Fatty Liver Disease Group Research Articles

Linking NAFLD and Nephrolithiasis: A CT-Based Investigation

Objective: To evaluate the association between NAFLD and renal stone detected on computed tomography. Method: This study encompassed 240 patients who underwent noncontrast CT abdomen-pelvis computed tomography between November 2023 and April 2024. The nonalcoholic fatty liver disease group included those who had a reduced mean Hounsfield unit (HU) of the right lobe, lateral and left medial segment of the liver as compared to that of the spleen. The control group included patients who had liver parenchyma HU larger than spleen HU. All patients were examined for the presence or absence of radiopaque kidney, ureter, or urinary bladder stones, whether symptomatic or not. Results: From 240 patients, 122 were healthy (50.8%) without NAFLD or renal stone disease. NAFLD was found in 88 individuals with a mean age of 46.8±17.7 years, 42 (47.7%) males and 46 (52.3%) women. Renal stone disease was detected in 70 patients, accounting for 29.1% of the total. The average age of these patients was 43.7± 19.3 years, with 32 males and 38 females. Forty individuals with NAFLD had renal stones (45.5%) which was significantly more than the prevalence in those who are NAFLD negative 13 (19.7%), p <0.001. Females with NAFLD had a considerably greater renal stone rate (52.2%) compared to those without NAFLD (16.3%), P < 0.001. Conclusion: Patients with non-alcoholic fatty liver disease (NAFLD) had a significantly higher incidence of renal stone disease compared to persons with a healthy liver, especially among women.

Health Inequalities and Nutritional Factors Affecting the Nonalcoholic Fatty Liver Disease of Korean Adults: Korea National Health and Nutrition Examination Survey 2013–2018

The aim of this study was to reduce the health inequalities by extracting subjects with nonalcoholic fatty liver disease using data from the Korea National Health and Nutrition Examination Survey and examining the relationship between nonalcoholic fatty liver disease and nutritional factors. Among a total of 13,686 patients, 1604 (11.4%) nonalcoholic fatty liver disease groups were classified using the nonalcoholic fatty liver disease liver fat score method. The proportion of those who answered that they were unhealthy on their own in nonalcoholic fatty liver disease group was high, the quality of life was significantly lower, and the rate of not being able to eat a nutritionally balanced diet due to economic difficulties was also higher. The factors affecting the occurrence of nonalcoholic fatty liver disease include male (OR 1.66), low-income level (OR 3.08), living in large cities (OR 1.62), overweight or obesity (OR 3.47), alcohol intake (OR 2.62), subjective body image as fat (OR 2.02), and high levels of stress (OR 1.81). For nonalcoholic fatty liver disease, which can increase the therapeutic effect through lifestyle improvement, individual living conditions have been shown to have a large influence, and if there are areas with relatively poor nutritional equity, active management and intervention are required.

Nonalcoholic Fatty Liver Disease and Continuous Metabolic Syndrome in Adolescents with Overweight/Obesity.

Nonalcoholic fatty liver disease is the leading cause of pediatric chronic liver disease. Although nonalcoholic fatty liver disease is closely associated with obesity, its relationship with metabolic syndrome in children is not fully understood. The main aim of this study was to evaluate the association between nonalcoholic fatty liver disease and a combination of cardiometabolic risk factors in adolescents with overweight/obesity, using a pediatric metabolic syndrome score (PsiMS) to predict metabolic syndrome. A retrospective cohort study was conducted. Subjects with overweight/obesity aged 10 to 17 followed at two clinical centers in Portugal (2018 - 2021) were enrolled. The independent association of nonalcoholic fatty liver disease with PsiMS, and of other potential predictors, was tested through multiple regression analyses. Receiver operator characteristic curve analysis was performed to estimate the optimal cutoff of PsiMS to discriminate metabolic syndrome. Eighty-four subjects were included (median age at baseline 11.5 years). The prevalence rate of nonalcoholic fatty liver disease was 51% and the prevalence rate of metabolic syndrome was 7%. The mean PsiMS was 2.05 ± 0.48 at the first evaluation, and 2.11 ± 0.52 at the last evaluation (mean follow-up time was 15 months). The nonalcoholic fatty liver disease group had significantly (p < 0.05) higher weight and body mass index z-scores, higher rate of severe obesity and higher waist circumference percentile. PsiMS was highly accurate in predicting metabolic syndrome (area under the curve = 0.96), with an optimal cutoff of 2.46 (sensitivity 100%, specificity 89%). In the univariate analysis, no statistically significant association was observed between nonalcoholic fatty liver disease and PsiMS. In the multiple regression analysis, female sex had a negative association with PsiMS (first and last evaluation). Independent predictors of a higher PsiMS at first evaluation were: ≥ 2 metabolic syndrome criteria, body mass index z-score, insulin resistance and dyslipidemia. At the last evaluation, independent predictors of a higher PsiMS were: nonalcoholic fatty liver disease, baseline PsiMS and body mass index increase from baseline. The results suggest a good performance of the PsiMS to assess metabolic syndrome and that nonalcoholic fatty liver disease is associated with PsiMS at follow-up.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Association between nonalcoholic steatohepatitis and high serum ferritin levels in type 2 diabetes mellitus.

