Steatosis Index Research Articles

1151-P: Improved Liver Steatosis Scores in T2DM after Randomization to Bariatric Surgery Related to Improvement in Insulin Sensitivity and Cardiometabolic Risk

NAFLD is common in T2DM, linked to insulin resistance and beta-cell dysfunction, and can be assessed with validated liver scores for steatosis and fibrosis. The longitudinal impact of weight loss with or without bariatric/metabolic surgery (BMS) on NAFLD in T2DM is not clear. Patients with T2DM (N=52, age 48±9 yrs, 30 (58%) female, BMI 36.3±2.9 kg/m2, T2DM duration of 8.3±5.0 yrs, A1c 9.7±1.7%) were randomized to intensive medical therapy (IMT, n=15) alone or IMT with laparoscopic Roux-en-Y gastric bypass (RYGB, n=18) or sleeve gastrectomy (SG, n=19) . The hepatic steatosis index (HSI) , NAFLD/liver fat score, FIB-4 index, and AST-to-platelet ratio index (APRI) were calculated at baseline and 24 months and correlated to baseline and change in weight, body fat percent (assessed with iDXA) , insulin sensitivity, beta-cell function (DI) and adipocytokine measurements during mixed meal tolerance testing. Baseline steatosis liver scores were abnormal in 52 patients (100%) by HSI and 38 (73%) by NAFLD/LFS. Abnormal liver scores at baseline were correlated with higher HOMA-IR, lower adiponectin levels, and higher blood pressure. At 24 months, HSI only normalized in 10/37 (27%) BMS patients (p=0.046) . NAFLD/LFS normalized in 21/27 (78%) BMS patients and 1/ (9%) medical patients (p=0.001) . Normalization of HSI and NAFLD/LFS were associated with weight and body fat reduction (p<0.001) . Normalization of HSI was associated with improvement in Disposition index (DI) (P = 0.08) , CRP (p=0.001) , and leptin levels (p=0.016) ; change in NAFLD/LFS was associated with HOMA-IR (p<0.001) . Liver steatosis was prevalent in all T2DM undergoing BMS and medical therapy and improved in a majority of subjects who underwent BMS but not IMT. Normalization of liver scores was associated with improvement in body weight, insulin sensitivity, beta-cell function, and markers of CVD risk. These data support the use of liver scores when assessing T2DM for BMS. Disclosure A.Kodali: None. M.D.Lundholm: None. R.Vangoitsenhoven: Speaker's Bureau; Boehringer Ingelheim International GmbH, Goodlife Pharma, Lilly, Mundipharma, Novo Nordisk, Sanofi. J.P.Kirwan: None. A.Aminian: Consultant; Medtronic, Research Support; Medtronic. P.Schauer: Advisory Panel; GI Dynamics, Keyron Ltd., Persona Nutrition, Consultant; Ethicon, Inc., Medtronic, Research Support; Ethicon, Inc., Medtronic, Pacira BioSciences, Inc., Stock/Shareholder; Mediflix, Inc., SE Healthcare LLC. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc.

1207-P: Hepatic Steatosis Index and Fibrosis-4 Scores in Relation to Cardiometabolic Risk in Healthy Offspring of Parents with Type 2 Diabetes

