Screening For Non-alcoholic Fatty Liver Disease Research Articles

Diagnostic Performance of Greyscale Ultrasound in Detecting Fatty Liver Disease in a Type 2 Diabetes Population Using FibroScan as the Reference Standard.

Introduction Brightness mode ultrasound (B-mode US) and FibroScan (Echosens, Paris, France) are the two ultrasound methods often recommended for screening non-alcoholic fatty liver disease (NAFLD) in persons with type 2 diabetes mellitus (T2DM). This study assessed the diagnostic performance of B-mode US using FibroScan as the reference standard. Methods Persons with a known history of T2DM were invited to screen for NAFLD using B-mode US and FibroScan on separate days within a one-month period. Assessors of B-mode US and FibroScan were blinded to each other's findings. Both B-mode US and FibroScan independently assessed and graded each participant for the presence of NAFLD. Using the diagnostic test findings of FibroScan as a reference standard, the sensitivity and specificity of B-mode US were analyzed.The area under the receiver operating characteristic curve (AUROC) was analyzed using Jamovi (version 2.3.21). A multinomial logistic regression of the B-mode US and FibroScan in predicting NAFLD grade was also analyzed. Results A total of 171 participants were assessed. B-mode US detected NAFLD in T2DM patients with 63.6% sensitivity, 65.6% specificity, and 0.646 AUROC. Sensitivity and specificity in overweight and obese participants were 36-43% and 76-85%, respectively. Multinomial logistic regression demonstrated an insignificant statistical relationship between FibroScan and B-mode US in predicting grade 1 steatosis (p-value = 0.397), which was significantly affected by a higher BMI (p-value = 0.034) rather than a higher liver fibrosis level (p-value = 0.941). The logistic regression further showed a significant relationship between B-mode US and FibroScan in predicting steatosis grade 2 (p-value = 0.045) and grade 3 (p-value < 0.001), which was not significantly affected by BMI (p-value = 0.091). Conclusion B-mode US can replace FibroScan for severe steatosis; however, it cannot be used to screen for NAFLD in T2DM patients due to lower sensitivity for early detection in the overweight.

1261-P: Prevalence of Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Type 1 Diabetes

Nonalcoholic fatty liver disease (NAFLD) is a common comorbid condition in patients with type 2 diabetes. However, little is known about its prevalence among patients with type 1 diabetes (T1D). We used transient elastography to measure controlled attenuation parameter (CAP) as steatosis indicator and liver stiffness measurement (LSM) as fibrosis indicator. We evaluated 537 patients with T1D: age 49±16 years; 55% females; 81% non-Hispanic whites; BMI 27.6±5.5 kg/m2; diabetes duration 29±15.6 years; A1C 7.1±1.0%; total daily insulin (TDI) 49±28 U/day; ALT 19±10 IU/L; AST 22±8 IU/L. The prevalence of NAFLD (CAP≥274 dB/m) was 28.5% (95% CI 24.6-32.6) and fibrosis (LSM≥7 kPa) 8.4% (95% CI 6-11). Moreover, 4.1% (95%CI 2.6-6.2) of NAFLD had ≥F2 fibrosis (LSM ≥ 8.2 kPa) suggesting nonalcoholic steatohepatitis (NASH). Higher CAP positively correlated with higher BMI (p&amp;lt;0.001); diabetes duration (p&amp;lt;0.01); and TDI (p&amp;lt;0.001). It was common in males (OR 2.1, 95%CI 1.3-3.5, p&amp;lt;0.01). Among those with NAFLD, mean ALT was 21±11 IU/L (p=0.02), AST 22±7 IU/L, BMI 32.7±5.8 kg/m2, and waist circumference (WC) 103±15 cm. Among those with fibrosis, mean ALT was 23±10 IU/L (p=0.01), AST 24±7 IU/L (p=0.03), BMI 31.7±6.4 kg/m2 and WC 104±15 cm. Obesity (BMI &amp;gt;30 kg/m2) and larger WC (&amp;gt;102 cm in men, &amp;gt;88 cm in women) were associated with increased risk for hepatic steatosis (OR 3.1, 95% CI 1.6-6.0, p=0.001; OR 4.0, 95% CI 2.2-7.5, p&amp;lt;0.001, respectively). In conclusion, prevalence of NAFLD and liver fibrosis is considerable among patients with T1D, while liver enzymes are within normal range. Obesity and large waist circumference are associated with increased risk of hepatic steatosis. Independent predictors of NAFLD include: higher BMI, longer diabetes duration, higher TDI and male gender. Screening for NAFLD and liver fibrosis is advisable for patients with T1D irrespective of their liver enzymes, particularly in patients with higher BMI, longer diabetes duration or among those treated with larger insulin dose. Disclosure T.Salah: None. R.Mccarragher: None. L.Demattos: None. M.Tran: 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. S.Tomah: Employee; Altimmune. M.Al-badri: None. K.Kibaa: None. S.E.Dhaver: None. M.P.Curry: Advisory Panel; Mallinckrodt PLC, Alexion Pharmaceuticals, Inc., Albireo. M.Lai: None. Z.Jiang: Advisory Panel; Olix Pharmaceutical, Research Support; Pfizer Inc., Gilead Sciences, Inc. A.Khater: None.

