Severity Of Nonalcoholic Fatty Liver Disease Research Articles

Relationship between serum β-hydroxybutyrate and hepatic fatty acid oxidation in individuals with obesity and NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation that can progress to inflammation (nonalcoholic steatohepatitis, NASH), and fibrosis. Serum β-hydroxybutyrate (β-HB), a product of the ketogenic pathway, is commonly used as a surrogate marker for hepatic fatty acid oxidation (FAO). However, it remains uncertain whether this relationship holds true in the context of NAFLD in humans. We compared fasting serum β-HB levels with direct measurement of liver mitochondrial palmitate oxidation in humans stratified based on NAFLD severity (n = 142). Patients were stratified based on NAFLD activity score (NAS): NAS = 0 (no disease), NAS = 1-2 (mild), NAS = 3-4 (moderate), and NAS ≥ 5 (advanced). Moderate and advanced NAFLD is associated with reductions in liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), serum β-HB, but not 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) mRNA, relative to no disease. Worsening liver mitochondrial complete palmitate oxidation corresponded with lower HMGCS2 mRNA but not total (complete + incomplete) palmitate oxidation. Interestingly, we found that liver HMGCS2 mRNA and serum β-HB correlated with liver mitochondrial β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity and CPT1A mRNA. Also, lower mitochondrial mass and markers of mitochondrial turnover positively correlated with lower HMGCS2 in the liver. These data suggest that liver ketogenesis and FAO occur at comparable rates in individuals with NAFLD. Our findings support the utility of serum β-HB to serve as a marker of liver injury and hepatic FAO in the context of NAFLD.NEW & NOTEWORTHY Serum β-hydroxybutyrate (β-HB) is frequently utilized as a surrogate marker for hepatic fatty acid oxidation; however, few studies have investigated this relationship during states of liver disease. We found that the progression of nonalcoholic fatty liver disease (NAFLD) is associated with reductions in circulating β-HB and liver 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2). As well, decreased rates of hepatic fatty acid oxidation correlated with liver HMGCS2 mRNA and serum β-HB. Our work supports serum β-HB as a potential marker for hepatic fatty acid oxidation and liver injury during NAFLD.

Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Histopathological Association of Non-alcoholic Fatty Liver Disease With Coronary Artery Atherosclerosis Grade

Background: The association between the severity of coronary atherosclerosis and histopathologic findings in patients with non-alcoholic fatty liver disease (NAFLD) is not entirely understood. Considering the gold standard method, this study evaluates the histopathologic association between the severity of NAFLD and the grades of coronary atherosclerosis. Methods: In this descriptive-analytical study, data from 205 cadavers who were referred to an Iranian (Tabriz) forensic medicine organization between 2015 and 2017 and underwent simultaneous liver and coronary artery biopsies were examined. Finally, 168 cases were entered based on the inclusion criteria. First, pathological slides of these cadavers were extracted from the forensic medicine archive and re-examined. Then, the selected cases’ blocks were extracted from the tissue block bank, and again, after preparing a new slide, they were stained with trichrome for accurate estimation of liver fibrosis. Results: The assessment of NAFLD histological status in the studied cases revealed that 75.6% of the cases were classified as severity I, 18.4% as severity II, and 6% as severity III. Most cases with coronary atherosclerosis were classified as American Heart Association staging (AHA), type V (19.6%), and normal (19.6%). There was no statistically significant relationship between the severity of simple steatosis, steatohepatitis, and NAFLD, with coronary atherosclerosis. In subjects with higher severity of coronary atherosclerosis, the liver fibrosis rate is also higher, but no statistically significant difference was observed. Conclusion: The present study revealed no significant histopathological association between NAFLD and coronary artery atherosclerosis grade.