The aim of this study was to assess the role of elevated serum ferritin levels in the onset, pathological progression and prognosis of nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease has been rapidly increasing worldwide. Despite extensive research on the pathogenesis of nonalcoholic fatty liver disease, a lack of sufficient clinical research on the relationship between nonalcoholic fatty liver disease and serum ferritin levels remains. We analysed 968 patients with type 2 diabetes mellitus who underwent liver ultrasound examination and had their serum ferritin levels measured. The presence of nonalcoholic fatty liver disease and advanced liver fibrosis was determined through abdominal ultrasound examination and the nonalcoholic fatty liver disease fibrosis score. Compared to that in the non-nonalcoholic fatty liver disease group, the presence of hyperferritinemia was significantly more common in the nonalcoholic fatty liver disease group (83.3 vs. 56.3%, p=0.005). When patients with nonalcoholic fatty liver disease were stratified by the nonalcoholic fatty liver disease fibrosis score, those with advanced liver fibrosis exhibited a higher prevalence of hyperferritinemia (56.3, 78.9, and 88.9% for none, simple steatosis, and advanced fibrosis, respectively; p for trend=0.002). In multivariate logistic regression, liver fibrosis was independently associated with hyperferritinemia (odds ratio [OR] 1.45; 95% confidence interval [CI] 1.18-2.02; p=0.014), and this association remained significant in male patients after adjusting for other risk factors (OR 2.66; 95% CI 1.43-5.48; p=0.026). Identifying nonalcoholic fatty liver disease patients at a risk of developing nonalcoholic steatohepatitis and advanced fibrosis is crucial for implementing timely interventions and improving patient outcomes. This study highlights the potential utility of serum ferritin levels as a serum biomarker for identifying nonalcoholic steatohepatitis patients and those at a risk of late-stage fibrosis, particularly in male patients with nonalcoholic fatty liver disease.

Role of Alanine Transaminase and Transient Elastography in Categorising Nonalcoholic Fatty Liver Disease Subgroups.

To investigate the association of alanine transaminase (ALT) with transient elastography grades to define various nonalcoholic fatty liver disease (NAFLD) groups for disease status. Cross-sectional, descriptive study. Place and Duration of the Study: Gastroenterology Outpatient Clinic, Ziauddin Hospital, from January to December 2022. This study included 194 NAFLD patients. Demographic data, body mass index, enzymes, and transient elastography (TE) findings were recorded. NAFLD patients were categorised as nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), steatofibrosis (significant fibrosis F2-F3 with normal ALT), and cirrhosis using TE grades. The median age of the patients was 44 [IQR 18.25] years; 146 (75.3%) were males. Out of 194 NAFLD patients, 21 (10.8%) were NAFL, 116 (59.8%) were NASH, 14 (7.2%) showed steatofibrosis, and 43 (22.2%) were cirrhotic. On transient elastography, the majority were with S3 steatosis (n=107, 55.2%) and 59 (30.2%) had F0-F1 fibrosis. There was a statistically significant difference in the mean rank of age, ALT, AST, and GGT levels within 4 groups of NAFLD (p <0.001). Most of the patients with all the stages of fibrosis had increased ALT levels (p=0.034). This study concluded that a combination of ALT levels and transient elastography findings could be considered for differentiating uncomplicated steatosis from NASH, steatofibrosis, and cirrhosis, hence limiting the use of liver biopsy. This may prove a reliable way to measure the severity of the disease. Nonalcoholic fatty liver disease, Cirrhosis, Transient elastography.