We explored the association between nonalcoholic fatty liver disease and cardiometabolic risk and the impact of race/ethnicity among healthy offspring of parents with type 2 diabetes (T2D) . These post hoc analyses were conducted on baseline data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC study) . Participants (N 376) were normoglycemic (NGT) White (N159) and Black (N 217) adults, aged 18-75 years, with at least 1 parent with T2D. The presence of hepatic steatosis was estimated by hepatic steatosis index (HSI; 8 × ALT/AST + BMI + 2 if female) ; and for hepatic fibrosis, fibrosis-4 score (FIB-4; [age × AST]/[platelets count × √ALT]) . We determined the association between HSI and Fib-4 vs. markers of the metabolic syndrome (MetS) , using a modified definition in our NGT cohort (waist≥100cm in men, ≥88 cm in women; BP ≥ 120/80mmHg, triglycerides ≥150mg/dl, HDL ≤40 in men, ≤50 in women) . HSI did not differ by sex or race, showed no correlation with age, but correlated significantly with MetS components: waist (r= 0.77, P<0.0001; systolic BP (r= 0.246, P <0.0001;) ; HDL (r= −0.224, P<0.0001; triglycerides (r= 0.11, P= 0.0009) . HSI increased cumulatively with MetS markers. FIB-4 score showed no sex or ethnic disparities, and correlated with BMI (r= −0.17, P= 0.0015) , total fat mass (r= −0.13, P= 0.02) and HDL (r=0.11, P=0.044) but not waist, BP or triglycerides. Unlike HSI, Fib-4 showed no cumulative association with MetS markers. These findings were similar in Black and White participants. Our data from POPABC study indicate that HSI is an informative early marker of the link between hepatic steatosis and cardiometabolic risk in normoglycemic Black and White offspring of parents withT2D. Disclosure B.Colon barreto: None. K.Siwakoti: None. C.Edeoga: None. S.Ebenibo: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. Funding American Diabetes Association (7-07-MN-13) ; National Institutes of Health (R01 DK067269)

RELATIONSHIPS BETWEEN NAFLD BIOCHEMICAL SCORES AND LEFT VENTRICULAR GEOMETRIC PATTERN IN NAÏVE ESSENTIAL HYPERTENSIVE PATIENTS

Objective: The not alcoholic fatty liver disease (NAFLD) is associated with an increased cardiovascular mortality and morbidity. An hypothesis for this association could be the left ventricular (LV) geometric alteration sometime found in hypertension that is a known prognostic factor for cardiovascular events in hypertension. We searched for a relationship between biochemical scores of NAFLD and left ventricular (LV) hypertrophy (LVH) or LV geometric patterns changes in a large group of never treated essential hypertensive (EH) patients. Design and method: In 434 naïve (49 ± 14 years, 234 males) we evaluated BMI, waist circumference, liver steatosis at abdominal echography, the biochemical scores of liver steatosis: Liver Fat Score (LFS), Fatty Liver Index (FLI), Hepatic Steatosis Index (NAÏVE), and the fibrosis scores: NAFLD Fibrosis Score (NFS), APRI, FIB-4, parameters of glucose and insulin homeostasis, liver blood tests, lipids, platelets count, glomerular filtration rate (GFR), reactive C protein. LV mass and relative wall thickness was calculated with echocardiography. Patients were classified in 4 groups of LV geometry: 1 = LV normal geometry, 2 = LV concentric remodeling, 3 = concentric LVH, 4 = eccentric LVH. Results: A LVH was present in 17.3% of patients, and these patients had higher LFS (P < 0.001), FLI (P = 0.008), NAÏVE (P = 0.004) and NFS (P = 0.011) scores than patients without LVH. LVH was independently associated with the FLI score but not with fibrosis scores. The steatosis scores (LFS, NAÏVE, FLI) linearly increased across the four LV geometric patterns (P = 0.007, P = 0.001, P = 0.003, respectively). The fibrosis score NFS was significantly higher in subjects with concentric LVH (P = 0.041). The LFS was independently associated with BMI, GAUC, G120, and triglycerides levels. The NFS was independently associated with waist circumference, GFR and weakly with fasting glucose level. Ultrasound steatosis was not different among the four LV geometric patterns. Conclusions: In naïve EH patients the biochemical steatosis scores show a relationship with LVH and LV geometric changes, while fibrosis is associated with concentric LVH. An accurate investigation to reveal a NAFLD should be done in EH patients with altered LV geometry and to better understanding of mechanisms linking the two conditions.