Comparison of size of the liver between patients with non-alcoholic fatty liver disease and healthy controls.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease across all age groups. Limited studies have been conducted to consider the relationship between NAFLD and liver size. This study aimed to compare the size of the liver between NAFLD patients and healthy controls. This case-control study was conducted on NAFLD patients (n = 300), and healthy subjects (n = 300) referred to the Golestan Hospital of Ahvaz from April to August 2021. All individuals underwent ultrasonography examination, and liver size was measured in the midclavicular line. Fatty liver was divided into three grades, I (mild), II (moderate), and III (severe), according to the disease severity. Anthropometric parameters, including age, sex, weight, height, and body mass index (BMI), were recorded. Finally, the size of the liver and its relationship with NAFLD and anthropometric parameters was evaluated. Patients had significantly higher weight, and BMI mean values than controls (P < 0.001). In comparison to controls, NAFLD patients had considerably larger livers on average. (149.05 ± 12.60 mm vs. 134.51 ± 12.09; P < 0.001). There was a significant tendency for larger liver size in normal to severe fatty liver patients (P < 0.001). In patients with mild, moderate, and severe NAFLD, the mean liver size was 144.34 ± 11.35, 154.21 ± 10.84, and 158.63 ± 13.45 mm, respectively. The mean liver size in both groups was significantly higher in males than females (P < 0.05). Age (P = 0.037), sex (P < 0.001), height (P < 0.001), BMI (P = 0.008), and steatosis (P < 0.001) were independent variables for predicting the liver size. The liver size of persons with fatty liver was substantially more considerable than healthy people. The size of the liver was substantially linked with sex, age, BMI, fatty liver, and hepatic steatosis grade. A straightforward way to predict fatty liver is to use ultrasonography to determine the size of the liver.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease.

Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Comparison of Serum C-Reactive Protein (CRP) Level Between Non-Alcoholic Fatty Liver Disease (NAFLD) Cases and Healthy Adults: A Cross-sectional Analytical Study.

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis and cirrhosis. Though accurate diagnosis of simple fatty liver (SFL) and non-alcoholic steatohepatitis (NASH) can be made by liver biopsy, it is not feasible to be done in all NAFLD patients. Relationship of C-reactive protein (CRP) with NAFLD was well documented in many populations, but comprehensive data is lacking in Bangladeshi people. Method: This case-control study was conducted at the Medicine, Gastroenterology and Hepatology departments in Dhaka Medical College Hospital from March to August 2018 involving 30 patients with NAFLD as case and apparently healthy 30 individuals as control. Abdominal ultrasound to detect fatty liver and serum CRP level estimation by nephelometry were performed for each subject to compare between two groups. Result: Majority of the NAFLD cases and healthy controls were female (70% and 60% respectively). Mean age was 47.53±9.69 year in NAFLD group and 46.03±8.44 year in healthy controls. NAFLD cases had significantly higher mean serum CRP concentration (6.27±1.80) mg/dl than that of healthy controls (3.94±2.16) mg/dl (p&lt;0.001). Overweight/obesity and dyslipidaemia were found as significant risk factors for NAFLD compared to the healthy control group (p&lt;0.05). Conclusion: NAFLD cases had significantly higher CRP than the control group. But, to find out the association of increasing CRP level with the severity of NAFLD and to establish it as a diagnostic tool, further extensive studies are recommended. J MEDICINE 2024; 25: 5-10

Comparison of triglyceride-glucose index and anthropometric obesity indices in predicting severe grades of hepatic steatosis in nonalcoholic fatty liver disease among non-diabetic obese individuals.

The triglyceride glucose index (TyG) has been proposed as a promising indicator of both insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). However, the efficacy of the TyG index in predicting NAFLD has not been adequately studied, particularly in obese individuals. We analyzed 190 morbidly obese individuals. The TyG index, anthropometric obesity indices, homeostatic model assessment (HOMA-IR), and biochemical parameters were compared. NAFLD was diagnosed by hepatic ultrasonography and classified into four grades (0, 1, 2, and 3). Individuals in grades 2 and 3 are considered to have severe steatosis, while those in grades 0 and 1 do not. The area under the curve (AUC) values of the TyG index, body mass index, neck circumferences, waist-to-hip ratio, and HOMA-IR did not differ significantly in predicting severe steatosis (0.640, 0.742, 0.725, 0.620, and 0.624 respectively). However, the AUC values of waist circumference and alanine aminotransferase provided better predictions than the TyG index (0.782, 0.744, and 0.640 respectively). The TyG index is highly effective in predicting both the presence and severity of NAFLD. However, it did not outperform simple obesity indices in predicting NAFLD and its severity in obese patients.

