The association between healthy eating index-2015 with anthropometric, cardiometabolic and hepatic indices among patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity, cardiovascular diseases, and metabolic disorders are common problems among participants with non-alcoholic fatty liver disease (NAFLD). However, the association between these problems and the healthy eating index-2015 (HEI-2015) remains unknown. Although the HEI-2015 originated from American dietary guidelines, its comprehensive evaluation of diet quality provides valuable insights for various populations, including Iranians. Therefore, the objective of this study was to investigate the association between anthropometric, hepatic, and cardio-metabolic indices with HEI-2015 scores in participants with NAFLD. METHODS: We conducted a cross-sectional analysis of data from the Hoveyzeh Cohort Study, which included adults aged 35 to 70 years between 2016 and 2018. A total of 664 participant with NAFLD (452 females and 212 males) were included in the analysis. The HEI-2015 was assessed using the Food Frequency Questionnaire (FFQ). Various indices, including the body shape index (ABSI), atherogenic index of plasma (AIP), visceral adiposity index (VAI), lipid accumulation product (LAP), cardiometabolic index (CMI), lipoprotein combine index (LCI), AST/ALT ratio, ALD/NAFLD index, and hepatic steatosis index (HSI), were calculated. RESULTS: No significant differences were observed in anthropometric, cardio-metabolic, and hepatic indices across the quartiles of HEI-2015. However, among participants with NAFLD, men had significantly higher AIP and LCI levels, while women had significantly higher BMI, ABSI, VAI, LAP, and CMI levels. Additionally, women with NAFLD exhibited higher AST/ALT and HSI levels but lower ALD/NAFLD levels compared to men with NAFLD. Linear regression analysis among men with NAFLD revealed a significant negative correlation between HEI-2015 score and HSI in both the unadjusted model (ß=-0.131, SE = 0.058, p = 0.024) and the adjusted model for energy intake (ß=-0.129, SE = 0.058, p = 0.028). CONCLUSION: The present study demonstrated a correlation between lower HEI-2015 scores and an increased risk of steatosis in men with NAFLD. Moreover, our findings highlighted gender-related differences in NAFLD and cardio-metabolic disorders.

Limitations of Noninvasive Tests-Based Population-Level Risk Stratification Strategy for Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are highly prevalent but underdiagnosed. AIMS: We used an electronic health record data network to test a population-level risk stratification strategy using noninvasive tests (NITs) of liver fibrosis. METHODS: Data were obtained from PCORnet® sites in the East, Midwest, Southwest, and Southeast United States from patients aged [Formula: see text] 18 with or without ICD-10-CM diagnosis codes for NAFLD, NASH, and NASH-cirrhosis between 9/1/2017 and 8/31/2020. Average and standard deviations (SD) for Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and Hepatic Steatosis Index (HSI) were estimated by site for each patient cohort. Sample-wide estimates were calculated as weighted averages across study sites. RESULTS: Of 11,875,959 patients, 0.8% and 0.1% were coded with NAFLD and NASH, respectively. NAFLD diagnosis rates in White, Black, and Hispanic patients were 0.93%, 0.50%, and 1.25%, respectively, and for NASH 0.19%, 0.04%, and 0.16%, respectively. Among undiagnosed patients, insufficient EHR data for estimating NITs ranged from 68% (FIB-4) to 76% (NFS). Predicted prevalence of NAFLD by HSI was 60%, with estimated prevalence of advanced fibrosis of 13% by NFS and 7% by FIB-4. Approximately, 15% and 23% of patients were classified in the intermediate range by FIB-4 and NFS, respectively. Among NAFLD-cirrhosis patients, a third had FIB-4 scores in the low or intermediate range. CONCLUSIONS: We identified several potential barriers to a population-level NIT-based screening strategy. HSI-based NAFLD screening appears unrealistic. Further research is needed to define merits of NFS- versus FIB-4-based strategies, which may identify different high-risk groups.

Blood glucose control and metabolic dysfunction-associated steatotic liver disease in people with type 1 diabetes.

PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) may have distinctive pathophysiological features in type 1 diabetes (T1D). We evaluated the independent role of blood glucose control on MASLD in T1D. METHODS: In a cross-sectional study on 659 T1D adult patients, MASLD was assessed by the Fatty Liver Index (FLI) and the Hepatic Steatosis Index (HSI). Anthropometric, biochemical, and clinical parameters were retrieved from electronic records. Blood glucose control status was evaluated by dividing participants into subgroups according to the median value of HbA1c [7.6% (60 mmol/mol)], and this analysis was repeated excluding overweight/obese patients. RESULTS: Patients with HbA1c above 7.6% (60 mmol/mol) showed significantly higher MASLD indices (HSI 38 ± 6 vs. 36 ± 5, p < 0.001; FLI 26 ± 26 vs.19 ± 19, p < 0.001), and higher proportions of MASLD identified by HSI (57 vs. 44%, p < 0.001) and FLI (14 vs. 7%, p < 0.001) than patients with HbA1c below 7.6% (60 mmol/mol). Similar results were obtained for HSI after the exclusion of overweight/obese patients. Stepwise linear regression analysis confirmed that HbA1c was independently associated with HSI (r = 0.496, p = 0.009) and FLI (r = 0.722, p = 0.007); waist circumference with HSI (r = 0.492, p < 0.001); and waist circumference (r = 0.700, p < 0.001), HDL cholesterol (r = 0.719, p < 0.001), and LDL cholesterol (r = 0.712, p < 0.001) with FLI. CONCLUSIONS: Blood glucose control is a main factor associated with MASLD in adults with T1D, also independently of overweight and obesity. Appropriate therapeutic strategies focused on tight blood glucose control may also be needed for the prevention and treatment of MASLD in T1D.

Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women.

BACKGROUND: Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM. METHODS: In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM. RESULTS: Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol. CONCLUSIONS: Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.

Linear Relationship between Hepatic Steatosis Index and Major Adverse Cardiovascular Events in Hypertensive Patients with Obstructive Sleep Apnea: A Real-World Cohort Study from China.

Background: Hypertensive patients with obstructive sleep apnea (OSA) are at a high risk of cardiovascular disease (CVD), but assessments of CVD risk in this population are frequently constrained by the presence of comorbid medical conditions. The noninvasive and convenient hepatic steatosis index (HSI) can not only predict the degree of fatty liver degeneration but also correlates well with the severity of numerous diseases. However, the relationship between the HSI and CVD in hypertensive patients with OSA remains unclear. Methods: This retrospective cohort study included patients aged ≥ 18 years with hypertension and a primary diagnosis of OSA and grouped them according to their baseline HSI. The primary outcome was new or recurrent major adverse cardiovascular and cerebrovascular events (MACCE), while the secondary outcomes were cardiac and cerebrovascular events. The relationship between the baseline HSI and the risk of endpoint events was evaluated using Kaplan-Meier curves, risk-factor graphs, and Cox regression models, while generalized additive models were used to identify linear relationships. The C-statistic, integrated discrimination improvement (IDI), and net reclassification index (NRI) were used to evaluate the predictive value of HSI increments for endpoint events. Results: A total of 2467 participants were included in the analysis and separated into four groups (Q1-Q4) based on their HSI quartiles. Kaplan-Meier survival curves indicated that patients in the Q4 group had the lowest survival time. The Q4 group also showed a significantly higher risk of MACCE (HR [hazard ratio], 2.95; 95% CI [confidence interva]: 1.99-4.39; p < 0.001), cardiac events (HR, 2.80; 95% CI: 1.68-4.66; p < 0.001), and cerebrovascular events (HR, 3.21; 95% CI: 1.71-6.03; p < 0.001). The dose-response curve revealed a linear association between the HSI and the occurrence of endpoint events. For every unit increase in the HSI, the risks of MACCE, cardiac events, and cerebrovascular events increased by 43%, 38%, and 51%, respectively. The C-statistic, IDI, and NRI all indicated that the model including the HSI showed better discriminatory and classification efficacy for endpoint events in comparison with the conventional model (p < 0.05). Conclusions: The HSI showed a linear relationship with the risk of MACCE in hypertensive OSA patients.

Cardiorenal outcomes by indices of liver steatosis and fibrosis in individuals with type 2 diabetes and atherosclerotic cardiovascular disease: Analyses from VERTIS CV, a randomized trial of the sodium-glucose cotransporter-2 inhibitor ertugliflozin.

