Nonalcoholic Fatty Liver Disease Score Research Articles

Intake of the different types of dairy products, genetic predisposition, and the risks of nonalcoholic fatty liver disease and cirrhosis: a prospective cohort study.

Background: The association of dairy product consumption with nonalcoholic fatty liver disease (NAFLD) and cirrhosis remains controversial. This study aimed to prospectively investigate the associations between the consumption of the different types of dairy products, genetic predisposition, and the risks of NAFLD and cirrhosis. Methods: This cohort study included 190 145 participants from the UK Biobank Study. The consumption of the different types of dairy products was assessed based on the Oxford WebQ at baseline and defined as the sum of milk, yogurt, and cheese. NAFLD and cirrhosis were evaluated using hospital inpatient records and death data in the UK Biobank. The weighted genetic risk score (GRS) for NAFLD and cirrhosis was constructed using 5 and 6 single-nucleotide variants (SNVs), respectively. Cox proportional hazards regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between genetic factors and different types of dairy products with the incidence of NAFLD and cirrhosis. Results: During a median follow-up of 11.6 years, 1512 NAFLD and 556 cirrhosis cases were ascertained. After adjusting for several potential confounders, the HRs (95% CIs) (Q4 vs. Q1) of NAFLD were 0.86 (0.74, 0.995) for total dairy products, 0.96 (0.84, 1.09) for high-fat dairy products, 0.78 (0.67, 0.92) for low-fat dairy products, 0.86 (0.74, 0.99) for unfermented dairy products, and 0.79 (0.68, 0.91) for fermented dairy products. The multivariable-adjusted HRs (95% CIs) (Q4 vs. Q1) of cirrhosis were 0.75 (0.59, 0.96) for total dairy products, 0.97 (0.78, 1.19) for high-fat dairy products, 0.67 (0.51, 0.89) for low-fat dairy products, 0.75 (0.59, 0.96) for unfermented dairy products, and 0.71 (0.56, 0.90) for fermented dairy products. The associations of high-fat dairy products and fermented dairy products with NAFLD and cirrhosis were found to be nonlinear (P for nonlinear <0.05). No interaction was observed between dairy product consumption and NAFLD or cirrhosis genetic susceptibility. Conclusions: Higher consumption of dairy products, except for high-fat dairy, was correlated with lower risks of NAFLD and cirrhosis, regardless of their differences in genetic susceptibility.

The sulfur microbial diet and risk of nonalcoholic fatty liver disease: a prospective gene–diet study from the UK Biobank

BackgroundThe gut microbiota is closely related to liver diseases. The dietary pattern associated with sulfur-metabolizing bacteria in stool has been found to influence intestinal health. ObjectiveWe aimed to investigate whether consuming the sulfur microbial diet is associated with nonalcoholic fatty liver disease (NAFLD). MethodsWe included 143,918 participants of European descent from the UK Biobank. Information on serving sizes used per diet component was recorded by an online 24-h dietary assessment tool (Oxford WebQ). The total sulfur microbial diet score was constructed by summing the product of β-coefficients and corresponding serving sizes. NAFLD was ascertained using hospital inpatient and death records. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). Mediation analyses were used to investigate underlying mediators including body mass index, waist circumference, glucose, triglyceride, urate, and C-reactive protein. A polygenic risk score for NAFLD was constructed and stratified to assess whether the association is modified by genetic predisposition. ResultsAfter a median follow-up of 11.7 y (interquartile range: 11.3–12.5 y), we documented 1540 incident cases of NAFLD. After adjustment for covariates, we observed an overall J-shaped relationship between the sulfur microbial diet and risk of NAFLD. Those in the highest quartile of sulfur microbial diet score had a 46% increased risk of NAFLD [HRQ4vsQ1 (95% CI): 1.46 (1.26, 1.69)]. We also found that this association is partly mediated by metabolic disorders and systemic inflammation. In addition, the positive association was stronger among individuals at higher genetic risk for NAFLD (Pinteraction = 0.044). ConclusionsThe sulfur microbial diet had adverse associations with incident NAFLD, particularly in those at a higher genetic risk. Our study may provide evidence on the role of sulfur-metabolizing bacteria in the diet–NAFLD association.