A Case Report of Nonalcoholic Fatty Liver Disease with Obesity and Dyslipidemia

Objectives: This study aims to report the clinical efficacy of Korean medical treatment of a patient with nonalcoholic fatty liver disease accompanied by obesity and dyslipidemia.Methods: A 52-year-old man with nonalcoholic fatty liver disease, obesity, and dyslipidemia was treated with <i>Saenggangunbi-tang</i> extract from November 3, 2021 to January 8, 2022. During the treatment period, the patient also undertook exercise and maintained a hypocaloric diet to reduce body weight. Changes were observed in the patient’s symptoms, laboratory findings, such as liver enzymes and lipid profiles, and bioelectrical impedance analyzer results.Results: After taking <i>Saenggangunbi-tang</i> extract for approximately two months, with concomitant adjustments to exercise and diet, the serum levels of liver enzymes and triglyceride were decreased and the patient’s body weight, body mass index, hepatic steatosis index, and visceral fat area were also reduced. In addition, symptoms including fatigue and dyspepsia improved.Conclusion: This study suggests that <i>Saenggangunbi-tang</i> extract with exercise and a regulated diet could be a helpful treatment strategy for managing nonalcoholic fatty liver disease with metabolic disorders.

Association Between Psoriasis and Nonalcoholic Fatty Liver Disease Among Outpatient US Adults

Recent studies have shown an association between psoriasis and nonalcoholic fatty liver disease (NAFLD) in US inpatients, but the association is still unclear in the outpatient US population. To assess whether psoriasis is associated with NAFLD in outpatient US adults. This population-based cross-sectional study used data on US adults aged 20 to 59 years from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014 cycles. Data were analyzed from June to September 2021. Self-reported psoriasis. The main outcome was NAFLD, defined as a US fatty liver index score greater than 30. Sampling weights were calculated according to NHANES guidelines. Among 5672 adults included in this study (mean age, 38.9 years [95% CI, 38.4-39.3 years]; 2999 [51.1%] female), 148 (3.0%) had psoriasis and 5524 (97.0%) did not have psoriasis. A total of 1558 participants (26.8%) were classified as having NAFLD. Compared with participants without psoriasis, those with psoriasis had a higher prevalence of NAFLD (32.7% [52] vs 26.6% [1506]). In a multivariable logistic regression model adjusted for age, sex, race and ethnicity, educational level, family income, marital status, NHANES cycles, diabetes, metabolic syndrome, and smoking and alcohol drinking status, psoriasis was associated with NAFLD (odds ratio [OR], 1.67; 95% CI, 1.03-2.70). In subgroup analyses, psoriasis was associated with NAFLD among men (OR, 2.16; 95% CI, 1.10-4.24), among those aged 20 to 39 years (OR, 2.48; 95% CI, 1.09-5.67), and among those without diabetes (1.70; 95% CI, 1.05-2.76). An association between psoriasis and NAFLD was found in sensitivity analyses that excluded potential hepatotoxic medication use (OR, 1.72; 95% CI, 1.01-2.95) or non-Hispanic Black participants (OR, 1.76; 95% CI, 1.07-2.87), redefined NAFLD based on the hepatic steatosis index score (OR, 1.59; 95% CI, 1.01-2.50), and used inverse probability of treatment weighting (OR, 1.43; 95% CI, 1.09-1.86). In this cross-sectional study, psoriasis was associated with NAFLD in the outpatient US adult population in adjusted models. This association may be important to consider in the context of clinicians prescribing potentially hepatotoxic medication for psoriasis management.

Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial.

AimTo evaluate if VSL#3® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08)] therapy could improve hepatic parameters.MethodsWe enrolled 60 Caucasian patients aged ≥ 18 years of either sex with the diagnosis of non-alcoholic fatty liver disease (NAFLD), according to practice guidance, in a double-blind, placebo-controlled study. Patients were randomized to take placebo or VSL#3®, 2 sachets/day in the morning for 3 months. VSL#3® and placebo were self-administered.ResultsWe did not observe any change in body mass index (BMI), circumferences, fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and adiponectin (ADN) with neither treatment. A statistically significant triglycerides (Tg) decrease (p < 0.05 vs. baseline, and p < 0.05 vs. placebo, respectively) and high-sensitivity C-reactive protein (Hs-CRP) decrease (p < 0.05 vs. baseline) was observed in the group of patients being treated with VSL#3® compared with placebo. Transaminases and gamma-glutamyltransferase (γ-GT) were significantly reduced in VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and hepatic steatosis index (HSI) were significantly lower than the VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. All patients reported an improvement or the disappearance of hepatic steatosis.ConclusionProbiotic therapy with VSL#3® ameliorates hepatic parameters and echography grading, while reducing Tg and the inflammatory status, without any difference between men and women.

