Independent Risk Factor For Nonalcoholic Fatty Liver Disease Research Articles

Causal relationship between air pollution, lung function, gastroesophageal reflux disease, and non-alcoholic fatty liver disease: univariate and multivariate Mendelian randomization study.

The association between air pollution, lung function, gastroesophageal reflux disease, and Non-alcoholic fatty liver disease (NAFLD) remains inconclusive. Previous studies were not convincing due to confounding factors and reverse causality. We aim to investigate the causal relationship between air pollution, lung function, gastroesophageal reflux disease, and NAFLD using Mendelian randomization analysis. In this study, univariate Mendelian randomization analysis was conducted first. Subsequently, Steiger testing was performed to exclude the possibility of reverse association. Finally, significant risk factors identified from the univariate Mendelian analysis, as well as important factors affecting NAFLD from previous observational studies (type 2 diabetes and body mass index), were included in the multivariable Mendelian randomization analysis. The results of the univariable Mendelian randomization analysis showed a positive correlation between particulate matter 2.5, gastroesophageal reflux disease, and NAFLD. There was a negative correlation between forced expiratory volume in 1 s, forced vital capacity, and NAFLD. The multivariable Mendelian randomization analysis indicated a direct causal relationship between gastroesophageal reflux disease (OR = 1.537, p = 0.011), type 2 diabetes (OR = 1.261, p < 0.001), and NAFLD. This Mendelian randomization study confirmed the causal relationships between air pollution, lung function, gastroesophageal reflux, and NAFLD. Furthermore, gastroesophageal reflux and type 2 diabetes were identified as independent risk factors for NAFLD, having a direct causal connection with the occurrence of NAFLD.

Relationship between albumin-corrected anion gap and non-alcoholic fatty liver disease varied in different waist circumference groups: a cross-sectional study

ObjectivesTo investigate the association of albumin-corrected anion gap (ACAG) with non-alcoholic fatty liver disease (NAFLD) and clinically significant fibrosis (CSF) defined by vibration-controlled transient elastography measurements.MethodsThis cross-sectional study including 4531 participants was conducted using the data from the NHANES database of cycles 2017–2018. The outcomes were set as NAFLD vs. non-NAFLD and NAFLD with CSF vs. NAFLD without CSF. The generalized additive model and restricted cubic spline analyses were used to assess the nonlinear relationship. The generalized linear models, logistic regression models, sensitivity analysis, P trend test, subgroup analysis, and mediation analysis were employed to analyze the association. Finally, an ACAG-based model was constructed and evaluated.ResultsA higher ACAG level was an independent risk factor for NAFLD (P < 0.05), but not for CSF (P > 0.05). The sensitivity analysis and P trend test results substantiated the significantly positive relationship between ACAG and NAFLD (P < 0.05). Interestingly, the obvious connection between ACAG and NAFLD varied in different waist circumference groups and played a central role in the central obesity group. In addition, alanine aminotransferase and waist circumference were the mediators in their relationship. Moreover, the ACAG-based model performed well in predicting NAFLD.ConclusionsACAG level is independently associated with NAFLD but not CSF. ACAG might be a novel and reliable biomarker for predicting NAFLD clinically especially in the central obesity population.

The Arg/Arg genotype of leptin receptor gene Gln223Arg polymorphism may be an independent risk factor for nonalcoholic fatty liver disease.

Given that obesity and insulin resistance play key roles in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and the connection between leptin and these metabolic diseases, the association between NAFLD and a leptin receptor gene (LEPR) polymorphism was examined. In this genetic case-control association study, 144 biopsy-proven NAFLD patients and 144 controls were genotyped for the LEPR gene Gln223Arg (rs1137101) polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The distributions of genotypes and alleles of Gln223Arg variant were in accordance with the Hardy-Weinberg equilibrium in the study groups (P>.05). Multivariate logistic regression analysis showed that the LEPR Gln223Arg Arg/Arg genotype was an independent risk factor for NAFLD; the Arg/Arg genotype, compared with the Gln/Gln genotype, was associated with a 2.09-fold increased risk for NAFLD (P=.036, odds ratio=2.09 [95% CI = 1.31-5.95]). We found that the LEPR Gln223Arg Arg/Arg genotype was independently associated with a more than 2-fold rise in biopsy-proven NAFLD risk. Our findings, however, need to be corroborated by further studies.