AIM: To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. MATERIALS AND METHODS: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention-to-treat analysis set). Cardiorenal outcomes (major adverse CV events [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB-4 quartiles (Q1-Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). RESULTS: Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2 , HSI 44.0 and FIB-4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB-4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval [CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 [95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB-4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. CONCLUSION: In VERTIS CV, higher FIB-4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI.

A healthy lifestyle during adolescence was inversely associated with fatty liver indices in early adulthood: findings from the DONALD cohort study.

A healthy lifestyle during adolescence is associated with insulin sensitivity or liver enzyme levels and thus might contribute to the prevention of non-alcoholic fatty liver disease (NAFLD). Therefore, we examined the association between adherence to a hypothesis-based lifestyle score including dietary intake, physical activity, sedentary behaviour, sleep duration and BMI in adolescence and fatty liver indices in early adulthood. Overall, 240 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed study completed repeated measurements of lifestyle score factors during adolescence (females: 8·5-15·5 years, males: 9·5-16·5 years). Multivariable linear regression models were used to investigate the association between adolescent lifestyle scores and NAFLD risk (hepatic steatosis index (HSI) and fatty liver index (FLI)) in early adulthood (18-30 years). Participants visited the study centre 4·9 times during adolescence and achieved on average 2·8 (min: 0·6, max: 5) out of five lifestyle score points. Inverse associations were observed between the lifestyle score and fatty liver indices (HSI: ß=-5·8 % (95 % CI -8·3, -3·1), P < 0·0001, FLI: ß=-32·4 % (95 % CI -42·9, -20·0), P < 0·0001) in the overall study population. Sex-stratified analysis confirmed these results in men, while inverse but non-significant associations were observed in women (P > 0·05). A higher lifestyle score was associated with lower HSI and FLI values, suggesting that a healthy lifestyle during adolescence might contribute to NAFLD prevention, predominantly in men. Our findings on repeatedly measured lifestyle scores in adolescents and their association with NAFLD risk in early adulthood warrant confirmation in larger study populations.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan.

BACKGROUND: The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score was recently developed with the intent to operationally define nonalcoholic fatty liver disease (NAFLD). However, there remained an external validation that confirmed its diagnostic performance, especially in patients with alcohol consumption or hepatitis virus infection. METHODS: Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®. Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score, fatty liver index (FLI), and hepatic steatosis index (HSI). RESULTS: K-NAFLD-moderate [adjusted odds ratio (aOR) = 2.53, 95% confidence interval (CI): 1.13-5.65] and K-NAFLD-high (aOR = 4.14, 95% CI: 1.69-10.13) groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics, and FLI-moderate and FLI-high groups revealed aORs of 2.05 (95% CI: 1.22-3.43) and 1.51 (95% CI: 0.78-2.90), respectively. In addition, the HSI was less predictive for Fibroscan®-defined fatty liver. Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection, and the adjusted area under curve values were comparable between K-NAFLD and FLI. CONCLUSIONS: Externally validation of the K-NAFLD and FLI showed that these scores may be a useful, noninvasive, and non-imaging modality for the identification of fatty liver. In addition, these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

Association between non-alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study.

BACKGROUND AND AIMS: Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. METHODS: We conducted a nationwide cohort study involving 4 031 948 subjects aged 40-69 years who underwent ≥2 health check-ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non-NAFLD (HSI <30 at all check-ups) and NAFLD (HSI >36 at one or more check-ups). Dementia defined by ICD-10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. RESULTS: At baseline, 31.3% had NAFLD. During the median follow-up of 9.5 years, 138 424 in NAFLD group and 69 982 in non-NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non-NAFLD group on multivariable-adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity-score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non-obese NAFLD subjects (BMI <25 kg/m2 , HR, 1.09; p < .001) than obese NAFLD subjects. CONCLUSIONS: This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non-obese NAFLD subjects.