Metabolic Stress Index Including Mitochondrial Biomarker for Noninvasive Diagnosis of Hepatic Steatosis.

BackgroundMitochondrial dysfunction with oxidative stress contributes to nonalcoholic fatty liver disease (NAFLD) progression. We investigated the steatosis predictive efficacy of a novel non-invasive diagnostic panel using metabolic stress biomarkers.MethodsAltogether, 343 subjects who underwent magnetic resonance imaging-based liver examinations from a population-based general cohort, and 41 patients enrolled in a biopsy-evaluated NAFLD cohort, participated in the development and validation groups, respectively. Serologic stress biomarkers were quantitated by enzyme-linked immunosorbent assay.ResultsMultivariate regression showed that waist-to-hip ratio, fibroblast growth factor (FGF) 21, FGF19, adiponectin-to-leptin ratio, insulin, albumin, triglyceride, total-cholesterol, and alanine-aminotransferase were independent predictors of steatosis (rank-ordered by Wald). The area under receiver-operator characteristics curve [AUROC (95%CI)] of the metabolic stress index for steatosis (MSI-S) was 0.886 (0.85−0.92) and 0.825 (0.69−0.96) in development and validation groups, respectively. MSI-S had higher diagnostic accuracy (78.1%−81.1%) than other steatosis indices. MSI-S notably differentiated steatosis severities, while other indices showed less discrimination.ConclusionMSI-S, as a novel non-invasive index, based on mitochondrial stress biomarker FGF21 effectively predicted steatosis. Furthermore, MSI-S may increase the population that could be excluded from further evaluation, reducing unnecessary invasive investigations more effectively than other indices.

Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial

BackgroundPatients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients.MethodsWe conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention.ResultsA total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: − 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: − 0.25 ± 1.1 vs. − 0.02 ± 0.6; P = 0.47), CRI-I (mean change: − 0.25 ± 0.9 vs. − 0.09 ± 0.5; P = 0.79), CRI-II (mean change: − 0.23 ± 0.7 vs. − 0.06 ± 0.6; P = 0.38) and AC (mean change: − 0.25 ± 0.9 vs. − 0.09 ± 0.5; P = 0.79).ConclusionsResveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies.Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734.

Concordance between indirect fibrosis and steatosis indices and their predictors in subjects with overweight/obesity.

The non-invasive assessment of steatosis/fibrosis tried to overcome some of peri-procedural risk of liver biopsy; for this, several indices of steatosis and fibrosis in liver have been proposed. To evaluate concordance of non-invasive fibrosis and steatosis indices in a large population of adult subjects at risk of NAFLD, and how obesity and its physio-pathological features may interact with steatosis/fibrosis indexes and related biomarkers of cardio-metabolic risk. Indices of steatosis (fatty liver index-FLI), NAFLD liver fat score-NLFS)) and fibrosis (Fibrosis 4 (FIB-4), BARD, BAAT and FORN) were calculated in 1145 outpatients with overweight or obesity at risk for T2D and NAFLD. Indices were correlated with clinical variables. Concordance between tests occurred in 81% of the overall values between FLI and NLFS, but was lower when comparing the other fibrosis scores (FIB-4 vs FORN 72%, FIB-4 vs BARD 36%, BARD vs FORN 46%, BARD vs BAAT 58%, FIB-4 vs BAAT 46%, BAAT vs FORN 62%). Each index was differently correlated with anthropometric, clinical and laboratory variables. Indices evaluated retain low concordance, clinicians should be aware of these differences between steatosis/fibrosis scores when expressing a differential liver disease diagnosis or assessing the progression of a known liver disease. Level V, descriptive research.

Changes in Indices of Steatosis and Fibrosis in Liver Grafts of Living Donors After Weight Reduction.