Non-alcoholic fatty liver disease associated with greater herpes zoster risk than alcoholic fatty liver disease

BackgroundDisease-related stress can trigger the occurrence of herpes zoster (HZ). Fatty liver disease (FLD) can have adverse effects on the human body and may induce stress in affected individuals. In this study, we investigated whether FLD is associated with an elevated risk of HZ.MethodsFor this study, we utilized data from the National Health Insurance Research Database, patients with FLD from 2000 to 2017 were observed (follow-up until 2018). Patients were considered to have FLD if they had at least two outpatient visits or at least one admission record with a diagnostic code of FLD. Patients with FLD were matched 1:1 by age, sex, comorbidities, and index year with control patients. Additionally, the FLD was further categorized into non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) groups. Multivariable Cox proportional hazards model was used to calculate the incidence rate and adjusted hazard ratio (aHR) of HZ for FLD and AFLD and for various age groups, sex and comorbidities. Cumulative incidence curve for HZ was plotted through the Kaplan–Meier method, and p-value was calculated using the log-rank test.ResultsAfter 1:1 propensity-score matching, each cohort comprised 62,418 patients. The FLD cohort was further divided into NAFLD and AFLD groups, which respectively comprised 55,709 and 6709 patients. The FLD cohort had a risk of HZ significantly higher than that of the control cohort (aHR = 1.06; p < 0.001). Additionally, the NAFLD group exhibited a significantly higher risk of HZ than did the AFLD group (aHR = 1.22; p < 0.001). Among patients without any comorbidities, those with FLD had a higher risk of HZ than did those without FLD (aHR = 1.14; p < 0.001).ConclusionPatients with FLD are at an increased risk of HZ development. Additionally, NAFLD is associated with a higher risk of HZ than AFLD. Therefore, patients with NAFLD should be informed of their increased risk of HZ.

A Plasma Exosomal Metabolic Profiling of Nonalcoholic Fatty Liver Disease Patients Complicated with Impaired Fasting Glucose.

Nonalcoholic fatty liver disease is considered as the hepatic manifestation of metabolic syndrome. Detection of circulating exosomes together with metabolomic analysis of their cargo would provide early signals for metabolic derangements and complications associated with nonalcoholic fatty liver disease. Therefore, this study profiled exosomal metabolome of patients with nonalcoholic fatty liver disease and impaired fasting glucose. Plasma exosomes were extracted from nonalcoholic fatty liver disease patients with or without impaired fasting glucose through differential ultracentrifugation. Their metabolite profiles were examined by ultrahigh-performance liquid chrom atography-quadrupole time-of-flight mass spectrometry. Pathway analysis was carried out on platform MetaboAnalyst 4.0. Thirty-nine patients were enrolled, including nonalcoholic fatty liver disease-alone group (n = 26) and age-and gender-comparable nonalcoholic fatty liver disease plus impaired fasting glucose group (n = 13). Although less than and different from their plasma counterparts, a total of 10 significantly differential exosomal metabolites were identified. Nonalcoholic fatty liver disease plus impaired fasting glucose group had higher concentrations of linoleic acid, palmitamide, stearamide, and oleamide, as well as a lower concentration of phosphatidylethanolamine [20:5(5Z,8Z,11Z,14Z,17Z)/20:5(5Z,8Z,11Z,14Z,17Z)]. Pathway analysis showed an obviously changed metabolism of linoleic acid. Metabolomic analysis of plasma exosomes revealed a distinct change in fatty acids and related pathways in nonalcoholic fatty liver disease patients with impaired fasting glucose. These preliminary results provide a metabolomic snapshot and basis for further investigation of exosome biology for these patients.

Differences Between Conventional and Newer Anthropometric Measures Among Individuals with and without Fatty Liver Disease.