Circulating fatty acids and risk of severe non-alcoholic fatty liver disease in the UK biobank: a prospective cohort of 116,223 individuals

Fatty acid (FA) metabolism plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). However, data on the relation of circulating FAs with NAFLD risk are limited....

Prunus mume extract and choline treatment in patients with non-alcoholic fatty liver disease estimated by b-mode ultrasonography and hepatorenal index.

The aim of this study was to find the difference between the liver function test (LFT) and hepatorenal index (HRI), before and after the administration of Prunus mume (PM) and choline i.e., to find the predictors of the non-alcoholic fatty liver disease (NAFLD) severity according its HRI, during the three-month follow-up period. LFT, glucose, and lipid tests were determined in 168 NAFLD patients, at baseline and after three-month drug treatment. HRI was calculated by Image J software analyzing the ultrasound images, and according its value, 3 groups of NAFLD were formed. The HRI at baseline (1.3598±0.1744) and after 3 months therapy (1.3061±0.1923) differs significantly (p<0.0001). Plasma glucose (FPG) (p<0.0001), glycated hemoglobin (HbA1c) (P=0.002), alanine aminotransferase (ALT) (p<0.0001), aspartate aminotransferase (AST) (P=0.0006), gamma-glutamil transferase (γ-GT) (P=0.0053), high density lipoprotein cholesterol (HDL-Ch) (p<0.0001) and triglycerides (P=0.041) differ significantly, too. HRI is positively correlated with: HbA1c (P=0.035), ALT (P=0.002), AST (P=0.003), γ-GT (P=0.043), and triglycerides (P=0.002) and inversely correlated with HDL-Ch (P=0.011). In multiple regression results (standard coefficient and p-value), the independent predictors for HRI in NAFLD patients were: HbA1c (0.1443, 0.0004), ALT (0.001142, 0.0081), triglycerides (0.0431, 0.0235) and γ-GT (0.001376, 0.0329). Three-month administration of PM and choline have beneficial effects on the regulation of glucose and lipid metabolism (HDL-Ch), and on LFT. This plant extract significantly reduces the levels of FPG, HbA1c, ALT, AST, γ-GT, triglycerides and increases HDL-Ch. The triglycerides, ALT, γ-GT and HbA1c are positive independent predictors for the severity of NAFLD.

Anthropometry, laboratory, and PNPLA3 polymorphisms in a novel model for early identification and evaluation of nonalcoholic fatty liver disease

BackgroundSome anthropometric, laboratory, and genetic variations, such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic variants, have been associated with nonalcoholic fatty liver disease (NAFLD). Liver biopsy is the most accurate NAFLD diagnostic method, but it is invasive; hence, noninvasive diagnostics are required for the early diagnosis and assessment of NAFLD. Patient and methodsThis prospective case-control study included 107 NAFLD patients and 107 healthy controls. All individuals underwent anthropometric measurements, abdominal ultrasonography, laboratory tests, and evaluation for PNPLA3 polymorphisms. ResultsPatients with NAFLD had higher levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) than healthy individuals (p = 0.03, p < 0.0001). Additionally, patients with NAFLD had substantially lower albumin (P = 0.01) and leptin (P < 0.0001) levels than healthy individuals. BMI leptin and CRP levels were independent indicators of NAFLD severity (p = 0.05–0.004). GG is the most prevalent genotype in patients with moderate to severe NAFLD. A novel model based on four markers (leptin, CRP, BMI, and PNPLA3 polymorphism) was developed. The AUC values for distinguishing between the healthy subjects and those with varying degrees of NAFLD severity (mild, moderate, and severe) were 0.99, 0.99, and 1.0, respectively. ConclusionAnthropometric measurements, such as BMI and laboratory results, including liver enzymes, CRP, inflammatory markers, lipid parameters, and genetic markers, especially PNPLA3 polymorphisms, can provide an accurate, sensitive, and specific noninvasive approach for the early identification and assessment of NAFLD and can guide its management. This may minimize the need for liver biopsy to assess NAFLD. Further large-scale studies are needed to confirm these findings and verify the model in larger studies.

