteristic (ROC) curves (AUCs)., Results: In subjects who had progressed to NAFLD, the baseline FGF21 concentration (319.12 pg/ml [172.65, 518.78]) was significantly higher than that in subjects who did not develop NAFLD (199.10 pg/ml [123.56, 322.80]) (p <0.001). At follow-up, significant increase of FGF21 level was observed in those subjects who developed NAFLD (p <0.05). Baseline FGF21 was an independent predictor of NAFLD (OR: 7.102 [95% CI 2.488-20.270]; p <0.001), together with body mass index (BMI) (OR: 1.489 [95% CI 1.310-1.691]; p <0.001). The ROC-AUC was 0.816 (95% CI 0.766-0.867) for the FGF21 Model, which was calculated with FGF21 and BMI. FGF21 Model <0.13 can be used to rule out (sensitivity=85.71%, negative likelihood ratio=0.23) and ≥0.30 can be rule in (specificity=86.34%, positive likelihood ratio=3.66) ultrasonography-diagnosed NAFLD after 3 years., Conclusions: High serum FGF21 concentration was an independent predictor of NAFLD in humans. The FGF21 Model and its cut-offs may be useful for early diagnosis and intervention of NAFLD., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data., Methods: A model was used to estimate NAFLD and NASH disease progression in eight countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections., Results: If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as a result of urbanization and the lowest growth in Japan as a result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as a result of an aging/increasing population., Conclusions: NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden., Lay Summary: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis can lead to advanced liver disease. Both conditions are becoming increasingly prevalent as the epidemics of obesity and diabetes continue to increase. A mathematical model was built to understand how the disease burden associated with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis will change over time. Results suggest increasing cases of advanced liver disease and liver-related mortality in the coming years., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a common and strong risk factor for cardiovascular disease and hepatocellular carcinoma. The rapid acceleration of the increase in NAFLD prevalence has exceeded the trends observed for obesity, and has been driven by multiple factors. The aim of this study was to investigate the correlation between the serum levels of folic acid, the endogenous source of methyl groups for DNA methylation, and NAFLD in Chinese adults., Methods: The correlations between the serum folic acid levels and NAFLD were investigated in two independent cohorts of 70 subjects who underwent a liver biopsy and 130 subjects with varying liver fat contents, as measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Independent correlations between serum folic acid levels and liver steatosis grades were detected using a multivariate ordinal regression analysis. The diagnostic performances of serum folic acid levels alone and in combination with existing NAFLD prediction scores were compared with those of traditional NAFLD prediction parameters using receiver operating characteristic (ROC) curve analyses., Results: Serum folic acid concentrations were inversely correlated with liver histological steatosis grades (ρ = -0.371, P < 0.001) and the 1 H-MRS-measured liver fat content (r = -0.199, P = 0.038). According to the multivariate ordinal regression analysis, serum folic acid levels were inversely correlated with liver steatosis grades (OR 0.739 [0.594-0.918], P = 0.006) independent of age, gender, BMI, components of metabolic syndrome and the serum TC, LDL-c and HOMA-IR levels. The AUROC of serum folic acid for the diagnosis of NAFLD was 0.75 (0.65-0.83), and the addition of serum folic acid to NAFLD prediction scores significantly improved the diagnostic prediction of NAFLD (AUROC = 0.88 [0.81-0.94])., Conclusion: Low serum folic acid levels were identified as an independent risk factor for NAFLD in the Chinese population. The addition of the serum folic acid levels to the current existing NAFLD prediction scores significantly improved the prediction of NAFLD., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China., Methods: The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search., Results: Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001)., Conclusions: Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found.