BackgroundA short-term weight reduction program for potential living donors was introduced to reduce the extent of hepatic steatosis prior to liver transplantation. We aimed to investigate changes in non-invasive hepatic steatosis and fibrosis indices among those who completed the program.MethodsAmong 1,950 potential living liver donors between January 2011 and May 2019, 160 living donors joined the weight reduction program. The prospectively collected clinical data of these potential liver donors were analyzed retrospectively. Hepatic steatosis and fibrosis scores were determined using the fatty liver index (FLI), hepatic steatosis index (HSI), and NAFLD fibrosis score (NFS) and compared to MR spectroscopy (MRS) fat fraction results before and after weight reduction.ResultsThirty-nine potential living donors who had undergone MRS both before and after weight reduction were included in the analysis. Their body weight decreased from 78.02 ± 10.89 kg to 72.36 ± 10.38 kg over a mean of 71.74 ± 58.11 days. FLI, HSI, and MRS values decreased significantly from 41.52 ± 19.05 to 24.53 ± 15.93, 39.64 ± 3.74 to 35.06 ± 3.82, and 12.20 ± 4.05 to 6.24 ± 3.36, respectively. No significant decreases in NFS were observed. There was a significant correlation between the extent of HSI change and the extent of MRS change (R2 value = 0.69, P < 0.001), although there was no correlation between MRS and FLI.ConclusionThe weight reduction program significantly improved non-invasive indices of hepatic steatosis over a short period. HSI may allow for prediction of simple decreases in hepatic steatosis.

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.

Comparison of the Modified TyG Indices and Other Parameters to Predict Non-Alcoholic Fatty Liver Disease in Youth.

Simple SummaryNon-alcoholic fatty liver disease (NAFLD) is associated with cardio-metabolic risk factors, including obesity, dyslipidemia, insulin resistance, and hepatic cirrhosis. The increasing prevalence of NAFLD among youths has become a public health concern. However, studies about reliable markers for assessing NAFLD in youths are limited. Thus, we investigated the markers including the triglycerides-glucose (TyG) index, modified TyG indices, hepatic steatosis index (HSI), aspartate transaminase-to-platelet ratio index (APRI), and modified APRIs for the prediction of NAFLD. This study demonstrated that the modified TyG indices, APRI-body mass index standard deviation score, and HSI are strongly associated with NAFLD in children and adolescents. Thus, these markers may be useful for identifying youths who require hepatic ultrasonography and early treatment.We investigated the modified triglycerides-glucose (TyG) indices and other markers for non-alcoholic fatty liver disease (NAFLD) in 225 participants aged 10–19 years, and the participants were divided into subgroups according to their NAFLD grade. We performed logistic regression analysis and calculated the odds ratios (ORs) with 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter, with those of tertile 1 as a reference. The area under the receiver operating characteristic (ROC) curve was calculated to compare the parameters for identifying NAFLD. TyG and modified indices, aspartate transaminase-to-platelet ratio index (APRI)-body mass index (BMI), APRI-BMI standard deviation score (SDS), APRI waist-to-hip ratio, fibrosis-4 index (FIB)-4, and hepatic steatosis index (HSI) were higher in participants with NAFLD than in those without NAFLD. The ORs and 95% CIs for NAFLD progressively increased across tertiles of each parameter. TyG and modified TyG indices, FIB-4, HSI, and modified APRIs, except APRI waist-to-height ratio, predicted NAFLD significantly through ROC curves. Modified TyG indices, APRI-BMI SDS, and HSI were superior to the other markers for NAFLD prediction. Modified TyG indices, APRI-BMI SDS, and HSI appear to be useful for assessing NAFLD in youths.

Association of thyroid autoimmunity with nonalcoholic fatty liver disease in euthyroid middle-aged subjects: A population-based study.

