Controlled Attenuation Parameter Score Research Articles

Association between the skeletal muscle mass to visceral fat area ratio and metabolic dysfunction-associated fatty liver disease: A cross-sectional study of NHANES 2017-2018.

Previous studies have shown that sarcopenic obesity (SO) was associated with nonalcoholic fatty liver disease (NAFLD). However, research is limited in the context of the NAFLD renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) defined by updated diagnostic criteria. The aim of this study was to use the index skeletal muscle mass to visceral fat area ratio (SVR) to describe SO in a large and representative US population (National Health and Nutrition Examination Survey 2017-2018) of adults and investigate their association with MASLD. A total of 2087 individuals were included in the analysis. SVR was calculated according to the measurement of dual-energy x-ray absorptiometry and MASLD was diagnosed with controlled attenuation parameter scores and cardiometabolic risk factors. SVR was divided into tertiles. Logistic regression adjusted for confounders was used to evaluate the association between SVR and MASLD. Several sensitivity analyses were performed to test the robustness of our findings. In a multivariate logistic regression analysis, a significant association between SVR and MASLD was shown (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 1.31-7.39, p = .010 for middle levels of SVR; OR: 3.82, 95% CI: 1.45-10.08, p = .007 for lowest levels of SVR). The sensitivity analyses confirmed that the association was robust. Our findings imply that decreased SVR is linked to MASLD.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

The prevalence and severity of MASLD in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes, and assessed which clinical features are most important in predicting MASLD severity. 453 individuals with type 1 diabetes (41.6±15.0 years, 64% female, BMI 25.4±4.2kg/m2, HbA1c 55.6±12mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥ 280.0dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥ 8.0kPa). A machine-learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis. The prevalence of hepatic steatosis and fibrosis was 9.5% [95% CI 6.8-12.2] and 3.5% [95% CI 1.8-5.2]. Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs. 15.0 [IQR 6.0-27.0] years) and individuals were older and had a higher BMI (mean 27.8 ±5.2 vs. 25.3 ±4.1kg/m2), and a higher CAP score (mean 211.4±51.7 dB/m vs. 241.4±75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean± standard deviation (SD) area under the curve of 0.73±0.03. Individuals with type 1 diabetes and high blood pressure, older age, BMI and duration of disease could be considered at high-risk for developing MASLD.

The effect of soy isoflavones on non-alcoholic fatty liver disease and the level of fibroblast growth factor-21 and fetuin A

A two-arm randomized open labeled controlled clinical trial was conducted on 50 patients with non-alcoholic fatty liver disease (NAFLD). Subjects were randomized to either receive two tablets of soy isoflavone (100 mg/day) or placebo. At week 12, the serum levels of alanine amino transferase (ALT), aspartate amino transferase (AST) and controlled attenuation parameter (CAP) score were significantly decreased only in the soy isoflavone group (P < 0.05). A significant decline in the gamma glutamyl transferase (GGT) level was observed only in the placebo group (P = 0.017). A significant increase in the serum level of fetuin A was shown in both groups at the end of the trial with a significantly greater increment in the soy isoflavone group compared to the placebo group (P < 0.05). The changes in the serum level of FGF-21 were not significant in any of the two groups. Steatosis grade significantly improved only in the soy isoflavone group (P = 0.045). There was no significant change in the fibrosis grade in the groups. Soy isoflavone intake led to a decrease in ALT, AST, CAP score, steatosis grade and an increase in the level of fetuin A. However, no significant changes were observed in the fibrosis grade and serum levels of GGT and FGF-21.

Non-invasive assessment of hepatic steatosis by ultrasound-derived fat fraction in individuals at high-risk for metabolic dysfunction-associated steatotic liver disease.

Given the increasing number of individuals developing metabolic dysfunction-associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound-derived fat fraction (UDFF) for hepatic steatosis in high-risk individuals. A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures during a single screening visit in Rome, Italy. Hepatic steatosis was defined by controlled attenuation parameter (CAP) or ultrasound-based Hamaguchi's score. UDFF performance for hepatic steatosis was estimated by the area under the receiver operating characteristic curve (AUC). Overall, median (IQR) UDFF was 12% (7-20). UDFF was positively correlated with CAP (ρ=0.73, p<0.0001) and Hamaguchi's score (ρ=0.79, p<0.0001). Independent predictors of UDFF were circulating triglycerides, alanine aminotransferase (ALT), and ultrasound-measured visceral adipose tissue (VAT). UDFF AUC was 0.89 (0.85-0.93) and 0.92 (0.88-0.95) for CAP- and ultrasound-diagnosed hepatic steatosis, respectively. UDFF AUC for hepatic steatosis was higher than those of fatty liver index (FLI), hepatic steatosis index (HSI), CAP-score (CAPS), and ALT (p<0.0001). Lower age, ALT, and VAT were associated with discordance between UDFF and ultrasound. UDFF may be a simple and accurate imaging biomarker to assess hepatic steatosis and monitor changes in hepatic fat content over time or in response to therapeutic interventions beyond clinical trials.