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.

1366-P: Nonalcoholic Fatty Liver Disease in Young-Onset Type 2 Diabetes Mellitus—A New Epidemic?

The prevalence of young-onset type 2 diabetes mellitus (YOT2DM), defined as T2DM diagnosed in adults &amp;lt;45 years old, is steadily increasing. Nonalcoholic fatty liver disease (NAFLD) is common in people with T2DM but its prevalence in YOT2DM is unknown. We therefore hypothesized that NAFLD is an emerging health concern in this population. A total of 161 adults aged 35-44 years with and without T2DM, underwent screening for NAFLD with laboratory tests and imaging by elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Of these, 25 (16%) had YOT2DM and 136 (84%) did not have diabetes mellitus (noDM). While obesity was very prevalent in the cohort (53%), those with YOT2DM had a higher BMI (35±7 vs. 31±7 kg/m2, p&amp;lt;0.01), and reported comorbidities more frequently: hypertension (48% vs. 24%, p=0.02) and atherogenic dyslipidemia (76% vs. 54%, p=0.04). Hepatic (HOMA-IR 4.6±2.8 vs 2.6±1.9, P&amp;lt;0.01) and adipose tissue (6.5±5.1 vs 3.9±3.5, p=0.01) insulin resistance were worse in people with YOT2DM. Adiponectin, a reflection of proper adipose tissue function, was lower in YOT2DM (4.2±2.3 vs 6.2±3.5 μg/mL, p=0.02). Hepatic steatosis (CAP ≥274 dB/m) was prevalent in both groups but higher in people with YOT2DM (64% vs. 47%), but much lower in people without obesity or diabetes (27%; p&amp;lt;0.01). Male sex was associated with a significantly higher risk of hepatic steatosis (OR 3.7, 95% CI 1.5-9.2). The frequency of any fibrosis as measured by LSM (≥7.0 kPa) was 3-fold higher in YOT2DM compared to people without diabetes (12% vs. 4%, p=0.08). Every 1 unit increase in BMI elevated the risk of both steatosis and fibrosis by 20% (OR 1.2, 95% CI 1.03-1.3). Conclusion: Hepatic steatosis is highly prevalent in young-onset type 2 diabetes (YOT2DM) and is strongly influenced by obesity. Hepatic fibrosis is relatively common and affects 1 in 8 people with YOT2DM. These results warrant the need for larger and longer follow-up studies in this population. Disclosure A. Sharma: None. E. Godinez Leiva: None. R. Lomonaco: None. E. Valdez Saenz: None. A. Ortiz Rocha: None. S.A. Marangi: None. M.A. Gonzalez: None. S. Shrestha: None. S.S. Shetty: None. J.T. Budd: None. D. Barb: None. S. Kalavalapalli: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns.