Exposure to per- and polyfluoroalkyl substances, neonicotinoid insecticides, benzotriazoles and benzothiazoles: Associations with human non-alcoholic fatty liver disease

Evidence of the joint association between exposure to multiple environmental chemicals and non-alcoholic fatty liver disease (NAFLD) is scarce. In this study, 281 participants from Zhuhai, China (138 patients with NAFLD vs. 143 healthy participants) were recruited to explore the associations of 40 per- and polyfluoroalkyl substances (PFAS), 11 neonicotinoid insecticides (NEOs), and 8 benzotriazoles (BTRs) and benzothiazoles (BTHs) with the risk of NAFLD. Perfluorooctane sulfonate (PFOS) and its emerging alternatives (6:2 chlorinated polyfluorinated ether sulfonate [6:2 Cl-PFESA] and 8:2 fluorotelomer sulfonic acid [8:2 FTSA]), NEO metabolites (m-NEOs), BTR, and BTH were the predominant PFAS, NEOs, BTRs and BTHs, respectively. The total median concentrations of PFAS (20.4 ng/mL vs. 7.16 ng/mL) and NEOs (7.24 ng/mL vs. 6.23 ng/mL) in NAFLD group were significantly higher than those in healthy group. Sex differences in PFAS exposure have been observed among patients with NAFLD. 8:2 FTSA and short-chain PFAS were more predominant in female patients with NAFLD, whereas other emerging (i.e., 6:2 and 8:2 Cl-PFESA) and legacy PFAS (i.e., PFOS and long-chain perfluoroalkyl carboxylic acids) easily accumulated in male patients with NAFLD. The results of the multiple linear regression analysis indicated a significant positive association between PFOS and alanine transaminase (ALT) in serum samples from patients with NAFLD (β = 23.2, 95% confidence intervals (CI): 7.82, 38.5). Conversely, negative correlations were observed between 5-hydroxy-imidacloprid (5-OH-IMI) and γ-glutamyl transpeptidase (GGT) (β = −2.73, 95% CI: −5.29, −0.18), as well as between tolyltriazole (TTR) and total bilirubin (TBIL) (β = −0.70, 95% CI: −1.33, −0.08) and direct bilirubin (DBIL) (β = −0.59, 95% CI: −0.98, −0.20). The Bayesian kernel machine regression model revealed a positive joint effect of exposure to PFAS and NEO on elevated NAFLD outcomes, suggesting that exposure to PFAS and NEO might exacerbate the severity of NAFLD. This study fills the knowledge gap between multi-pollutant exposure and NAFLD risk.

Mitofusin-2 induced by exercise modifies lipid droplet-mitochondria communication, promoting fatty acid oxidation in male mice with NAFLD