The association between thyroid autoimmunity and nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we aimed to investigate the relationship between thyroid autoimmunity and NAFLD in a large cohort of euthyroid subjects. We analyzed clinical and biochemical data from a nationwide, population-based, cross-sectional survey (KNHANES VI). A total of 1589 middle-aged participants aged 45-65years, with normal thyroid function, were included in this study. NAFLD was defined as a hepatic steatosis index of >36. We estimated the odds ratios (ORs) for NAFLD according to anti-thyroid peroxidase antibody (TPOAb) positivity by using logistic regression models, and adjusted for potential confounders. Overall, 24% (n=378) of the subjects had NAFLD. Subjects with NAFLD showed a higher positivity for TPOAb (11% vs 7%, P=0.014) compared with those without NAFLD. TPOAb positivity was a significant risk factor for NAFLD [OR 1.668, 95% confidence interval (CI) 1.019-2.730, P=0.042] even after adjusting for confounding variables, including age, sex, household income, education, smoking, alcohol consumption, walking activity, abdominal obesity, elevated blood pressure, dyslipidemia and hyperglycemia. In addition, TPOAb positivity predicted the risk of advanced liver fibrosis (OR 3.112, 95% CI 1.256-7.713, P=0.014) in subjects with NAFLD, independent of the confounding variables. In euthyroid subjects, thyroid autoimmunity is associated with NAFLD and advanced liver fibrosis, independent of known metabolic risk factors. Large longitudinal studies in the future will help clarify the causality.

Dietary carbohydrate-to-protein ratio influences growth performance, hepatic health and dynamic of gut microbiota in atlantic salmon (Salmo salar)

Atlantic salmon (Salmo salar) fed a carbohydrate-rich diet exhibit suboptimal growth performance, along with other metabolic disturbances. It is well known that gut microbes play a pivotal role in influencing metabolism of the host, and these microbes can be modified by the diet. The main goal of the present study was to determine the effect of feeding graded levels of digestible carbohydrates to Atlantic salmon on the distal intestine digesta microbiota at 3 sampling times (i.e., weeks 4, 8 and 12), during a 12-week trial. A low carbohydrate-to-high protein diet (LC/HP, 0% wheat starch), a medium carbohydrate-to-medium protein diet (MC/MP, 15% wheat starch) or a high carbohydrate-to-low protein diet (HC/LP, 30% wheat starch) was fed to triplicate fish tanks (27 to 28 fish per tank). We performed an in-depth characterization of the distal intestine digesta microbiota. Further, growth parameters, liver histology and the expression of genes involved in hepatic neolipogenesis in fish were measured. Fish fed a HC/LP diet showed greater hepatosomatic and viscerosomatic indexes (P = 0.026 and P = 0.018, respectively), lower final weight (P = 0.005), weight gain (P = 0.003), feed efficiency (P = 0.033) and growth rate (P = 0.003) compared with fish fed the LC/HP diet. Further, feeding salmon a high digestible carbohydrate diet caused greater lipid vacuolization, steatosis index (P = 0.007) and expression of fatty acid synthase (fas) and delta-6 fatty acyl desaturase (d6fad) (P = 0.001 and P = 0.001, respectively) in the liver compared with fish fed the LC/HP diet. Although, the major impact of feeding a carbohydrate-rich diet to Atlantic salmon in beta diversity of distal intestine digesta microbiota was observed at week 4 (HC/LP vs MC/MP and HC/LP vs LC/HP; P = 0.007 and P = 0.008, respectively) and week 8 (HC/LP vs MC/MP; P = 0.04), no differences between experimental groups were detected after 12 weeks of feeding. Finally, at the end of the trial, there was a negative correlation between lactic acid bacteria (LAB) members, including Leuconostoc and Lactobacillus, with hepatic steatosis level, the hepatosomatic and viscerosomatic indexes as well as the expression of fas and d6fad. Weissella showed negative correlation with hepatic steatosis level and the hepatosomatic index. Finally, further research to explore the potential use of LAB as probiotics to improve liver health in carnivorous fish fed fatty liver-induced diet is warranted.

