Dietary inflammatory index in relation to the progression of hepatic steatosis and liver fibrosis: evaluation by elastography/Fibroscan.

One of the proposed mechanisms by which nutrition influences the progression of hepatic steatosis to fibrosis is inflammation. The study investigated how the inflammatory potential of the diet affects the risk of liver damage in patients with nonalcoholic fatty liver disease (NAFLD), a condition where fat accumulates in the liver. This cross-sectional study included 170 outpatients with newly diagnosed NAFLD. This study used a device called Fibroscan® to measure the degree of liver fibrosis, which is the scarring of the liver tissue due to chronic inflammation. The study also used a tool called the Dietary Inflammatory Index (DII) to measure the inflammatory potential of the diet based on the intake of different foods and nutrients. In the findings of the study, patients with more severe fat accumulation in the liver (hepatic steatosis) had higher DII scores, meaning they had more inflammatory diets. The study also found that higher DII scores were associated with higher weight and body mass index (BMI). One standard deviation (SD) increase in DII scores was associated with a 0.29 kilopascal (95% CI: 0.10-0.44; P-value 0.001) increase in the mean liver stiffness, an indicator of liver fibrosis. The study concluded that patients with higher DII scores had a higher risk of developing liver fibrosis than those with lower DII scores, even after adjusting for confounding factors (odds ratio: 5.89; P-value: 0.001). The study suggested that eating less inflammatory foods may help prevent or slow down the progression of hepatic steatosis and liver in patients with NAFLD.

Non-alcoholic fatty liver disease in Tanzania: prevalence, determinants, and diagnostic performance of triglycerides-glucose index and triglycerides-glucose index -body mass index compared to the hepatic ultrasound in overweight and obese individuals.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), which is closely associated with metabolic syndrome (MetS), is rarely reported in Tanzania, where MetS is prevalent. The purpose of this study was to determine the prevalence and associated factors of this condition in overweight and obese individuals and to correlate standard ultrasound diagnosis with triglyceride-glucose index (TyG) and TyG-body mass index (TyG-BMI). METHODS: A cross-sectional analysis was performed in 181 adult outpatients attending a general medical clinic. The presence of fatty liver was detected by ultrasound. Demographic, clinical, and laboratory data were collected and analyzed using STATA 15. To compare categorical variables, a chi-square test was employed, while a Student's t-test was used to compare continuous variables. Additionally, a multivariate regression analysis was conducted to identify the determinants of NAFLD. A significance level was set at p < 0.05. The discriminatory power of TyG and TyG-BMI for diagnosing NAFLD was evaluated using Receiver Operating Characteristic (ROC) Curve analysis and the Area Under the ROC Curve (AUC) was reported. RESULTS: The overall prevalence of NAFLD was 30.4% (55/181). The prevalence's of NAFLD in patients with class III obesity, class II obesity, class I obesity and overweight were 50.0% (12/24),, 38% (19/50), 23.7% (18/76), and 19.5% (6/31),respectively. NAFLD was strongly predicted by hyperuricemia (≥ 360 µmol/L) (p = 0.04) and TyG ≥ 8.99 (p = 0.003). The best cut-off values of TyG and TyG-BMI to predict NAFLD were 8.99 [AUC 0.735; sensitivity 70.9%, specificity 79.3%] and 312 [AUC 0.711; sensitivity 60% and specificity 75.4%] respectively. CONCLUSIONS: The prevalence of NAFLD is high among people with overweight and obesity in Tanzania. We did not find sufficient evidence to recommend the use of TyG and TyG-BMI as surrogates for hepatic ultrasound in detecting NAFLD, and further evaluation is recommended.