Validity of fatty liver disease indices in the presence of alcohol consumption.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease frequently coexist. While several blood-based indices exist for the detection of NAFLD, few studies have examined how alcohol use possibly impacts their diagnostic performance. We analysed the effects of alcohol use on the performance of indices for detecting fatty liver disease (FLD). METHODS: We included participants from the Cardiovascular Risk in Young Finns Study (Finnish sample) and KORA study (German sample) who underwent abdominal ultrasound or magnetic resonance imaging, respectively, for detection of FLD and had serum analyses available for calculation of Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and Dallas Steatosis Index (DSI). Alcohol use was estimated by questionnaires as mean daily consumption and binge drinking (Finnish sample only). Predictive performance for FLD was assessed according to alcohol consumption. RESULTS: The study included 1426 (Finnish sample) and 385 (German sample) individuals, of which 234 (16%) and 168 (44%) had FLD by imaging. When alcohol consumption was <50 g/day, all indices discriminated FLD with area under the receiver operating characteristics (AUROC) of 0.82-0.88. AUROCs were 0.61-0.66 among heavy drinkers (>50 g/day). AUROCs decreased to 0.74-0.80 in the highest binge-drinking category (>2 times/week). Alcohol use correlated with FLI and LAP (r-range 0.09-0.16, p-range <.001-.02) in both samples and with DSI (r = 0.13, p < .001) in the Finnish sample. CONCLUSIONS: Indices perform well and comparably for detection of FLD with alcohol consumption <50 g/day and with different binge-drinking behaviour.

Plasma Calprotectin Levels Associate with Suspected Metabolic-Associated Fatty Liver Disease and All-Cause Mortality in the General Population.

Metabolic-associated fatty liver disease (MAFLD) is characterized by hepatic steatosis, metabolic dysregulation, and neutrophilic inflammation. In this study, we hypothesized that systemic levels of plasma calprotectin, as a biomarker of neutrophilic inflammation, may be associated with suspected MAFLD. Plasma calprotectin levels were measured in subjects (n = 5446) participating in the Prevention of Renal and Vascular ENd-stage Disease (PREVEND) cohort study. Suspected MAFLD was defined by the fatty liver index (FLI ≥ 60) and hepatic steatosis index (HSI ≥ 36) as proxies. Plasma calprotectin levels were significantly higher in subjects with FLI ≥ 60 (0.57 [IQR: 0.42−0.79] mg/L, n = 1592) (p < 0.001) compared to subjects with FLI < 60 (0.46 [0.34−0.65] mg/L, n = 3854). Multivariable logistic regression analyses revealed that plasma calprotectin levels were significantly associated with suspected MAFLD (FLI ≥ 60), even after adjustment for potential confounding factors, including current smoking, alcohol consumption, hypertension, diabetes, cardiovascular diseases, insulin resistance (HOMA-IR), hs-CRP, eGFR, and total cholesterol levels (OR 1.19 [95% CI: 1.06−1.33], p = 0.003). Interaction analyses revealed significant effect modifications for the association between plasma calprotectin and suspected MAFLD by BMI (p < 0.001) and hypertension (p = 0.003), with the strongest associations in subjects with normal BMI and without hypertension. Prospectively, plasma calprotectin levels were significantly associated with all-cause mortality after adjustment for potential confounding factors, particularly in subjects without suspected MAFLD (FLI < 60) (hazard ratio (HR) per doubling: 1.34 (1.05−1.72), p < 0.05). In conclusion, higher plasma calprotectin levels are associated with suspected MAFLD and with the risk of all-cause mortality, the latter especially in subjects without suspected MAFLD.

Early life factors and their relevance for markers of cardiometabolic risk in early adulthood.

BACKGROUND AND AIMS: Early life exposures could be pertinent risk factors of cardiometabolic diseases in adulthood. We assessed the prospective associations of early life factors with markers of cardiometabolic risk among healthy German adults. METHODS AND RESULTS: We examined 348 term-born DONALD Study participants with measurement of fasting blood at the age of 18-24 years to assess metabolic indices: fatty liver index (FLI), hepatic steatosis index (HSI), pro-inflammatory score and insulin sensitivity (HOMA2-%S). Early life factors (maternal weight in early pregnancy, maternal early pregnancy BMI, gestational weight gain (GWG), maternal age, birth weight and full breastfeeding (>17 weeks)) were assessed at enrolment of the offspring into the study. Multivariable linear regression models were used to analyze associations between early life factors and markers of cardiometabolic risk in early adulthood with adjustment for potential confounders. A higher early pregnancy BMI was related to notably higher levels of offspring FLI, HSI, pro-inflammatory score and a lower HOMA2-%S (all p < 0.0001). Similarly, a higher gestational weight gain was associated with a higher FLI (p = 0.044), HSI (p = 0.016), pro-inflammatory score (p = 0.032) and a lower HOMA2-%S among females (p = 0.034). Full breastfeeding was associated with a lower adult FLI (p = 0.037). A casual mediation analysis showed that these associations were mediated by offspring adult waist circumference (WC). CONCLUSION: This study suggests that early pregnancy BMI, gestational weight gain, and full breastfeeding are relevant for offspring markers of cardiometabolic risk which seems to be mediated by body composition in young adulthood.

