Nonalcoholic Fatty Liver Disease In Men Research Articles

Endogenous sex hormones and nonalcoholic fatty liver disease in US adults.

Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone-to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults. A cross-sectional analysis using the 2013-2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease. Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women. The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD.

FRI429 Association Between Nonalcoholic Fatty Liver Disease And Fib-4 In Patients With Hypogonadism

Abstract Disclosure: C.M. Godar: None. K.F. Brown: None. A.J. Spiro: None. N.O. Vietor: None. T.D. Hoang: None. M.K. Shakir: None. Introduction: Recent studies have reported a strong bidirectional association between non-alcoholic fatty liver disease (NAFLD) and hypogonadism in both genders. Men with hypogonadism may have higher noninvasive indices of NAFLD via hepatic steatosis index (HSI, reference range <36) and hepatic fibrosis via FIB-4 (reference range <1.3). However, there is limited clinical data on the association between serum testosterone concentrations and NAFLD in men. We report here HSI and FIB-4 in 3 men with hypogonadism. Case #1: 56-year-old male with a 20-year history of idiopathic hypogonadism, hypertension on telmisartan and amlodipine, and obstructive sleep apnea with regular CPAP use. Pituitary MRI is normal. He uses 3 pumps of topical testosterone gel daily. Vital signs: BP 139/83mmHg, HR 59bpm and BMI 36.2. Examination of heart and lungs is normal, testes are 15cc bilaterally. Serum testosterone is 400-500 ng/dL, alanine aminotransferase (ALT) 88 U/L (0-50), aspartate aminotransferase (AST) 71 U/L (17-59), alkaline phosphatase (ALP) 78 U/L (38-126), iron saturation 43.1% (20-55), ferritin 452 ng/mL (30-400). Calculated FIB-4: 2.3, HSI: 46. Case #2: 71-year-old male with 46XX phenotype with hypogonadism and gynecomastia on 2 pumps of transdermal testosterone gel daily. Vital signs: BP 150/79 mmHg, HR 67/min, BMI 36.8. Examination of heart and lungs is normal, and testes are 5cc bilaterally. Serum testosterone is 416 ng/dL, ferritin 509 ng/mL, iron saturation 41.3%, ALT 19 U/L, AST 22 U/L, ALP 136 U/L. Liver ultrasound demonstrated diffuse hepatic steatosis with borderline hepatomegaly. Calculated FIB-4: 1.38, HSI: 48.4. Case #3: 48-year-old male with central hypogonadism currently taking testosterone 100 mg IM every week. Evaluation for central hypogonadism was unrevealing for pituitary lesion. Vital signs of BP 130/91, HR 76/min, BMI 27.2. Examination of heart and lungs is normal, and testes are 20cc bilaterally. ALT 201U/L, AST 80U/L, ALP 136U/L, serum testosterone 241 ng/dL. Liver ultrasound is consistent with hepatic steatosis. Calculated FIB-4: 1.22, HSI 59.2. Conclusion: Patients with a combination of hypogonadism, high BMI, mild or moderate elevations of AST/ALT/ALP, elevated serum ferritin or transferrin saturation should undergo screening for NAFLD. In this series, all 3 patients had high HSI, an early indicator of fibrosis although only 1 patient had a high FIB-4 level. As fibrosis is the strongest predictor for long-term clinical outcomes among patients with NAFLD there is growing interest in employing non-invasive methods such as HSI, FIB-4, NFS and APRI for risk stratification. In conclusion, it is recommended that high risk patients with hypogonadism need to be screened for NAFLD and hepatic fibrosis with these simple tools. Presentation: Friday, June 16, 2023