Relation between non-alcoholic fatty liver disease and carotid artery intimal media thickness as a surrogate for atherosclerosis: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis without heavy alcohol consumption or other chronic conditions, encompasses a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis leading to cirrhosis. This analysis aimed to investigate the correlation between NAFLD and carotid intimal media thickness (C-IMT), a non-invasive surrogate for atherosclerosis. METHODOLOGY: Database searches, including PubMed, EMBASE and Cochrane Library, yielded studies up to April 2023. Included were studies exploring the NAFLD-C-IMT relationship in populations aged >18 years. Exclusions comprised non-English papers, those involving animals or pediatric populations and studies lacking control groups. RESULTS: No statistical significance was noted between mild and moderate NAFLD compared to the control group regarding C-IMT [95% confidence intervals (CI): -0.03, 0.12] and (95% CI: -0.03, 0.21), respectively. There was a statistically significant difference only in the Severe NAFLD group ( P value 0.03). NAFLD with and without metabolic syndrome showed statistically significant differences compared to control regarding C-IMT (95% CI: 0.04, 0.12) and (95% CI: 0.01, 0.07), respectively. Fifty-nine studies were mentioned without classification of NAFLD severity and revealed a high statistically significant difference between NAFLD and controls regarding C-IMT with (95% CI: 0.09, 0.12, P < 0.00001). Stratified analysis according to sex was done in two studies and revealed statistical differences between NAFLD and control regarding C-IMT in both groups. CONCLUSION: This meta-analysis underscores a significant association between NAFLD and increased C-IMT, emphasizing the importance of assessing C-IMT in NAFLD patients to identify cardiovascular risk and tailor therapeutic interventions for improved patient outcomes.

Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort.

BACKGROUND AND AIMS: Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. METHODS: This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. RESULTS: The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95 % CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend = 0.04, and 1.63 (1.19-2.21); Ptrend = 0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95 % CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend = 0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend = 0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend = 0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95 % CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend = 0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95 % CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend = 0.02]. CONCLUSIONS: Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

Relationship between skeletal muscle mass loss and metabolic dysfunction-associated fatty liver disease among Chinese patients with metabolic dysregulation.

OBJECTIVE: The aim of this study was to explore the correlation between skeletal muscle content and the presence and severity of metabolic dysfunction-associated fatty liver disease in patients with metabolic dysregulation in China. METHODS: A cross-sectional study was conducted among patients from the endocrinology outpatient department at Ningbo First Hospital, in Ningbo, China, in April 2021. Adult patients with metabolic dysregulation who accepted FibroScan ultrasound were included in the study. However, those without clinical data on skeletal muscle mass were excluded. FibroScan ultrasound was used to noninvasively evaluate metabolic dysfunction-associated fatty liver disease. The controlled attenuation parameter was used as an evaluation index for the severity of liver steatosis. Bioelectrical impedance analysis was used to measure the skeletal muscle index. RESULTS: A total of 153 eligible patients with complete data were included in the final analysis. As the grading of liver steatosis intensifies, skeletal muscle index decreases (men: Ptrend<0.001, women: Ptrend=0.001), while body mass index, blood pressure, blood lipid, uric acid, aminotransferase, and homeostatic model assessment of insulin resistance increase (Ptrend<0.01). After adjusting for confounding factors, a negative association between skeletal muscle index and the presence of metabolic dysfunction-associated fatty liver disease was observed in men (OR=0.691, p=0.027) and women (OR=0.614, p=0.022). According to the receiver operating characteristic curve, the best cutoff values of skeletal muscle index for predicting the metabolic dysfunction-associated fatty liver disease presence were 40.37% for men (sensitivity, 87.5%; specificity, 61.5%) and 33.95% for women (sensitivity, 78.6%; specificity, 63.8%). CONCLUSION: Skeletal muscle mass loss among patients with metabolic dysregulation was positively associated with metabolic dysfunction-associated fatty liver disease severity in both sexes. The skeletal muscle index cutoff value could be used to predict metabolic dysfunction-associated fatty liver disease.

Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity.

Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24 h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r = 0.82, p < 0.001) and the mean value (r = 0.78, p < 0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r = 0.85, p < 0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.