Association of Hepatic Steatosis Index and Fatty Liver Index with Carotid Atherosclerosis in Type 2 Diabetes.

Background/aim: Previous studies have suggested that the hepatic steatosis index (HSI) and fatty liver index (FLI) can be used as a predictor of non-alcoholic fatty liver disease (NAFLD). The aim of our study was to determine whether non-invasive indices of hepatic steatosis (HSI and FLI) are associated with carotid atherosclerosis in type 2 diabetes mellitus (T2DM). Methods: This was a cross-sectional study conducted in the T2DM patients (n=768). Carotid intima-media thickness (CIMT) was measured by the Color Doppler ultrasound. The HSI was calculated based on gender, body mass index (BMI), and transaminases level. The FLI was based on BMI, waist circumference (WC), triacylglycerols (TG) and g-glutamyl transferase (GGT). Results: Raised HSI and FLI levels was associated with increased CIMT levels in T2DM patients. Patients with greater CIMT had higher HSI (39.10 ± 5.70 vs 36.10 ± 4.18, P < 0.001) and FLI (46.35 (29.96, 65.54) vs 36.93 (18.7, 57.93), P < 0.001) than those with lower CIMT. Subjects with existing carotid plaque had higher HSI (38.28 ± 5.63 vs 35.69 ± 3.45 P < 0.001) and FLI (47.41 (27.77, 66.62) vs 37.19 (17.71, 51.78), P < 0.001) accordingly. HSI (r = 0.343, P < 0.001) and FLI (r = 0.184, P < 0.001) were positively related with the CIMT. In the linear regression, after full adjustment metabolic risk factors, smoking, and measures of insulin resistance, HSI and FLI were independently associated with CIMT (HSI: ß = 0.011, FLI: ß = 0.001, all P < 0.01). Further, logistic regression analyses showed that higher HSI and FLI had an impact on the risk for carotid atherosclerosis [HSI: OR (95%CI): 1.174 (1.123-1.228), FLI: OR (95%CI): 1.011(1.004-1.019), all P < 0.01]. Overall, increasing values of HSI and FLI were associated with CIMT (P < 0.05) significantly across different categories of age and hypertension. Conclusion: Current data suggest HSI and FLI are independently correlated with carotid atherosclerosis in T2DM. They may be a simple and useful marker for assessing the progression of diabetic macrovascular complications.

Non-alcoholic Fatty Liver Disease and COVID-19 Susceptibility and Outcomes: a Korean Nationwide Cohort.

BACKGROUND: Evidence for the association between underlying non-alcoholic fatty liver disease (NAFLD), the risk of testing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive, and the clinical consequences of coronavirus disease 2019 (COVID-19) is controversial and scarce. We aimed to investigate the association between the presence of NAFLD and the risk of SARS-CoV-2 infectivity and COVID-19-related outcomes. METHODS: We used the population-based, nationwide cohort in South Korea linked with the general health examination records between January 1, 2018 and July 30, 2020. Data for 212,768 adults older than 20 years who underwent SARS-CoV-2 testing from January 1 to May 30, 2020, were obtained. The presence of NAFLDs was defined using three definitions, namely hepatic steatosis index (HSI), fatty liver index (FLI), and claims-based definition. The outcomes were SARS-CoV-2 test positive, COVID-19 severe illness, and related death. RESULTS: Among 74,244 adults who completed the general health examination, there were 2,251 (3.0%) who were SARS-CoV-2 positive, 438 (0.6%) with severe COVID-19 illness, and 45 (0.06%) COVID-19-related deaths. After exposure-driven propensity score matching, patients with pre-existing HSI-NAFLD, FLI-NAFLD, or claims-based NAFLD had an 11-23% increased risk of SARS-CoV-2 infection (HSI-NAFLD 95% confidence interval [CI], 1-28%; FLI-NAFLD 95% CI, 2-27%; and claims-based NAFLD 95% CI, 2-31%) and a 35-41% increased risk of severe COVID-19 illness (HSI-NAFLD 95% CI, 8-83%; FLI-NAFLD 95% CI, 5-71%; and claims-based NAFLD 95% CI, 1-92%). These associations are more evident as liver fibrosis advanced (based on the BARD scoring system). Similar patterns were observed in several sensitivity analyses including the full-unmatched cohort. CONCLUSION: Patients with pre-existing NAFLDs have a higher likelihood of testing SARS-CoV-2 positive and severe COVID-19 illness; this association was more evident in patients with NAFLD with advanced fibrosis. Our results suggest that extra attention should be given to the management of patients with NAFLD during the COVID-19 pandemic.

