Non-alcoholic Fatty Liver Disease Subjects Research Articles

Higher intakes of lysine, threonine and valine are inversely associated with non-alcoholic fatty liver disease risk: A community-based case-control study in the Chinese elderly

The associations of individual amino acid with non-alcoholic fatty liver disease (NAFLD) risk remained unclear. The present study aimed to investigate the associations between the two in the Chinese elderly. MethodsA community-based health check-up program was conducted in Qingdao, China. NAFLD was diagnosed by ultrasonography accompanied by epidemiological investigation. The dietary intakes of amino acids were investigated with 3-day, 24-h dietary records and calculated by Nutrition Calculator software. Restricted cubic spline model was used to evaluate a nonlinear relationship between amino acid intake and NAFLD risk. Results400 NAFLD subjects were identified, and 400 participants were randomly selected as controls and matched by gender and age (± 3 years) Dose-response analysis showed that 1 000 mg increment of aromatic amino acids (AAAs) was associated with reduced 16 % risk of NAFLD. Dietary increments of 750 mg/d threonine, 950 mg/d valine, or 1 700 mg/d lysine were associated with a 20 % reduction in the NAFLD risk (all P for linearity < 0.05). ConclusionThe present study demonstrated that the dietary increases in milk, eggs and deep-sea fish, which are rich in the amino acids, might contribute to protecting against NAFLD in the elderly.

Enhanced inflammasome-mediated inflammation and impaired autophagy in peripheral blood mononuclear cells is associated with non-alcoholic fatty liver disease severity

AimsIdentification of the progress of non-alcoholic fatty liver disease (NAFLD) is crucial for their effective treatment. Circulating peripheral blood mononuclear cells (PBMC) could be a surrogate monitor instead of complicated and expensive biopsies. Changes in immuno-metabolic status in NAFLD patients may be reflected by an expression of different PBMC-specific molecular markers. It was hypothesized that impaired autophagy with enhanced inflammasome activation is a critical molecular event in PBMC that could contribute to systemic inflammation associated with NAFLD progression. Main methodsA cross-sectional study with a sample size of 50 subjects were undertaken from a governmental facility in Kolkata, India. Major anthropometric, biochemical, and dietary parameters were recorded. Cellular and serum samples of NAFLD patients were analyzed for oxidative stress, inflammation, inflammasome activation, and autophagic flux by western blot, flow cytometry, immunocytochemistry. Key findingsBaseline anthropometric and clinical parameters were found associated with NAFLD severity. Elevated systemic inflammation was reflected by higher proinflammatory markers like iNOS, Cox-2, IL-6, TNF-α, IL-1β, hsCRP in the serum of NAFLD subjects (p < 0.05). ROS-induced NLRP3 inflammasomes marker proteins were upregulated (p < 0.05) in PBMC along with NAFLD severity. Expression of autophagic markers such as LC3B, Beclin-1 and its regulator pAMPKα were found diminished (p < 0.05) with a concomitant rise of p62. Colocalization of NLRP3 with LC3B proteins in PBMC was found diminished along NAFLD severity. SignificancePresent data provide mechanistic evidence of impaired autophagy and intracellular ROS triggered inflammasome activation in PBMC, which could potentially exacerbate NAFLD severity.

A non-linear relationship between triglyceride glucose waist circumference and nonalcoholic fatty liver disease in a Japanese population: a secondary analysis.

Nonalcoholic fatty liver disease (NAFLD) is a common metabolic disorder associated with insulin resistance (IR). Triglyceride glucose waist circumference (TyG-WC) is a novel index of IR that reflects both visceral fat and hepatic steatosis. However, it is not known whether TyG-WC and NAFLD exhibit a nonlinear relationship in Japanese subjects with normal plasma glucose level. Thus, we examined the relationship between TyG-WC and NAFLD, in addition to determining the threshold level of TyG-WC associated with NAFLD. A secondary analysis was performed based on a previous study that extracted medical examination records from Murakami Memorial Hospital between 2004 and 2015 in order to detect chronic diseases and their risk factors. TyG-WC was determined at baseline. NAFLD is the dependent variable. Univariate and multivariate logistic regression models were used to evaluate the risk of NAFLD incidence. Based on the smoothing plot, a two-piecewise linear regression model was used to examine the threshold effect of TyG-WC on NAFLD. A subgroup analysis was carried out in order to study other factors that may influence the association between TyG-WC and NAFLD. 14,280 met the criteria for inclusion in the current secondary analysis. The adjusted OR (95% CI) for NAFLD in all subjects was 1.007 (95% CI 1.006-1.009, P < 0.001). The relationship between TyG-WC and NAFLD in Japanese subjects with normal plasma glucose level is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. In subgroup analyses, there was a significant interaction between BMI and TyG-WC associated NAFLD risk (P for interaction <0.001). The relationship between TyG-WC and NAFLD is nonlinear. TyG-WC is positively associated with NAFLD when TyG-WC is ranged between 480 and 800. There is potential clinical significance for the TyG-WC in identifying groups at high risk for NAFLD in subjects with normal plasma glucose level.

Utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-alcoholic liver cirrhosis

The purpose of this research is to determine whether or not there is a correlation between a high neutrophil-to-lymphocyte ratio (NLR) and a high platelet-to-lymphocyte ratio (PLR) and nonalcoholic fatty liver disease (NAFLD). Methods: This was a retrospective study in the medicine department of a tertiary care facility. The demographic and clinical data was retrieved in a methodical fashion from the case records. Along with this, the data regarding the biopsy and other laboratory parameters was recorded to. This data was compared with non-NAFLD patients. Results: The non-NAFLD participants were separated from the NAFLD subjects and placed in one of the two groups. According to the findings of our investigation, a low PLR score was connected with a higher risk of NAFLD (P 0.001), whereas a high NLR score was not significantly linked to NAFLD (P &gt; 0.05). While there was shown to be a positive correlation between NLR and NAFLD, a negative association between PLR and NAFLD was discovered to exist. Conclusion: The findings of this study indicated that a strong association exists between NLR and PLR and NAFLD. we According to the findings, a lower PLR and NLR could be a risk factor for morbidity in NAFLD patients.

Vitamin E supplementation in the treatment on nonalcoholic fatty liver disease (NAFLD): Evidence from an umbrella review of meta-analysis on randomized controlled trials.

We conducted this umbrella review of meta-analysis on randomized controlled trials to clarify the effects of vitamin E administration on alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), degrees of steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). PubMed, MEDLINE, SCOPUS, EMBASE, and Web of Science were searched to identify pertinent articles published up to June 2023. To calculate the overall effect size (ES) and confidence intervals (CI), random-effects model was used. Six meta-analyses were included in the umbrella review. By pooling ES based on the random-effects model, we found that vitamin E supplementation significantly decreased ALT (ES -6.47, 95% CI -11.73 to -1.22, P = 0.01), AST (ES -5.35, 95% CI -9.78 to -0.93, P = 0.01), degrees of fibrosis (ES -0.24, 95% CI -0.36 to -0.12, P < 0.001) and steatosis (ES -0.67, 95% CI -0.88 to -0.45, P < 0.001) in NAFLD patients, but had no effect on GGT. In the subgroup analyses, we detected that fibrosis scores notably decreased when vitamin E dosage was >600 IU/day (ES -0.25, 95% CI -0.41 to -0.10, P = 0.002) and when the treatment duration was ≥12 months (ES -0.24, 95% CI -0.37 to -0.12, P < 0.001). Vitamin E administration improves ALT, AST, fibrosis, and steatosis in NAFLD subjects. Fibrosis scores were significantly reduced when vitamin E dosage exceeded 600 IU/day or with a treatment duration of at least 12 months.

VASCULAR REMODELING AND FIBROSIS INDEXES IN NAFLD SUBJECTS

Objective: Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem and is related to an increased burden of cardiovascular disease. Aim of the study: to assess the relation between non-invasive scoring systems for liver fibrosis (Fibrosis-4 Index and NAFLD Fibrosis Score) and structural and functional vascular properties in NAFLD patients. Design and method: The study enrolled 30 consecutive patients (mean age 64±13, BMI 29.3±6.1 kg/m2, male 60%) who underwent hepatological evaluation in our department. Atherosclerotic burden was evaluated by B-mode ultrasound in each carotid artery segment (common, bulb, internal), bilaterally, and expressed as mean of carotid intima-media thickness (mean-IMT) and mean of maximum IMT (M-MAX), right common carotid artery distensibility and stiffness (CardioVascular Suite 4, Quipu, Italy). Aortic stiffness was measured by applanation tonometry (PulsePen DiaTecne, Italy) and was expressed as carotid-femoral pulse wave velocity (PWV). Results: In our cohort vascular properties were: carotid mean-IMT 0.83±0.15 mm, M-MAX 0.98±0.17 mm, carotid distensibility 18.8±8.3 10-3/kPa, and carotid compliance CC 0.88±0.40 mm2/kPa. We found a significant correlation between NAFLD Fibrosis Score and PWV (mean PWV = 10.9±2.9m/s; Fibrosis Score = -0.97±1.80; R = 0.422, p = 0.020), which remained significant after adjustment for mean arterial blood pressure and sex (p = 0.017). No correlation was found between carotid ultrasound parameters and fibrosis scores. Conclusions: In NAFLD patients, our preliminary observation shows a correlation between a liver fibrosis score and PWV, an established marker of aortic stiffness, while no correlation was observed with carotid atherosclerosis markers. This vascular remodeling phenotype needs to be confirmed in a larger population.