Screening the General Population for Non-Alcoholic Fatty Liver Disease: Model Development and Validation.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Screening the general population for this may help to select appropriate diagnostic and preventive measures before disease progression. AIMS: We aimed to develop a screening method to identify patients with NAFLD in the general population. METHODS: We analyzed cross-sectional data from a large Japanese study of NAFLD. Principal component analysis was used to analyze the data. Candidate predictors were patients' demographic, clinical, and laboratory characteristics. The resulting model was externally validated using three data sets from different populations. RESULTS: Of 15,464 (54.5% men) included patients, 2,741 (17.7%) had NAFLD as determined by ultrasonography. An index was calculated as the arithmetic mean of the scaled body mass index and serum triglyceride levels for both men and women. The area under the receiver operating characteristic curve, sensitivity, specificity, and false positive rate were 0.875, 0.824, 0.770, and 17.6%, respectively. The mean index values were significantly different between the patients with and without non-alcoholic fatty liver disease (p <0.001). The odds ratio of the index cutoff was 15.6 (95% confidence interval [CI]:14.05, 17.39). The model yielded areas under the curve of 0.828, 0.851, and 0.836 for a Chinese (N = 2,319), an Iranian (N = 2,160), and a Brazilian (N = 45,029) data set, respectively. CONCLUSIONS: The proposed composite index demonstrated high performance and generalizability, suggesting its potential use as a screening tool for NAFLD in the general population.

Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare.

BACKGROUND: A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission. METHODS: This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi. RESULTS: The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67-1.00, P = 0.05) and HDL-C (OR = 1.17, 95% CI = 1.03-1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis. CONCLUSION: The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD. TRIAL REGISTRATION: ICTRP, cris.nih.go.kr (KCT0006380).

Association of Diabetic Retinopathy with Midlife Hepatic Steatosis Diagnosed by Elastography and Hepatic Steatosis Index in Type 2 Diabetes in an Indian Population.

Aims: People with type 2 diabetes mellitus are at increased risk of developing hepatic steatosis. We determined the prevalence of hepatic steatosis in middle-aged patients with and without diabetic retinopathy (DR) in an Indian population. We feel this information is critical, with trends of increasing chronic liver disease-related mortality at younger ages. Method: Institution-based analytical cross-sectional study with 114 middle-aged type 2 diabetes patients; 57 in each group with <15 years of duration of DM and without excessive drinking. Hepatic steatosis was determined by the hepatic steatosis index (HSI), hepatic ultrasonography (USG), and elastography. Result: The HSI in DR (37.9 ± 3.9) was more (P = 0.012) than in without diabetic retinopathy (NODR) (36.3 ± 3.3). There was no difference between two groups in liver span (P = 0.829) or in the prevalence of fatty liver (P = 0.562) as determined by conventional USG. Elastography value (kPa) was more (P = 0.001) in DR (6.51 ± 1.85) than in NODR (5.14 ± 1.60). On elastography, 50.9% in DR had a likelihood ratio (Metavir score for a stiffness value) for stage 2 Metavir score. In DR, 11.8% of those missed by USG had a likelihood ratio for ≥ stage 2 Metavir score on elastography. The presence of DR was independently correlated with kPa value (P < 0.001). Conclusion: A significantly higher prevalence of hepatic steatosis was observed in DR in this population. DR can be a useful biomarker for early hepatic screening in midlife, particularly with hepatic elastography, so that timely diagnosis of hepatic steatosis can be made.