Barriers to Exercise in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Patient Survey.

Although adequate physical activity is an essential component of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD), the majority of people with MASLD do not engage in regular exercise and lead sedentary lifestyles. We aimed to identify perceived barriers to exercise and to examine awareness about the role of exercise in the treatment of MASLD. Individuals aged 18 years and above were recruited from a hepatology outpatient clinic. MASLD severity was assessed using controlled attenuation parameter (CAP) and transient elastography (TE) determined liver stiffness measurement (LSM) for the severity of hepatic steatosis and fibrosis, respectively. An online questionnaire was administered to record self-reported exercise patterns, barriers to exercise, and knowledge regarding effectiveness of different types of exercise for MASLD. Eighty-one participants (57% female) with a mean age of 55.3 ± 13.4 years and a mean body mass index (BMI) of 33.8 ± 6.4 answered the questionnaire. The mean CAP score was 335.7 ± 47.8 dB/m, and the median LSM was 12.45 kPa. While most patients (83%) considered MASLD to be a serious health concern, 73% did not achieve the recommended exercise levels of ≥ 150 min of moderate-intensity physical activity per week, and 54% were unsure about the role of exercise in the treatment of MASLD. Commonly reported barriers to exercise included physical and mental health issues (57%), lack of time (43%), lack of enjoyment in exercising (31%), fatigue caused by exercise (24%), and others (25%). Most participants with MASLD were unaware of the role of exercise as a potential treatment option and were not achieving recommended exercise levels. Inadequate time, physical and mental health problems, lack of enjoyment in exercise, and fatigue were major barriers.

Predictors of controlled attenuation parameter in metabolic dysfunction.

Hepatic fat content can be non-invasively estimated by controlled attenuation parameter (CAP) during transient elastography. The aim of this study was to examine the determinants and predictors of CAP values in individuals with metabolic dysfunction. We enrolled 1230 consecutive apparently healthy individuals (Liver-Bible-2022 cohort) with ≥3 metabolic dysfunction features. CAP was measured by Fibroscan. CAP determinants and predictors were identified using backward stepwise analysis and introduced in generalized linear models. Participants were predominantly males (82.9%), mean age was 53.8±6.4years, 600 (48.8%) had steatosis (CAP≥275dB/m), and 27 had liver stiffness measurement (LSM)≥8kPa. CAP values correlated with LSM (p<10-22). In multivariable analysis, fasting insulin and abdominal circumference (AC) were the main determinants of CAP (p<10-6), together with body mass index (BMI; p<10-4), age, diabetes, triglycerides, ferritin, and lower HDL and thyroid stimulating hormone (TSH; p<0.05 for all). In a subset of 592 participants with thyroid hormone measurement, we found an association between higher free triiodothyronine levels, correlating with lower TSH, and CAP values, independent of TSH and of levothyroxine treatment (p=0.0025). A clinical CAP score based on age, BMI, AC, HbA1c, ALT, and HDL predicted CAP≥275dB/m with moderate accuracy (AUROC=0.73), which was better than that of the Fatty Liver Index and of ALT (AUROC=0.70/0.61, respectively) and validated it in multiple cohorts. Abdominal adiposity and insulin resistance severity were the main determinants of CAP in individuals with metabolic dysfunction and may improve steatotic liver disease risk stratification. CAP values were modulated by the hypophysis-thyroid axis.

A scientifically validated combination of garcinol, curcuminoids, and piperine for mild to moderate nonalcoholic steatohepatitis patients-results from a randomized, double-blind, placebo-controlled study.