Does the Mediterranean Diet Have Any Effect on Lipid Profile, Central Obesity and Liver Enzymes in Non-Alcoholic Fatty Liver Disease (NAFLD) Subjects? A Systematic Review and Meta-Analysis of Randomized Control Trials.

The effectiveness of the Mediterranean diet (MD) in non-alcoholic fatty liver disease (NAFLD) subjects has been evaluated in several randomized controlled trials (RCTs). This systematic review and meta-analysis aimed to evaluate the overall effects of MD intervention in a cohort of NAFLD patients targeting specific markers such as central obesity, lipid profile, liver enzymes and fibrosis, and intrahepatic fat (IHF). Google Scholar, PubMed, and Scopus were explored to collect relevant studies from the last 10 years. RCTs with NAFLD subjects were included in this systematic review with a mean intervention duration from 6 weeks to 1 year, and different intervention strategies, mainly including energy restriction MD (normal or low glycaemic index), low-fat MD with increased monounsaturated and polyunsaturated fatty acids, and increased exercise expenditure. The outcomes measured in this meta-analysis were gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), total cholesterol (TC), waist circumference (WC), and liver fibrosis. Ten randomized controlled trials, which involved a total of 737 adults with NAFLD, were included. According to the results, the MD seems to decrease the liver stiffness (kPa) by -0.42 (CI95% -0.92, 0.09) (p = 0.10) and significantly reduce the TC by -0.46 mg/dl (CI95% -0.55, -0.38) (p = 0.001), while no significant findings were documented for liver enzymes and WC among patients with NAFLD. In conclusion, the MD might reduce indirect and direct outcomes linked with NAFLD severity, such as TC, liver fibrosis, and WC, although it is important to consider the variations across trials. Further RCTs are necessary to corroborate the findings obtained and provide further evidence on the role of the MD in the modulation of other disorders related to NAFLD.

Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease.

Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG2), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO2max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG2, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.

Relevance of vitamin D on NAFLD and liver fibrosis detected by vibration controlled transient elastography in US adults: a cross-sectional analysis of NHANES 2017–2018

Background The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration controlled transient elastography was investigated in US adults. Methods The National Health and Nutrition Examination Survey of 2017–2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships. Results Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70–1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38–0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37–1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41–1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30–0.79). Conclusions No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects. Key messages: Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults. High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.

Involvement of eNAMPT/TLR4 inflammatory signaling in progression of non-alcoholic fatty liver disease, steatohepatitis, and fibrosis.

Although the progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to steatohepatitis (NASH) and cirrhosis remains poorly understood, a critical role for dysregulated innate immunity has emerged. We examined the utility of ALT-100, a monoclonal antibody (mAb), in reducing NAFLD severity and progression to NASH/hepatic fibrosis. ALT-100 neutralizes eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a novel damage-associated molecular pattern protein (DAMP) and Toll-like receptor 4 (TLR4) ligand. Histologic and biochemical markers were measured in liver tissues and plasma from human NAFLD subjects and NAFLD mice (streptozotocin/high-fat diet-STZ/HFD, 12 weeks). Human NAFLD subjects (n=5) exhibited significantly increased NAMPT hepatic expression and significantly elevated plasma levels of eNAMPT, IL-6, Ang-2, and IL-1RA compared to healthy controls, with IL-6 and Ang-2 levels significantly increased in NASH non-survivors. Untreated STZ/HFD-exposed mice displayed significant increases in NAFLD activity scores, liver triglycerides, NAMPT hepatic expression, plasma cytokine levels (eNAMPT, IL-6, and TNFα), and histologic evidence of hepatocyte ballooning and hepatic fibrosis. Mice receiving the eNAMPT-neutralizing ALT-100 mAb (0.4mg/kg/week, IP, weeks 9 to 12) exhibited marked attenuation of each index of NASH progression/severity. Thus, activation of the eNAMPT/TLR4 inflammatory pathway contributes to NAFLD severity and NASH/hepatic fibrosis. ALT-100 is potentially an effective therapeutic approach to address this unmet NAFLD need.