The Prevalence of Non-Alcoholic Fatty Liver Disease in Iranian Children and Adult Population: A Systematic Review and Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) is the world's most common etiology of chronic liver disease. In this systematic review and meta-analysis, we estimated the prevalence of NAFLD in the Iranian children and adult population. A comprehensive search of five international databases, including PubMed, ISI/WOS, ProQuest, Scopus, and Google Scholar, was done from inception to Nov 2022. Studies on NAFLD patients and their risk factors were selected for meta-analysis. The quality of the included studies was assessed by The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for cross-sectional, and cohort studies. The heterogeneity between studies was investigated using Cochran test and I2 statistics. Random and fixed effect models were used for heterogenic and non-heterogenic studies, respectively. We used Comprehensive Meta-Analysis version 3 for conducting meta-analysis. Twenty studies were finally included. The total prevalence of NAFLD in children, boys, and girls was 6.7% (95% CI: 0.02-0.18), 12.5% (95% CI: 0.04-0.29) and, 10.1% (95% CI: 0.04-0.21), respectively. The total prevalence of NAFLD in obese children, obese boys, and obese girls was 42% (95% CI: 0.18-0.69), 44% (95% CI: 0.13-0.80), and 33 % (95% CI: 0.13-0.62), respectively. The total prevalence of NAFLD in adults was 36.9% (95% CI: 0.31-0.42). The prevalence of NAFLD in men and women was 33.8% (95% CI: 0.27-0.41) and 29.9% (95% CI: 0.21-0.40), respectively. NAFLD prevalence in Iranian adults and obese children is considerable; however, data about the children population was insufficient.

The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study.

Sleep can affect nonalcoholic fatty liver disease (NAFLD). We investigated the association between sleep duration, sleep quality, and NAFLD. From January to December 2018, 1,073 patients (age: 37.94 ± 10.88, Body Mass Index (BMI): 22.85 ± 3.27) were enrolled. Pittsburgh Sleep Quality Index Questionnaire and Munich Chronotype Questionnaire were used to assess sleep duration, quality, and habits. Ultrasonography was used to diagnose NAFLD. Multivariate logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the risk of NAFLD by different types of sleep duration and sleep quality. No significant differences in sleep time, sleep quality, and sleep habits between the NAFLD and the non-NAFLD groups were observed (P > 0.05). There was no correlation between sleep duration and NAFLD in the whole cohort. After adjusting for age, exercise, fasting plasma glucose, and BMI, the group with long sleep duration showed a decreased risk of NAFLD in men (OR = 0.01, 95% CI: 0.001-0.27, P = 0.032). However, in all four adjusted models, no correlation between sleep duration, quality, and NAFLD was found in women. In conclusion, sleep duration was significantly and negatively associated with NAFLD in men but not women. Prospective studies are required to confirm this association.

Adiponectin–leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance

Background Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin–leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. Materials and methods A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. Results The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12–0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82–0.88), 0.83 (95% CI 0.78–0.87) and 0.86 (95% CI 081–0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). Conclusions The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3] Key messages The prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early. Adiponectin–leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio. Our study found that adiponectin–leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin–leptin ratio was 0.28(95%CI: 0.12–0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82–0.88). Further rigorous investigation is necessary and should be promptly performed.

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus.

Non-alcoholic fatty liver disease (NAFLD) is considered as both a vital risk factor and a consequence of type 2 diabetes mellitus (T2DM). Low total testosterone (TT) is common in men with T2DM, contributing to increased risks of metabolic diseases. This study aimed to investigate the association between TT levels and the prevalence of NAFLD in men with T2DM. In this cross-sectional study, 1005 men with T2DM were enrolled in National Metabolic Management Center (MMC) of First Affiliated Hospital of Wenzhou Medical University between January 2017 and August 2021. NAFLD was diagnosed using ultrasound as described by the Chinese Liver Disease Association. Overweight/obesity was defined as body mass index (BMI) ≥ 25kg/m2 according to WHO BMI classifications. Individuals without NAFLD had higher serum TT levels than those with NAFLD. After adjustments for potential confounding factors, the top tertile was significantly associated with lower prevalence of NAFLD compared with the bottom tertile of TT level [odds ratio (OR) 0.303, 95% confidence interval (CI) 0.281-0.713; P < 0.001]. The association between TT with NAFLD in individuals with normal weight (OR 0.175, 95% CI 0.098-0.315; P < 0.001) was stronger than in individuals with overweight/obesity (OR 0.509, 95% CI 0.267-0.971; P = 0.040). There was a significant interaction of TT with overweight/obesity (P for interaction = 0.018 for NAFLD). Higher serum TT was significantly associated with a lower prevalence of NAFLD in men with T2DM. We found that the relationship of TT and NAFLD was stronger in individuals with non-overweight/obesity.