1342-P: Are Plasma Aminotransferases of Value in Screening Patients with T2DM for NAFLD or Fibrosis?

The ADA recommends to screen for NASH and liver fibrosis individuals with type 2 diabetes (T2DM), obesity (OB) and/or elevated alanine aminotransferase (ALT). However, recent studies have questioned the clinical value of measuring ALT and AST for the detection of patients at risk of nonalcoholic fatty liver disease (NAFLD) or advanced liver fibrosis or cirrhosis. The aim of this study was to assess the clinical value of ALT and AST ≥40 IU/L, or their lower cut-offs ≥30 IU/L as recommended by recent AACE guidelines, to screen populations at risk. To this end, we recruited 714 participants (age: 56 ± 11 years, male: 42%; BMI: 30.8 ± 6.5 kg/m2; T2DM: 35%; A1c: 6.0 ± 1.2%) from primary care or endocrinology clinics, unaware of having NAFLD/fibrosis. Screening for NAFLD included laboratory tests and imaging with elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Elevated transaminases were more common in patients with vs. without T2DM, with ALT ≥40 IU/L occurring in 13% vs. 8% and AST in 9% vs. 3% of patients (both p&amp;lt;0.05). If using a cutoff of ≥30 IU/L: 25% vs. 18% and 20% vs. 13%; respectively (both p&amp;lt;0.05). Elevated ALT ≥30 IU/L was the highest in patients with T2DM and OB (n=164) vs. controls (without T2DM or OB; n=269; 27% vs 15%; p=0.02). The sensitivity for diagnosing steatosis by ALT or AST was very low, with ALT and AST ≥40 IU/L present in only 16% and 9%, respectively. However, steatosis by imaging (CAP) was often present if ALT or AST were high (81 and 90%, respectively). An ALT ≥40 IU/L was also not useful for diagnosing patients with fibrosis of any stage (LSM ≥7.0), missing the diagnosis in 63% of patients, and this did not improve when examining only those with more advanced fibrosis (≥F3) being elevated in only 40%. Conclusions: Plasma aminotransferases are of limited diagnostic value when screening patients with T2DM for NAFLD or fibrosis. This supports the ADA recent guidelines for using FIB-4 and additional noninvasive testing for screening. Disclosure A. Ortiz Rocha: None. E. Godinez Leiva: None. S. Kalavalapalli: None. R. Lomonaco: None. S.S. Shetty: None. S.A. Marangi: None. E. Valdez Saenz: None. S. Shrestha: None. M.A. Gonzalez: None. X. Chi: None. M.J. Gurka: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns. Funding National Institutes of Health (R01120331-01A1)

1367-P: Type 2 Diabetes Mellitus and Obesity Amplifies Nonalcoholic Fatty Liver Disease Risk with Age

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent in the general population with multiple known metabolic risk factors. There is limited evidence on the impact of age on the prevalence of hepatic steatosis and fibrosis, and their relationship to cardiometabolic risk factors. To this end, we recruited 761 patients 35-75 years of age, with and without T2DM, who underwent screening for NAFLD with laboratory tests and imaging by elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Patients were divided into 3 age groups: &amp;lt;45 years (young), 45-64 years (middle age), and ≥65 years old (older age), with results reported in this order. Of the 761 patients included, 21% (n=161) were young, 52% (n=397) middle age, and 27% (n=203) older. In the older age group, prevalence of obesity was lower (53% vs. 53% vs. 40%, p=0.01) but T2DM was higher (15% vs. 39% vs. 44%; p&amp;lt;0.01). Similarly, hypertension, atherogenic dyslipidemia, and use of antihypertensives and statins were more frequent in the older age group. Despite this, there were no differences in steatosis (CAP ≥274 dB/m: 50% vs. 54% vs. 52%, p=0.7). A marker of NAFLD disease activity (NIS4) worsened with increasing age (p&amp;lt;0.01). There was a trend for fibrosis (LSM≥7.0 kPa) to be higher in middle (11%) and older (8%) vs. younger (5%) age. After multivariable analysis (sex, race, ethnicity, BMI, A1c, cardiometabolic risk factors), BMI was associated with both steatosis and fibrosis in all age groups (p&amp;lt;0.01). There was a significant association between A1c as a continuous variable and steatosis only in the older age group (OR 2.8, 95% CI 1.6-4.9), while its association with fibrosis started at middle age (OR 1.3, 95% CI 1.1-1.7) and was stronger in older age (OR 1.8, 95% CI 1.01-3.2). Conclusion: Age was not associated with steatosis or fibrosis. BMI was the strongest predictor of hepatic steatosis and synergizes with T2DM for the development of fibrosis with age. Disclosure A. Sharma: None. E. Godinez Leiva: None. R. Lomonaco: None. E. Valdez Saenz: None. A. Ortiz Rocha: None. M.A. Gonzalez: None. S.A. Marangi: None. S. Shrestha: None. S.S. Shetty: None. J.T. Budd: None. S. Kalavalapalli: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns.