The association between telomere length and non-alcoholic fatty liver disease: a prospective study

BackgroundResearch on the association between telomere length (TL) and incident non-alcoholic fatty liver disease (NAFLD) is limited. This study examined this association and further assessed how TL contributes to the association of NAFLD with its known risk factors.MethodsQuantitative PCR (polymerase chain reaction) was employed to assess leucocyte telomere length. Polygenic risk score (PRS) for NAFLD, air pollution score, and lifestyle index were constructed. Cox proportional hazard models were conducted to estimate the hazard ratios (HRs) and 95% confidence intervals.ResultsAmong 467,848 participants in UK Biobank, we identified 4809 NAFLD cases over a median follow-up of 12.83 years. We found that long TL was associated with decreased risk of incident NAFLD, as each interquartile range increase in TL resulted in an HR of 0.93 (95% CI 0.89, 0.96). TL partly mediated the association between age and NAFLD (proportion mediated: 15.52%). When assessing the joint effects of TL and other risk factors, the highest risk of NAFLD was found in participants with low TL and old age, low TL and high air pollution score, low TL and unfavorable lifestyle, and low TL and high PRS, compared to each reference group. A positive addictive interaction was observed between high PRS and low TL, accounting for 14.57% (2.51%, 27.14%) of the risk of NAFLD in participants with low telomere length and high genetic susceptibility.ConclusionsLong telomere length was associated with decreased risk of NAFLD incidence. Telomere length played an important role in NAFLD.Graphical

Repeated detection of non-alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults.

This study aimed to investigate the effects of repeated detection of non-alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults. In this nationwide population-based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20-39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0-4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points. The multivariable-adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57-2.921), 3.45 (3.221-3.694), 4.588 (4.303-4.892) and 6.126 (5.77-6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores. Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.

THU300 Assessment Of NAFLD Burden In An Employee Wellness Program Among Non-obese Patients Without Evident Metabolic Abnormalities

Abstract Disclosure: F. Bril: None. J. Louie: Employee; Self; Quest Diagnostics. D. Shiffman: Consulting Fee; Self; Quest Diagnostics. M.J. McPhaul: Employee; Self; Quest Diagnostics. Stock Owner; Self; Quest Diagnostics. The increasing prevalence of obesity in the US and worldwide has fueled a dramatic increase in the number of patients affected with nonalcoholic fatty liver disease (NAFLD). NAFLD is the deposition of excess fat in hepatocytes and is associated with increased insulin resistance. Unfortunately, there is a widespread belief that NAFLD is the liver manifestation of the metabolic syndrome (MetS). The aim of the study was to determine whether NAFLD can exist in the absence of the typical metabolic abnormalities that define MetS (i.e., obesity, hyperglycemia, dyslipidemia), and whether patients with NAFLD and without metabolic abnormalities would be missed if NAFLD scores based on adiposity, dyslipidemia or glycemia are used. Methods: We studied employees and spouses who participated in an annual wellness program that includes laboratory tests and anthropometric measurements. To assess the proportion of individuals likely to be affected with NAFLD we used the product of fasting intact insulin (II) and alanine transaminase (ALT) levels (II*ALT), a measure highly correlated with liver fat as measured by magnetic resonance spectroscopy in non-diabetic individuals (Bril et al, JCEM 2021) as well as fatty liver index (FLI, a clinical score for NAFLD based on BMI, triglycerides [TG], waist circumference and gamma-glutamyl transferase [GGT]). NAFLD was defined as II*ALT ≥ 290 or FLI ≥ 60. Individuals with diabetes, BMI &amp;lt;18.5, and those with missing data were excluded from the analysis. Results: In total, 29,977 participants met our criteria. Of these, 9,642 (32%) had prediabetes (PreD) and 20,335 (68%) were normoglycemic (NG: normal HbA1c and normal fasting plasma glucose). In the NG population, 2,443 (12.0%) individuals were identified as likely having NAFLD using II*ALT criteria. Even among non-obese patients (&amp;lt;30 kg/m2) with normal TG (&amp;lt;150 mg/dL) and normal HDL-C (males: ≥40 mg/dL; females ≥50 mg/dL), we identified 4.1% (n =426) who were likely to have NAFLD by the II*ALT criteria. Moreover, among patients considered ‘metabolically healthy obese’ due to the absence of hyperglycemia or dyslipidemia, 17.2% were likely to have NAFLD. Of note, FLI detected a smaller percentage of patients at risk of NAFLD among non-obese patients without hyperglycemia and dyslipidemia: 223 (2.1%). Among patients with PreD, those non-obese with normal TG and HDL-C showed a prevalence of NAFLD of 12.4% based on II*ALT, and only 5.5% based on FLI. Conclusion: A substantial percentage of patients has NAFLD even in the absence of obesity, dyslipidemia, and hyperglycemia. This implies that NAFLD can exist in the absence of MetS. While longitudinal studies are needed for confirmation, it suggests that NAFLD can predate the development of these metabolic abnormalities. Therefore, diagnostic methods that do not rely in adiposity, hyperglycemia, or dyslipidemia are needed to identify these patients. Presentation: Thursday, June 15, 2023

The Effect of Testosterone Replacement Therapy on Nonalcoholic Fatty Liver Disease in Older Hypogonadal Men.