Value of constructing a non-invasive diagnostic model based on serum heme oxygenase-1 and glucose regulatory protein 78 for non-alcoholic fatty liver disease

Objective: To analyze the clinical application value of serum heme oxygenase (HO)-1expression level in non-alcoholic fatty liver disease (NAFLD) and, based on that, establish a diagnostic model combined with glucose regulatory protein 78 (GRP78) so as to clarify its diagnostic effectiveness and application value. Methods: A total of 210 NAFLD patients diagnosed by abdominal B-ultrasound and liver elastography were included, and at the same time, 170 healthy controls were enrolled. The general clinical data, peripheral blood cell counts, and biochemical indicators of the research subjects were collected. The expression levels of HO-1 and GRP78 were detected using an enzyme-linked immunosorbent assay. Multivariate analysis was used to screen independent risk factors for NAFLD. Visual output was performed through nomogram diagrams, and the diagnostic model was constructed. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the diagnostic effectiveness of NAFLD. Measurement data were analyzed using a t-test or Mann-Whitney U rank sum test to detect data differences between groups. Enumeration data were analyzed using the Fisher's exact probability test or the Pearson χ(2) test. Results: Compared with the healthy control group, the white blood cell count, aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase (GTT), fasting blood glucose (Glu), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum HO-1, and GRP78 levels were significantly increased in the NAFLD group patients (P < 0.05). Binary logistic analysis results showed that AST, TG, LDL-C, serum HO-1, and GRP78 were independent risk factors for NAFLD (P < 0.05). A nomogram clinical predictive model HGATL was established using HO-1 (H), GRP78 (G) combined with AST (A), TG (T), and LDL-C (L), with the formula P=-21.469+3.621×HO-1+0.116 ×GRP78+0.674×AST+6.250×TG+4.122 ×LDL-C. The results confirmed that the area under the ROC curve of the HGATL model was 0.965 8, with an optimal cutoff value of 81.69, a sensitivity of 87.06%, a specificity of 92.82%, a P < 0.05, and the diagnostic effectiveness significantly higher than that of a single indicator. The calibration curve and DCA both showed that the model had good diagnostic performance. Conclusion: The HGATL model can be used as a novel, non-invasive diagnosis model for NAFLD and has a positive application value in NAFLD diagnosis and therapeutic effect evaluation. Therefore, it should be explored and promoted in clinical applications.

The association of Neuromedin U levels and non-alcoholic fatty liver disease: A comparative analysis

This comprehensive study delves into the potential link between Neuromedin U (NmU) serum levels and the development of non-alcoholic fatty liver disease (NAFLD), a condition of increasing global prevalence and significant public health concern. The research provides a nuanced understanding of the disease's etiology by examining a cohort of 112 participants, including individuals with and without NAFLD. The study meticulously considers a spectrum of variables such as demographic factors, body composition metrics, and blood parameters. Advanced diagnostic tools like Fibroscan® are employed to ascertain NAFLD presence, ensuring accurate and reliable results.The investigation reveals a noteworthy correlation between NAFLD and several risk factors, notably obesity, increased waist and neck circumferences, hypertriglyceridemia, and insulin resistance. These findings underscore the multifactorial nature of NAFLD and its intricate connection with metabolic syndromes. Intriguingly, the study observes lower NmU levels in individuals diagnosed with NAFLD. However, the role of NmU as an independent risk factor for NAFLD remains inconclusive, warranting further investigation. Although triglyceride level was observed to be an independent risk factor for NAFLD, this relationship was not associated with NmU.This research contributes significantly to the existing knowledge on NAFLD, highlighting the disease's complexity and the interplay of various risk factors. It also opens up new avenues for future research, particularly in exploring the role of NmU within the metabolic pathways associated with NAFLD. The insights gained from this study could guide the development of novel diagnostic and therapeutic strategies for NAFLD, addressing a crucial need in contemporary healthcare.In conclusion, the findings of this study not only enhance the understanding of NAFLD's pathophysiology but also emphasize the importance of comprehensive risk factor analysis in the management and prevention of this growing health concern.