Background and aimThe excessive accumulation of lipid droplets (LDs) is a defining characteristic of nonalcoholic fatty liver disease (NAFLD). The interaction between LDs and mitochondria is functionally important for lipid metabolism homeostasis. Exercise improves NAFLD, but it is not known if it has an effect on hepatic LD-mitochondria interactions. Here, we investigated the influence of exercise on LD-mitochondria interactions and its significance in the context of NAFLD. Approach and resultsMice were fed high-fat diet (HFD) or HFD-0.1 % methionine and choline-deficient diet (MCD) to emulate simple hepatic steatosis or non-alcoholic steatohepatitis, respectively. In both models, aerobic exercise decreased the size of LDs bound to mitochondria and the number of LD-mitochondria contacts. Analysis showed that the effects of exercise on HOMA-IR and liver triglyceride levels were independent of changes in body weight, and a positive correlation was observed between the number of LD-mitochondria contacts and NAFLD severity and with the lipid droplet size bound to mitochondria. Cellular fractionation studies revealed that ATP-coupled respiration and fatty acid oxidation (FAO) were greater in hepatic peridroplet mitochondria (PDM) from HFD-fed exercised mice than from equivalent sedentary mice. Finally, exercise increased FAO and mitofusin-2 abundance exclusively in PDM through a mechanism involving the curvature of mitochondrial membranes and the abundance of saturated lipids. Accordingly, hepatic mitofusin-2 ablation prevented exercise-induced FAO in PDM. ConclusionsThis study demonstrates that aerobic exercise has beneficial effects in murine NAFLD models by lessening the interactions between hepatic LDs and mitochondria, and by decreasing LD size, correlating with a reduced severity of NAFLD. Additionally, aerobic exercise increases FAO in PDM and this process is reliant on Mfn-2 enrichment, which modifies LD-mitochondria communication.

Identification of Predictors of Non-alcoholic Steatohepatitis and Its Severity in Individuals Undergoing Bariatric Surgery.

As obesity reached epidemic proportions, non-alcoholic fatty liver disease (NAFLD) also had a worrisome parallel increase. The non-invasive differentiation of non-alcoholic steatohepatitis (NASH) from uncomplicated NAFLD remains an important challenge in current clinical practice. To identify predictors of the occurrence and severity of NAFLD and NASH. This is an analytical cross-sectional study which included individuals undergoing bariatric surgery. Participants were histologically classified according to the presence NASH and severity of NAFLD. Demographic, clinical, anthropometric, and biochemical aspects were analyzed and compared. Out of 171 individuals, 87.7% were female and the mean age was 38.4±9.3 years. The average BMI was 38±3.0 kg/m2. NAFLD was histologically confirmed in 74.9%; the commonest histopathological abnormalities were macrovesicular steatosis (74.9%) and ballooning (40.4%). Simple steatosis occurred in 30.4%, 44.4% presented with NASH, and 31% had severe NAFLD. NASH associated with higher levels of ALT (0.03), ALP (0.02), and glucose (0.02). Cutoff values were, respectively, 23 U/L, 67 U/L, and 81 mg/dL. Their concomitant use provided an 83.1% specificity for NASH. Severe NAFLD associated with diabetes (p=0.02), higher BMI (p=0.01), AST (p=0.04), ALT (p<0.01), ALP (p=0.01), glucose (p=0.02), and ferritin (p<0.01). BMI over 39.3 kg/m2 and ferritin over 178 ng/mL concomitantly provided a 70.5% accuracy for severe NAFLD. NASH and severe NAFLD associated with higher levels of ALT, ALP, and glucose. Severe NAFLD associated with higher BMI and higher ferritin levels in this group. The concomitant evaluation of these laboratory tests could help ruling out NASH and safely screening severe NAFLD.