Male hypogonadism is associated with visceral obesity and the metabolic syndrome: factors important for the development of nonalcoholic fatty liver disease (NAFLD). The Testosterone Trials (The T Trials) showed testosterone (T) treatment compared with placebo in older hypogonadal men was associated with decreases in cholesterol and insulin levels suggesting that T treatment may improve NAFLD. Compare effects of T vs placebo treatment on NAFLD scores and liver scans in elderly hypogonadal men. Secondary data analyses from 479 older hypogonadal men with total T < 275 ng/dL from The T Trials were performed. Three clinical liver fat scores-lipid accumulation product index, hepatic steatosis index, nonalcoholic fatty liver disease-metabolic syndrome score-and liver computed tomography (CT) Hounsfield units and liver to spleen ratio were evaluated at baseline and 12 months after treatment. There were no statistically significant differences of change in lipid accumulation product index (P = .98), hepatic steatosis index (P = .67), and nonalcoholic fatty liver disease-metabolic syndrome (P = .52) in 246 men treated with T compared with 233 treated with placebo for 12 months. Liver CT showed no statistically significant difference of change in Hounsfield units (P = .24; n = 71 for T, n = 69 for placebo) and liver to spleen ratio (P = .74; n = 55 for T, n = 62 for placebo) between the 2 groups. Our study did not show improvement of NAFLD in older hypogonadal men after 12 months of T vs placebo treatment, as assessed by 3 clinical scores and liver CT for hepatic steatosis. Future studies with longer treatment duration and additional NAFLD diagnostic modalities as primary outcome are warranted.

Role of Circulating Endocan as a Biomarker in Non-Alcoholic Fatty Liver Disease

Abstract Background Nonalcoholic fatty liver disease (NAFLD) has a prevalence of 25% worldwide and is described as the leading cause of chronic liver disease. Liver disease was found to be the third leading cause of death among persons with NAFLD. Its prevalence is increasing in conjunction with metabolic syndrome due to engaged risk factors, which include high body mass index and abdominal obesity, type 2 diabetes, dyslipidemia (high triglycerides and/or low high-densitylipoproteins), age, male sex, and alcohol consumption. Aim of the Work The aim of this study is to study serum level of Endocan in patients with nonalcoholic Fatty Liver disease (NAFLD) to detect its relation to the incidence and severity of nonalcoholic Fatty Liver Disease (NAFLD). Patients and Methods This study was conducted at Ain Shams University hospitals to evaluate the role of serum endocan as a diagnostic biomarker for NAFLD. We included a total of 100 subjects who were divided into two equal groups; Group 1 included 50 patients with NAFLD, and Group 2 included 50 healthy controls. Results Both BMI and waist circumference showed a significant increase in cases compared to controls. The prevalence of DM in the NAFLD group was 36% which was statistically significantly higher as compared with the control group. The mean SBP was statistically significantly higher in the NAFLD group, while DBP showed comparable findings. The mean liver size as detected by US was statistically significantly higher in the NAFLD group as compared with the control group, while spleen size didn’t reveal a statistically significant difference between the two groups. The mean fasting blood glucose, mean HbA1C, mean post-prandial glucose, mean cholesterol level, mean TGs, mean LDL, mean ALT and mean AST, mean ALP, mean GGT and mean ferritin level were statistically significantly higher in the NAFLD group as compared with the control group. The mean HDL level was statistically significantly lower in the NAFLD group as compared with the control group. Other laboratory variables were comparable between the two groups. The mean serum endocan level was statistically significantly higher in the NAFLD group as compared with the control group (54.58 ± 18.61 and 30.69 ± 6.49 respectively). Each of APRI, FIB-4 and NAFLD scores showed significant difference between the two groups. Conclusion Based on the previous findings, one can conclude that: Serum endocan may act as a surrogate marker for the diagnosis of NAFLD as it was significantly elevated in cases compared to controls. As well as detection of disease severity as it has a positive correlation with APRI, FIB-4 score yet still further studies on larger scales are required. This confirms the state of endothelial dysfunction associated with this disease NAFLD is associated with impaired lipid profile, impaired liver functions, and higher incidence of diabetes compared to controls.