A cross-sectional analysis was conducted to compare conventional and emerging anthropometric measures among male participants with and without fatty liver disease (FLD). The objective was to assess differences and diagnostic efficiency of anthropometric-parameters using receiver operating curve (ROC) analysis at Combined Military Hospital Multan, NUMS from April to October 2022. Comparison for anthropometric measurements between non-FLD (n=164) vs. FLD (n=85) indicated significant differences in weight (74.01 + 11.96 vs. 85.91 + 14.07 kg, p<0.001), waist circumference (9.38 + 9.82 vs. 101.35 + 10.74 cm, p<0.001), BMI (24.81 + 4.0 vs. 29.21 + 4.38 kg/m2, p<0.001), waist-to-hip ratio (WHpR) (0.924 + 0.054 vs. 0.971 + 0.054, p<0.001), waist-to-height ratio (WHtR) (0.508 + 0.054 vs. 0.578 + 0.062, p<0.001), and abdominal volume index (AVI) (16.17 + 3.56 vs. 20.77 + 4.61, p<0.001). Fatty liver index (FLI) also showed significant difference between non-FLD vs. FLD groups (38.35 + 27.12 vs. 72.01 + 21.31, p<0.001). AUCs for various significant anthropometric measurements from highest to lowest as 0.821 (95% CI: 0.767-0.874) for FLI, 0.815 (95% CI: 0.761-0.869) for WHtR, 0.809 (95% CI: 0.754-0.863) for AVI, and 0.808 (95% CI: 0.754-0.863) for waist circumference with lowest recorded AUC for height as 0.422 (95% CI: 0.347-0.497). Key Words: Fatty liver disease (FLD), Body mass index (BMI), A body shape index (ABSI), C-index, Abdominal volume index (AVI), Body roundness index (BRI).

Iron metabolism and metabolic dysfunction-associated fatty liver disease

Abstract Objective: The primary objective of this study was to investigate the association between biomarkers of iron metabolism and metabolic dysfunction-associated fatty liver disease in individuals with type 2 diabetes and non-diabetic individuals compared to a control group. We also examined the possible association between estimated liver fibrosis and serum ferritin levels in all three groups. Methods: We conducted a descriptive, cross-sectional, comparative study involving subjects diagnosed with diabetes and/or metabolic dysfunction-associated fatty liver disease from an outpatient diabetology clinic and two general practices in Târgu Mureș. The patient population was divided into 3 groups: first group including diabetic patients suffering from fatty liver disease, second group including patients without fatty liver disease and third group with non-diabetic patients suffering from fatty liver disease. We compared the three groups based on specific laboratory tests. Results: Patients with fatty liver disease had significantly higher ferritin and transferrin saturation levels than non-fatty liver disease sufferers (p&lt;0.05). Transferrin saturation of the first group was significantly (p&lt;0.05) higher compared to the non-diabetic fatty liver disease group. Ferritin correlated well with Fibrosis-4 index level (τ= 0.193, p&lt;0.01) considering the whole sample and especially in the first group. Conclusions: In our study, there was a clear association between higher ferritin levels and the presence of metabolic dysfunction-associated fatty liver disease. The higher transferrin saturation observed in diabetic patients suffering from metabolic dysfunction-associated fatty liver disease may indicate the possible etiological significance of iron overload. Higher ferritin levels in diabetes increase the risk of liver fibrosis.

Serum Ferritin and Non-alcoholic Fatty Liver Disease: A Meta-analysis and Systematic Review.

Previous studies have shown that hyperferritinemia is a common phenomenon in non-alcoholic fatty liver dis- ease patients. We aim to further explore the relationship between serum ferritin levels and non-alcoholic fatty liver disease using a meta-analysis. Four Library databases were electronically searched from inception until December 2021 to find prospective cohort or case-control studies examining the relationship between serum ferritin levels and non-alcoholic fatty liver disease, and all kinds of literature were screened according to the inclusion and exclusion criteria. The odds ratio and other related data were extracted, and a meta-analysis was performed. Eleven studies examining the relationship between serum ferritin levels and non-alcoholic fatty liver disease were included. The serum ferritin levels in the non-alcoholic fatty liver disease group were significantly higher than those without non-alcoholic fatty liver disease group (1.54 ng/mL, 95% CI: 0.85-2.23, P < .001). Serum ferritin levels were significantly associated with the risk of non-alcoholic fatty liver disease in both men and women (odds ratio = 2.36, 95% CI: 1.41-3.93, P = .001 and odds ratio = 2.93, 95% CI: 1.83-4.69, P < .001, respectively), and after adjusting for the parameters, the relationships were still shown to be significant in men and women (odds ratio = 2.24, 95% CI: 1.64-3.05, P < .001 and odds ratio = 3.30, 95% CI: 2.13-5.11, P < .001, respectively). Serum ferritin levels were higher in patients with non-alcoholic fatty liver disease than in those without non-alcoholic fatty liver disease and were associated with the risk of non-alcoholic fatty liver disease in both men and women.