Garcinol is a naturally occurring compound from the fruit rind of the Garcinia indica, with antioxidant, anti-inflammatory, and anticancer properties. Curcuminoids are the active molecule from the rhizome of Curcuma longa, studied extensively for its health benefits as an anti-inflammatory and antioxidant activities. Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic steatohepatitis characterized by liver fat and inflammation. To evaluate the clinical efficacy and safety of Garcinol, Curcuminoids and piperine (GCP) combination in patients with mild to moderate NASH in a randomized, double-blind, placebo-controlled study. The patients received one tablet (450 mg) of GCP containing garcinol-50 mg, curcuminoids -250 mg and piperine 5 mg or a placebo (450 mg of microcrystalline cellulose) twice daily for 90 days. Changes in circulating aspartate aminotransferase (AST), alanine transaminase (ALT) levels, liver stiffness measurement (LSM), and controlled attenuation parameter (CAP) using Fibroscan were compared from baseline to day 90. Anthropometric parameters, serum levels of lipids, Interleukin (IL-6), hsCRP, and adiponectin were estimated. Safety was evaluated by laboratory parameters and by monitoring adverse events. Seventy-two patients were randomized and 63 (GCP = 32, Placebo = 31) completed the study. The mean age of the patients was 48.3 ± 8.7 years (36 males and 27 females). The mean reduction in AST (U/L) was 9.53 in GCP and 3.16 in placebo (p < 0.001) and that of ALT (U/L) was 13.47 in GCP and 7.43 in Placebo (p = 0.002). The liver stiffness and CAP scores showed a better reduction in GCP (0.56 kPa and 12.38 db/m) compared to placebo (0.064 kPa and 10.42 db/m) p < 0.05. Consequently, the noninvasive Fibroscan-AST (FAST) score reduction was also found to be significant in GCP compared to placebo. Additionally, body weight, lipid levels, hsCRP, and IL-6 in serum decreased, while adiponectin levels increased in GCP-supplemented participants compared to placebo. The combination of garcinol and curcuminoids was well tolerated with no significant changes in hematological and clinical laboratory parameters during the 90-day supplementation. Our results suggest that GCP could be a possible supplement for the management of NASH.Clinical trial registration: https://clinicaltrials.gov/, identifier CTRI/2019/11/022147.

Case-control analysis of venous thromboembolism risk in non-alcoholic steatohepatitis diagnosed by transient elastography.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Studies have shown a strong association between non-alcoholic steatohepatitis (NASH) cirrhosis and portal vein thrombosis. Specifically, there is paucity of data on the association of NASH and venous thromboembolism (VTE), with one such study predicting a 2.5-fold increased risk for VTE compared to other liver diseases in hospitalized patients. The mechanism is believed to be a hepatocellular injury, which causes a chronic inflammatory state leading to the unregulated activation of procoagulant factors. There has been no prior analysis of the degree of steatosis and fibrosis (measured using transient elastography, commonly known as FibroScan) in NASH and its association with VTE. To examine the association between the degree of hepatic steatosis and fibrosis, quantified by transient elastography, and the incidence of VTE in patients with NASH. In our case-control study, we included patients with a documented diagnosis of NASH. We excluded patients with inherited thrombophilia, hemoglobinopathy, malignancy, alcohol use disorder, autoimmune hepatitis, and primary biliary cirrhosis. The collected data included age, demographics, tobacco use, recreational drug use, medical history, and vibration controlled transient elastography scores. VTE-specific data included the location, type of anticoagulant, need for hospital stay, and history of VTE recurrence. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate to severe) based on the controlled attenuation parameter score. Fibrosis was classified based on the kilopascal score and graded as F0-F1 (Metavir stage), F2, F3, and F4 (cirrhosis). χ2 and Mann-Whitney U tests were used for the qualitative and quantitative variable analyses, respectively. Furthermore, we performed a logistic regression using VTE as the dependent variable. A total of 415 patients were analyzed, and 386 met the inclusion criteria. 51 and 335 patients were included in the VTE and non-VTE groups, respectively. Patients with VTE had a mean age of 60.63 years compared to 55.22 years in the non-VTE group (P < 0.014). Patients with VTE had a higher body mass index (31.14 kg/m² vs 29.30 kg/m²) and a higher prevalence of diabetes mellitus (29.4% vs 13.1%). The history of NASH was significantly higher in the VTE group (45.1% vs 30.4%, P < 0.037). Furthermore, moderate-to-severe steatosis was significantly higher in the VTE group (66.7% vs 47.2%, P < 0.009). Similarly, the F2-F4 fibrosis grade had a prevalence of 58.8% in the VTE group compared to 38.5% in the non-VTE group (P < 0.006). On logistic regression, using VTE as a dependent variable, diabetes mellitus had an odds ratio (OR) =1.702 (P < 0.015), and F2-F4 fibrosis grade had an OR = 1.5 (P < 0.033). Our analysis shows that NASH is an independent risk factor for VTE, especially deep vein thrombosis. There was a statistically significant association between the incidence of VTE, moderate-to-severe steatosis, and fibrosis. All hospitalized patients should be considered for medical thromboprophylaxis, particularly those with NASH.

Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

Predictive Algorithm for Hepatic Steatosis Detection Using Elastography Data in the Veterans Affairs Electronic Health Records

Background and AimsNonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans’ Affairs hospital.MethodsWe identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018–6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used to identify predictors of NAFLD. To identify a CAP threshold for HS detection, receiver operating characteristic analysis was applied using liver biopsy, MRI, and ultrasound as the gold standards.ResultsThe cohort was racially/ethnically diverse (26% Black/African American; 20% Hispanic). Significant positive predictors of elevated CAP score included diabetes, cholesterol, triglycerides, BMI, and self-identifying as Hispanic. Our predictions of CAP scores using this model strongly correlated (r = 0.61, p < 0.001) with actual CAP scores. The NAFLD model was validated in an independent Veteran cohort and yielded a sensitivity of 82% and specificity 83% (p < 0.001, 95% CI 0.46–0.81%). The estimated optimal CAP for our population cut-off was 273.5 dB/m, resulting in AUC = 75.5% (95% CI 70.7–80.3%).ConclusionOur HS predictive algorithm can identify at-risk Veterans for NAFLD to further risk stratify them by non-invasive tests and link them to sub-specialty care. Given the biased referral pattern for VCTEs, future work will need to address its applicability in non-specialty clinics.Graphical Proposed clinical algorithm to identify patients at-risk for NAFLD prior to fibrosis staging in Veteran.

OR15-06 Measuring Hepatic Steatosis With Transient Elastography In Adolescents With Obesity

Abstract Disclosure: D. Sundararajan: None. J.S. Lo: None. N. Morelli: None. Y. Garcia-Reyes: None. M.A. Ware: None. H. Rahat: None. S. Sundaram: None. C. Severn: None. L.L. Pyle: None. E. Tas: None. M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Amino Corp. Obesity affects nearly 20% of adolescents in the United States. Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity, affecting between 40-70% of youth with obesity, thus approximately 10% of United States youth. Traditional diagnostic methods for NAFLD are expensive or invasive, and recently, transient elastography has been used to diagnose hepatic steatosis (HS). We sought to determine if transient elastography accurately diagnosed HS as compared to MRI in adolescents with obesity. Baseline data from adolescents (age 12-18 years) with obesity studied in 3 clinical trials were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed with 2 methods: MRI proton density fat fraction and transient elastography controlled attenuation parameter (CAP) score. Demographics, anthropometrics, liver scans and fasting serum laboratory measures were collected. HS was defined as MRI fat fraction ≥ 5.0%. Group data means, standard deviation, and ranges were calculated, and CAP for those with and without HS by MRI were compared with Mann Whitney U tests. Receiver operator curves (ROC) for CAP were generated based on MRI-determined HS. Data from 84 adolescents (age 15.6 ± 1.4 years, BMI 36.5 ± 5.96 kg/m2, 81% female) were included. Fifty-one had HS by MRI, with liver fat % different by HS status [9.3 (6.7, 14.0)% HS vs 3.1 (2.2, 3.9); p &amp;lt; 0.001]. CAP scores were different by MRI based on HS status [293 (267, 325) HS vs 267 (248, 282); p = 0.012]. With the recommended CAP cutoff for HS of 241, there was only a 59% concordance of HS status between the MRI and CAP. For CAP, ROC for HS was significant (r = 0.66, p = 0.012) and the Youden index had a sensitivity of 70.0% (56.3-80.9) and a specificity of 62% (42.3-74.5) at a CAP score of &amp;gt; 270. Additionally, BMI was not significantly related to hepatic fat (by MRI), AUC (0.44, 0.69, p-value = 0.323), or to CAP-determined HS, AUC 0.613 (0.425-0.802, p-value = 0.2686). In adolescents with significant obesity, the transient elastography CAP is not an accurate measure of HS compared to MRI. A CAP score of 270 to identify HS is higher than previously described in pediatrics, but may be needed in youth with obesity to improve accuracy. Presentation: Friday, June 16, 2023

Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial

HU6 is a controlled metabolic accelerator that is metabolised in the liver to the mitochondrial uncoupler 2,4-dinitrophenol and increases substrate utilisation so that fat and other carbon sources are oxidised in the body rather than accumulated. We aimed to assess the safety and efficacy of HU6 compared with placebo in people with non-alcoholic fatty liver disease (NAFLD) and high BMI. This randomised, double-blind, placebo-controlled, phase 2a trial was done at a single community site in the USA. Adults (aged 28-65 years) with a BMI of 28-45 kg/m2, a FibroScan controlled attenuation parameter score of more than 270 decibels per metre, and at least 8% liver fat by MRI-proton density fat fraction (MRI-PDFF) were randomly assigned (1:1:1:1) to receive, under fasting conditions, either once-daily HU6 100 mg, HU6 300 mg, HU6 450 mg, or matching placebo by oral administration for 61 days. Randomisation was blocked (groups of four) and stratified by baseline glycated haemoglobin (<5·7% vs ≥5·7%; 39 mmol/mol). All participants and study personnel involved with outcome assessments were masked to treatment assignment. The primary endpoint was the relative change in liver fat content from baseline to day 61, as assessed by MRI-PDFF, and was analysed in the full analysis set (FAS), which comprised all participants who were randomly assigned, received at least one dose of treatment, and had less than 4·5 kg of weight gain or weight loss from the time of screening to day 1 of treatment. The safety population included all participants who were randomly assigned and received at least one dose of study drug. This study was registered at ClinicalTrials.gov, NCT04874233, and is complete. Between April 28, 2021, and Nov 29, 2021, 506 participants were assessed for eligibility and 80 adults (39 [49%] women and 41 [51%] men) were enrolled and randomly assigned to placebo (n=20), HU6 150 mg (n=20), HU6 300 mg (n=21), or HU6 450 mg (n=19). One participant in the HU6 450 mg group was excluded from the FAS due to weight gain. Relative mean change in liver fat content from baseline to day 61 was -26·8% (SD 17·4) for the HU6 150 mg group, -35·6% (13·8) for the HU6 300 mg group, -33·0% (18·4) for the HU6 450 mg group, and 5·4% (19·8) for the placebo group. Three people treated with HU6 (two treated with 150 mg and one treated with 300 mg) and two people treated with placebo discontinued treatment due to treatment-emergent adverse events (TEAEs). No serious TEAEs were reported. In those treated with HU6, flushing (19 [32%] participants), diarrhoea (15 [25%] participants), and palpitations (seven [12%] participants) were the most frequently reported TEAEs (in the placebo group, two [10%] participants had flushing, none had diarrhoea, and one [5%] had palpitations). There were no deaths. HU6 could be a promising pharmacological agent for treating patients with obesity and NAFLD and its metabolic complications. Rivus Pharmaceuticals.

The Efficacy of Anthropometric Indicators in Predicting Non-Alcoholic Fatty Liver Disease Using FibroScan® CAP Values among the Taiwanese Population.

The controlled attenuation parameter (CAP) measurement obtained from FibroScan® is a low-risk method of assessing fatty liver. This study investigated the association between the FibroScan® CAP values and nine anthropometric indicators, including the abdominal volume index (AVI), body fat percentage (BFP), body mass index (BMI), conicity index (CI), ponderal index (PI), relative fat mass (RFM), waist circumference (WC), waist-hip ratio (WHR), and waist-to-height ratio (WHtR), and risk of non-alcoholic fatty liver disease (fatty liver). We analyzed the medical records of adult patients who had FibroScan® CAP results. CAP values <238 dB/m were coded as 0 (non- fatty liver) and ≥238 dB/m as 1 (fatty liver). An individual is considered to have class 1 obesity when their body mass index (BMI) ranges from 30 kg/m2 to 34.9 kg/m2. Class 2 obesity is defined by a BMI ranging from 35 kg/m2 to 39.9 kg/m2, while class 3 obesity is designated by a BMI of 40 kg/m2 or higher. Out of 1763 subjects, 908 (51.5%) had fatty liver. The BMI, WHtR, and PI were found to be more strongly correlated with the CAP by the cluster dendrogram with correlation coefficients of 0.58, 0.54, and 0.54, respectively (all p < 0.0001). We found that 28.3% of the individuals without obesity had fatty liver, and 28.2% of the individuals with obesity did not have fatty liver. The BMI, CI, and PI were significant predictors of fatty liver. The BMI, PI, and WHtR demonstrated better predictive ability, indicated by AUC values of 0.72, 0.68, and 0.68, respectively, a finding that was echoed in our cluster group analysis that showed interconnected clustering with the CAP. Therefore, of the nine anthropometric indicators we studied, the BMI, CI, PI, and WHtR were found to be more effective in predicting the CAP score, i.e., fatty liver.

Dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2017-2018.

Whether there is an association between dietary choline intake and non-alcoholic fatty liver disease (NAFLD) in American adults remains unclear. Data came from the National Health and Nutrition Examination Survey 2017-2018. Choline intake was defined by the mean amounts of two 24 h dietary recalls, and choline intake was categorized into three groups according to the quartiles: inadequate (<P25), average (P25-P75), and optimal (>P75). Hepatic steatosis was assessed with FibroScan®, in which VCTE was employed with controlled attenuation to derive the controlled attenuation parameter (CAP), and NAFLD was defined as a CAP score ≥285 dB/m. Multivariable linear regression was performed to assess the linear relationship between choline intake and CAP. Multivariable logistics regression models were conducted to assess the association between choline intake status and NAFLD in the final sample and subgroup analysis was then performed in men and women. The amount of dietary choline was inversely associated with CAP score (β = -0.262, 95% CI: -0.280, -0.245). Compared to inadequate choline intake, optimal choline intake was related to a lower risk of NAFLD (OR: 0.705, 95% CI: 0.704-0.706) in the final sample. Subgroup analysis by gender revealed that the highest choline intake status was associated with a lower risk of NAFLD both in females (OR: 0.764, 95% CI: 0.762-0.766), and males (OR: 0.955, 95% CI: 0.953-0.958) when compared to the lowest choline intake. With the latest NHANES data, we found that higher dietary choline was associated with a lower risk of NAFLD in American adults, and such a relationship exists in both females and males.

Cardiac Structure and Function in Patients With Obesity and Non-alcoholic Fatty Liver Disease.

Introduction Non-alcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide. The global prevalence of NAFLD is expected to increase dramatically with the increasing prevalence of obesity and type 2 diabetes mellitus (T2DM). The role of NAFLD as a cardiometabolic risk factor or component of metabolic syndrome on the heart remains unclear. Thus, the independent effect of NAFLD on structural and functional heart parameters warrants validation. Our goal was to study cardiac structure and function in subjects with obesity and NAFLD. Methods A total of 164 patients were examined in this cross-sectional study. Participants were grouped based on BMIand the presence or absence of abdominal obesity (AO) and/or NAFLD. The subjects were divided into four groups:group 1: normal BMI without AO and NAFLD; group 2: BMI ≥ 25 kg/m2or AO without NAFLD; group 3: BMI ≥ 25 kg/m2and AO without NAFLD;group 4: patients with BMI ≥ 25 kg/m2,AO, and NAFLD. We performed a thorough clinical examination, a biochemical blood analysis, and echocardiography. Indices of liver steatosis and fibrosis were calculated. A study of liver assessment of the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) was conducted. Statistical analysis was performed using IBM SPSS Statistics version 26 (IBM Corp., Armonk, NY). Results The mean age of the participants was 35.0 (31.0-38.5) years. We found a higher frequency of multiple cardiometabolic risk factors in the general cohort. However, on comparing groups 3 and 4, we found a higher frequency of hyperinsulinemia, homeostatic model assessment of insulin resistance (HOMA-IR), and obesity (p < 0.05). To assess the role of NAFLD independent of obesity, we conducted further analyses after adjusting for BMI. Among patients with NAFLD, we observed a similar trend for parameters of carbohydrate metabolism (p < 0.005).In individuals with NAFLD, an increase in left atrial (LA) volume, interventricular septal (IVS) thickness, and left ventricular (LV) myocardial mass, and a decrease in LV ejection fraction and LV stroke volume index were found (p < 0.005). The hepatic steatosis index (HSI) correlated with LA volume, LV end-systolic volume (ESV) and LV end-diastolic volume (EDV), stroke volume, and LV myocardial mass. An association between an increase in CAP score and an increase in the LA volume, stroke volume index, IVS thickness, LV myocardial mass, and the values of LSM with an increase in the LA volume was established. Conclusion The presence of NAFLD without cardiovascular disease and diabetes mellitus revealed an association with the structural and functional parameters of the heart.The results of this study can also be used to improve the effectiveness of a comprehensive assessment of patients and to develop strategies for the primary and secondary prevention of heart failure with preserved ejection fraction in NAFLD.

Bioactive oxylipins in type 2 diabetes mellitus patients with and without hypertriglyceridemia.