Objectives: To explore the longitudinal effect of metabolic syndrome (MetS) and its components on the development of non-alcoholic fatty liver disease (NAFLD) and to evaluate the significance of MetS and its components as early markers of NAFLD risk in a northern urban Han Chinese population., Materials and Methods: A total of 15,791 cohort members without NAFLD at baseline were included in the current study between 2005 and 2011. The baseline characteristics of the cohort were compared by MetS status at baseline and NAFLD status after follow-up. Cox proportional hazards models were used to estimate the unadjusted or adjusted hazard ratios (HRs) for development of NAFLD among individuals with MetS compared with individuals without MetS at baseline., Results: During 51,652 person-years of follow-up, 3913 (24.78%) new cases of NAFLD occurred between 2005 and 2011. In the unadjusted model, the HR (95% confidence interval [CI]) for NAFLD was 2.51 (2.30, 2.73). After adjusting for gender, age, diet, smoking status, and regular exercise, the HR was 1.94 (1.78, 2.13). Gender differences were observed, with adjusted HRs (95% CIs) of 1.89 (1.71, 2.09) and 1.72 (1.43, 2.07) among males and females, respectively. Compared with individuals without MetS components, the HRs were 1.92 (1.76, 2.09), 2.64 (2.40, 2.90) and 3.51 (3.15, 3.91) for individuals with one, two, or three or more MetS components, respectively. Moreover, participants with obesity or hyperlipidemia had a higher risk of NAFLD than patients with hypertension or hyperglycemia, with HRs of 2.03 (1.83, 2.25) for obesity, 1.94 (1.72, 2.19) for hyperlipidemia, and 3.01 (2.68, 3.37) for these factors in combination., Conclusion: The present study indicates that MetS and its components independently predict the risk of NAFLD in a northern urban Han Chinese population and suggests that people with MetS or its component should initiate lifestyle changes to prevent the development of NAFLD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To review the current state of research in non-alcoholic fatty liver disease (NAFLD)., Data Resources: Searching Medline (1994-2002) and Chinese Medical Journals Index (1998- 2002) for articles on NAFLD., Results: NAFLD is a new and challenging field with increasing recognition although its pathogenesis is poorly understood. "Two hits" hypothesis is still the leading theory guiding current research., Conclusions: Genetic study is a promising way that might lead to breakthrough in NAFLD research. NAFLD study in China is at an initial stage and there is a long way to go.

Background: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. However, this association could be influenced by the coexisting metabolic abnormalities. This study aimed to investigate the role of obesity and metabolic abnormalities in NAFLD among elderly Chinese., Methods: A cross-sectional study was performed among elderly residents who took their annual health checkups during 2016 in Keqiao District, Shaoxing, China., Results: A total of 3359 elderly adults were retrospectively included in this study. The overall prevalence of NAFLD was 28.7%. The prevalence of NAFLD were 7.14%, 27.92%, 34.80%, and 61.02% in participants with metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO), respectively. NAFLD patients in MHO group had more unfavorable metabolic profiles than those in MHNW group. Logistic regression analysis showed that sex, body mass index (BMI), fasting blood glucose, and serum uric acid were the risk factors of NAFLD., Conclusions: Both obesity and metabolic health were significantly associated with NAFLD in elderly Chinese. Screening for obesity and other metabolic abnormalities should be routinely performed for early risk stratification of NAFLD., (Copyright © 2020. Published by Elsevier B.V.)

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with potential sex-based difference in the prevalence and prognosis. Copper deficiency may affect the antioxidant defense system and lead to the progression of NAFLD. This study aimed to evaluate the association between blood copper and NAFLD according to sex difference., Methods: A case-control study of 1816 cases of NAFLD and 1111 sex- and age-matched control cases was conducted in Tangshan, China, from January 1, 2016, to December 31, 2017, based on the Kailuan cohort. In men and women, logistic regression analysis was separately applied to determine the risk of NAFLD, severity of NAFLD based on hepatic steatosis, the NAFLD fibrosis score, and fibrosis-4 score, for each quartile of blood copper with the lowest quartile as the reference. In addition, the effect of metabolic syndrome on the association between copper and NAFLD was assessed., Results: In men, blood copper concentration was lower in the NAFLD group (mean ± SD: 0.617 ± 0.117 μg/mL) than in the control group (mean ± SD: 0.655 ± 0.133 μg/mL) (P < 0.001). After adjustment for possible confounders, the odds ratio of NAFLD at the highest quartile of copper compared to the lowest quartile was 0.57 (95% CI: 0.41-0.80) and the protective effect of higher blood copper was increased with the severity of NAFLD. In the results of stratified analysis, lower copper concentration was a significant additional factor that contributed to higher risk of NAFLD in male subjects with metabolic syndrome. However, no significant association was observed between copper and NAFLD in women with different characteristics, except an NAFLD fibrosis score < -1.455 and moderate hepatic steatosis., Conclusions: Higher copper levels achieved significant protective effect against NAFLD in men but not in women. Sex-specific intervention is a potential tool for the prevention of development of NAFLD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Polysaccharide has been considered as an important bioactive compound in Codonopsis lanceolata. High fat/high sucrose (HFHS) diet-induced insulin resistance is implicated in multiple metabolic diseases, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), these metabolic diseases has become epidemic health issue worldwide. In this study, the effect of C. lanceolata polysaccharide (CLPS) on improving insulin sensitivity in chronic HFHS diet-fed mice was investigated. Our data indicates that CLPS significantly reduced fasting blood glucose (FBG), fasting serum insulin (FINS) and