The association between urinary bisphenol A levels and nonalcoholic fatty liver disease in Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD. METHODS: The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases. RESULTS: There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively. CONCLUSIONS: Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

Association between sitting time and non-alcoholic fatty live disease in South Korean population: a cross-sectional study.

BACKGROUND: To examine the association between sitting time and non-alcoholic fatty liver disease among South Koreans aged ≥20 years. METHODS: Data from the 2016-2018 Korea National Health and Nutrition Examination Survey were used for the analysis. Non-alcoholic fatty liver disease was diagnosed according to a hepatic steatosis index of > 36. Sitting time was categorized into as Q1, Q2, Q3, and Q4 using the age-adjusted quartile with Q4 being the longest sitting hour. Multiple logistic regression analysis was used to examine the association between sitting time and non-alcoholic fatty liver disease in South Korean population. RESULTS: A total of 13,518 participants were enrolled. The odds for having NAFLD in Q1, Q2, Q3, and Q4 (sitting hours) were 1.07 (CI: 0.88-1.31), 1.16 (CI: 1.96-1.41), and 1.34 (CI: 1.11-1.61), respectively. The odds ratio increased in magnitude with longer hours of sitting time (test for trend: P-value = 0.0002). CONCLUSION: Advising physical exercises and discouraging sedentary activities may help to alleviate NAFLD among the South Korean population.

Serum paraoxonase 1 activity is paradoxically maintained in nonalcoholic fatty liver disease despite low HDL cholesterol.

Nonalcoholic fatty liver disease (NAFLD) is characterized by low HDL cholesterol, but the activity of the HDL-associated antioxidative enzyme paraoxonase-1 (PON-1) remains unclear. To determine the association of PON-1 with suspected NAFLD, we measured serum enzyme activity in 7,622 participants of the Prevention of Renal and Vascular End-Stage Disease cohort. A fatty liver index (FLI) ≥60, a proxy of NAFLD, was present in 2,083 participants (27.3%) and coincided with increased prevalence of T2D, metabolic syndrome (MetS), (central) obesity, elevated triglycerides, and low HDL cholesterol (all P < 0.001). In men and women combined, serum PON-1 activity did not vary according to elevated FLI (P = 0.98), whereas in men with elevated FLI PON-1 activity was increased (P = 0.016). In multivariable linear regression analyses (adjusted for age, sex, T2D, MetS, alcohol use, and smoking), PON-1 activity was unexpectedly associated with elevated FLI (ß = 0.083; P < 0.001). In a sensitivity analysis (n = 5,126) that excluded subjects with positive cardiovascular history, impaired estimated glomerular filtration rate, elevated urinary albumin excretion, and drug use, PON-1 activity was also independently associated with elevated FLI (ß = 0.045; P = 0.017). These results indicate that PON-1 is paradoxically maintained and may even be increased in NAFLD despite inverse associations with metabolic disorders and low HDL cholesterol.

Reducing NAFLD-screening time: A comparative study of eight diagnostic methods offering an alternative to ultrasound scans.