ALT poorly predicts Nonalcoholic Fatty Liver Disease (NAFLD) and liver fibrosis as determined by vibration-controlled transient elastography in adult National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND: Non-alcoholic fatty liver disease is a growing problem in the United States, contributing to a range of liver disease as well as cardiovascular disease. ALT is the most widely used liver chemistry for NAFLD evaluation. We hypothesized that the normal range many laboratories use was too high, missing many patients with clinically important steatosis and/or fibrosis. METHODS: This study utilized 2017-2018 NHANES data including 9254 participants. We compared four different upper limits of normal for ALT with specific measurements of steatosis and liver stiffness as determined by liver elastography with FibroScan®. Liver stiffness was further characterized as showing any fibrosis or advanced fibrosis. After exclusions, our final pool was 4184 for liver stiffness measurement and 4183 for steatosis grade as measured by Controlled Attenuation Parameter (CAP). Using these variables, we performed logistic regression between ALT and CAP, and ALT and fibrosis/advanced fibrosis, and did a Receiver Operating Characteristic curve. RESULTS: Based on three of the most widely used cut off values for ALT, we found that ALT does not reliably rule out NAFLD in over 50% of cases. It also missed 45.9-64.2% of patients with liver fibrosis. CONCLUSIONS: Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.

Liver fat volume fraction measurements based on multi-material decomposition algorithm in patients with nonalcoholic fatty liver disease: the influences of blood vessel, location, and iodine contrast.

BACKGROUND: In recent years, spectral CT-derived liver fat quantification method named multi-material decomposition (MMD) is playing an increasingly important role as an imaging biomarker of hepatic steatosis. However, there are various measurement ways with various results among different researches, and the impact of measurement methods on the research results is unknown. The aim of this study is to evaluate the reproducibility of liver fat volume fraction (FVF) using MMD algorithm in nonalcoholic fatty liver disease (NAFLD) patients when taking blood vessel, location, and iodine contrast into account during measurement. METHODS: This retrospective study was approved by the institutional ethics committee, and the requirement for informed consent was waived because of the retrospective nature of the study. 101 patients with NAFLD were enrolled in this study. Participants underwent non-contrast phase (NCP) and two-phase enhanced CT scanning (late arterial phase (LAP) and portal vein phase (PVP)) with spectral mode. Regions of interest (ROIs) were placed at right posterior lobe (RPL), right anterior lobe (RAL) and left lateral lobe (LLL) to obtain FVF values on liver fat images without and with the reference of enhanced CT images. The differences of FVF values measured under different conditions (ROI locations, with/without enhancement reference, NCP and enhanced phases) were compared. Friedman test was used to compare FVF values among three phases for each lobe, while the consistency of FVF values was assessed between each two phases using Bland-Altman analysis. RESULTS: Significant difference was found between FVF values obtained without and with the reference of enhanced CT images. There was no significant difference about FVF values obtained from NCP images under the reference of enhanced CT images between any two lobes or among three lobes. The FVF value increased after the contrast injection, and there were significant differences in the FVF values among three scanning phases. Poor consistencies of FVF values between each two phases were found in each lobe by Bland-Altman analysis. CONCLUSION: MMD algorithm quantifying hepatic fat was reproducible among different lobes, while was influenced by blood vessel and iodine contrast.

Comparative study of ultrasound attenuation analysis and controlled attenuation parameter in the diagnosis and grading of liver steatosis in non-alcoholic fatty liver disease patients.