insulin resistance index, in parallel with improved glucose and insulin tolerance impaired by HFHS diet. Impaired phosphorylation of PKB/Akt and hyperphosphorylation of IRS-1 at Ser307 were observed in the mice fed with HFHS diet, and those defects were also rescued by CLPS administration. In addition, CLPS caused a significant decrease in the level of malondialdehyde (MDA), and an increase in reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio; concurrent with enhanced expression of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), and activated Nrf2 signaling. In summary, these findings suggest that CLPS ameliorates HFHS diet-induced insulin resistance through activating anti-oxidative signaling pathway, providing new insights into the protective effects of C. lanceolata polysaccharide in metabolic disease., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Backgrounds: Non-obese nonalcoholic fatty liver disease (NAFLD) is paradoxically associated with improved metabolic and pathological features at diagnosis but worse prognosis relative to obese NAFLD., Aim: To compare predictors of disease severity in NAFLD with different body mass index (BMI) categories., Methods: All 1509 consecutive NAFLD patients were classified as lean (20.2%), overweight (23.1%) and obese (56.7%). Liver fat content (LFC) and fibrosis were estimated with magnetic resonance imaging-based proton density fat fraction and shear wave elastography respectively., Results: Lipid profiles and uric acid (UA) were significantly increased in parallel with BMI categories (pairwise comparison P < 0.001), but insulin resistance (IR) was significantly different between the non-obese and obese groups. For LFC ≥ 10%, increased waist circumference (WC) was an independent predictor in all groups, while UA elevation (P = 0.02) was predictive in the overweight patients, but BMI ≥ 28 kg/m 2 (P = 0.029) and IR (P = 0.026) were significant in the obese patients. For fibrosis, alanine aminotransferase (ALT) > 40 U/L (P = 0.031), increased WC (P = 0.012) and BMI ≥ 28 kg/m 2 (P < 0.001) plus ALT > 40 U/L (P = 0.007) were predictors in the lean, overweight and obese patients, respectively., Conclusions: WC was strongly predictive of disease severity in all NAFLD, while UA and BMI plus IR were additional predictors in the overweight and obese NAFLD respectively. Individualized screening strategies should be established for NAFLD according to different BMIs., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Obesity is closely related to non-alcoholic fatty liver disease (NAFLD), which has become an important public health problem because of its high prevalence and association with metabolic syndromes. Irisin was recently identified as a novel peptide to improve obesity and glucose homeostasis, and considered to be therapeutic for human metabolic diseases. The aim of this study was to examine the association of serum irisin concentration and liver triglyceride contents in obese Chinese adults., Methods: Serum irisin levels were measured and liver fat contents determined by (1)H MRS in 296 obese adults. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose, and lipid profiles were detected. The liver triglyceride contents of subjects were measured by (1)H MRS. The protein levels of irisin were determined by quantitative ELISA., Results: We found that serum irisin levels were reduced in obese adults with NAFLD. By dividing the distribution of intrahepatic triglyceride (IHTG) contents into quartiles, serum irisin levels were reduced gradually with the increase of IHTG contents (p<0.01). Higher serum irisin levels were associated with preferable TG levels. Serum ALT and AST concentrations were inversely correlated with serum irisin levels. Multivariate linear regression analysis demonstrated that serum irisin levels were independently associated with liver fat (p<0.01). By logistic regression analysis, the odds ratio for higher IHTG contents was reduced by 12.4% per 1 SD increase in serum irisin concentrations after adjustment for multivariate metabolic factors [OR (95% CI); 0.876 (0.777-0.987)]., Conclusions: These results demonstrated that serum irisin concentrations were inversely associated with the triglyceride contents in the liver and liver enzymes in obese Chinese adults., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Bitter gourd (BG) is a popular fruit in Asia with numerous well-known medicinal uses, including as an antidiabetic. In the current study, we aimed to explore the effects of BG on mitochondrial function during the development of obesity-associated fatty liver. C57BL/6 mice were divided into 4 experimental groups: mice fed a normal diet (control; included for reference only), mice fed a high-fat diet (HFD), and mice fed an HFD supplemented with freeze-dried BG powder through daily gavage at doses of 0.5 (HFD+0.5BG) and 5 (HFD+5BG) g/kg, respectively. After 16 wk, mice in the HFD+5BG group showed less body and tissue weight gain and less hyperglycemia and hyperlipidemia compared with those in the HFD group (P < 0.05). In both HFD+0.5BG and HFD+5BG groups, serum interleukin-6 concentration was lower than that in the HFD group (P < 0.02). The serum C-reactive protein concentration was lower in the HFD+5BG group compared with the HFD group (P < 0.04). An analysis of liver tissue revealed lower liver triglyceride and cholesterol concentrations in both HFD+0.5BG and HFD+5BG groups than in the HFD group (P < 0.01). The HFD+5BG group had less activation of the sterol regulatory element binding protein/fatty acid synthase (SREBP-1/FAS) pathway, greater superoxide dismutase activity, and less total protein and mitochondrial protein oxidation than did the HFD group (P < 0.05). Mitochondrial complex I, II, III, and V activity was greater in the HFD+0.5BG group than in the HFD group (P < 0.03). The HFD+5BG group only had greater complex V activity compared with the HFD group (P < 0.05). Mitochondrial dynamics regulators, including dynamin related protein 1 (DRP1) and mitofusin 1 (MFN1), as well as proapoptotic protein expression levels were restored by BG treatment (P < 0.02). Taken together, our results suggest that BG prevents inflammation and oxidative stress, modulates mitochondrial activity, suppresses apoptosis activation, and inhibits lipid accumulation during the development of fatty liver.