The role of predicted lean body mass and fat mass in non-alcoholic fatty liver disease in both sexes: Results from a secondary analysis of the NAGALA study.

High body mass index (BMI) is an important risk factor for non-alcoholic fatty liver disease (NAFLD). However, the association of body composition such as fat mass (FM) and lean body mass (LBM) with NAFLD has not been adequately studied. The purpose of this study was to clarify the contribution of body composition FM and LBM to NAFLD. We analyzed data from 7,411 men and 6,840 women in the NAGALA cohort study. LBM and FM were estimated for all subjects using validated anthropometric prediction equations previously developed from the National Health and Nutrition Examination Survey (NHANES). Using multiple logistic regression and restricted cubic spline (RCS) to analyze the association and the dose-response curve of predicted LBM and FM with NAFLD in both sexes. The prevalence of NAFLD in man and woman subjects was 27.37 and 6.99%, respectively. Predicted FM was positively and linearly associated with NAFLD in both sexes, with each 1 kg increase in predicted FM associated with a 27 and 40% increased risk of NAFLD in men and women, respectively. In contrast, predicted LBM was negatively associated with NAFLD in both sexes, with each 1 kg increase in predicted LBM reducing the risk of NAFLD by 4 and 19% in men and women, respectively. In addition, according to the RCS curve, the risk of NAFLD did not change in men when the predicted LBM was between 47 and 52 kg, and there seemed to be a saturation effect; further, the threshold value of the saturation effect was calculated to be about 52.08 kg by two-piecewise logistic regression, and the protective effect on NAFLD would be significantly enhanced when the man predicted LBM was greater than 52.08 kg. The current findings suggested that body composition LBM and FM had opposite associations with NAFLD in both sexes, with higher LBM associated with a lower risk of NAFLD and higher FM increasing the risk of NAFLD, especially in women.

Dysglycemia in young women attenuates the protective effect against fatty liver disease.

Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age. To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia. We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia. The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender. While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liverdisease.

Low Serum Total Testosterone Is Associated with Non-Alcoholic Fatty Liver Disease in Men but Not in Women with Type 2 Diabetes Mellitus.

Materials and Methods There were 1155 patients with T2DM included in the analysis. Serum levels of total testosterone and the precursors of androgens, including androstenedione, DHEA, and DHEAS, were quantified using liquid chromatography-tandem mass spectrometry assays. Results The risk of NAFLD decreased as total testosterone concentration increased in men with T2DM. After adjusting for age, current smoking, current drinking, body mass index, duration of T2DM, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein/high-density lipoprotein cholesterol ratio, uric acid, C-reactive protein, and sex hormones in model 4, the adjusted odds ratio (OR) and 95% confidence interval (CI) of NAFLD for tertile3 vs tertile1 was 0.37 (0.17–0.77; P = 0.024 for trend). When taken as a continuous variable, this association was still robust in model 4 (OR, 0.58; 95% CI, 0.42–0.80; P < 0.05). No significant associations were found between increasing levels of the precursors of androgens and the odds of NAFLD in men with T2DM (all P > 0.05). Moreover, women showed no significant associations of total testosterone, androstenedione, DHEA, and DHEAS, with the odds of NAFLD (all P > 0.05). Conclusions Serum total testosterone was independently associated with the risk of NAFLD among men with T2DM. This study highlights the potential role of testosterone as a risk factor for NAFLD in patients with T2DM.