1606-P: Tg/HDL Ratio and Liver Fibrosis in Diabetic Patients at an Indian Tertiary Care Center

Introduction: According to the most recent International Diabetes Federation (IDF) atlas, there are 537 million persons worldwide who have diabetes. Indians had increased central adiposity and insulin resistance. Diabetes patients are more likely to develop Nonalcoholic Fatty Liver Disease (NAFLD) due to high insulin resistance. An increasingly sensitive indicator of insulin resistance is the TG/HDL ratio. Measuring liver stiffness helps diabetics predict progressive fibrosis. The current investigation uses fibro scans to evaluate the TG/HDL ratio and liver stiffness in diabetic patients. Methods: After receiving consent, 181 newly diagnosed diabetics underwent fibro scans to measure their liver stiffness. Participants who had already had thiazolidinedione treatment or lipid-lowering therapy were disqualified from the study. Results: The median stiffness ranged from 2.3 kpa to 34.8 kpa (8.0 kpa), and the median TG/HDL ratio ranged from 0.5 to 29.3 (4.5). The connection between the median stiffness and the TG/HDL ratio was 0.2. Further, 26.5% of participants (Liver stiffness measurement (LSM) &amp;gt; 9.1), 23.7% of subjects who were men, and 30% of subjects who were women, showed advanced fibrosis. Both men and women with LSM &amp;gt; 9.1 had high TG/HDL ratios, with a mean of 4.9 in the former group and 4.9 in the latter. These numbers were significantly higher than the TG/HDL cut-offs for predicting insulin resistance, which were 0.9 and 1.2 for females and males, respectively. Conclusion: TG/HDL ratio and NAFLD have previously been linked utilising ultrasonography in nondiabetic persons. The more precise and sensitive method for NAFLD screening is the fibro scan. Liver fibrosis is predicted by median stiffness. In the index research, there is a high incidence of advanced fibrosis, which is associated with the TG/HDL ratio. The TG/HDL ratio was high in all of the male and female individuals with advanced fibrosis. Disclosure A. Chandra: None. J. Dinkar: None. R. Ranjan: None.

Transgender Women with HIV Demonstrate Unique Non-Alcoholic Fatty Liver Disease Profiles.