THE IMPACT OF VITAMIN D ON HEPATIC ENZYMES AND NON-ALCOHOLIC FATTY LIVER DISEASE ACROSS–SECTIONAL STUDY

Non-Alcoholic Fatty Liver Disease (NAFLD) has become increasingly common globally, raising serious concerns for public health. NAFLD is a complex and multifaceted disease that includes a range of liver diseases, such as cirrhosis, non-alcoholic steatohepatitis (NASH), and simple hepatic steatosis. A combination of environmental, metabolic, and genetic factors causes it. Recent data suggests that vitamin D, a fat-soluble vitamin with various physiological roles, may be crucial for liver health and the development of NAFLD. This cross-sectional study aimed to investigate vitamin D's potential impact on liver function and the development of NAFLD. A Cross-Sectional Study was conducted at the Department of Medicine, MTI, LRH, Peshawar, from August 2019 to January 2020. Participants for this study were selected from the Department of Medicine at MTI, LRH, Peshawar, between August 2019 and January 2020. The study population included individuals with NAFLD identified by laboratory, radiographic, and clinical criteria. Blood samples were taken to measure the serum levels of vitamin D and liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Additional clinical and demographic information was also collected. The average age of the participants in this study was forty years, and there was an equal distribution of genders. Following treatment, the severity of NAFLD significantly decreased. At the beginning of the study, 12.3% of participants had severe steatosis, 40.3% had moderate, and 48.4% had mild steatosis. After treatment, 40.3% of patients had no steatosis, 47.8% had mild steatosis, and 17% had significant steatosis. ALT, ALP, and bilirubin levels showed significant improvements in liver function, with p-values &lt;0.05. While an increase in ALP indicated improved liver function, decreased ALT levels demonstrated reduced liver inflammation. Lower bilirubin levels indicated improved liver health. These findings suggest that treatment, possibly involving vitamin D supplementation, improved liver function and reduced the severity of NAFLD, highlighting the need for further research. This study indicates that vitamin D supplementation may benefit liver function and non-alcoholic fatty liver disease severity. The findings suggest that vitamin D may be a helpful treatment option for managing NAFLD, calling for further investigation and clinical testing.

Tryptophan Prevents the Development of Non-Alcoholic Fatty Liver Disease.

The main aim of this research is to study the protective effects of tryptophan on the histomorphological and biochemical abnormalities in the liver caused by a high-calorie diet (HCD), as well as its ability to normalize mitochondrial functions in order to prevent the development of non-alcoholic fatty liver disease (NAFLD). The study was conducted in male Wistar rats aged 3 months at the start of the experiment. Control animals (group I) were fed a standard diet. Group II experimental animals were fed a diet with an excess of fat (45%) and carbohydrates (31%) for 12 weeks. Group III experimental animals also received L-tryptophan at a dose of 80 mg/kg body weight in addition to the HCD. The presence of NAFLD, functional activity, physiological regeneration, and the state of the liver parenchyma and connective tissue were assessed using physiological, morphological, histo-morphometric, biochemical, and biophysical research methods. HCD induced the development of NAFLD, which is characterized by an increase in liver weight, hypertrophy of hepatocytes and an increase in the concentration of lipids, cholesterol and triglycerides in liver tissue. Increased alanine aminotransferase activity in the liver of obese rats also confirm hepatocytes damage. Tryptophan added to the diet lowered the severity of NAFLD by reducing fat accumulation and violations of bioelectric properties, and prevented a decrease in mitochondrial ATP synthesis. The addition of tryptophan can have a potential positive effect on the liver, reducing the severity of structural, biochemical, mitochondrial and bioelectric damage caused by HCD.

Ultrasound Attenuation Imaging vs MRI-PDFF, Echogenicity and Liver Function for Assessing Degree of Steatosis in NAFLD and Non-NAFLD Patients.

Nonalcoholic fatty liver disease (NAFLD) is a primary cause of parenchymal liver disease globally. There are currently several methods available to test the degree of steatosis in NAFLD patients, but all have drawbacks that limit their use.The objective of this study is to determine if a new technique, ultrasound (US) attenuation imaging (ATI), correlates with magnetic resonance proton density fat fraction imaging and hepatic echogenicity as seen on gray scale US imaging.Fifty-four patients were recruited at the University of Washington Medical Center from individuals who had already been scheduled for hepatic US or magnetic resonance imaging (MRI). All participants then underwent both hepatic MRI proton density fat fraction and US. Ultrasound images were then evaluated using ATI with 2 observers who individually determined relative grayscale echogenicity.Analysis showed positive correlation between ATI- and MRI-determined fat percentage in the case group (Spearman correlation: 0.50; P = 0.015). Furthermore, participants with NAFLD tended to have a higher ATI than controls (median: 0.70 vs 0.54 dB/cm/MHz; P < 0.001).This study demonstrates that US ATI combined with grayscale imaging is an effective way of assessing the degree of steatosis in patients with moderate to severe NAFLD.

Association of five diet scores with severe NAFLD incidence: A prospective study from UK Biobank.