Trend of Non-Alcoholic Fatty Liver Disease in Type II Diabetes Mellitus

Background: Non-alcoholic fatty liver disease (NAFLD) is becoming quite common in Type II Diabetes Mellitus (TIIDM) as obesity and insulin resistance are common within TIIDM and it is becoming a widespread liver condition globally. This study evaluated the prevalence of NAFLD patients who also had type II diabetes. Methods: The demographic data (name, age, body mass index (BMI), gender, occupation, duration of TIIDM, and treatment taking for TIIDM), as well as the results of the tests for these enzymes, were also recorded. Alanine transaminase (ALT) and Aspartate transaminase (AST) levels, as well as abdominal ultrasound findings of the liver, were recorded in a proforma after informed consent for a total of 200 Type II diabetic patients. Using SPSS, the data were analyzed, and stratified groups were subjected to the Chi-square tests. Results: There was a significant difference (p&lt;0.05) observed in NAFLD patients of TIIDM concerning age, gender, BMI, treatment, occupation, and duration of diabetes. The sample size consisted of 200 patients of which 111 (55.5%) were men and 89 (44.5%) were women. Patients ranged in the age range of 40-70 years old, with a mean age of 55.08 ± 8.98 years and a mean BMI of 29.69±4.04, respectively. It was concluded that 64% of cases with diabetes mellitus had NAFLD. Conclusion: TIIDM is an independent risk factor for NAFLD so early screening, diagnosis, and appropriate treatment are mandatory to reduce the risk of NAFLD and its related complications.

Association between serum ferritin and uric acid levels and nonalcoholic fatty liver disease in the Chinese population.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Accumulating evidence suggests that serum ferritin and uric acid (UA) are strongly associated with the risk of NAFLD, but no consensus has been reached. We sought to demonstrate the association between serum ferritin, UA levels, and NAFLD risk in a large cohort study. We separated 2,049 patients into non-NAFLD and NAFLD groups. The NAFLD group had four subgroups based on serum ferritin and four subgroups based on UA quartile levels. We used binary logistic regression to evaluate the correlation between serum ferritin, UA, and NAFLD. Additionally, an area under the curve (AUC) of receiver operating characteristic analysis (ROC) was used to predict the diagnostic value of combined serum ferritin and UA for NAFLD. Serum ferritin and UA levels were higher in the NAFLD group compared with the non-NAFLD group. Serum lipid and liver transaminase concentrations were elevated with the increase of serum ferritin and UA. The logistic regression results showed an independent correlation between serum ferritin, UA, and NAFLD. In the NAFLD group, the AUC value of serum ferritin and UA was 0.771. Increased serum ferritin and UA levels are independent risk factors for NAFLD. Increased serum UA is a stronger risk factor for NAFLD than elevated serum ferritin. Serum ferritin and UA can be important predictors of NAFLD risk.

THU140 Triglyceride Glucose-body Mass Index Is A Reliable Surrogate Marker To Predict Non-alcoholic Fatty Liver Disease In Children And Adolescents