PURPOSE: To assess the diagnostic performance of Ultrasound Attenuation Analysis (USAT) in the diagnosis and grading of hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) using Controlled Attenuation Parameters (CAP) as a reference. MATERIALS AND METHODS: From February 13, 2023, to September 26, 2023, participants underwent CAP and USAT examinations on the same day. We used manufacturer-recommended CAP thresholds to categorize the stages of hepatic steatosis: stage 1 (mild) - 240 dB/m, stage 2 (moderate) - 265 dB/m, stage 3 (severe) - 295 dB/m. Receiver Operating Characteristic curves were employed to evaluate the diagnostic accuracy of USAT and determine the thresholds for different levels of hepatic steatosis. RESULTS: Using CAP as the reference, we observed that the average USAT value increased with the severity of hepatic steatosis, and the differences in USAT values among the different hepatic steatosis groups were statistically significant (p < 0.05). There was a strong positive correlation between USAT and CAP (r = 0.674, p < 0.0001). When using CAP as the reference, the optimal cut-off values for diagnosing and predicting different levels of hepatic steatosis with USAT were as follows: the cut-off value for excluding the presence of hepatic steatosis was 0.54 dB/cm/MHz (AUC 0.96); for mild hepatic steatosis, it was 0.59 dB/cm/MHz (AUC 0.86); for moderate hepatic steatosis, it was 0.73 dB/cm/MHz (AUC 0.81); and for severe hepatic steatosis, it was 0.87 dB/cm/MHz (AUC 0.87). CONCLUSION: USAT exhibits strong diagnostic performance for hepatic steatosis and shows a high correlation with CAP values.

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. METHODS: Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. RESULTS: Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. CONCLUSION: This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

Ultrasonographic findings of metabolic dysfunction-associated fatty liver disease: A comparative study with non-alcoholic fatty liver disease and clinical characteristics.

PURPOSE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new term proposed to replace non-alcoholic fatty liver disease (NAFLD). We analyzed the ultrasonographic findings of MAFLD and NAFLD. METHODS: We conducted a retrospective cross-sectional study of subjects aged ≥19 years who underwent a health screening examination, including ultrasonography, (n = 17,066). Patients were separated into one of three groups; pure MAFLD (n = 5304), pure NAFLD (n = 579), and both NAFLD & MAFLD (n = 11,183). The outcomes were the degree of fatty liver disease and liver cirrhosis, defined by ultrasonography. In addition, the risk of ultrasonographic cirrhosis was assessed in the MAFLD group based on clinical characteristics. RESULTS: The pure NAFLD group had a lower risk of severe fatty liver disease than the both NAFLD & MAFLD groups (0.9 % vs. 4.4 %, p < 0.001). Cirrhosis was not diagnosed in the NAFLD group. Cirrhosis was more common in the pure MAFLD group than in the both NAFLD & MAFLD group (0.3 % vs. 0.0 %, p < 0.001). In the MAFLD group, multivariable analysis showed that diagnosis by hepatic steatosis index (Odds ratio [OR], 12.39; 95 % confidence interval [CI], 3.40-45.19; p < 0.001) or significant alcohol intake (OR, 9.58, 95 % CI, 1.93-47.61; p = 0.006) was independently associated with risk of liver cirrhosis on ultrasonography. CONCLUSION: Liver cirrhosis was more frequently identified on ultrasonography in patients with MAFLD than in NAFLD. MAFLD diagnosed using the hepatic steatosis index or significant alcohol intake is a risk factor for liver cirrhosis.

Correlation and Performance of three Ultrasound Techniques to Stage Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

AIMS: There is a need to assess the severity of steatosis caused by Nonalcoholic Fatty Liver Disease (NAFLD). We explored new techniques in which Ultrasound-Guided Attenuation Parameter (UGAP), Liver Steatosis Analysis (LiSA) and Hepatorenal Index (HRI) can be applied to the grading of steatosis. MATERIALS AND METHODS: We enrolled 120 patients with or without NAFLD in this study who underwent UGAP, LiSA, HRI and controlled attenuation parameter (CAP) measurements in our hospital from September 2022 to April 2023. Spearman correlation coefficient was used to calculate the correlation between UGAP, LiSA, HRI and CAP values, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of UGAP, LiSA, and HRI for different grades of steatosis. RESULTS: The cohort was classified into four groups based on means of CAP: S0 (no steatosis): 30/120, S1 (mild): 30/120, S2 (moderate): 15/120, and S3 (severe): 45/120. The cut-off values and areas under the receiver operating characteristic curve (AUC) of UGAP, LiSA and HRI for predicting different grades of steatosis were: S≥S1:227dB/m (AUC=0.904), 241dB/m (AUC=0.873), 1.19 (AUC=0.696); S≥S2:251dB/m (AUC=0.978), 264dB/m (AUC=0.913), 1.37 (AUC=0.770); S=S3:263dB/m (AUC=0.962), 289dB/m (AUC=0.923), 1.45 (AUC=0.809). The diagnostic efficacy of UGAP and LiSA was significantly better than HRI, and there were statistically significant differences (all p<0.05). A strong correlation was found between UGAP, LiSA and CAP values (UGAP: r=0.865; LiSA: r=0.810), moderate correlation between HRI and CAP values (r=0.476). CONCLUSION: Both UGAP and LiSA have a strong correlation with CAP and are more accurate than HRI in diagnosing different grades of hepatic steatosis, which can be widely used in the diagnosis of liver steatosis.