Sex-specific metabolic risk factors and their trajectories towards the non-alcoholic fatty liver disease incidence.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. This study examined sex-specific associations between NAFLD and metabolic factors and investigated the trajectory of risk factors. We retrospectively investigated 16,140 individuals from Beijing Health Management Cohort. Univariate and multivariate time-dependent Cox regression analyses were performed to identify independent risk factors for new-onset NAFLD. The trajectory of risk factors was investigated using the latent growth curve model and growth mixture model. Over a median follow-up of 3.15years, 2,450 (15.18%) participants developed NAFLD. The risk factors for NAFLD in men were increased body mass index (BMI); waist circumference (WC); triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), haemoglobin (Hb), and serum uric acid (SUA) levels; and platelet (PLT) count and decreased serum creatinine-to-body weight (sCr/bw) and high-density lipoprotein cholesterol (HDL-C) levels. In women, the risk factors were increased BMI, WC, and fasting plasma glucose (FPG), TG, LDL-C, SUA, white blood cell (WBC), and PLT and decreased sCr/bw and HDL-C levels. In addition, BMI, LDL-C, sCr/bw and PLT changing trajectories were associated with NAFLD in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends was associated with NAFLD risk in women. Development of NAFLD is associated with BMI, LDL-C, sCr/bw and PLT changing trajectories in men; BMI, WC, TG, LDL-C, SUA and sCr/bw trends are associated an increased risk of NAFLD in women. Deterioration of metabolic risk factors status can be a predictor of NAFLD many years before its occurrence.

Association between lower plasma adiponectin levels and higher liver stiffness in type 2 diabetic individuals with nonalcoholic fatty liver disease: an observational cross-sectional study

PurposeLittle is known about the association between plasma adiponectin levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). We examined whether there is an association between lower plasma adiponectin levels and the presence/severity of NAFLD in people with T2DM.MethodsWe cross-sectionally recruited 79 men with non-insulin-treated T2DM and no known liver diseases, who had consecutively attended our diabetes outpatient service over a 6-month period and who underwent both ultrasonography and Fibroscan-measured liver stiffness (LSM). Nine single nucleotide polymorphisms (PNPLA3 rs738409 and other genetic variants) associated with NAFLD were investigated.ResultsAmong the 79 participants included (mean age 67 ± 10 years, BMI 27.7 ± 4 kg/m2), 28 did not have NAFLD, 32 had steatosis alone, and 19 had NAFLD with coexisting significant fibrosis (LSM ≥ 7.0 kPa by Fibroscan®). Compared to those without NAFLD, patients with hepatic steatosis alone and those with hepatic steatosis and coexisting significant fibrosis had lower high-molecular-weight adiponectin levels (5.5 [IQR 2.3–7.6] vs. 2.4 [1.8–3.7] vs. 1.6 [1.0–2.9] µg/mL; p < 0.001). After adjustment for age, body mass index, insulin resistance, and the PNPLA3 rs738409 variant, lower plasma adiponectin levels were found to be associated with increased odds of both steatosis alone (adjusted-odds ratio [OR] 2.44, 95% CI 1.04–5.56, p = 0.042) and NAFLD with coexisting significant fibrosis (adjusted-OR 3.84, 95% CI 1.23–10.0, p = 0.020). Similar findings were observed after adjustment for the other eight genotyped NAFLD-related polymorphisms.ConclusionLower plasma adiponectin levels are closely associated with the presence and severity of NAFLD in men with T2DM, pointing to a role of adiponectin in NAFLD development and progression.

Reduced Equol Production and Gut Microbiota Features in Men With Lean Nonalcoholic Fatty Liver Disease.