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects:A population-based study.

To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.

Molecular Screening via Sanger Sequencing of the Genetic Variants in Non-Alcoholic Fatty Liver Disease Subjects in the Saudi Population: A Hospital-Based Study.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, along with steatosis and non-alcoholic steatohepatitis (NASH), and is associated with cirrhosis and hepatocellular carcinoma. Candidate gene and genome-wide association studies have validated the relationships between NAFLD, NASH, PNPLA3, TM6SF2, and HFE. The present study utilized five polymorphisms in three genes: PNPLA3 (I148M and K434E) TM6SF2 (E167K), and HFE (H63D and C282Y), based on undocumented case−control studies in the Saudi Arabian population. A total of 95 patients with NAFLD and 78 non-NAFLD subjects were recruited. Genomic DNA was isolated, and polymerase chain reaction and Sanger sequencing were performed using specific primers for the I148M, K434E, E167K, H63D, and C282Y. NAFLD subjects were older when compared to controls and showed the significant association (p = 0.0001). Non-significant association was found between gender (p = 0.26). However, both weight and BMI were found to be associated. Hardy−Weinberg equilibrium analysis confirmed that H63D, I148M, and K434E polymorphisms were associated. Genotype analysis showed only K434E variant was associated with NAFLD and non-NAFLD (OR-2.16; 95% CI: 1.08−4.31; p = 0.02). However, other polymorphisms performed with NAFLD and NASH were not associated (p > 0.05), and similar analysis was found when ANOVA was performed (p > 0.05). In conclusion, we confirmed that K434E polymorphism showed a positive association in the Saudi population.

The relationship between non-alcoholic fatty liver disease and incidence of chronic kidney disease for diabetic and non-diabetic subjects: A meta-analysis.

The prevalence of chronic kidney disease (CKD) rises with age and co-morbid diseases such as liver diseases. The main aim of the current meta-analysis is to assess the relationship between Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease incidence in both diabetic and non-diabetic subjects compared with control. A systematic literature search of papers published from January 1, 2005, till April 30, 2022, found 19 studies including 1,111,046 subjects; 310,804 were diagnosed with NAFLD, and 800,242 were non-NAFLD. The measured outcome was the incidence of CKD among NAFLD subjects compared to non-NAFLD subjects in diabetic and non-diabetic subjects. Dichotomous analysis methods were used within the random effects model to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs). The incidence of CKD is highly significant in NAFLD subjects compared with controls (OR: 1.95; 95% CI: 1.65-2.31). The diabetic non-NAFLD subjects showed a significantly increased incidence of CKD compared to the non-diabetic subjects with NAFLD (OR: 1.79; 95% CI: 1.35-2.38).. In addition, the incidence of CKD was significantly higher in the NAFLD group compared with the non-NAFLD non-diabetic subjects (OR: 2.52; 95% CI: 1.91-3.32). Diabetes acts as an independent risk factor for CKD, as proven by a significant increase in incidence of diabetic subjects compared to non-diabetic NAFLD subjects (OR: 1.82; 95% CI: 1.15-2.88). Non-alcoholic fatty liver disease is significantly related to an increased incidence of CKD, which is significantly higher in diabetic subjects.

Dysglycemia in young women attenuates the protective effect against fatty liver disease.

Sexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age. To investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia. We analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia. The global prevalence of NAFLD was higher in men than in women (50% and 34%; P<0.001), and the prevalence increased with age in both sexes. Older women (≥ 50 years) had a higher prevalence than younger women (<50 years), both in the overall cohort and in non-dysglycemic subjects. In dysglycemic subjects, the prevalence of NAFLD was slightly higher in men (68% vs 61%, p=0.021); in younger subjects, there were no differences in the prevalence of NAFLD between men and women (68% vs 64%, respectively; p=0.635). We found an interaction between dysglycemia and female sex (odds ratio [OR] 1.6 95% confidence interval [CI] 1.0-2.4, p=0.030), and between and age ≥50 years (OR 0.6, 95% CI 0.3-1.0, p=0.046). The global prevalence of LSM ≥8.0 kPa was higher in men compared with women (8% vs 4%; p< 0.001). This prevalence increased with age, mainly in men. We did not find any association between liver fibrosis and age and gender. While the global prevalence of NAFLD is higher in men than in women across all ages, younger women with dysglycemia have a similar risk of developing NAFLD as men of a similar age. Therefore, the presence of dysglycemia may erase the protective effect of female sex against fatty liverdisease.