Abstract Disclosure: J. Yoon: None. K. Yi: None. Background: The triglyceride glucose (TyG) index is significantly associated with the presence of nonalcoholic fatty liver disease (NAFLD) and is a reliable insulin resistance (IR) surrogate marker. TyG index combined with body mass index (BMI) were reported to be superior to TyG index alone in predicting NAFLD in youths. Ultrasound fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting hepatitis in children with NAFLD. Objects: In this study, TyG-BMI detection ability was evaluated in children and adolescents with NAFLD diagnosed by US-FLI and compared with TyG index. We also analyzed the association between TyG-BMI and severity of NAFLD according to the US-FLI scores. Methods: Alanine aminotransferase (ALT) was used as the screening method for NAFLD (&amp;gt;26IU/L in boys and &amp;gt;22IU/L in girls), and US-FLI was performed on children who met these criteria. The US-FLI is a scoring system ranging 2-8 that evaluates based on intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. TyG index was calculated as ln(fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2), and TyG-BMI were calculated as TyG × BMI. The diagnostic value of TyG-BMI for NAFLD detection was evaluated based on area under the receiver operating characteristic curve (AUC). Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. The TyG-BMI was significantly correlated with AST (r=0.282, p=0.005), ALT (r=0.395, p&amp;lt;0.001), HOMA-IR (r=0.444, p&amp;lt;0.001), and US-FLI (r=0.557, p&amp;lt;0.001) after controlling for sex and age. Multiple linear regression analysis showed that TyG-BMI were significantly associated with ALT (β=0.156, p=0.024), HOMA-IR (β =0.247, p&amp;lt;0.001), US-FLI (β=0.366, p&amp;lt;0.001) after adjusting for confounders. TyG-BMI was independent risk factor for NAFLD (odds ratio: 1.13, 95% confidence interval: 1.041-1.228) after controlling sex and age. In the receiver operating characteristic analysis, the TyG–BMI index (AUC=0.994, p&amp;lt;0.001) showed a better performance for detection of NAFLD than the TyG index (AUC=0.834, p&amp;lt;0.001). Conclusions: TyG-BMI is associated with insulin resistance and severity of US-FLI in NAFLD. In addition, TyG-BMI was superior to TyG index alone in detecting NAFLD. TyG-BMI is expected to be useful in detecting NAFLD and predicting disease progression in children and adolescents. Presentation: Thursday, June 15, 2023

THU139 The Triglyceride-glucose Index Combined With Alanine Aminotransferase Is A Superior Predictor Of The Severity Of Nonalcoholic Fatty Liver Disease In Children And Adolescents

Abstract Disclosure: J. Yoon: None. I. Hwang: None. Background: The triglyceride–glucose (TyG) index is significantly associated with the presence of nonalcoholic fatty liver disease (NAFLD). Alanine aminotransferase (ALT) has been commonly used to screen for NAFLD. Ultrasound fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting NAFLD and accurately identifies histological severity. Objects: We hypothesized that the combination of TyG and ALT would increase the sensitivity and specificity in determining the severity of NAFLD. We evaluated the usefulness of a newly proposed TyG-ALT index for differentiating NAFLD severity and compared it with TyG index. Methods: ALT was used as the screening method for NAFLD (&amp;gt;26 IU/L in boys and &amp;gt;22 IU/L in girls), and the US-FLI was performed on children who met these criteria. US-FLI is a new scoring system ranging 2-8 based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. The TyG index and the TyG–ALT index were calculated as follows: TyG index=ln(fasting TG [mg/dL]×fasting glucose [mg/dL]/2) and TyG–ALT index= ln(fasting triglyceride [mg/dL]×fasting glucose [mg/dL]×ALT [IU/L]/2). Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. Multiple linear regression analysis showed that TyG-ALT index were significantly associated with US-FLI (β=0.356, p&amp;lt;0.001) after controlling for sex, age, and BMI. TyG-ALT index was independent risk factor for NAFLD (odds ratio: 4.218, 95% confidence interval: 1.366-13.020) after controlling for sex, age, and BMI. In the receiver operating characteristic analysis, the area under the curve (AUC) of TyG index was 0.681(p&amp;lt;0.001), 0.681(p&amp;lt;0.001), and 0.782(p&amp;lt;0.001), and AUC of TyG-ALT index was 0.797, (p&amp;lt;0.001), 0.797(p&amp;lt;0.001), and 0.813(p&amp;lt;0.001) in US-FLI ≥4, ≥5, and ≥6, respectively. Conclusions: The TyG–ALT index showed consistently superior detection ability than the TyG index at all severity levels of NAFLD. Further studies are needed to determine its potential role as a noninvasive method for NAFLD screening. Presentation: Thursday, June 15, 2023

Crohn´s disease is an independent risk factor for liver fibrosis in patients with inflammatory bowel disease and non-alcoholic fatty liver disease

Background and aimsControversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. MethodsCross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. ResultsThe prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001–1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001–1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78–8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87–0.98)). ConclusionsAlthough we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.

HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population.