Tumor Necrosis Factor Alpha and Neutrophil Lymphocytic Ratio in Non-Alcoholic Fatty Liver Diseases

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Some patients with NAFLD progress to liver fibrosis, cirrhosis and hepatocellular carcinoma. Therefore, the precise diagnosis and staging of NAFLD patients is clinically important. Objective To investigate the relationship between tumor necrosis factor alpha level and neutrophil lymphocytic ratio with the development of nonalcoholic fatty liver disease (NAFLD) from simple steatosis stage to liver fibrosis. Patients and Methods In the present study, we assess the value of TNF-α and N/L ratio as a noninvasive biomarker for diagnosis of NAFLD and NASH. All patients enrolled in the study fulfilled the mentioned inclusion criteria. They all were subjected to history taking and clinical examination upon admission. An informed consent was taken from all patients before enrollment in the study. Privacy of the participants and confidently of the data is preserved. Any unexpected risk appeared during the course of the study were being cleared to the participants and ethical committee on time. Results Patients with NASH had lower platelet count, higher INR, higher total bilirubin, higher serum AST, and higher serum ALT, lower serum albumin than normal controls and NAFLD patients. Likewise, patients with NAFLD had lower platelet count, higher INR, higher total bilirubin, higher serum AST, and higher serum ALT, lower serum albumin than normal controls. Patients with NASH had higher serum FBS and serum cholesterol, higher NAFLD score than normal controls and NAFLD patients. Likewise, patients with NAFLD had higher serum FBS and serum cholesterol, higher NAFLD score than normal controls. Patients with NASH had significantly higher values of TNF-α and N/L ratio. Conclusion Nonalcoholic fatty liver disease (NAFLD) increasing in parallel with obesity, insulin resistance, hypertension and dyslipidemia and is now regarded as the liver manifestation of the metabolic syndrome. Serum levels of TNF-α and N/L ratio may represent novel, noninvasive biomarkers of diagnosis and histological disease severity in patients with NAFLD and NASH. And can be a useful predictive marker of liver fibrosis.

Liver fibrosis scores and coronary artery ectasia.

Although scoring systems showing liver fibrosis using non-invasive methods have been accepted as effective tools for predicting cardiovascular risk, their role in predicting coronary ectasia (CAE) has not been evaluated. This study investigated whether aprison (APRI) and fibrosis-4 indices (FIB-4), which are indicators of fibrosis in nonalcoholic fatty liver disease (NAFLD), are associated with CAE. A retrospective, cross-sectional study consisted of 215 patients, 108 with CAE and 107 without CAE, as diagnosed by angiography. The mean age of all patients was 61.8±9.9 yrs, and 171 (78.8 %) were males. The relationships between APRI, FIB-4, NAFLD, and Bard scores and CAE were evaluated. APRI, FIB-4, NAFLD, and Bard scores were independent predictors of CAE. Fib 4, APRI, NAFLD, and Bard scores were higher in the CAE patients. There were a moderate, positive correlations for FIB-4, APRI, and NAFLD scores with coronary ectasia (r=0.55, p&lt;0.001; r=0.52, p&lt;0.001; r=0.51, p&lt;0.001, respectively). A weak-moderate positive correlation was observed between the Bard score and CAE (r=0.34, p&lt;0.001). Univariate and multivariate regression analysis showed that APRI score, low HDL, and Bard score were independent risk factors for CAE ectasia (p&lt;0.001). Cut-off values to predict CAE as determined by ROC curve analysis were: FIB-4 index ≥1.43 (AUC=0.817, 95 % confidence interval (CI): 0.762 to 0.873, p&lt;0.001), APRI index ≥0.25 (AUC=0.804, 95 % CI: 0.745 to 0.862, p&lt;0.001), NAFLD score ≥-0.92 (AUC=0.798, 95 % CI: 0.738 to 0.857.p&lt;0.001), Bard score ≥2 (AUC=0.691, 95 % CI: 0.621 to 0.761, p&lt;0.001). APRI, FIB-4, NAFLD, and Bard scores are associated with CAE.

Combined GIP receptor and GLP1 receptor agonism attenuates NAFLD in male APOE∗3-Leiden.CETP mice.