Patients with lean nonalcoholic fatty liver disease (NAFLD) may have different metabolic profiles than those with NAFLD. Estrogenic activity is associated with NAFLD pathogenesis. We evaluated the production ability of equol, which has estrogenic activity, in lean NAFLD and assessed their gut microbiota in relation to their equol-producing ability. Among 684 adult participants, 276 (40%) had NAFLD and 293 (43%) were equol producers. The rates of equol producers in the normal and NAFLD groups were 43% and 42%, respectively. Among the patients with NAFLD, 55 (20%) had lean NAFLD of which 18 (33%) were equol producers. The rate of equol production in men with lean NAFLD was 8%, which was the lowest, while the corresponding rate in the other participants was approximately 40%. The gut microbiota composition of equol producers and nonproducers showed many significant differences. The gut microbiota of men with lean NAFLD showed increased abundance of Caulobacter and decreased abundances of Slackia and Terrisporobacter. Thus, almost all men with lean NAFLD lacked equol-producing ability, and their gut microbiota showed a reduced abundance of Slackia, which is related to equol production. The pathology of lean NAFLD in men may be strongly associated with equol-producing ability and gut microbiota.

Relationship between prevalence and risk of osteoporosis or osteoporotic fracture with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The aim of this meta-analysis was to investigate the relationship between prevalence and risks of osteoporosis or osteoporotic fracture and non-alcoholic fatty liver disease (NAFLD). Five databases, including PubMed, Web of Science, Embase, Scopus and Cochrane Library, were searched since the conception of these databases until December 2021. The cohort studies, cross-sectional analyses or case-control studies evaluating the relationship between osteoporosis or osteoporotic fracture and NAFLD were retrieved from these databases. Relevant data were extracted from the included studies, and a meta-analysis was performed. A total of seven studies were included. The prevalence of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.17, 95%CI(1.04,1.31)], while the prevalence of osteoporosis was higher in the NAFLD group than in the non-NAFLD group [OR = 1.46, 95%CI (1.21,1.77) and OR = 1.48, 95%CI (1.31,1.68), respectively] in men and women. The risk of osteoporosis or osteoporotic fractures was higher in the NAFLD group than in the non-NAFLD group [OR = 1.33,95%CI (1.24,1.44) and OR = 1.57,95%CI (1.08,2.29), respectively]. The risk of osteoporosis or osteoporotic fractures was higher in male and female NAFLD groups than that in the non-NAFLD group [OR = 1.29, 95%CI(1.14,1.47) and OR = 1.36, 95%CI (1.25,1.48), respectively]. After parameter adjustment, the risk of osteoporosis or osteoporotic fracture was higher in the male NAFLD group than in the non-NAFLD group [OR = 2.10, 95%CI(1.36,3.25)], while no significant difference was found among women [OR = 1.13, 95%CI (0.86,1.48)]. The prevalence and risk of osteoporosis or osteoporotic fractures were significantly associated with NAFLD in men and women. PROSPERO 2022 CRD42022304708.

Conjunctional Relationship between Serum Uric Acid and Serum Nickel with Non-Alcoholic Fatty Liver Disease in Men: A Cross-Sectional Study.

Serum uric acid (SUA) and heavy metals are closely related to non-alcoholic fatty liver disease (NAFLD). Yet, the conjunctional relationship between SUA and serum nickel (Ni) concentrations with the risk of NAFLD in men has not yet been investigated. Therefore, we designed this cross-sectional study to investigate the association of SUA or serum Ni with NAFLD in men. The cross-sectional study was based on data obtained from a prospective cohort study of common chronic non-communicable diseases in Central China, conducted in Xinxiang city, Central China’s Henan Province, between April and June 2017. A total of 1709 male participants completed the physical examination. B-ultrasound was used to examine the liver and to diagnose NAFLD. Binary logistic regression models and restricted cubic splines were performed to estimate the association of the SUA and serum Ni with NAFLD. The prevalence of NAFLD among 1709 male participants was 46.6%. After adjusting for potential confounders, with the highest quartile compared to those with the lowest quartile, SUA (OR = 1.579, 95% CI: 1.140–2.189) and serum Ni (OR = 1.896, 95% CI: 1.372–2.625) were associated with NAFLD, respectively. At the same time, the associations for the second and third SUA quartiles were null. Restricted cubic splines showed a positive linear relationship between serum Ni (ln-transformed) and NAFLD risk. Intriguingly, high SUA and high Ni (OR = 2.370, 95% CI: 1.577–3.597) increased the risk of NAFLD, compared with those with low SUA and low Ni. Our findings demonstrate a positive linear trend between serum Ni concentrations and NAFLD risk. Men with elevated serum Ni had a higher risk of developing NAFLD when compared to those with high SUA. Furthermore, the conjunctional relationship of SUA and serum Ni with NAFLD risk was observed in men.