Dyslipidemia, in particular elevated triglycerides (TGs) contribute to increased cardiovascular risk in type 2 diabetes mellitus (T2DM). In this pilot study we aimed to assess how increased TGs affect hepatic fat as well as polyunsaturated fatty acid (PUFA) metabolism and oxylipin formation in T2DM patients. 40 patients with T2DM were characterized analyzing routine lipid blood parameters, as well as medical history and clinical characteristics. Patients were divided into a hypertriglyceridemia (HTG) group (TG ≥ 1.7mmol/l) and a normal TG group with TGs within the reference range (TG < 1.7mmol/l). Profiles of PUFAs and their oxylipins in plasma were measured by gas chromatography and liquid chromatography/tandem mass spectrometry. Transient elastography (TE) was used to assess hepatic fat content measured as controlled attenuation parameter (CAP) (in dB/m) and the degree of liver fibrosis measured as stiffness (in kPa). Mean value of hepatic fat content measured as CAP as well as body mass index (BMI) were significantly higher in patients with high TGs as compared to those with normal TGs, and correlation analysis showed higher concentrations of TGs with increasing CAP and BMI scores in patients with T2DM. There were profound differences in plasma oxylipin levels between these two groups. Cytochrome P450 (CYP) and lipoxygenase (LOX) metabolites were generally more abundant in the HTG group, especially those derived from arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), γ-linolenic acid (γ-LA), and α-linolenic acid (α-LA), and a strong correlation between TG levels and plasma metabolites from different pathways was observed. In adult patients with T2DM, elevated TGs were associated with increased liver fat and BMI. Furthermore, these patients also had significantly higher plasma levels of CYP- and LOX- oxylipins, which could be a novel indicator of increased inflammatory pathway activity, as well as a novel target to dampen this activity.

Vibration Controlled Transient Elastography in Screening for Silent Liver Diseases.

The objective of this study was to screen for significant hepatic fibrosis or steatosis in asymptomatic, apparently healthy subjects by using Vibration-controlled transient elastography and controlled attenuation parameter (CAP). Prospectively, 433 asymptomatic apparently healthy adults were included. Fibroscan/CAP examination was performed for all of them. Subjects with liver stiffness measurement > 6 kPa or CAP >248 dB/m were further evaluated to assess underlying chronic liver disease. According to fibroscan/CAP examination, subjects were classified into four subgroups: normal (119) with CAP score of 215.85 ± 24.81 dB/m and fibrosis score of 4.47 ± 0.81 kPa, subjects with steatosis only 133 with CAP score of 309.41 ± 42.6 dB/m and fibrosis score of 4.74 ± 0.82 kPa, subjects with both steatosis and fibrosis 95 with CAP score of 318.20 ± 39.89 dB/m and fibrosis score of 7.92 ± 2.58 kPaand subjects with fibrosis only 86 with CAP score of 213.48 ± 22.62 dB/m and fibrosis score of 6.96 ± 1.11 kPa. S0 was present in 205 (47.3%), S1 in 48 (10.2%), S2 in 16 (3.7%) and S3 in 168 (38.8%) of studied subjects, whereas F0-1 was present in 371 (85.7%), F2 in 44 (10.16%), F3 in 16 (3.7%) subjects and F4 in only one (0.23%) subject. Subjects with both steatosis and fibrosis showed significantly higher transaminases, triglycerides and total cholesterol levels than other subgroups. Most asymptomatic, apparently healthy subjects (72%) have significant steatosis and fibrosis. Liver stiffness measurement and CAP might represent promising first-line noninvasive procedures to screen for silent liver diseases in the general population.

Exploring the Potential Performance of Fibroscan for Predicting and Evaluating Metabolic Syndrome using a Feature Selected Strategy of Machine Learning.

Metabolic syndrome (MetS) includes several conditions that can increase an individual's predisposition to high-risk cardiovascular events, morbidity, and mortality. Non-alcoholic fatty liver disease (NAFLD) is a predominant cause of cirrhosis, which is a global indicator of liver transplantation and is considered the hepatic manifestation of MetS. FibroScan® provides an accurate and non-invasive method for assessing liver steatosis and fibrosis in patients with NAFLD, via a controlled attenuation parameter (CAP) and liver stiffness measurement (LSM or E) scores and has been widely used in current clinical practice. Several machine learning (ML) models with a recursive feature elimination (RFE) algorithm were applied to evaluate the importance of the CAP score. Analysis by ANOVA revealed that five symptoms at different CAP and E score levels were significant. All eight ML models had accuracy scores > 0.9, while treebags and random forest had the best kappa values (0.6439 and 0.6533, respectively). The CAP score was the most important variable in the seven ML models. Machine learning models with RFE demonstrated that using the CAP score to identify patients with MetS may be feasible. Thus, a combination of CAP scores and other significant biomarkers could be used for early detection in predicting MetS.