This study aimed to investigate the correlation between homeostasis model assessment of insulin resistance (HOMA-IR) and non-alcoholic fatty liver disease (NAFLD) in the non-diabetic population and establish its diagnostic efficacy. This observational study involved participants divided into NAFLD and non-NAFLD groups, and baseline data were analyzed. Univariate and multivariate logistic regression analyses were used to correlate HOMA-IR with the risk of NAFLD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of HOMA-IR for NAFLD. Subgroup analyses of non-obese individuals were performed. Overall, 2234 non-diabetic participants were included. The HOMA-IR was significantly higher in the NAFLD group than in the non-NAFLD group. Multivariate logistic regression analysis showed that HOMA-IR was a strong and independent risk factor for NAFLD after correcting for confounding factors. The area under the ROC curve (AUC) value of HOMA-IR for predicting NAFLD was 0.792. In the non-obese non-diabetic population, HOMA-IR was an independent risk factor for increased risk of lean NAFLD after correcting for confounding factors. The AUC value of HOMA-IR for predicting lean NAFLD was 0.770. HOMA-IR is independently associated with the risk of NAFLD in the non-diabetic and non-obese non-diabetic populations and has good diagnostic value.

Influence of genetically predicted autoimmune diseases on NAFLD.

Non-alcoholic fatty liver disease (NAFLD), the emerging cause of end-stage liver disease, is the most common liver disease. Determining the independent risk factors of NAFLD and patients who need more monitoring is important. Two-Sample Mendelian randomization (MR) was performed in the analysis to investigate the causal association of different autoimmune diseases with NAFLD using summary level data. Genome-wide association study (GWAS) of 5 autoimmune diseases including celiac disease (CeD), Crohn's disease (CD), multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D) were selected for Instrument variables (IVs). NAFLD was included as outcome. After adjusting for confounding factors, genetic predisposition of CeD (OR= 0.973, [0.949,0.997], IVW p-value=0.026), MS (OR= 1.048, [1.012,1.085], IVW p-value= 0.008), RA (OR= 1.036, [1.006,1.066], IVW p-value=0.019), T1D (OR= 1.039, [1.002,1.079], IVW p-value= 0.041) is causally associated with NAFLD. No causal effect was found between CD and NAFLD. CeD itself may be a protective factor for NAFLD, the results of previous observational studies have been influenced by confounding factors, and the morbidity of NAFLD may be higher in patients with MS, RA, and T1D than in common populations, and monitoring the prevalence of NAFLD in these populations is considerable.

Controlled attenuation parameters to assess liver steatosis in obese patients with polycystic ovary syndrome.

This study was performed to investigate the changes and influencing factors of liver controlled attenuation parameter (CAP) in obese patients with polycystic ovary syndrome (PCOS), and to determine the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) in PCOS patients with obesity. Forty-one PCOS patients with obesity and twenty age- and body mass index (BMI)-matched control women without PCOS were enrolled in this study. General data, body composition, biochemical parameters, sex hormones, and liver CAP in the two groups were collected and compared. Liver CAP was measured using transient elastography. NAFLD was more common in the Obese PCOS group than in the control group (75.61% vs. 45.00%, P=0.018). Compared to the control group, the obese PCOS group showed apparent increases in alanine transaminase (ALT), aspartate transaminase (AST), CAP, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), totle testosterone (TT), free androgen index (FAI), fasting insulin (FIns), and homeostasis model assessment-insulin resistance (HOMA-IR), along with lower high-density lipoprotein cholesterol (HDL-C) and sex hormone binding globulin (SHBG) levels. In addition, as shown by Spearman analysis, liver CAP in PCOS patients with obesity had a positive correlation with ALT, AST, TG, TT, FAI, FIns, and HOMA-IR, and a negative correlation with SHBG. Logistic regression analysis showed that TG, TT, FIns, and HOMA-IR were risk factors for NAFLD, while TT was an independent risk factor for NAFLD in PCOS patients with obesity. PCOS patients with obesity had a significantly higher prevalence of NAFLD. Furthermore, in PCOS patients with obesity, liver CAP was associated with disorders of lipid metabolism, insulin resistance, and hyperandrogenemia, with elevated testosterone levels being an independent risk factor for NAFLD in PCOS patients with obesity.