Skeletal muscle mass and abdominal obesity are independent predictors of hepatic steatosis and interact to predict ten-year cardiovascular disease incidence: Data from the ATTICA cohort study

Sarcopenia and sarcopenic obesity may be associated with nonalcoholic fatty liver disease (NAFLD). This study examined the association between low skeletal muscle mass, with or without central obesity, with NAFLD, as well as their interaction on predicting 10-year incidence of cardiovascular disease (CVD).This was a post-hoc analysis of the ATTICA study. At baseline, 3042 participants from the Attica region of Greece were recruited; 2020 completed the 10-year follow-up visit for CVD. NAFLD was assessed through hepatic steatosis index (HSI). Skeletal muscle mass index (SMI) was calculated to assess skeletal muscle mass. SMI was studied in tertiles, stratified by sex; the first tertile corresponds to the lowest SMI, the second to middle, and the third to highest SMI. Abnormal waist circumference was defined as ≥102 cm for men and ≥88 cm for women. The combined 10-year endpoint was the development of a fatal or nonfatal CVD event. Logistic regression analysis was used to assess the association between NAFLD prevalence and SMI as well as Cox regression analysis to assess the interaction of both variables on the incidence of CVD over 10 years.Higher rates of NAFLD were observed in the first (45%) compared to the second [33%; odds ratio (OR): 0.50, 95% confidence interval (95%CI): 0.41-0.61] and the third (22%; OR: 0.24, 95%CI: 0.19-0.29) SMI tertile. This association remained robust after multiple adjustments; significance was marginally lost, when waist circumference was added to the model. When SMI and waist circumference were evaluated jointly, participants with moderate/high SMI and normal waist circumference had the lowest and those with low SMI and abnormal waist circumference the highest NAFLD rate (24.3 and 60.5%, respectively; P < 0.001). Ten-year CVD incidence was gradually lower from the first (22.8%) to second (16.1%) and third SMI tertile (8.2%) (P < 0.001). The hazard ratio (HR) for the third vs. the first SMI tertile for predicting CVD in fully adjusted model was 0.69 (95%CI: 0.46, 1.00). The unadjusted HR for NAFLD predicting CVD was 3.00 (95%CI: 2.28-3.95). Finally, there was a significant interaction among NAFLD, SMI and waist circumference (P = 0.04) in determining the 10-year CVD incidence; the association between NAFLD and 10-year CVD remained significant for the participants with low SMI and normal or abnormal waist circumference, but not those with moderate/high SMI and normal or abnormal waist circumference.Increasing SMI and lower abdominal obesity are independently associated with lower rates of NAFLD, and the two interact as key determinants of NAFLD. Low SMI and central obesity are independent predictors of CVD and were shown to interact with NAFLD in determining 10-year CVD risk.

Hepatic drug metabolism in older people with body composition changes.

Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m2 ) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI ≥36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients. Geriatr Gerontol Int 2022; 22: 449-454.

Interrelationship between physical activity and depression in nonalcoholic fatty liver disease.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is associated with a sedentary lifestyle and depressive symptoms. It is also well established that physical inactivity and depressive symptoms are related. However, an investigation of the interaction between all of these factors in NAFLD has not been previously conducted.AIMTo investigate the interrelationship between physical inactivity and depressive symptoms in individuals with NAFLD.METHODSData from the Rancho Bernardo Study of Healthy Aging were utilized. 589 individuals were included in the analyses (43.1% male; 95.8% non-Hispanic white; aged 60.0 ± 7.0 years). NAFLD was defined by using the hepatic steatosis index, depression using the Beck Depression Inventory, and physical activity by self-report of number of times per week of strenuous activity. Multivariable generalized linear regression models with Gamma distribution were performed to investigate the proposed relationship.RESULTSAbout 40% of the sample had evidence of NAFLD, 9.3% had evidence of depression, and 29% were physically inactive. Individuals with NAFLD and depression were more likely to be physically inactive (60.7%) compared to individuals with neither NAFLD nor depression (22.9%), individuals with depression without NAFLD (37.0%), and individuals with NAFLD without depression (33.3%). After accounting for various comorbidities (i.e., age, sex, diabetes, hypertension, obesity), individuals with NAFLD and higher levels of physical activity were at a decreased odds of having depressive symptoms [16.1% reduction (95% confidence interval: -25.6 to -5.4%), P = 0.004], which was not observed in those without NAFLD.CONCLUSIONIndividuals with NAFLD have high levels of physical inactivity, particularly those with depressive symptoms. Because this group is at high risk for poor outcomes, practitioners should screen for the coexistence of depressive symptoms and NAFLD. This group should receive appropriate interventions aimed at increasing both participation and levels of intensity of physical activity.