Non-alcoholic fatty liver disease (NAFLD) prevalence and severity may be higher in people with human immunodeficiency virus (HIV) than the general population, and vary with sex and age. We explored NAFLD characteristics by gender. Adult transgender women (TW), cisgender women (CW), and cisgender men (CM) with HIV on antiretroviral therapy and without other known causes of liver disease underwent screening for NAFLD (2017-2020). Circulating factors associated with NAFLD were measured. Hepatic steatosis and fibrosis were assessed using transient elastography by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. Analysis of variance/Wilcoxon testing compared normally/non-normally distributed variables, respectively. Logistic regression evaluated factors associated with CAP and LSM. Participants (n=194) had median age 48 years and body mass index 28.3 kg/m2; 42% were CM, 37% TW, and 21% CW; 95% were non-white; and 16% had diabetes, 40% dyslipidemia, and 49% hypertension. NAFLD prevalence was 59% using CAP ≥248 dB/m (≥S1 steatosis), 48% using CAP ≥260 dB/m (≥S2 steatosis), and 32% using CAP ≥285 dB/m (≥S3 steatosis). Compared to CM and CW, TW had the highest median CAP scores, were more likely to have ≥S2 steatosis, and had the highest insulin resistance, interleukin-6, and fetuin-A values. TW off versus on gender-affirming hormone therapy (GAHT) had slightly higher median CAP scores. TW on GAHT had less hepatic steatosis than TW not on GAHT, although overall NAFLD severity was greater than expected for TW compared to CM and CW. The effects of estrogen supplementation and androgen deprivation on liver health in TW require further study.

Hepatálne zmeny obéznych pediatrických pacientov

Rationale: Non-alcoholic fatty liver disease (NAFLD) is emerging clinical issue in childhood and adolescent age. Present knowledge of NAFLD suggests an important role of genetic and environmental risk factors in the pathogenesis of the disease. Most of the patients are obese, however, NAFLD also occurs in the non-obese group and interestingly, in obese individuals it may be absent. The transabdominal ultrasound examination is the most widely used imaging method for NAFLD screening. Aim: The aim of the study was to assess the impact of paediatric obesity as the main risk factor in NAFLD development. Materials and methods: The degree of steatosis (represented by hepatorenal index) and hepatic parenchyma stiffness (represented by fibrosis liver index) were quantitatively evaluated using ultrasound device in a total of 240 paediatric and adolescent patients divided in subgroups according to age and weight criteria. Results from ultrasound examination were subsequently correlated with anthropometric and laboratory parameters. Results: Hepatorenal index (HRI) and liver fibrosis index (LFI) in healthy term neonates with normal birth weight was significantly lower compared to the control group of healthy normal weight children aged 10–18 years (p &lt;0.001). We did not observe an effect of gender on changes in HRI (p = 0.332) and LFI (p = 0.339) in teenage and adolescent controls. Regardless of gender, normal HRI values in paediatric heathy control group ranged from 1.02–1.23 (10th–90th percentile). The group of obese children aged 10–18 years had HRI and LFI values significantly higher in contrast with healthy normal weight controls. Obese individuals had liver stiffness proportional to BMI (p = 0.005, rs = 0.310), however, the steatosis degree remained unchanged (p = 0.357). Hepatic parenchyma stiffness also increased with waist circumference gain in corpulent patients (p &lt;0.01). Conclusion: Results of this study point to a significant association of obesity and NAFLD in paediatric population. The assessment of HRI and liver stiffness using ultrasound methods have been employed in the diagnosis of early stages of hepatic changes in obese children and adolescent patients at risk of NAFLD development. In addition to the early detection in these changes, ultrasound determination enables non-invasive and real-time assessment of dynamics of the disease and the effect of the administered therapy, which improves control over the disease. Keywords non-alcoholic fatty liver disease, obesity, hepatorenal index, real-time elastography, body roundness index, paediatric age, adolescent age

NAFLD: A BRIEF REVIEW OF THE RECENT GLOBAL EPIDEMIC

Non-alcoholic fatty liver disease (NAFLD) has become a metabolism-related severe illness, and during the next ten years, it will continue to be a major global liver health concern. According to epidemiological research, the incidence of NAFLD in the general population of India ranges from 9% to 32%, with a higher frequency in people who are obese and have diabetes. NAFLD is most strongly associated with obesity and insulin resistance, increasing the risk of type 2 diabetes, cardiovascular and cardiac diseases, chronic kidney disease, and a causal link in sleep apnea, colorectal cancer, osteoporosis, psoriasis, various endocrinopathies such as polycystic ovary syndrome, as well as liver cancer and a liver transplant. Although liver biopsy is still the gold standard for a conclusive diagnosis, developing non-invasive advanced imaging like USG, biochemical, and genetic tests will undoubtedly give future clinicians a wealth of knowledge and the chance to understand the pathogenesis better and develop targeted treatments. Several drugs and nutritional supplements are now used to treat NAFLD, but none appear to be the "magic cure" for this escalating issue. To better understand this condition and manage NAFLD patients, we have compiled the most recent information on NAFLD epidemiology, risk factors, prevalence, pathogenesis, diagnosis, staging, screening, and treatment in this study.