Analysis of risk factors for non-alcoholic fatty liver disease in hospitalized children with obesity before the late puberty stage.

This study aimed to determine the clinical characteristics of obese pediatric non-alcoholic fatty liver disease (NAFLD) in central China and verify the applicability of some known risk factors for pediatric NAFLD before late puberty. This was a retrospective case-control study. A total of 1,029 inpatients at Wuhan Children's Hospital before the late puberty stage were enrolled in the study, including 815 children with obesity (non-NAFLD group) and 214 children with obesity and NAFLD (NAFLD group) diagnosed by liver ultrasound. Subgroup analyses were performed according to sex and puberty. The anthropometric indices and laboratory test data of these 1,029 children were sorted. After intergroup comparison, a logistic regression model was used to determine the risk factors for pediatric NAFLD. Significant risk factors for NAFLD were further tested using receiver operating characteristic (ROC) curves to evaluate their ability to predict an early diagnosis of NAFLD. The NAFLD group had a mean age of 11.03 ± 1.66, with 11.18 ± 1.66 and 10.27 ± 1.45 years for male and female children, respectively (p < 0.05 and p < 0.01, respectively). Even subdivided by both sex and puberty, raised body mass index (BMI), homeostatic model-insulin resistance, triglycerides, alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γ-GT) were still found in the non-NAFLD and NAFLD groups (p < 0.05 and p < 0.01, respectively). The results of logistic regression analysis showed that BMI (odds ratio [OR], 1.468;95% confidence interval [CI], 1.356-1.590; p<0.001) and ALT (OR, 1.073;95%CI, 1.060-1.087; P<0.001) were two most independent risk factors for NAFLD. The maximal OR for BMI was 1.721 (95% CI, 1.336-2.217). In the female group, the maximal OR of ALT was found to be 1.104 (95% CI, 1.061-1.148). Age and thyroid-stimulating hormone (TSH) and γ-GT levels were also risk factors, but they appeared only in some groups. The results of the ROC analysis showed that ALT was a better predictor of pediatric NAFLD than BMI. The maximum area under the ROC curve in six of the nine groups belongs to ALT. BMI, ALT, and age are risk factors for NAFLD in children with obesity before late puberty. BMI had the greatest exposure risk for NAFLD, and ALT had the highest predictive value for the diagnosis of NAFLD. At the stratified level, for exposure risk, age was specific to the male sex, TSH was specific to the early puberty stage, and γ-GT was specific to the female sex plus the prepuberty stage. On a stratified level, for the female sex, even with age stratification, BMI rather than ALT has a better ability for the diagnosis of NAFLD.

Association between hemoglobin glycation index and non-alcoholic fatty liver disease.

The hemoglobin glycation index (HGI) reflects biological variability in hemoglobin A1c. Even so, studies on the relationship between HGI and non-alcoholic fatty liver disease (NAFLD) are limited. Therefore, this study aimed to explore the relationship between HGI and NAFLD. In addition, the study also aimed to provide new methods to identify patients with a high risk for the development of NAFLD. This was a retrospective study based on physical examination data from Japan. Patients were divided into quartiles (Q1-Q4) according to their HGI level; the lowest quartile (Q1) was used as the reference group. Patents were also classified into two subgroups based on the presence or absence of NAFLD. Baseline characteristics between the groups were compared. Multivariate logistic regression analysis was used to investigate the association between the HGI and NAFLD. A mediation analysis examined the mediation relationship between HGI and NAFLD. Subgroup analyses were performed to the reliability of the results. A total of 14280 patients were eligible for inclusion in this study; 2515 had NAFLD. Patients in the NAFLD group had higher levels of HGI than patients in the non-NAFLD group. Increases in HGI correlated with an increased risk of NAFLD. After adjusting for confounding factors, the multivariate logistic regression analysis revealed that HGI was positively related to the prevalence of NAFLD. In addition, mediation analysis showed that body mass index (BMI) partly mediated the indirect impact of HGI on NAFLD preference. Subgroup analyses were performed according to age, sex, smoking status, and waist circumference. Our results indicated that HGI significantly correlated with NAFLD in patients with one of the following factors: age ≤60 years, BMI >28 kg/m2, female sex, a history of smoking, and abdominal obesity. HGI was an independent risk factor for NAFLD, and BMI partly mediated the association between HGI and NAFLD.