Visceral Fat Area Is an Independent Risk Factor for Overweight or Obese Nonalcoholic Fatty Liver Disease in Potential Living Liver Donors

The present study aimed to evaluate the correlation between hepatic steatosis (HS), determined by biopsy, and visceral adiposity, measured by computed tomography (CT), in overweight or obese potential living liver donors, and to investigate the risk factors for overweight or obese nonalcoholic fatty liver disease (NAFLD). This retrospective study included 375 overweight or obese (body mass index ≥23 kg/m2) potential living liver donors (mean age, 30.4 ± 9.5 years; 273 men) who underwent liver biopsies and abdominal CT examinations in 2017 and 2018. Anthropometry, laboratory parameters, body composition, and HS were assessed. Correlations were analyzed using Pearson's correlation coefficient, and logistic regression was used to identify independent predictors of overweight or obese NAFLD. Visceral fat area (VFA) was positively correlated with the degree of HS in men (r=0.307; P < .001) and women (r=0.387; P < .001). Multivariable logistic regression analysis showed that alanine aminotransferase (odds ratio [OR], 1.017; 95% confidence interval [CI], 1.001-1.033; P = .033) and VFA (OR, 1.015; 95% CI, 1.008-1.022; P < .001) were independent risk factors for overweight or obese NAFLD in men, and VFA (OR, 1.029; 95% CI, 1.011-1.047; P = .002) was an independent risk factor for overweight or obese NAFLD in women. Visceral adiposity was positively correlated with the degree of HS in overweight or obese potential living liver donors. Additionally, visceral adiposity may be an independent risk factor for overweight or obese NAFLD in potential living liver donors.

Dose-Response Associations of Metabolic Score for Insulin Resistance Index with Nonalcoholic Fatty Liver Disease among a Nonobese Chinese Population: Retrospective Evidence from a Population-Based Cohort Study.

Purpose This study is aimed at investigating the association between the metabolic score for insulin resistance (METS-IR) index and nonalcoholic fatty liver disease (NAFLD) in the nonobese population and its predictive value. Methods 10730 nonobese subjects were selected from longitudinal cohort research conducted from January 2010 to December 2014. Cox proportional hazards models were employed to assess the relationship between METS-IR and new-onset NAFLD. Generalized additive models were used to identify nonlinear relationships. In addition, we performed subgroup analyses and interaction tests. The time-dependent receiver operating curve (ROC) and area under the ROC (AUC) were utilized to measure the discriminatory ability of METS-IR for new-onset NAFLD. Beyond clinical risk factors, the incremental predictive value of METS-IR was appraised using integrated discrimination improvement (IDI), C-index, and net reclassification index (NRI). Results Over a median period of 804.50 days of follow-up, 1859 (17.33%) participants had a new onset of NAFLD. After adjusting for confounders, the HR for new-onset NAFLD in the Q4 group was 6.40 compared with the Q1 group. When METS-IR was considered a continuous variable, the risk of NAFLD increased by 34% for every 1 SD increase in METS-IR. The smoothing curve shows the dose-response relationship between METS-IR and the presence of new-onset NAFLD. Using a two-piecewise linear regression model, we derived a METS-IR inflection point of 36. HRs were 1.31 on the left side of the inflection point and 1.04 on the right side of the inflection point (log-likelihood ratio test, P < 0.001). Subgroup analyses and interaction tests revealed an interaction between gender and SBP in the association between METS-IR and new-onset NAFLD. In the subgroup analysis of gender and SBP, we observed a higher risk of new-onset NAFLD in men and in those with abnormal SBP levels. We evaluated the ability of METS-IR to identify new-onset NAFLD at different time points. The AUCs at 1, 2, 3, and 4 years were 0.784, 0.756, 0.758, and 0.752, respectively, which represent good discrimination of new-onset NAFLD. The addition of METS-IR greatly improved the reclassification and differentiation of clinical risk factors, with an NRI of 0.276 and an IDI of 0.068. In addition, the addition of METS-IR increased the C-index from 0.719 to 0.771. Conclusion In a nonobese Chinese population, elevated METS-IR was independently associated with an enhanced risk of NAFLD development and a dose-response relationship existed. In addition, METS-IR might be a reliable indicator for screening individuals at risk for early NAFLD, especially in nonobese populations.