Screening for NAFLD-Current Knowledge and Challenges.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function tests worldwide, with an estimated prevalence ranging between 19-46% in the general population. Of note, NAFLD is also expected to become a leading cause of end-stage liver disease in the next decades. Given the high prevalence and severity of NAFLD, especially in high-risk populations (i.e., patients with type-2 diabetes mellitus and/or obesity), there is a major interest in early detection of the disease in primary care. Nevertheless, substantial uncertainties still surround the development of a screening policy for NAFLD, such as limitations in currently used non-invasive markers of fibrosis, cost-effectiveness and the absence of a licensed treatment. In this review, we summarise current knowledge and try to identify the limitations surrounding the screening policy for NAFLD in primary care.

Assessing the clinical utility of major indices for nonalcoholic fatty liver disease in EastAsian populations.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease. The growing prevalence of NAFLD is strongly associated with the high incidence of metabolic syndrome. NAFLD affects as much as 19% of the USpopulation with a disproportionate impact on minority racial groups such as Asian Americans. If not promptly managed, NAFLD may progress to more feared complications. Liver indices for NAFLD screening have been proposed butwere often developed using study populations with different anthropometrics than patients of East Asian descent. This review compares the accuracy of five indices for NAFLD screening in Asian cohorts. The Fatty Liver Index performed well in multiple large-scale community studies, although other indices may be more suited for specific patient cohorts. This is important, as the utilization of liver indices could accelerate screening for NAFLD for early management and to reduce liver disease-related health disparities among AsianAmericans.

Assessing the causal relationships between human blood metabolites and the risk of NAFLD: A comprehensive mendelian randomization study.

Background: Non-alcoholic fatty liver disease (NAFLD) is a liver disease associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and metabolic syndrome. The risk factors for NAFLD have not been identified. Metabolic dysfunction has been found to be an important factor in the pathogenesis and progression of NAFLD. However, the causal impact of blood metabolites on NAFLD is unclear. Methods: We performed a two-sample Mendelian randomization (MR) study. A genome-wide association study (GWAS) with 7824 participants provided data on 486 human blood metabolites. Outcome information was obtained from a large-scale GWAS meta-analysis of NAFLD, which contained 8,434 cases and 770,180 controls of Europeans. The inverse variance weighted (IVW) model was chosen as the primary two-sample MR analysis approach, followed by sensitivity analyses such as the heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. In addition, we performed replication, meta-analysis, and metabolic pathway analysis. We further conducted colocalization analysis to deeply reflect the causality. Results: After rigorous genetic variant selection, IVW, sensitivity analysis, replication, and meta-analysis, two known metabolites were identified as being associated with the development of NAFLD [biliverdin: OR = 1.45; 95% CI 1.20-1.75; p = 0.0001; myristoleate: OR = 0.57; 95% CI 0.39-0.83; p = 0.0030]. Conclusion: By combining genomics with metabolomics, our findings provide a new perspective on the underlying mechanisms of NAFLD and have important implications for the screening and prevention of NAFLD.