Fibrosis-4 Index Score Predicts Concomitant Coronary Artery Diseases Across the Spectrum of Fatty Liver Disease.

25% of US adults have nonalcoholic fatty liver disease (NAFLD). The independent association between hepatic fibrosis and cardiovascular disease remains controversial. Metabolic dysfunction-associated fatty liver disease (MAFLD) precisely characterizes hepatic steatosis. We aimed to determine if degree of hepatic fibrosis, with differing metabolic risk factors, is associated with presence of coronary artery disease (CAD). Retrospective review of patients with hepatic steatosis at a single center from January 2016-October 2020 was performed. MAFLD diagnosis was based on presence of fatty liver disease and metabolic factors. Descriptive statistics and stepwise multivariable logistic regression were performed. 5288 patients with hepatic steatosis were included. 2821 patients with steatosis and metabolic risks were classified as NAFLD-MAFLD. 1245 patients with steatosis without metabolic risks were classified as non-MAFLD NAFLD. 812 patients with metabolic risks and other liver disease and were classified as non-NAFLD MAFLD. On Multivariate analysis, Fib-4 ≥ 2.67 was an independent risk factor for CAD in the overall fatty liver disease and NAFLD-MAFLD groups. Fib-4 as a continuous variable showed linear association with CAD risk in the overall fatty liver disease, Non-MAFLD NAFLD and NAFLD-MAFLD groups, at Fib-4 values below 2.67. Fib-4 ≥ 2.67 is independently predicts concomitant CAD in patients with hepatic steatosis. Fib-4, at levels below 2.67, is significantly associated with concomitant CAD in the all fatty liver disease, Non-MAFLD NAFLD, and NAFLD-MAFLD groups. Emphasizing clinical phenotypes and Fib-4 levels may help target those with an increased risk for CAD.

Increased risk of incident diabetes in patients with MAFLD not meeting the criteria for NAFLD

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4–8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

The effect of obstructive sleep apnea on fatty liver disease may be obscured by alcohol consumption: An ordinal logistic regression analysis

BackgroundObstructive sleep apnea (OSA) is closely associated with non-alcoholic fatty liver disease (NAFLD). The current definition of NAFLD cannot exclude the involvement of alcohol consumption in the development of fatty liver disease (FLD), but alcohol can aggravate OSA and participate in steatosis. There is limited evidence on the relationship between OSA and alcohol and its effect on FLD severity. ObjectiveTo determine the effect of OSA on FLD severity based on ordinal responses, and its relationship with alcohol consumption, in order to develop strategies for the prevention and treatment of FLD. MethodsPatients with chief complaints of "snoring" who underwent polysomnography and abdominal ultrasound between January 2015 and October 2022 were selected. A total of 325 cases were divided into three groups according to abdominal ultrasound results: no FLD (n = 66), mild FLD (n = 116), and moderately severe FLD (n = 143) group. Patients were also categorized into alcoholic and nonalcoholic groups. Univariate analysis was used to examine the correlation between OSA and FLD severity. Multivariate ordinal logistic regression analysis was further used to identify the determinants of FLD severity and differences between the alcoholic and nonalcoholic groups. ResultsA higher proportion of moderately severe FLD was observed in the group with an apnea/hypopnea index (AHI) > 30 compared to the AHI<15 group in all participants and in the nonalcoholic population (all p < 0.05). There was no significant difference among these groups in the alcoholic population. Ordinal logistic regression analysis found that in all participants, age [OR = 0.966(0.947–0.986)], BMI [OR = 1.293 (1.205–1.394)], diabetes mellitus [OR = 1.932(1.132–3.343)], hyperlipidemia [OR = 2.432(1.355–4.464)], severe OSA [OR = 2.36(1.315–4.259)] (all p < 0.05) were the independent risk factors for more severe FLD. However, different risk factors applied according to alcohol consumption. In addition to age and BMI, the independent risk factors for the alcoholic group also included diabetes mellitus [OR = 3.323(1.494–7.834)] while in the non-alcoholic group risk factors included hyperlipidemia [OR = 4.094(1.639–11.137)], and severe OSA[OR = 2.956(1.334–6.664)] (all p < 0.05). ConclusionSevere OSA is an independent determinant for developing more severe NAFLD in nonalcoholic population, and alcohol consumption may obscure the effect of OSA on the progression of FLD.