This study aimed to contrast the associations of five common diet scores with severe non-alcoholic fatty liver disease (NAFLD) incidence. In total, 162 999 UK Biobank participants were included in this prospective population-based study. Five international diet scores were included: the 14-Item Mediterranean Diet Adherence Screener (MEDAS-14), the Recommended Food Score (RFS), the Healthy Diet Indicator (HDI), the Mediterranean Diet Score and the Mediterranean-DASH Intervention for Neurodegenerative Delay score. As each score has different measurements and scales, all scores were standardized and categorized into quartiles. Cox proportional hazard models adjusted for confounder factors investigated associations between the standardized quartiles and severe NAFLD incidence. Over a median follow-up of 10.2 years, 1370 participants were diagnosed with severe NAFLD. When the analyses were fully adjusted, participants in quartile 4 using the MEDAS-14 and RFS scores, as well as those in quartiles 2 and 3 using the HDI score, had a significantly lower risk of severe incident NAFLD compared with those in quartile 1. The lowest risk was observed in quartile 4 for the MEDAS-14 score [hazard ratio (HR): 0.76 (95% confidence interval (CI): 0.62-0.94)] and the RFS score [HR: 0.82 (95% CI: 0.69-0.96)] and as well as in quartile 2 in the HDI score [HR: 0.80 (95% CI: 0.70-0.91)]. MEDAS-14, RFS and HDI scores were the strongest diet score predictors of severe NAFLD. A healthy diet might protect against NAFLD development irrespective of the specific approach used to assess diet. However, following these score recommendations could represent optimal dietary approaches to mitigate NAFLD risk.

Remnant cholesterol and severity of nonalcoholic fatty liver disease

BackgroundSerum remnant cholesterol levels are being increasingly acknowledged as a causal risk factor for atherosclerotic disease, regardless of conventional lipid parameters. The positive association between remnant cholesterol and nonalcoholic fatty liver disease (NAFLD) has been revealed in previous studies. However, whether remnant cholesterol is associated with the severity of NAFLD remains unknown. This study aimed to explore the association between serum remnant cholesterol and the risk of NAFLD severity.MethodsThis cross-sectional study included a total of 6,053 participants who attended health checkups. The severity of hepatic steatosis was evaluated by liver ultrasound transient elastography. Univariable and multivariable logistic regression analyses were performed to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between remnant cholesterol and the severity of hepatic steatosis. To explore whether the association between remnant cholesterol and NAFLD severity was independent of conventional lipid parameters, we further investigated this association in individuals with normal values of low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides.ResultsIn total, 36.9% of individuals had mild steatosis, and 5.9% had moderate-to-severe steatosis. The serum level of remnant cholesterol in nonsteatosis, mild steatosis and moderate-to-severe steatosis gradually increased (0.71 ± 0.33, 0.97 ± 0.52 and 1.07 ± 0.63 mmol/L, respectively). In the multivariable mode, remnant cholesterol was positively associated with mild hepatic steatosis (OR: 1.730, 95% CI: 1.541 − 1.941, P < 0.001) and moderate-to-severe steatosis (OR: 2.342, 95% CI: 1.765 − 3.109, P < 0.001). These associations were not significantly altered in individuals with normal triglycerides, HDL-C and LDL-C (OR: 1.664, 95% CI: 1.448 − 1.911, P < 0.001; OR: 2.269, 95% CI: 1.619 − 3.180, P < 0.001, respectively).ConclusionsHigher levels of serum remnant cholesterol were associated with more severe hepatic steatosis, regardless of conventional lipid parameters. Individuals with higher remnant cholesterol may need more attention in regular surveillance of NAFLD.