Helicobacter pylori infection increases the risk of nonalcoholic fatty liver disease in diabetic population.

The effect of Helicobacter pylori (H. pylori) on nonalcoholic fatty liver disease (NAFLD) in the population is still controversial. Diabetes and NAFLD are both metabolically related diseases, and no studies have classified the population to study the effect of H. pylori infection on NAFLD in diabetics. A population of people who were examined in the Taizhou Hospital Health Examination Center from 2017 to 2022 was included, and hematological indicators, body parameters, ultrasound data, and H. pylori detection by urea nitrogen test were collected from patients. All physical examination populations were divided into diabetic and non-diabetic populations. After multivariate logistic regression, H. pylori infection remained an independent risk factor for NAFLD in diabetics, but it had no significant effect on NAFLD in non-diabetic population. Additionally, there was a nonlinear relationship between glycosylated hemoglobin and H. pylori infection in diabetic population. Moreover, the incidence of NAFLD in diabetics increased with persistent H. pylori infection. In the diabetic population, H. pylori infection does increase the risk of developing NAFLD. Glycemic control and eradication of H. pylori infection may have positive implications for reducing the incidence of NAFLD in diabetic population.

The triglyceride and glucose index and risk of nonalcoholic fatty liver disease: A dose-response meta-analysis.

The triglyceride and glucose (TyG) index is associated with the risk of nonalcoholic fatty liver disease (NAFLD), but the dose-response relationship between them is still unknown. We conducted a comprehensive meta-analysis to study the dose-response association between the TyG index and the risk of NAFLD. We systematically searched the Cochrane Library, PubMed, and Embase databases until July 2022 for relevant studies. The robust error meta-regression method was used to investigate the dose-response association between the TyG index and NAFLD. Summary relative risks (ORs) and 95% CIs were estimated by using a random-effects model. A total of 4 cohort and 8 cross-sectional studies were included, with 28,788 NAFLD cases among the 105,365 participants. A positive association for the risk of NAFLD was observed for each additional unit of the TyG index with a linear association (p=0.82), and the summary OR was 2.84 (95% CI, 2.01-4.01). In the subgroup analyses, a stronger association of the TyG index with NAFLD was shown in females than in males (men: OR=2.97, 95% CI 2.55-3.46, women: OR=4.80, 95% CI 3.90-5.90, Psubgroup<0.001). The TyG index may be a novel independent risk factor for NAFLD beyond traditional risk factors. https://www.crd.york.ac.uk/prospero, identifier (CRD42022347813).

Management of non-alcoholic fatty liver disease patients with sleep apnea syndrome

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with sleep apnea syndrome (SAS). Many NAFLD patients have SAS, and obstructive sleep apnea hypopnea syndrome is also considered to be an independent risk factor for NAFLD, as it contributes to the progression of NAFLD via oxidative stress, lipid peroxidation, inflammation, and insulin resistance. This review aims to provide some recommendations for the management of NAFLD patients with SAS, including diet, exercise, weight loss, and continuous positive airway pressure. This review also highlights the importance of effective strategies in NAFLD prevention and treatment.

ODP181 Diabetes Mellitus and Advanced Liver Fibrosis – is Cirrhosis Reversible and Who Should We Screen?