Hepatic steatosis is associated with anthropometry, cardio-metabolic disease risk, sex, age and urbanisation, but not with ethnicity in adult Kenyans.

We aimed to determine the associations of non-alcoholic fatty liver disease (NAFLD) with cardio-metabolic risk factors for diabetes in adult Kenyans. A cross-sectional study was undertaken among rural and urban Kenyans of different ethnic origin. Ultrasonography scanning (USS) methods were used for the assessment of hepatic fat accumulation for NAFLD assessment and abdominal fat distribution, and simple anthropometry measurements were performed. All participants underwent a 2-h oral glucose tolerance test, and biochemical, haemodynamic and lifestyle data were obtained. Multivariate logistic regression analyses were used to assess sex, age, residency and ethnic differences in the association between NAFLD and various metabolic parameters. In total, 743 individuals (59.1% women) with a mean age of 38.0 (range 18-68) years participated in the study. Overall, 118 individuals (15.9%) had NAFLD, of whom 94.1% had mild steatosis. Age >40years was significantly associated with having NAFLD compared with <30years of age with no difference found in NAFLD between ethnic groups (Luo, Kamba, Maasai). All body composition and clinical measurements were associated with NAFLD (p<0.045 for OR). Finding lower odds for NAFLD in men was unexpected, as was the lack of differences in NAFLD among the ethnic groups, while higher odds for NAFLD with increasing age and in urban vs. rural populations was expected. Especially the sex-specific results warrant further studies in black African populations on biology of body composition for having NAFLD, and whether this translates into insulin resistance and higher risk of diabetes and consequently cardiovascular disease in black African women.

Association of remnant cholesterol with nonalcoholic fatty liver disease: a general population-based study

BackgroundRemnant cholesterol (RC) mediates the progression of coronary artery disease, diabetic complications, hypertension, and chronic kidney disease. Limited information is available on the association of RC with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether RC can be used to independently evaluate the risk of NAFLD in the general population and to analyze the predictive value of RC for NAFLD.MethodsThe study included 14,251 subjects enrolled in a health screening program. NAFLD was diagnosed by ultrasound, and the association of RC with NAFLD was assessed using the receiver operating characteristic (ROC) curve and logistic regression equation.ResultsSubjects with elevated RC had a significantly higher risk of developing NAFLD after fully adjusting for potential confounding factors (OR 1.77 per SD increase, 95% CI 1.64–1.91, P trend< 0.001). There were significant differences in this association among sex, BMI and age stratification. Compared with men, women were facing a higher risk of RC-related NAFLD. Compared with people with normal BMI, overweight and obesity, the risk of RC-related NAFLD was higher in thin people. In different age stratifications, when RC increased, young people had a higher risk of developing NAFLD than other age groups. Additionally, ROC analysis results showed that among all lipid parameters, the AUC of RC was the largest (women: 0.81; men: 0.74), and the best threshold for predicting NAFLD was 0.54 in women and 0.63 in men.ConclusionsThe results obtained from this study indicate that (1) in the general population, RC is independently associated with NAFLD but not with other risk factors. (2) Compared with traditional lipid parameters, RC has a better predictive ability for NAFLD in men.