Application of machine learning in predicting non-alcoholic fatty liver disease using anthropometric and body composition indices

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which can progress from simple steatosis to advanced cirrhosis and hepatocellular carcinoma. Clinical diagnosis of NAFLD is crucial in the early stages of the disease. The main aim of this study was to apply machine learning (ML) methods to identify significant classifiers of NAFLD using body composition and anthropometric variables. A cross-sectional study was carried out among 513 individuals aged 13 years old or above in Iran. Anthropometric and body composition measurements were performed manually using body composition analyzer InBody 270. Hepatic steatosis and fibrosis were determined using a Fibroscan. ML methods including k-Nearest Neighbor (kNN), Support Vector Machine (SVM), Radial Basis Function (RBF) SVM, Gaussian Process (GP), Random Forest (RF), Neural Network (NN), Adaboost and Naïve Bayes were examined for model performance and to identify anthropometric and body composition predictors of fatty liver disease. RF generated the most accurate model for fatty liver (presence of any stage), steatosis stages and fibrosis stages with 82%, 52% and 57% accuracy, respectively. Abdomen circumference, waist circumference, chest circumference, trunk fat and body mass index were among the most important variables contributing to fatty liver disease. ML-based prediction of NAFLD using anthropometric and body composition data can assist clinicians in decision making. ML-based systems provide opportunities for NAFLD screening and early diagnosis, especially in population-level and remote areas.

Machine learning classifiers for screening nonalcoholic fatty liver disease in general adults

Nonalcoholic fatty liver disease (NAFLD) is one of major causes of end-stage liver disease in the coming decades, but it shows few symptoms until it develops into cirrhosis. We aim to develop classification models with machine learning to screen NAFLD patients among general adults. This study included 14,439 adults who took health examination. We developed classification models to classify subjects with or without NAFLD using decision tree, random forest (RF), extreme gradient boosting (XGBoost) and support vector machine (SVM). The classifier with SVM was showed the best performance with the highest accuracy (0.801), positive predictive value (PPV) (0.795), F1 score (0.795), Kappa score (0.508) and area under the precision-recall curve (AUPRC) (0.712), and the second top of area under receiver operating characteristic curve (AUROC) (0.850). The second-best classifier was RF model, which was showed the highest AUROC (0.852) and the second top of accuracy (0.789), PPV (0.782), F1 score (0.782), Kappa score (0.478) and AUPRC (0.708). In conclusion, the classifier with SVM is the best one to screen NAFLD in general population based on the results from physical examination and blood testing, followed by the classifier with RF. Those classifiers have a potential to screen NAFLD in general population for physician and primary care doctors, which could benefit to NAFLD patients from early diagnosis.

Using Real-World Electronic Health Record Data to Assess Chronic Disease Screening in Children: A Case Study of Non-Alcoholic Fatty Liver Disease.

Background: Data sources for assessing pediatric chronic diseases and associated screening practices are rare. One example is non-alcoholic fatty liver disease (NAFLD), a common chronic liver disease prevalent among children with overweight and obesity. If undetected, NAFLD can cause liver damage. Guidelines recommend screening for NAFLD using alanine aminotransferase (ALT) tests in children ≥9 years with obesity or those with overweight and cardiometabolic risk factors. This study explores how real-world data from electronic health records (EHRs) can be used to study NAFLD screening and ALT elevation. Research Design: Using IQVIA's Ambulatory Electronic Medical Record database, we studied patients 2-19 years of age with body mass index ≥85th percentile. Using a 3-year observation period (January 1, 2019 to December 31, 2021), ALT results were extracted and assessed for elevation (≥1 ALT result ≥22.1 U/L for females and ≥25.8 U/L for males). Patients with liver disease (including NAFLD) or receiving hepatotoxic medications during 2017-2018 were excluded. Results: Among 919,203 patients 9-19 years of age, only 13% had ≥1 ALT result, including 14% of patients with obesity and 17% of patients with severe obesity. ALT results were identified for 5% of patients 2-8 years of age. Of patients with ALT results, 34% of patients 2-8 years of age and 38% of patients 9-19 years of age had ALT elevation. Males 9-19 years of age had a higher prevalence of ALT elevation than females (49% vs. 29%). Conclusions: EHR data offered novel insights into NAFLD screening: despite screening recommendations, ALT results among children with excess weight were infrequent. Among those with ALT results, ALT elevation was common, underscoring the importance of screening for early disease detection.