pH-triggered hydrophility-adjustable fluorescent probes for simultaneously imaging lipid droplets and lysosomes and the application in fatty liver detection.

To study the collaboration between lipid droplets (LDs) and lysosomes, and the lipid change in nonalcoholic fatty liver disease (NAFLD), herein two pH-triggered hydrophility-adjustable fluorescent probes (LD-Lyso and LD-Lyso 1) are designed. The mechanism is based on cyclization and ring-opening with thorough consideration of pH and hydrophilic differences between LDs and lysosomes. Both of the two probes exist in ring-opening form and emit red fluorescence in acidic environment, while they exist in cyclized form and the emission is blueshifted in alkaline environment due to reduced conjugate planes. Moreover, LD-Lyso exhibits near infrared fluorescence at 740 nm under ring-opening form, which facilitates further cell, tissue, and in vivo imaging. The cell imaging results show that LD-Lyso can simultaneously target LDs and lysosomes by two different colors. Impressively, LD-Lyso cannot only detect NAFLD tissues from the normal tissue, but also distinguish different degrees of NAFLD tissues and mice, which provides a very promising tool for timely diagnosis of early NAFLD.

Vitamin E intake is inversely associated with NAFLD measured by liver ultrasound transient elastography.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, whose severe form is associated with oxidative stress. Vitamin E as an antioxidant has a protective potential in NAFLD. Whether dietary intake of vitamin E, supplementary vitamin E use, and total vitamin E have a preventive effect on NAFLD requires investigation. A cross-sectional study used data from the National Health and Nutrition Examination Survey (2017-2020) was conducted. Vitamin E intake, including dietary vitamin E, supplementary vitamin E use, and total vitamin E, was obtained from the average of two 24-h dietary recall interviews. The extent of hepatic steatosis was measured by liver ultrasound transient elastography and presented as controlled attenuated parameter (CAP) scores. Participants were diagnosed with NAFLD based on CAP threshold values of 288 dB/m and 263 dB/m. The statistical software R and survey-weighted statistical models were used to examine the association between vitamin E intake and hepatic steatosis and NAFLD. Overall, 6122 participants were included for NAFLD analysis. After adjusting for age, gender, race, poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, abdominal circumference, hyperlipidemia, hypertension, diabetes, and supplementary vitamin E use, dietary vitamin E was inversely associated with NAFLD. The corresponding odds ratios (OR) and 95% confidence intervals (CI) of NAFLD for dietary vitamin E intake as continuous and the highest quartile were 0.9592 (0.9340-0.9851, P = 0.0039) and 0.5983 (0.4136-0.8654, P = 0.0091) (Ptrend = 0.0056). Supplementary vitamin E was significantly inversely associated with NAFLD (fully adjusted model: OR = 0.6565 95% CI 0.4569-0.9432, P = 0.0249). A marginal improvement in total vitamin E for NAFLD was identified. The ORs (95% CIs, P) for the total vitamin E intake as continuous and the highest quartile in the fully adjusted model were 0.9669 (0.9471-0.9871, P = 0.0029) and 0.6743 (0.4515-1.0071, P = 0.0538). Sensitivity analysis indicated these findings were robust. The protective effects of vitamin E significantly differed in the stratum of hyperlipidemia (Pinteraction < 0.05). However, no statistically significant results were identified when the threshold value was set as 263 dB/m. Vitamin E intake, encompassing both dietary and supplemental forms, as well as total vitamin E intake, demonstrated a protective association with NAFLD. Augmenting dietary intake of vitamin E proves advantageous in the prevention of NAFLD, particularly among individuals devoid of hyperlipidemia.