Purpose: To evaluate the possible relationship between self-reported history of abortion and nonalcoholic fatty liver disease (NAFLD) in middle-aged and elderly Chinese women., Methods: A cross-sectional study was performed in 5911 women aged 40 years or older in Jiading District, Shanghai, China. Reproductive histories, including miscarriage and induced abortion, were collected using a validated questionnaire by trained physicians. Abdominal B-mode ultrasound evaluation and serum liver enzymes levels were used in the diagnosis of NAFLD., Results: The percentage reporting history of abortion in women with NAFLD was higher than in those without NAFLD (72.4% vs. 69.3%, age-adjusted P = .001). Compared with women without a history of abortion, the fully adjusted odds ratio (OR) for NAFLD in those with a history of abortion was increased by 28% (OR, 1.28 and 95% confidence interval [CI], 1.06-1.55). Histories of miscarriage and induced abortion were also associated with increased risk of prevalent NAFLD in fully adjusted models (OR, 1.84 and 95% CI, 1.24-2.72; OR, 1.23 and 95% CI, 1.02-1.50, respectively)., Conclusions: Both miscarriage and induced abortion are associated with prevalent NAFLD in middle-aged and elderly Chinese women., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Nonalcoholic fatty liver disease is closely associated with metabolic syndrome and cardiovascular disease (CVD). We investigated whether the liver fat content (LFC) is independently associated with carotid artery intima-media thickness (CIMT) and evaluated the contribution of the LFC to the increased CIMT., Methods: We conducted a community-based study among 1809 participants (682 males and 1127 females) from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The CIMT was determined by ultrasonography. A large CIMT value was defined as 75th percentile of the maximum CIMT. A standardised ultrasonographic hepatic-renal ratio was used to assess the LFC., Results: The median LFC value was 6% (interquartile range, 3-14%), and 34% of the subjects had hepatic steatosis based on the criteria for diagnosis of steatosis by quantitative ultrasound. The maximum CIMT, average CIMT and plaque score were strongly associated with the LFC (β = 0.319, 0.324 and 1.361, respectively; all P < 0.05) after adjustment for age, gender, smoking history, low-density lipoprotein cholesterol and metabolic syndrome. The multiple logistic regression analysis showed that a 1 SD increase in the LFC, the OR for having a large CIMT was 1.350 (95% CI 1.180-1.545; P < 0.001) after adjustment for all potential confounders., Conclusions: These results suggest that the LFC is independently associated with carotid atherosclerosis in the Chinese population, and that the risk of atherosclerosis is proportional to the degree of hepatic steatosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Fatty liver is a common chronic liver disease worldwide. It is associated with an increasing morbidity in China in recent years. The aim of this study was to analyze the effect of drinking alcohol on the hemoglobin and biochemical values of patients with fatty liver., Methods: We investigated the clinical and laboratory data of 669 patients with fatty liver. Of the 669 patients, 166 consumed alcohol more than 60 g per week for at least 2 years, and 503 did not have a history of long-term alcohol consumption. We further analyzed the relationship between alcohol consumption and clinical characteristics of these patients., Results: The values of aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and hemoglobin in the long-term consumption group were significantly higher than those in the non long-term consumption group (P<0.05). In the patients without long-term alcohol consumption, the values of GGT and hemoglobin in patients with light alcohol consumption were significantly higher than those in non alcohol consumers (P<0.05)., Conclusion: Alcohol consumption is associated with significantly increased values of AST, GGT, and hemoglobin in patients with fatty liver, suggesting their potential roles in hepatic steatosis.

Background: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults., Methods: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2., Results: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis., Conclusion: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD., (Copyright © 2024. Published by Elsevier Inc.)