Combined glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP1R) agonism is superior to single GLP1R agonism with respect to glycemic control and weight loss in obese patients with or without type 2 diabetes. As insulin resistance and obesity are strong risk factors for nonalcoholic fatty liver disease (NAFLD), in the current study we investigated the effects of combined GIPR/GLP1R agonism on NAFLD development. Male APOE∗3-Leiden.CETP mice, a humanized model for diabetic dyslipidemia and NAFLD when fed a high-fat high-cholesterol diet, received subcutaneous injections with either vehicle, a GIPR agonist, a GLP1R agonist, or both agonists combined every other day. GIPR and GLP1R agonism reduced body weight and additively lowered fasting plasma levels of glucose, triglycerides and total cholesterol. Strikingly, we report an additive reduction in hepatic steatosis as evidenced by lower hepatic lipid content and NAFLD scores. Underlying the lipid-lowering effects were a reduced food intake and intestinal lipid absorption and an increased uptake of glucose and triglyceride-derived fatty acids by energy-combusting brown adipose tissue. Combined GIPR/GLP1R agonism also attenuated hepatic inflammation as evidenced by a decreased number of monocyte-derived Kupffer cells and a reduced expression of inflammatory markers. Together, the reduced hepatic steatosis and inflammation coincided with lowered markers of liver injury. We interpretate that GIPR and GLP1R agonism additively attenuate hepatic steatosis, lower hepatic inflammation, ameliorate liver injury, together preventing NAFLD development in humanized APOE∗3-Leiden.CETP mice. We anticipate that combined GIPR/GLP1R agonism is a promising strategy to attenuate NAFLD progression in humans. This work was supported by a grant from the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences [CVON-GENIUS-II] to P.C.N.R., a Lilly Research Award Program [LRAP] Award to P.C.N.R. and S.K., a Dutch Heart Foundation [2017T016] grant to S.K., and an NWO-VENI grant [09150161910073] to M.R.B.; J.F.D.B. is supported by the Nutrition and Health initiative of the University of Groningen; Z.Y. is supported by a full-time PhD scholarship from the China Scholarship Council (201806850094 to Z.Y.).

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

HMGA2 knockdown alleviates the progression of nonalcoholic fatty liver disease (NAFLD) by downregulating SNAI2 expression

Non-alcoholic fatty liver disease (NAFLD) is a complex disease that is considered as the next major health epidemic with alarmingly increasing global prevalence. To explore the pathogenesis of NAFLD, data from GSE118892 were analyzed. High mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, is declined in liver tissues of NAFLD rats. However, its role in NAFLD remains unknown. This study attempted to identify the multiple roles of HMGA2 in NAFLD process. NAFLD was induced in rats using a high-fat diet (HFD). In vivo, HMGA2 knockdown using adenovirus system attenuated liver injury and liver lipid deposition, accompanied by decreased NAFLD score, increased liver function, and decreased CD36 and FAS, indicating the deceleration of NAFLD progression. Moreover, HMGA2 knockdown restrained liver inflammation by decreasing the expression of related inflammatory factors. Importantly, HMGA2 knockdown attenuated liver fibrosis via downregulating the expression of fibrous proteins, and inhibiting the activation of TGF-β1/SMAD signaling pathway. In vitro, HMGA2 knockdown relieved palmitic acid (PA)-induced hepatocyte injury and attenuated TGF-β1-induced liver fibrosis, consistent with in vivo findings. Strikingly, HMGA2 activated the transcription of SNAI2, which was evidenced by the dual luciferase assays. Moreover, HMGA2 knockdown largely downregulated SNAI2 levels. Indeed, SNAI2 overexpression effectively blocked the inhibitory effect of HMGA2 knockdown on NAFLD. Totally, our findings reveal that HMGA2 knockdown alleviates the progression of NAFLD by directly regulating the transcription of SNAI2. HMGA2 inhibition may emerge as a potential therapeutic target for NAFLD.

Noninvasive assessment of paediatric hepatic steatosis by using attenuation imaging.