Non-obese or lean non-alcoholic fatty liver disease was associated with increased risk of cancer in patients with type 2 diabetes mellitus

IntroductionRisk of non-obese or lean non-alcoholic fatty liver disease (NAFLD) for cancer in patients with type 2 diabetes mellitus (T2DM) is less known. We aimed to evaluate independent associations of...

A natural history study of paediatric non-alcoholic fatty liver disease over 10 years

The long-term outcome of paediatric non-alcoholic fatty liver disease (NAFLD) has not been well established. Between 2008 and 2012, an unselected cohort of 133 children with severe obesity was screened for NAFLD. The aim of this study was to determine the 10-year natural history of NAFLD in this cohort. All 133 participants of the original study were approached. Proton magnetic resonance spectroscopy (1H-MRS) and the Enhanced Liver Fibrosis® (ELF) test were used to assess longitudinal changes in steatosis and fibrosis, respectively. Risk factors for disease progression were explored. Fifty-one of the 133 participants (38%) from the original cohort were included. The mean follow-up time was 10.3 years (range 7-13 years), 65% were female and 92% had persistent obesity. The proportion of participants with steatosis remained unchanged (47%). Nine individuals developed steatosis and in nine individuals steatosis resolved. Predefined relevant individual changes in 1H-MRS were seen in 38% of the participants. The mean ELF test did not change significantly (8.70 ± 0.58 vs. 8.51 ± 0.71, p= 0.22). However, 16% had a relevant increase in ELF test and 6% of those with NAFLD developed advanced fibrosis at follow-up. Changes in steatosis correlated with changes in established metabolic risk factors, alanine aminotransferase, and bariatric surgery. A change in the ELF test was associated with a change in triglycerides. This 10-year follow-up study shows that one-third of the young adults who had childhood obesity develop steatosis and in one-third steatosis resolves. Six percent of those with NAFLD had developed advanced fibrosis at follow-up. These data underscore the importance of screening for NAFLD and monitoring for progression to advanced NAFLD in young people with obesity. Childhood obesity accompanied by fat accumulation in the liver persists into young adulthood in the vast majority, and 6% develop serious liver injury. Worsening of metabolic disturbances increases the risk of liver injury.

Relative Enhancement in Gadoxetate Disodium-Enhanced Liver MRI as an Imaging Biomarker in the Diagnosis of Non-Alcoholic Fatty Liver Disease in Pediatric Obesity.

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE (p = 0.033). In conclusion, the relative enhancement and hepatic fat fraction can be considered as non-invasive tools for the screening and follow-up of NAFLD in pediatric obesity, superior to echogenicity on ultrasound.

Analysis of clinical findings and serum micronutrients in pediatric patients with nonalcoholic fatty liver disease

Aim: Nonalcoholic fatty liver disease (NAFLD) is the hepatic finding of systemic lipid and energy metabolism disorder. NAFLD is frequently observed in people with higher body mass index. Serum micronutrient levels play an important role in hepatic metabolism. Material and Method: This study included 60 NAFLD and 66 control patients. . NAFLD and control groups were compared in terms of ultrasonography (USG) and shear wave elastography (SWE) results. The two groups were compared in serum lipid profile, aminotransferase, insulin, glucose, and HOMA-IR. Both groups were then analyzed in terms of serum ferritin, B12, and vitamin D levels.Results: . 35% (n=21) of the patients in the NAFLD group had grade 1, 55% (n=33) had grade 2 and 10% (n=6) had grade 3 adiposity. HOMA-IR and insulin levels were higher in the NAFLD group (p=0.02; p=0.001). While the serum ferritin level of the patients in the NAFLD group was higher than the control group (p=0.001); the B12 level was lower (p=0.006). In terms of vitamin D, there was no difference (p=0.368). Conclusion: It is essential to identify risk factors in children on follow-up due to NAFLD. USG and liver function tests remain the first option in the diagnosis and screening of NAFLD in children. Serum ferritin, B12, and vitamin D levels of children on follow-up due to NAFLD should be analyzed in consideration of liver fattening.