1203-P: Elevated HOMA-IR and IL-6 in Pregnant Women with Metabolic-Dysfunction–Associated Fatty Liver Disease and Gestational Diabetes Mellitus

Background: It is uncertain whether biomarkers differ in singleton pregnant women with metabolic dysfunction-associated fatty liver disease (MAFLD) and gestational diabetes mellitus (GDM). Methods: A prospective cohort study was conducted. A FibroScan® was performed between 10-24 weeks. A controlled attenuation parameter score ≥233.5dB/m indicated MAFLD. GDM was diagnosed with IADPSG criteria. Between 24-30 weeks, fasting blood was collected to determine serum levels of tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6), fibroblast growth factor 21 (FGF-21), high molecular weight adiponectin (HMW-APN), glucose and insulin. HOMA-IR was calculated: [insulin (mU/L) × glucose (mmol/L)]/22.5. Four groups of control (no GDM/MAFLD), MAFLD only, GDM only, MAFLD &amp; GDM were formed. Biomarkers were analyzed by general linear models after log transformation, adjusted for age, body mass index, ethnicity and nulliparity. Results: Of 120 women, 47 were control, 37 MAFLD only, 14 GDM only and 22 MAFLD &amp; GDM. Compared to controls, MAFLD &amp; GDM had 1.8-fold higher HOMA-IR and IL-6, significantly elevated over GDM only and MAFLD only (Table 1). No significant differences in TNF-α, FGF-21 or HMW-APN occurred (Table 1). Conclusions: Significantly elevated HOMA-IR and IL-6 in pregnant women with MAFLD &amp; GDM suggests a more insulin resistant and inflammatory phenotype. Disclosure T.Y.L.Chai: None. D.Pasupathy: None. J.George: None. N.Cheung: None. Funding Diabetes Australia Research Program (Y21GCHEW)

1565-P: Relationship between Glycemic Control, Body Weight, and Nonalcoholic Fatty Liver Disease in Patients with Type 1 Diabetes

Increased body weight is a common risk factor for nonalcoholic fatty liver disease (NAFLD). Although the prevalence of overweight and obesity among patients with type 1 diabetes (T1D) is rising, most patients are still lean. Currently, little is known about the relationship between glycemic parameters, body weight and NAFLD in patients with T1D. In this study, we evaluated glycemic parameters in 200 participants with T1D (mean age 46.9±16.5 years, 55.5% females, mean diabetes duration 27.4±15.7 years, mean BMI 26.9±5.0 kg/m2) who underwent screening for NAFLD. We used transient elastography to measure controlled attenuation parameter (CAP) as an indicator of hepatic steatosis, and liver stiffness measurement (LSM) as an indicator of hepatic fibrosis. We assessed glycemic parameters by measuring A1C and collecting 3 months of continuous glucose monitoring (CGM) data. CAP score was found to be positively correlated with A1C (p=0.009) and BMI (p&amp;lt;0.001). Participants with NAFLD (CAP≥274 dB/m) had significantly higher A1C (p=0.025). Using CGM parameters, CAP positively correlated with average blood glucose (p=0.029) and Glucose Management Indicator (GMI) (p=0.008). CAP positively correlated with coefficient of glucose variability (CV) only in lean individuals (BMI≤25 kg/m2) (p=0.031), suggesting a link between blood glucose variability and hepatic steatosis in the absence of overweight or obesity. LSM score positively correlated with BMI (p&amp;lt;0.001), but not with A1C or CGM parameters. We conclude that poor glycemic control is associated with hepatic steatosis while high BMI is associated with increased risk of hepatic fibrosis in patients with T1D. Blood glucose variability is particularly associated with hepatic steatosis in lean patients with T1D. These results may suggest the need of evaluating uncontrolled patients with T1D for NAFLD, specifically those with high BMI and those with high glucose variability. Disclosure S.E.Dhaver: None. T.Salah: None. M.Al-badri: None. K.Kibaa: None. A.Khater: None. R.Mccarragher: None. F.Al-roomi: None. L.Demattos: None. O.Hamdy: Advisory Panel; Abbott Nutrition, Nemaura Medical, L-Nutra Inc., Twin Health, Consultant; Sanofi, Research Support; Novo Nordisk, Eli Lilly and Company, Gilead Sciences, Inc., Stock/Shareholder; Healthimation.