RF17 | P715 Contribution of Low Muscle Mass and Genetic Factors in NAFLD and Liver Cirrhosis

Abstract Introduction Both sarcopenia and genetic risk factors are important risk factors for non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the independent effects of low muscle mass and genetic risk factors in the development of NAFLD and liver cirrhosis (LC) in the Korean population. Method: A prospective community-based cohort consisted of adults with age 40–70 years were followed-up biennially from 2001–2002 to 2017–2018. NAFLD was defined as hepatic steatosis index of ≥36, and liver cirrhosis (LC) was defined as a fibrosis-4 index score of ≥1.3. The subjects were divided into four groups according to body mass index (BMI)-adjusted muscle mass. Cox proportional hazards models incorporating age, sex, BMI≥ 25 kg/m2, metabolic syndrome, and PNPLA3, and TM6SF2 risk alleles were used to assess the independent determinants for the incident NAFLD and development of LC among individuals with NAFLD at baseline. Results Among the 4,038 participants without NAFLD at baseline, 920 (22.8%) developed NAFLD during the follow-up. Both the TM6SF2 risk alleles (hazard ratio [HR]. 1.19, [95% confidence interval (CI), 1.00–1.40], P=0.044) and muscle mass index quartiles (Q) (HR per 1 Q, 1.18, 95% CI, 1.11–1.27, P&amp;lt;0.001) were associated with development of NAFLD in the fully adjusted model. Of the 1,442 patients with NAFLD at baseline, LC was eventually confirmed in 552 (38.3%) patients. Only the PNPLA3 risk variant, but not the TM6SF2 genotype nor muscle mass index, was an independent risk factor for developing LC among NAFLD subjects (HR 1.22, 95% CI 1.08–1.38, P=0.001) Conclusion Both the lower muscle mass index and genetic risk variants are important contributors in the development of NAFLD. In patients already diagnosed with NALFD however, PNPLA3 conferred a greater risk for the progression to LC than lower muscle mass. Presentation: No date and time listed

Expression of SARS-Cov-2 Entry Factors in Patients with Chronic Hepatitis.

Chronic hepatitis (CH) of dysmetabolic or viral etiology has been associated with poor prognosis in patients who experienced the severe acute respiratory coronavirus virus-2 (SARS-Cov-2) infection. We aimed to explore the impact of SARS-Cov-2 infection on disease severity in a group of patients with CH. Forty-two patients with CH of different etiology were enrolled (median age, 56 years; male gender, 59%). ACE2 and TMPRSS2 were measured in plasma samples of all patients by ELISA and in the liver tissue of a subgroup of 15 patients by Western blot. Overall, 13 patients (31%) experienced SARS-Cov-2 infection: 2/15 (15%) had CHB, 5/12 (39%) had CHC, and 6/15 (46%) had non-alcoholic fatty liver disease (NAFLD). Compared to viral CH patients, NAFLD subjects showed higher circulating ACE2 levels (p = 0.0019). Similarly, hepatic expression of ACE2 was higher in subjects who underwent SARS-Cov-2 infection compared to the counterpart, (3.24 ± 1.49 vs. 1.49 ± 1.32, p = 0.032). Conversely, hepatic TMPRSS2 was significantly lower in patients who experienced symptomatic COVID-19 disease compared to asymptomatic patients (p = 0.0038). Further studies are necessary to understand the impact of COVID-19 in patients with pre-existing liver diseases.

Association between triglyceride–glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus

BackgroundLipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride–glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population.MethodsA total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD.ResultsLogistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03–5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders. In stratified analysis, an elevated TyG index were more remarkably associated with NAFLD in younger patients (< 65 years; OR, 2.35; 95% CI, 1.83–3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67–4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01–3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (< 1 mmol/L; OR, 2.76; 95% CI, 1.98–3.83; P < 0.001).ConclusionThe TyG index is significantly associated with NAFLD and shows superior ability for identify NAFLD risk compared with other lipid and glycemic parameters in T2DM.