Association between fatty liver disease and hearing impairment in Korean adults: a retrospective cross-sectional study.

We hypothesized that fatty liver disease (FLD) is associated with a high prevalence of hearing loss (HL) owing to metabolic disturbances. This study aimed to evaluate the association between FLD and HL in a large sample of the Korean population. We used a dataset of adults who underwent routine voluntary health checkups (n=21,316). Fatty liver index (FLI) was calculated using Bedogni's equation. The patients were divided into two groups: the non-FLD (NFLD) group (n=18,518, FLI <60) and the FLD group (n=2,798, FLI ≥60). Hearing thresholds were measured using an automatic audiometer. The average hearing threshold (AHT) was calculated as the pure-tone average at four frequencies (0.5, 1, 2, and 3 kHz). HL was defined as an AHT of >40 dB. HL was observed in 1,370 (7.4%) and 238 patients (8.5%) in the NFLD and FLD groups, respectively (p=0.041). Compared with the NFLD group, the odds ratio for HL in the FLD group was 1.16 (p=0.040) and 1.46 (p<0.001) in univariate and multivariate logistic regression analyses, respectively. Linear regression analyses revealed that FLI was positively associated with AHT in both univariate and multivariate analyses. Analyses using a propensity score-matched cohort showed trends similar to those using the total cohort. FLD and FLI were associated with poor hearing thresholds and HL. Therefore, active monitoring of hearing impairment in patients with FLD may be helpful for early diagnosis and treatment of HL in the general population.

Effect of Atractylodes lancea on nonalcoholic fatty liver disease rat induced by high fat - high fructose diet

Non-alcoholic fatty liver disease (NAFLD) induced by long term high-fat and high-fructose diet has led to serious medical problems such as non-alcoholic steatohepatitis or cirrhosis. NAFLD has related to obesity, insulin resistance or type Ⅱ diabetes induced by western diet. With the increasing the incidence of obesity and NFALD due to western diet consisting of high-fat and high-fructose diets, research of the treatment or prevention of NFALD due to western diets is urgently needed. Atractylodes lancea (AL) is traditional Chinese medicine and has been used for diuretic, sedation or antibacterial effect. To investigate effect of AL on NAFLD rat model induced by high-fat and high fructose diet, present study was performed. To induce NAFLD, wistar rats, which were 9-weeks-old, were fed with 45 kcal% high fat diet and 10% fructose water daily for 16 weeks. The olmesartan and atractylodes lancea were treated by oral administration for 8 weeks every day. The groups were composed of 5 groups; control (CON, n=9) fed with 10 kcal% general diet, non-alcoholic fatty liver disease group (NFD, n=9) induced by 45 kcal% high fat diet and 10% fructose diet, NFD group with 10 mg/kg/day Olmesartan orally (OLM, n=9), NFD group with 100 mg/kg/day AL (ALL, n=9) and NFD group with 200 mg/kg/day AL (ALH, n=9). AL decreased body weight, liver weight and epididymal fat pads weight compared with NFD group induced by high-fat and high fructose diet. In serum biomarkers, glucose level of plasma, triglyceride level and total cholesterol level in plasma were increased in NFD group compared with CON. AL restored the serum biomarkers including glucose, or triglycerides and total cholesterol level in serum. The plasma HDL-Cholesterol level, which was decreased in NFD group, attenuated by AL treatment. The atherogenic coeffient was upregulated by chronic high-fat and high-fructose diet, however, the atherogenic coeffient was significantly restored in AL treatment group. Glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) were significantly deteriorated by long term high-fat and high-fructose diet. However, the GOT and GPT level in serum were alleviated in AL treatment groups. Oil red O staining showed that the lipid accumulation in the liver was increased in NFD group compared with CON. However, the lipid accumulation was restored by AL treatment groups. The fibrosis in liver was deteriorated in NFD induced by chronic high-fat and high fructose diet, however, the AL inhibited collagen deposition in liver. Also, AL suppressed the mRNA expressions of TGF-β, collagen Ⅰ and collagen Ⅲ in liver compared with NFD group. In liver tissue, the LXR and SREBP-1c mRNA expressions were downregulated in ALH group. Taken together, these results showed that AL could be potential supplements for NAFLD induced by long term high-fat and high-fructose diet by regulating fibrosis and LXR/SREBP-1c signaling pathway in liver. This study was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIP) (2017R1A5A2015805) (2022R1A6A3A01087272). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Variation in hepatic segmental portal venous pulsed wave Doppler flow distribution in patients with NAFLD: A pilot study.