BACKGROUND & AIMS: The use of ultrasound scan (US) in non-alcoholic fatty liver disease (NAFLD) screening overloads US waiting lists. We hypothesized and tested a hybrid two-step method, consisting of applying a formula, to exclude subjects at low risk, before US. METHODS: The sample included 2970 males and females (937 with NAFLD) diagnosed by US. We selected eight formulas: Fatty Liver Index (FLI), Hepatic Steatosis Index (HIS), body mass index (BMI), waist circumference (WC), Abdominal Volume Index (AVI), waist-to-height ratio (WHtR), waist/height0.5 (WHT.5R) and Body Roundness Index (BRI), and calculated their performance in the two-step method evaluating percentage reduction of the number of liver US (US reduction percentage), percentage of false negative and percentage of NAFLD identified. RESULTS: The US reductions percentage were 52.2% (WHtR), 52.1% (HIS), 51.8% (FLI), 50.8% (BRI), 50.7% (BMI and WHt_5R), 46.5% (WC) and 45.2% (AVI). The false negative percentage were 8.5% (WHtR), 7.9% (BRI), 7.3% (WHt_5R), 7.2% (BMI), 6.7% (HIS), 6.6% (FLI), 5.6% (WC) and 5.2% (AVI). The best percentage of NALFD identified was obtained using AVI (83.6%) before US, then WC (82.2%), FLI (79%), HIS (78.9%), BMI (77.3%), WHt_5R (76.9%), BRI (74.8%) and WHtR (73%). CONCLUSION: The best formula to use in two-step diagnostic NAFLD screening was AVI, which showed a low false negative rate and a higher percentage of identified NAFLD. Other studies evaluating the economic advantages of this screening method are warranted.

Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes.

BACKGROUND AND AIM: Little is known about the diagnostic value of hepatic steatosis index (HSI) and fatty liver index (FLI), as well as their link to metabolic syndrome in type 1 diabetes mellitus. We have screened the effectiveness of FLI and HSI in an observational pilot study of 40 patients with type 1 diabetes. METHODS: FLI and HSI were calculated for 201 patients with type 1 diabetes. Forty patients with FLI/HSI values corresponding to different risk of liver steatosis were invited for liver magnetic resonance study. In-phase/opposed-phase technique of magnetic resonance was used. Accuracy of indices was assessed from the area under the receiver operating characteristic curve. RESULTS: Twelve (30.0%) patients had liver steatosis. For FLI, sensitivity was 90%; specificity, 74%; positive likelihood ratio, 3.46; negative likelihood ratio, 0.14; positive predictive value, 0.64; and negative predictive value, 0.93. For HSI, sensitivity was 86%; specificity, 66%; positive likelihood ratio, 1.95; negative likelihood ratio, 0.21; positive predictive value, 0.50; and negative predictive value, 0.92. Area under the receiver operating characteristic curve for FLI was 0.86 (95% confidence interval [0.72; 0.99]); for HSI 0.75 [0.58; 0.91]. Liver fat correlated with liver enzymes, waist circumference, triglycerides, and C-reactive protein. FLI correlated with C-reactive protein, liver enzymes, and blood pressure. HSI correlated with waist circumference and C-reactive protein. FLI ≥ 60 and HSI ≥ 36 were significantly associated with metabolic syndrome and nephropathy. CONCLUSIONS: The tested indices, especially FLI, can serve as surrogate markers for liver fat content and metabolic syndrome in type 1 diabetes.

Validation of simple indexes for nonalcoholic fatty liver disease in western China: a retrospective cross-sectional study.

Various noninvasive algorithms have been developed for predicting the presence of nonalcoholic fatty liver disease (NAFLD). The evaluation of the indexes' diagnostic performance has been reported in Europe and Asia over the past decade; however, external validation of them in China is rare. This study was aimed to evaluate various indexes for NAFLD in western China. It was a retrospective cross-sectional study, using data from a large-scale health check-up project at Sichuan provincial hospital. Receiver operating characteristic (ROC) curves of eight indexes, including the fatty liver index (FLI), the hepatic steatosis index, lipid accumulation product and etc., were developed to predict ultrasonographic NAFLD. There were 13,122 subjects in this study (2,692 NAFLD patients and 10,430 non-NAFLD participants). The area under ROC curve of FLI for predicting NAFLD was 0.880 (95% confidence interval, 0.874-0.886), which was significantly higher than other seven indexes. Accuracy, sensitivity and specificity of FLI for NAFLD were good (cut-off value = 30, 0.782, 0.832, 0.770 and cut-off value = 60, 0.838, 0.443, 0.940, respectively). Furthermore, FLI also presented advantages in expenditure and accessibility, compared with other indexes. It supports FLI as an easily accessible index for physicians and a reliable predictor for NAFLD screening in western China.