Long-term exposure to air pollution, habitual physical activity and risk of non-alcoholic fatty liver disease: A prospective cohort study

BackgroundEmerging studies suggest a positive association between air pollution exposure and risk of non-alcoholic fatty liver disease (NAFLD), however, the combined effects of long-term exposure to air pollution, physical activity (PA), and risk of NAFLD is unclear. MethodsWe included 58,026 Taiwan residents who received a standard medical screening program between 2001 and 2016. Levels of fine particulate matter (PM2.5) at each participant’s residential address were estimated using multiple satellite-based aerosol optical depth data combined with a chemical transport model. PA volume was calculated as hours of metabolic equivalent tasks per week (MET-h/week) based on a standard self-administered questionnaire. Incident NAFLD was defined as the first occurrence of a fatty liver index (FLI) value > 30 or a hepatic steatosis index (HSI) value > 36 in participants without NAFLD at the baseline. Time-varying Cox regression was used to evaluate the combined effects of PA and PM2.5. ResultsExposure to PM2.5 was positively associated with NAFLD. A 1 μg/m3 increase in PM2.5 above 23.5 μg/m3 was associated with a hazard ratio (HR) of 1.06 (95% CI: 1.04, 1.09) and 1.05 (95% CI: 1.03, 1.07) for NAFLD identified by FLI and HSI, respectively. Performing PA was inversely associated with NAFLD. Compared with participants in high PM2.5 [≥ 27.5 μg/m3]–very low PA [< 3.75 MET-h/week] group, low PM2.5 [< 23.5 μg/m3]–very high PA [≥ 25.50 MET-h/week] group had a 57% (95% CI: 50%, 63%) and 42% (95% CI: 33%, 50%) lower risk of NAFLD defined by FLI and HSI, respectively. We found no evidence of any additive or multiplicative interaction between PA and PM2.5. ConclusionLong-term PM2.5 exposure was positively associated with NAFLD, whereas performing PA was inversely associated with NAFLD. The benefits of PA on NAFLD remained stable in participants exposed to various PM2.5 levels.

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

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. We conducted a nationwide cohort study involving 4031 948 subjects aged 40-69years 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. At baseline, 31.3% had NAFLD. During the median follow-up of 9.5years, 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 <25kg/m2 , HR, 1.09; p<.001) than obese NAFLD subjects. 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.

Validation of five hepatic steatosis algorithms in metabolic-associated fatty liver disease: A population based study.

Non-invasive hepatic steatosis algorithms are recommended in detecting metabolic-associated fatty liver disease (MAFLD) in epidemiological studies. However, the diagnostic accuracy of these models is unclear. This study aimed to evaluate the diagnostic efficiency of five common models in a national survey population. The Third National Health and Nutrition Examination Survey (NHANES III) datasets were used in this study. The fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic liver disease-liver fat score (NAFLD-LFS), the steato text (ST), and visceral adiposity index (VAI) were evaluated. The prevalence of MAFLD in the general population was 31.2%. The proportion of MAFLD estimated using the NAFLD-LFS (30.8%) was the closest to the real number, whereas the ST model (66.1%) significantly overestimated the prevalence of MAFLD in this cohort. The FLI (36.9%) and HSI models (38.5%) also slightly overestimated the prevalence of MAFLD in the study population. The FLI had the highest area under the receiver operating characteristic (AUROC) value (0.793) among all models, with a sensitivity of 57.0%, a specificity of 83.8%, a positive predictive value (PPV) of 67.3%, and a negative predictive value (NPV) of 77.0%. The combination of the original algorithm with additional metabolic dysfunction criteria did not improve the diagnostic efficiency. The discriminative ability for MAFLD in all models was lower in participants with a normal body mass index (BMI). Non-invasive models, especially the FLI, have satisfactory diagnostic performance in detecting MAFLD. However, models in people with normal BMIs require further development.