Plasma ceramides are associated with MRI-based liver fat content but not with noninvasive scores of liver fibrosis in patients with type 2 diabetes

BackgroundThere is growing evidence that ceramides play a significant role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), a highly prevalent condition in patients with type 2 diabetes associated with hepatic and cardiovascular events. However, the relationship between plasma ceramide levels and NAFLD severity in type 2 diabetes remains unclear. The main purpose of the present study was to investigate whether circulating levels of ceramides in patients with type 2 diabetes are associated with liver steatosis assessed by the highly accurate magnetic resonance imaging proton density fat fraction (MRI-PDFF). The secondary objective was to assess the relationship between plasma ceramides and noninvasive scores of liver fibrosis.MethodsIn this cross-sectional single-center study, plasma concentrations of 7 ceramides were measured by liquid chromatography-mass spectrometry in 255 patients with type 2 diabetes (GEPSAD cohort). Liver fat content was assessed by MRI-PDFF, and noninvasive scores of liver fibrosis (i.e. Fibrosis-4 index, NAFLD Fibrosis Score, FibroTest® and Fibrotic NASH Index) were calculated. A validation cohort of 80 patients with type 2 diabetes was also studied (LIRA-NAFLD cohort).ResultsLiver steatosis, defined as a liver fat content > 5.56%, was found in 62.4 and 82.5% of individuals with type 2 diabetes in the GEPSAD and LIRA-NAFLD cohorts, respectively. In GEPSAD, MRI-PDFF-measured liver fat content was positively associated with plasma levels of total ceramides (r = 0.232, p = 0.0002), and 18:0, 20:0, 22:0 and 24:0 ceramides in univariate analysis (p ≤ 0.0003 for all). In multivariate analysis, liver fat content remained significantly associated with total ceramides (p = 0.001), 18:0 (p = 0.006), 22:0 (p = 0.0009) and 24:0 ceramides (p = 0.0001) in GEPSAD, independently of age, diabetes duration, body mass index and dyslipidemia. Overall, similar relationship between plasma ceramides and liver fat content was observed in the LIRA-NAFLD validation cohort. No significant association was found between plasma ceramides and noninvasive scores of fibrosis after adjustment for age in both cohorts.ConclusionsPlasma ceramide levels are associated with liver steatosis in patients with type 2 diabetes, independently of traditional risk factors for NAFLD. The independent association between plasma ceramides and liver steatosis adds new insights regarding the relationship between ceramides and NAFLD in type 2 diabetes.

Abstract 12321: Discordant Association of Nonalcoholic Fatty Liver Disease With Lipoprotein(a) and Markers of Atherogenic Dyslipidemia

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia and an increased risk of cardiovascular events. Previous studies have suggested a paradoxical inverse relationship between NAFLD severity and Lp(a) level, an independent cardiovascular risk factor. However, contemporary data in patients with biopsy-proven NAFLD in the U.S. are lacking. Hypothesis: NAFLD severity on liver biopsy has a discordant association with Lp(a) and other markers of atherogenic dyslipidemia. Methods: Lp(a), traditional lipid profile, apolipoproteins, and nuclear magnetic resonance-based lipoprotein particle concentration were measured in 151 patients with NAFLD. Levels were compared between those with nonalcoholic fatty liver (NAFL) on histology and non-alcoholic steatohepatitis (NASH), the clinically aggressive NAFLD variant. Results: Median age was 55 [48, 62] years, 67% of patients were women, 83% were White, 43% had NAFL, and 57% had NASH. Demographic characteristics were similar among those with NAFL and NASH. Triglyceride level was higher and High-Density Lipoprotein-cholesterol (HDL-C) was lower among those with NASH as compared with NAFL. Circulating concentration of two key markers of atherogenic dyslipidemia, Apolipoprotein-B (apoB) and Low-Density Lipoprotein particle concentration (LDL-P) was 9% and 17% higher in the NASH group as compared with NAFL, respectively. Contrastingly, Lp(a) concentration was 50% lower in NASH relative to NAFL group (Figure). Hepatocyte ballooning, lobular inflammation, and fibrosis on histology were inversely associated with Lp(a) concentration, while steatosis severity was not. Conclusions: NAFLD severity has a discordant association with Lp(a) and markers of atherogenic dyslipidemia. The mechanistic basis of this relationship may have implications for prognosticating cardiovascular disease risk and determining the safety of targeted Lp(a) lowering in patients with NAFLD.