To evaluate the diagnostic performance of attenuation imaging (ATI) with an ultrasound scanner (US) in the detection of paediatric hepatic steatosis. Ninety-four prospectively enrolled children were classified into normal weight and overweight/obese (OW/OB) groups according to body mass index (BMI). US findings, including hepatic steatosis grade and ATI value, were examined by two radiologists. Anthropometric and biochemical parameters were obtained, and nonalcoholic fatty liver disease (NAFLD) scores, including the Framingham steatosis index (FSI) and hepatic steatosis index (HSI), were calculated. After screening, 49 OW/OB and 40 normal weight children aged 10-18years old (55 males and 34 females) participated in this study. The ATI value was significantly higher in the OW/OB group than in the normal weight group and showed a significant positive correlation with BMI, serum alanine transferase (ALT), uric acid, and NAFLD scores (p < 0.05). In the multiple linear regression adjusted for age, sex, BMI, ALT, uric acid, and HSI, ATI showed a significant positive association with BMI and ALT (p < 0.05). The receiver operating characteristic analysis showed a very good ability of ATI to predict hepatic steatosis. The intraclass correlation coefficient (ICC) of interobserver variability was 0.92, and the ICCs of intraobserver variability were 0.96 and 0.93 (p < 0.05). According to the two-level Bayesian latent class model analysis, the diagnostic performance of ATI showed the best performance for predicting hepatic steatosis among other known noninvasive NAFLD predictors. This study suggests that ATI is an objective and possible surrogate screening test for detecting hepatic steatosis in paediatric patients with obesity. Using ATI as a quantitative tool in hepatic steatosis allows clinicians to estimate the extent of the condition and track changes over time. This is helpful for monitoring disease progression and guiding treatment decisions, especially in paediatric practice. • Attenuation imaging is a noninvasive US-based method for the quantification of hepatic steatosis. • Attenuation imaging values were significantly higher in the OW/OB and steatosis groups than in the normal weight and no steatosis groups, respectively, with a meaningful correlation with known clinical indicators of nonalcoholic fatty liver disease. • Attenuation imaging performs better than other noninvasive predictive models used to diagnose hepatic steatosis.

0512 Apnea-Hypopnea Index does not correlate with Non-Alcoholic Fatty Liver Disease scores

Abstract Introduction Obstructive Sleep Apnea (OSA) and Nonalcoholic Fatty Liver Disease (NAFLD) are two conditions that have increased in prevalence in the United States. NAFLD is a spectrum of liver disease ranging from steatosis to non-alcoholic steatohepatitis (NASH) to cirrhosis. The purpose of this project is to study the relationship between OSA, measured by apnea-hypopnea index and/or arterial oxygen saturation nadir (O2 nadir) during sleep (independent variable) vs. extent of NAFLD as measured by non-invasive scores such as NAFLD Fibrosis score, aminotransferase to platelet ratio index (APRI), BARD score and FIB-4 score (dependent variable). Methods A convenient sample of 91 haphazardly selected veterans with OSA and NAFLD from the Veterans Affairs (VA) Computerized Record System (CPRS) system were included in the study. NAFLD eligibility was determined by abdominal ultrasound, CT scan, MRI, or biopsy. Dependent variables were NAFLD scores of APRI, NAFLD Fibrosis, BARD, and FIB-4. OSA was determined by in-lab polysomnogram or home sleep study. Independent variables were AHI, O2 nadir, age and body mass index (BMI). Patients with a history of alcohol abuse or Hepatitis B or C were excluded from the study. A multiple regression analysis was used to describe the relationship between OSA and NAFLD scores. P&amp;lt; 0.05 was considered statistically significant. Results Age correlated with FIB-4 score, BARD score, and NAFLD fibrosis score (p = &amp;lt; 0.001, 0.003, &amp;lt; 0.001, respectively). BMI correlated with NAFLD fibrosis score (p &amp;lt; 0.001). When controlled for age and BMI, AHI and O2 nadir did not correlate with APRI, NAFLD fibrosis, BARD, or FIB-4 scores. Conclusion OSA measured by AHI and O2 nadir do not correlate with severity of fatty liver disease as measured by APRI, NAFLD fibrosis, BARD, or FIB-4 scores. Support (if any) None

Association between the dual use of electronic and conventional cigarettes and NAFLD status in Korean men.

This study investigated the association between smoking types, including dual use (usage of both combustible cigarettes and e-cigarettes), and non-alcoholic fatty liver disease (NAFLD) status in Korean men. Data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2020 were used. The presence of NAFLD was defined by the respective cut-off values for the Hepatic Steatosis Index (HSI), NAFLD Ridge Score (NRS), and Korea National Health and Nutrition Examination Survey NAFLD score (KNS). Multivariate logistic regression analyses were used to determine the associations between smoking types and NAFLD as determined by HSI, NRS, and KNS. After adjustment for confounders, an independent association was observed between dual use and NAFLD (HSI: AOR=1.47; 95% CI: 1.08-1.99, p=0.014; NRS: AOR=2.21; 95% CI: 1.70-2.86, p=0.000; KNS: AOR=1.35; 95% CI: 1.01-1.81, p=0.045). Cigarette only smokers also had significantly higher odds of NAFLD compared to never smokers for all of the NAFLD indices (HSI: AOR=1.22; 95% CI: 1.05-1.42, p=0.008; NRS: AOR=2.13; 95% CI: 1.87-2.42, p=0.000; KNS: AOR=1.33; 95% CI: 1.14-1.55, p=0.000). In subgroup analyses, no significant interaction effects were found for age, BMI, alcohol consumption, income, physical activity, and the diagnosis of T2DM. Moreover, cigarette only smokers and dual users differed significantly in terms of log-transformed urine cotinine and pack-years. The relationship between smoking type and pack-years was attenuated after stratification by age. This study shows that the dual use of e-cigarettes and combustible cigarettes is associated with NAFLD. Age differences may explain why dual users, with a greater proportion of young people, appear to have fewer pack-years than cigarette only smokers. Further research should be conducted to investigate the adverse effects of dual use on hepatic steatosis.