The Effect of Steatosis on Shear-Wave Velocity and Viscoelastic Properties Related to Liver Fibrosis Progression in Rat Models.

OBJECTIVE: Hepatic fibrosis has recently been evaluated using ultrasonography or magnetic resonance elastography. Although the shear wave velocity (SWV) obtained using point shear wave elastography (pSWE) provides a valuable measure of fibrosis, underlying steatosis may affect its measurement. METHODS: Using hepatic fibrosis samples, this study evaluated the effect of steatosis on the shear wave velocity of pSWE (Vs) and viscoelastic properties (assessed by dynamic mechanical analysis) of rat liver. Fifty rats with various grades of steatosis and fibrosis underwent open abdominal in vivo Vs measurements using a commercial ultrasound scanner. The mechanical properties of hepatic tissue were also characterized under ex vivo conditions using dynamic mechanical analysis and the Zener model of viscoelasticity. RESULTS: Fibrosis and steatosis progression influenced Vs and elasticity. The SWV computed using the Zener model and Vs showed a substantial correlation (r > 0.8). Fibrosis progression increased SWV. Steatosis was also related to SWV. Steatosis progression obscured the SWV change associated with fibrosis progression. CONCLUSION: We conclude that steatosis progression affects the evaluation of fibrosis progression. This finding could aid discrimination of non-alcoholic steatohepatitis from non-alcoholic fatty liver disease using SWV.

Effects of polyphenol supplementation on hepatic steatosis, intima-media thickness and non-invasive vascular elastography in obese adolescents: a pilot study protocol.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent in obese adolescents. Increased systemic inflammation and decreased gut microbial diversity linked to obesity affect the liver and are also associated with cardiovascular diseases in adulthood. However, NAFLD and vascular alterations are reversible. METHODS AND ANALYSIS: This pilot study evaluated the feasibility of a prospective open-label randomised controlled trial evaluating the effects of polyphenols on NAFLD and vascular parameters in obese adolescents. Children aged 12-18 years with hepatic steatosis (n=60) will be recruited. The participants will be randomised with a 1:1 allocation ratio to receive polyphenol supplementation one time per day for 8 weeks along with the clinician-prescribed treatment (group B, n=30) or to continue the prescribed treatment without taking any polyphenols (group A, n=30). The outcome measures will be collected from both the groups at day 1 before starting polyphenol supplementation, at day 60 after 8 weeks of supplementation and at day 120, that is, 60 days after supplementation. The changes in hepatic steatosis and vascular parameters will be measured using liver and vascular imaging. Furthermore, anthropometric measures, blood tests and stool samples for gut microbiome analysis will be collected. After evaluating the study's feasibility, we hypothesise that, as a secondary outcome, compared with group A, the adolescents in group B will have improved NAFLD, vascular parameters, systemic inflammation and gut microbiome. ETHICS AND DISSEMINATION: This study is approved by Health Canada and the hospital ethics. Participants and their parents/tutors will both provide consent. Trial results will be communicated to the collaborating gastroenterologists who follow the enrolled participants. Abstracts and scientific articles will be submitted to high-impact radiological societies and journals. CLINICALTRIALS: gov ID: NCT03994029. Health Canada authorisation referral number: 250 811. Protocole version 13, 2 June 2023. TRIAL REGISTRATION NUMBER: NCT03994029.