Abstract Recent evidence shows an association between type 2 diabetes mellitus (T2DM) and liver steatosis, fibrosis, and hepatocellular carcinoma. Studies suggest that improved glycemic control, weight loss, and GLP-1 agonists may halt progression and even improve non-alcoholic fatty liver disease (NAFLD); however, little is known about the extent of improvement these factors have on liver fibrosis. ADA guidelines suggest only patients with T2DM or pre-DM and elevated liver enzymes (or fatty liver on ultrasound) should be evaluated for NAFLD and fibrosis. Three patients ages 65-71 with long-standing T2DM, HLD, obesity, and no history of liver disease or current alcohol use were followed in our diabetic clinic and referred for screening for liver steatosis and fibrosis. The transient elastography method (fibroscan) was used to determine the degree of liver fibrosis. On initial fibroscans, all three patients were found to have F4 scores consistent with liver cirrhosis. The first patient is a 71-year-old male with T2DM (BMI 37.5kg/m 2), treated with semaglutide, empagliflozin, glipizide, and insulin. Over two years, he experienced a 4-lb weight loss and improvement in HbA1c(7.8% to 7.1%). Repeat fibroscan after two years showed improved fibrosis score – F3 (11.6 kPa to 10.2 kPa), consistent with moderate fibrosis. The second patient is a 69-year-old female with T2DM (BMI 37.3kg/m 2) and transient mild LFT abnormalities, found to have cirrhosis on fibroscan – F4 score. She was managed with semaglutide, empagliflozin, metformin, and insulin; weight decreased 9-lbs over two years and HbA1c improved(10.8% to 7.8%). Repeat fibroscan showed improvement in fibrosis score to F2 (15.1 kPa to 8.9 kPa), and her LFT abnormalities resolved. The third patient is a 65-year-old male with T2DM (BMI 35kg/m 2). His initial fibroscan showed cirrhotic liver – F4 score. He was maintained on empagliflozin and dulaglutide- then switched to semaglutide. He experienced a 10-lb weight loss during this time and had a stable HbA1c(6.6%). Repeat fibroscan after one year showed improvement to F0-F1(11.3 kPa to 6.1 kPa) consistent with little to no liver scarring. These cases highlight two important factors: 1) ADA liver screening guidelines should be expanded to include obesity and dyslipidemia; and 2) advanced liver fibrosis in patients with diabetes is, to some degree, reversible. Not all of the patients initially met standard ADA screening criteria, mostly without elevated liver enzymes and no prior abnormal liver imaging. Yet, all were diabetic and obese with dyslipidemia, which are independent risk factors for NAFLD. Additionally, patients with improved glycemic control on GLP-1 treatment as well as some weight loss have promising results on repeat fibroscan. These findings may improve screening and management of diabetes-related liver disease. Further studies are needed to investigate to what extent GLP-1 agonists alone or in combination with glycemic control and weight loss contribute to these improvements. Presentation: No date and time listed

Effect of Liraglutide on Serum TSH Levels in Patients with NAFLD and its Underlying Mechanisms.

This study aimed to evaluate the effect of liraglutide on serum thyroid-stimulating hormone (TSH) levels in patients with type 2 diabetes mellitus (T2DM) and explore the underlying mechanisms via bioinformatics analysis. A total of 49 obese/overweight patients with T2DM received liraglutide during outpatient visits or hospitalization in the Department of Endocrinology. Meanwhile, the control group included 49 patients with T2DM but without nonalcoholic fatty liver disease (NAFLD) who were matched for age and sex (baseline from July 2016 to June 2021). Follow-up data on the last use of liraglutide were also retrieved. Age, sex, body mass index (BMI), and duration of diabetes were obtained from the participants' records. All patients were tested for biochemical markers hemoglobin A1c (HbA1c), alanine transaminase, aspartate transaminase, free triiodothyronine, free thyroxine (FT4), and TSH at baseline and follow-up. After adjusting for all factors with a p-value < 0.05, BMI, HbA1c, LDL, FT4, and TSH were identified as significant independent risk factors for NAFLD in the univariate analysis. Following liraglutide therapy (average time 16 months), these patients had significantly lower BMI, HbA1c, and TSH but higher high-density lipoprotein (HDL) levels than those in the baseline data (all p < 0.05), and further subgroup analysis stratified by duration of liraglutide use showed that the test for time trends had statistical differences in BMI and TSH but not in HbA1c and HDL. After the therapy, the NAFLD and NASH groups showed significantly decreased TSH levels after liraglutide therapy compared with the corresponding baseline data. Furthermore, the expression of THRB, which encodes TRβ, was significantly decreased in the NAFLD group, which may explain the thyroid hormone resistance-like manifestation in the clinical findings. In conclusion, liraglutide improves hepatic thyroid hormone resistance in T2DM with NAFLD, and restoration of impaired TRβ expression in NAFLD is a potential mechanism involved in the process of liraglutide therapy.