To evaluate the segmental variations in portal venous pulsed wave colour Doppler flow velocity in patients with moderate to severe non-alcoholic fatty liver disease in comparison with healthy controls. In this prospective, observational, case-control study, the maximum velocity of all the segmental branches of portal vein were evaluated on colour Doppler in patients with moderate to severe non-alcoholic fatty liver disease, and the values were compared between three groups (1) Healthy controls (n = 30), (2) non-alcoholic fatty liver disease group, that is moderate to severe fatty liver without features of portal hypertension (n = 32) and (3) non-alcoholic steatohepatitis-portal hypertension group, that is those non-alcoholic fatty liver disease patients with features of portal hypertension (n = 13). Compared to controls, non-alcoholic fatty liver disease group showed a lower velocity in all the eight segments of liver. The ratio of segment 2 to segment 7 peak portal vein maximum velocity was significantly higher in non-alcoholic fatty liver disease (1.03 ± 0.21) compared to controls (0.90 ± 0.17) and even higher in non-alcoholic steatohepatitis-Portal hypertension group (1.83 ± 0.40) with p value of 0.003. Our study demonstrates the occurrence of flow redistribution occurring in cases of non-alcoholic fatty liver disease patients with the left lobe receiving higher portal venous flow. This flow redistribution was even more pronounced in a subset of non-alcoholic fatty liver disease patients who developed features of portal hypertension.

Comparative Associations of Nonalcoholic Fatty Liver Disease and Metabolic Dysfunction-Associated Fatty Liver Disease With Coronary Artery Calcification: A Cross-Sectional and Longitudinal Cohort Study.

In cross-sectional and retrospective cohort studies, we examined comparative associations between nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) and risk of having or developing coronary artery calcification (CAC). Participants who had health examinations between 2010 and 2019 were analyzed. Liver ultrasonography and coronary artery computed tomography were used to diagnose fatty liver and CAC. Participants were divided into a MAFLD and no-MAFLD group and then NAFLD and no-NAFLD groups. Participants were further divided into no fatty liver disease (reference), NAFLD-only, MAFLD-only, and both NAFLD and MAFLD groups. Logistic regression modeling was performed. Cox proportional hazard model was used to examine the risk of incident CAC in participants without CAC at baseline and who had at least two CAC measurements. In cross-sectional analyses, 162 180 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of prevalent CAC (NAFLD: adjusted odds ratio [OR], 1.34 [95% CI, 1.29-1.39]; MAFLD: adjusted OR, 1.44 [95% CI, 1.39-1.48]). Among the 4 groups, the MAFLD-only group had the strongest association with risk of prevalent CAC (adjusted OR, 1.60 [95% CI, 1.52-1.69]). Conversely, the NAFLD-only group was associated with a lower risk of prevalent CAC (adjusted OR, 0.76 [95% CI, 0.66-0.87]). In longitudinal analyses, 34 233 participants were included. Compared with either the no-NAFLD or no-MAFLD groups, the NAFLD and MAFLD groups were associated with a higher risk of incident CAC (NAFLD: adjusted hazard ratio, 1.68 [95% CI, 1.43-1.99]; MAFLD: adjusted hazard ratio, 1.82 [95% CI, 1.56-2.13]). Among these 4 groups, the MAFLD-only group had the strongest associations with risk of incident CAC (adjusted hazard ratio, 2.03,[95% CI, 1.62-2.55]). The NAFLD-only group was not independently associated with risk of incident CAC (adjusted hazard ratio, 0.88 [95% CI, 0.44-1.78]) Conclusions: Both NAFLD and MAFLD are significantly associated with an increased prevalence and incidence of CAC. These associations tended to be stronger for MAFLD.

Relationship of liver fat content with systemic metabolism and chronic complications in patients with type 2 diabetes mellitus

ObjectiveThis study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients.MethodsEighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared.ResultsBMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05).ConclusionLFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

Maternal betaine supplementation ameliorates fatty liver disease in offspring mice by inhibiting hepatic NLRP3 inflammasome activation.

Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.