Non-alcoholic fatty liver disease and the risk of fibrosis in Italian primary care services: GPS-NAFLD Study: GPS-NAFLD Study.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing globally. This study aimed to determine the prevalence of NAFLD and the probability of liver fibrosis in Italian primary care services. We carried out a population-based and nested case-control study including all individuals aged 18 years and above registered at Italian primary care services. Data were collected from the general practitioners' network from 2010 to 2017. NAFLD cases were identified via the ICD-9-CM and Hepatic Steatosis Index score > 36 and were matched each up to 10 controls. Other causes of liver diseases were excluded. The risk of fibrosis was assessed using the FIB-4 and NAFLD fibrosis scores (NFS). NAFLD was present in 9% of the primary care population with high regional variability. Among NAFLD subjects: 25% had diabetes, 10% had chronic kidney disease, 11% had cardiovascular disease and 28% were obese. Furthermore, 30% had at least two comorbidities and 13% had cirrhosis. Once cirrhosis was excluded, the risk of any degree of fibrosis was 13.8% with NFS and 20.5% with FIB-4 in subjects <65 years. Even if there is an identification gap in primary care, recorded cases with NAFLD have a high frequency of associated comorbidities. Despite regional variability, a close relation between cirrhosis and NAFLD exists (OR: 3.48, 95% CI: 3.23-3.76). Therefore, the use of non-invasive tests should be promoted in primary care as a useful tool for the early identification of fibrosis risk, independently of evidence of steatosis.

Non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD in type 2 diabetic patients

BackgroundNon-obese non-alcoholic fatty liver disease (NAFLD) has been reported to share clinical outcomes with its obese counterpart in the general population. However, conflicting results have been observed regarding the cardio-metabolic risk profile of non-obese NAFLD as compared to obese NAFLD. Moreover, in the context of type 2 diabetes mellitus (T2DM), this issue has been even less addressed. We hence aimed to examine the association of NAFLD with the cardio-metabolic risk profile in patients with T2DM according to their obesity status.MethodsA total of 2,708 patients with T2DM who were hospitalized between June 2018 and May 2021 were cross-sectionally assessed.ResultsThe prevalence of NAFLD was 49.3%. NAFLD was found in 34.1% of non-obese patients and 66.0% of obese patients. Non-obese NAFLD patients had more and worse metabolic disorders than obese patients without NAFLD in both men and women. Comparable cardio-metabolic risk profiles were noted between non-obese and obese NAFLD subjects. The associations of worse cardio-metabolic risk profiles with NAFLD were overall stronger in non-obese than in obese subjects among women with T2DM, while more pronounced in obese than in non-obese subjects among men with T2DM.ConclusionIn patients with T2DM, non-obese NAFLD had no better cardio-metabolic risk profile than obese NAFLD. The associations of metabolic disorders with NAFLD were stronger in non-obese than in obese patients in women patients with T2DM.

The association between visceral adipocyte hypertrophy and NAFLD in subjects with different degrees of adiposity.

To investigate the association between visceral adipocyte hypertrophy and the onset and development of non-alcoholic fatty liver disease (NAFLD) in subjects with different degrees of adiposity. Omental adipose tissue and liver biopsies were collected from obese subjects. NAFLD was defined according to the NASH Clinical Research Network scoring system. Adipocyte size was measured using pathological section analysis. Adipose tissue insulin resistance (Adipo-IR) was calculated as fasting insulin (pmol/L) × fasting free fatty acid concentration (mmol/L). In total, 275 obese patients were enrolled, including 158 females and 58 males with NAFLD. In females, adipocyte size was significantly larger in NAFLD participants as compared to the controls (99.37 ± 14.18 vs. 84.14 ± 12.65[Formula: see text]m, p < 0.001). Moreover, adipocyte size was larger in females with non-alcoholic steatohepatitis (NASH) as compared to those with non-alcoholic fatty liver (NAFL) (101.45 ± 12.77 vs. 95.79 ± 15.80[Formula: see text]m, p = 0.015). Mediation analysis showed that adipocyte size impacted the NAFLD activity score through Adipo-IR (b = 0.007 [95% bootstrap CI 0.002, 0.013]). Furthermore, the females were divided into: Q1 (BMI < 32.5kg/m2), Q2 (BMI 32.5-35.5kg/m2), Q3 (BMI 35.5-38.8kg/m2) and Q4 (BMI ≥ 38.8kg/m2) according to BMI quartiles. Omental adipocyte size was larger in NAFLD subjects in Q1-Q3, but not in Q4. No similar results were observed in males. For the first time, we reported that visceral adipocyte hypertrophy was associated with the onset and progression of NAFLD in mild to moderate adiposity but not in severe obesity, which may be mediated by adipose tissue insulin resistance.