A low follicle-stimulating hormone level is a protective factor for non-alcoholic fatty liver disease in older men aged over 80

PurposeRecent studies have suggested the significant relationship between follicle-stimulating hormone (FSH) and non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. However, it is unknown whether FSH impacts the risk of NAFLD in men. This study aimed to investigate the association between serum FSH levels and NAFLD in elderly Chinese men aged 80–98, a particular group with worse outcomes of NAFLD.Patients and methodsA cross-sectional analysis was performed in 444 subjects in a geriatric health center. The highest quartile of serum FSH was used as reference. Hepatic steatosis was defined according to the results of liver ultrasound. Fibrosis-4 (FIB-4) Index > 2.67 was defined as advanced fibrosis.ResultsBased on liver ultrasound, 108 (24.3%) subjects had NAFLD. FSH level were negatively correlated with total testosterone, estradiol, nutritional risk, and the prevalence of high education level (all P < 0.01), and positively correlated with age, luteinizing hormone, alanine aminotransferase and aspartate aminotransferase (all P < 0.05). The correlation between FSH and body mass index or antihypertensive drug usage was marginally significant (P = 0.057; P = 0.066, respectively). The percentage of subjects with NAFLD had a trend to increase following the quartiles of serum FSH (20.0% in quartile 1, 18.2% in quartile 2, 27.3% in quartile 3, and 31.6% in quartile 4). After adjustment for common pathogenic risk factors, nutritional risk, and other sex hormones, serum FSH were progressively associated with odds ratios for NAFLD. The adjusted odds ratios and 95% CIs for quartile 1, quartile 2, and quartile 3, compared with quartile 4 were 0.132 (0.034–0.516), 0.190 (0.052–0.702), and 0.404 (0.139–1.173), respectively. Obesity was not involved in the potential negative role of circulating FSH on the risk of NAFLD in our population. Furthermore, our results revealed no significant association between FSH and advance fibrosis, the OR (95% CI) for advanced fibrosis was 1.018 (0.983–1.054) (P = 0.316) after adjusting for the potential covariates, although a positive correlation of FSH and FIB-4 score was observed (r = 0.325, P = 0.001).ConclusionLow FSH level may decrease the risk of NAFLD in elderly Chinese men. These findings warrant replication in more extensive studies.

Dairy protein intake is inversely related to development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is closely related to metabolic dysfunction, including insulin resistance, obesity, and metabolic syndrome. Dairy protein, rich in casein and whey protein, could help to reduce metabolic diseases. Therefore, we investigated the relationship between dairy protein intake and incident NAFLD. We analyzed data for 5171 adults aged 40-69 years from the Korean Genome and Epidemiology Study.(KoGES) Participants were separated as men, women aged ≥50 years, and women aged <50 years and then divided into tertiles based on dairy protein intake. NAFLD was defined as NAFLD liver fat score >-0.640. Scores were calculated as 1.18 × metabolic syndrome (Yes: 1, No: 0)+0.45 × diabetes mellitus (Yes: 2, No: 0)+0.15 × serum insulin+0.04 × AST-0.94 × (AST/ALT)-2.89. Cox proportional hazards spline curves were drawn to visualize dose-response relationships between dairy protein intake and incident NAFLD. Multiple Cox hazard regression analysis was conducted to examine associations between dairy protein intake and incident NAFLD. The Cox proportional hazards spline curves revealed a negative linear relationship between dairy protein intake and incident NAFLD. The cumulative incidence of NAFLD significantly decreased with increasing tertiles of dairy protein intake in men and women aged ≥50 years. After adjusting for confounding factors, the hazard ratios and 95% confidence intervals for NAFLD in the middle and highest tertiles, compared to the lowest tertile, were 0.80 (0.67-0.96) and 0.71 (0.57-0.88) in men, 0.89 (0.72-1.09) and 0.72 (0.56-0.92) in women aged ≥50 years, and 1.01 (0.80-1.27) and 0.91 (0.67-1.24) in women aged <50 years, respectively. We found that higher dairy protein intake was significantly and inversely associated with the risk of incident NAFLD in men and women aged ≥50 years. Consumption of milk and other dairy products could help prevent the development of NAFLD.