The association of dietary inflammatory index (DII) and central obesity with non-alcoholic fatty liver disease (NAFLD) in people with diabetes (T2DM)

Background & ObjectiveHigh prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus results in deleterious complications and morbidities related to both diseases. Thus, we aimed to investigate dietary and anthropometric risk factors for progression of Non-alcoholic Fatty Liver Disease (NAFLD) in diabetic people. MethodsAnthropometric, and dietary intakes, and hepatic steatosis and fibrosis were assessed in two hundred participants with type two diabetes (T2DM). Subjects with CAP score of more than 270 dB/m were considered to have NAFLD. Multivariable-adjusted ORs and 95% CIs were used to investigate the association between NAFLD and dietary inflammatory index (DII) score and anthropometric indices. ResultsParticipants in the highest tertile of DII had 2.41 (95% CI:1.16-4.97), 2,53 (95% CI: 1.04-6.16), 2.78 (95% CI: 1.09-7.13) times higher odds of developing NAFLD in comparison to the lowest tertile in crude, adjusted model 1 and 2, respectively. Among those with the highest relative to the lowest tertile of trunk-to-leg fat ratio (TLR), ORs and 95% CI were OR = 1.88, 95% CI = 0.9-3.91, and OR = 7.99, 95% CI = 2.43-26.26 in crude and full-adjusted models. Odds of NAFLD in the third tertile of metabolic score for visceral fat (METS-VF) was higher than the first tertile in crude (OR = 9.5, 95% CI = 4.01-22.46) and full-adjusted models (OR = 4.55, 95% CI = 1.46-14.2). ConclusionsIn conclusion, this study highlighted an association between greater DII (pro-inflammatory diet) and higher NAFLD risk. Moreover, TLR and METS-VF are known as novel estimators of central obesity as a risk factor for NAFLD in diabetes.

A Review on the Role of Low Glycemic Index Foods for Glycemic Control in Chronic Liver Disease

Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation and destruction of liver parenchyma. The development of glucose intolerance and hepatogenous diabetes (HD) in patients with CLD is an inevitable event. Diabetes and CLD can coexist, and function synergistically to cause unfavorable clinical consequences, including poor treatment outcomes and frequent hospitalization. The complications associated with liver disease (malnutrition, hypoglycemia, acute kidney injury, lactic acidosis, etc.) and lack of guidelines limit pharmacological management of HD. Dietary recommendations by The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines (2019), suggested weight reducing hypocaloric diet along with adequate branched-chain amino acid (BCAA) and micronutrient consumption to improve steatosis and insulin sensitivity in patients with CLD. Dietary glycemic index controls prognosis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The importance of low GI diet in reducing fasting blood glucose, hepatic glucose influx and fat accumulation, thereby improving weight loss and NAFLD score, is being published in patients with diabetes or liver disease. Several countries have already incorporated GI into their national health policies, for identification of the nutrient value, resulting in establishment of worldwide GI and glycemic load tables for specific food items. However, the apparent complexity of GI and lack of low GI meal choices need to be resolved in order to enhance patient’s quality of life, health and well-being. Low GI nutritional supplements, comprising of balanced proportion of carbohydrate, protein, BCAAs, fibers and micronutrients, may reduce the complexity related to dietary management of HD. The review summarizes the importance of nutritional management in HD with focus on low GI diet in people with CLD.

Factors Associated with Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, Among Chinese Young Adults.

Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of study assessing awareness and knowledge of NAFLD among them. This study aimed to assess awareness and knowledge of NAFLD, and identify the factors associated with awareness and knowledge of NAFLD among CYA. We conducted a survey to assess awareness and knowledge of NAFLD among students who enrolled in one university undergraduate program in 2018, 2019, and 2020 through a newly developed web-based, self-administered questionnaire. The outcomes included awareness of NAFLD and knowledge score of NAFLD. We conducted unadjusted and adjusted analyses of associated factors with these outcomes. A total of 1373 students participated in the survey. Of all participants, 26.2% reported that they had heard of NAFLD, 7.7% reported that they had heard of lean NAFLD, and 11.1% received ≥ 20 points in the knowledge section of NAFLD. The mean and median scores were 9.35 (Std = 7.67) and 9 (range 0-27). Factors associated with having awareness and knowledge (≥ 20 points) of NAFLD included medical background, high medical knowledge level, and family history of NAFLD. There was low NAFLD awareness and knowledge among CYA aged 18 to 25years. Our findings point to the need to develop an educational intervention for CYA to improve their NAFLD awareness and knowledge. Further studies should include information on physical activity and dietary habits to test whether NAFLD awareness and knowledge impact those habits.

Investigating microRNAs to Explain the Link between Cholesterol Metabolism and NAFLD in Humans: A Systematic Review.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by hepatic free cholesterol accumulation. In addition, microRNAs (miRNAs) might be involved in NAFLD development. Therefore, we systematically reviewed the literature to examine the link between miRNAs and cholesterol metabolism in NAFLD. Nineteen studies were retrieved by a systematic search in September 2022. From these papers, we evaluated associations between 13 miRNAs with NAFLD and cholesterol metabolism. Additionally, their diagnostic potential was examined. Four miRNAs (miR122, 34a, 132 and 21) were associated with cholesterol metabolism and markers for NAFLD. MiR122 was upregulated in serum of NAFLD patients, increased with disease severity and correlated with HDL-C, TAG, VLDL-C, AST, ALT, ALP, lobular inflammation, hepatocellular ballooning and NAFLD score. Serum and hepatic levels also correlated. Serum and hepatic miR34a levels were increased in NAFLD, and correlated with VLDL-C and TAG. Serum miR379 was also higher in NAFLD, especially in early stages, while miR21 gave ambiguous results. The diagnostic properties of these miRNAs were comparable to those of existing biomarkers. However, serum miR122 levels appeared to be elevated before increases in ALT and AST were evident. In conclusion, miR122, miR34a, miR21 and miR132 may play a role in the development of NAFLD via effects on cholesterol metabolism. Furthermore, it needs to be explored if miRNAs 122, 34a and 379 could be used as part of a panel in addition to established biomarkers in early detection of NAFLD.

Endothelial Extracellular Signal-Regulated Kinase/Thromboxane A2/Prostanoid Receptor Pathway Aggravates Endothelial Dysfunction and Insulin Resistance in a Mouse Model of Metabolic Syndrome.

Background Metabolic syndrome is characterized by insulin resistance, which impairs intracellular signaling pathways and endothelial NO bioactivity, leading to cardiovascular complications. Extracellular signal-regulated kinase (ERK) is a major component of insulin signaling cascades that can be activated by many vasoactive peptides, hormones, and cytokines that are elevated in metabolic syndrome. The aim of this study was to clarify the role of endothelial ERK2 in vivo on NO bioactivity and insulin resistance in a mouse model of metabolic syndrome. Methods and Results Control and endothelial-specific ERK2 knockout mice were fed a high-fat/high-sucrose diet (HFHSD) for 24 weeks. Systolic blood pressure, endothelial function, and glucose metabolism were investigated. Systolic blood pressure was lowered with increased NO products and decreased thromboxane A2/prostanoid (TP) products in HFHSD-fed ERK2 knockout mice, and Nω-nitro-l-arginine methyl ester (L-NAME) increased it to the levels observed in HFHSD-fed controls. Acetylcholine-induced relaxation of aortic rings was increased, and aortic superoxide level was lowered in HFHSD-fed ERK2 knockout mice. S18886, an antagonist of the TP receptor, improved endothelial function and decreased superoxide level only in the rings from HFHSD-fed controls. Glucose intolerance and the impaired insulin sensitivity were blunted in HFHSD-fed ERK2 knockout mice without changes in body weight. In vivo, S18886 improved endothelial dysfunction, systolic blood pressure, fasting serum glucose and insulin levels, and suppressed nonalcoholic fatty liver disease scores only in HFHSD-fed controls. Conclusions Endothelial ERK2 increased superoxide level and decreased NO bioactivity, resulting in the deterioration of endothelial function, insulin resistance, and steatohepatitis, which were improved by a TP receptor antagonist, in a mouse model of metabolic syndrome.