Fatty Liver Fibrosis Research Articles

Association of nonalcoholic fatty liver disease and liver fibrosis detected by transient elastography with serum retinol in American adults.

Retinol is a precursor of vitamin A, which is metabolized and maintained in the liver and is involved in the pathogenesis of the nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. The relationship between NAFLD and liver fibrosis with serum retinol levels remains insufficient and inconclusive. Our study aimed to investigate the correlation between NAFLD, fibrosis, and serum retinol levels in American adults. A cross-sectional analysis was conducted using information from the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). The exposure factors were NAFLD and liver fibrosis status detected using transient elastography (TE), and the outcome was serum retinol levels. Weighted multivariate regressions were established to assess the correlation between NAFLD and liver fibrosis and serum retinol levels. Subgroup analyses were also performed. This study included 3,537 participants. Compared to the group without NAFLD, NAFLD was positively correlated with serum retinol levels (β = 1.28, 95% CI: 0.19, 2.37). In the subgroup analysis, a positive correlation between NAFLD and serum retinol levels was found in people aged < 60 years, Mexican Americans, and those with a body mass index (BMI) < 25. On the contrary, compared to the group without liver fibrosis, there was a significant negative association between liver fibrosis and serum retinol (β = -3.46, 95% CI: -5.16, -1.75), especially in people aged < 60 years, non-Hispanic white/black individuals, and people with a BMI ≥ 25. Our study suggests that NAFLD status may be positively associated with serum retinol levels in adult patients, and liver fibrosis may be negatively associated with serum retinol levels. Further studies are required to examine the associations found in our study.

Abstract P501: Midlife and Late-Life Non-Alcoholic Fatty Liver Disease and Incident Dementia: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Associations of nonalcoholic fatty liver disease (NAFLD) with dementia are controversial. The full spectrum of NAFLD from simple steatosis to fibrosis has been less investigated. Hypothesis: The severity of NAFLD, especially with the stage of liver fibrosis, is associated with dementia. Methods: The associations between midlife (1990-92, N=9283, mean age 57, female 55%) and late-life (2011-13, N=5138, mean age 75, female 58%) NAFLD and all cause dementia were quantified by Cox regression. NAFLD was characterized using the fatty liver index and liver fibrosis assessment model (FIB-4). Dementia was adjudicated and ascertained through Dec. 31, 2019 from neuropsychological assessments, annual participant or informant contact, and medical record surveillance. We used Cox models with adjustment for demographics, APOE ε4, alcohol, and kidney function. Additional adjustments were made for metabolic factors to explore the independent contribution of NAFLD to dementia. Results: During a median follow-up of 24.5 years after midlife NAFLD assessment, 1854 participants developed dementia. During a median of 6.3 years in late-life, there were 893 dementia cases. A graded increase in dementia risk across the spectrum of NAFLD was observed at midlife (p-trend &lt;0.001), but not at older age ( Figure ). In fact, NAFLD in late-life tended to be protective against dementia. After adjusting for the metabolic factors, the associations remained statistically significant in some categories. Conclusions: Remodeling of hepatic architecture and dysregulation in hepatocellular function in NAFLD at midlife plausibly induce peripheral promoters of neurodegeneration and may expose a large segment of the population to increased risk of dementia. The inverse association of NAFLD with dementia at late-life requires further investigation, possibly reflecting the depletion of susceptibles, the reversibility of NAFLD due to weight loss, and the lack of accuracy in identifying NAFLD using clinical prediction models at older age.

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.

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity.

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population.

Quantitative Ultrasound Biomarkers to Assess Nonalcoholic Fatty Liver Disease.

To assess diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis. We prospectively recruited 125 participants (mean age 54 years) who underwent liver QUS, magnetic resonance imaging (MRI), and laboratory tests within 30 days in this IRB approved study. Based on MRI-proton density fat fraction (MRI-PDFF) and MRE, we divided 125 participants into normal liver, nonalcoholic fatty liver (NAFL) and liver fibrosis (≥F1) groups. We examined diagnostic performance of ultrasound attenuation coefficient (AC), normalized local variance (NLV), superb microvascular imaging-based vascularity index (SMI-VI), and shear wave velocity (SWV) for determining hepatic steatosis and fibrosis using area under receiver operating characteristic curve (AUC). We also analyzed correlations of QUS biomarkers to MRI using Spearman correlation coefficient. We observed significant differences in AC, NLV, and SMI-VI among the three groups (22 participants with normal liver, 78 with NAFL, and 25 with liver fibrosis). AUC of AC, NLV, and SMI-VI for determining ≥ mild steatotic livers (MRI-PDFF ≥5%) was 0.95, 0.90, and 0.92, respectively. AUC of SWV for determining ≥ F1 liver fibrosis was 0.93. The correlation of MRI-PDFF was positive to AC (r=0.91) and negative to NLV (r=-0.74), SMI-VI (r=-0.8) in NAFL group. There was a significant difference in regression slope of AC to MRI-PDFF in livers with and without ≥F1 (0.84 vs 0.91, P=.02). QUS biomarkers have high sensitivity and specificity to determine and grade hepatic steatosis and detect liver fibrosis. The effect of liver fibrosis on the performance of QUS biomarkers in quantifying liver fat content warrants further investigation.

Unraveling the pathophysiologic role of galectin-3 in chronically injured liver.

Galectin-3 (Gal-3) previously referred to as S-type lectins, is a soluble protein that specifically binds to β-galactoside carbohydrates with high specificity. Gal-3 plays a pivotal role in a variety of pathophysiological processes such as cell proliferation, inflammation, differentiation, angiogenesis, transformation and apoptosis, pre-mRNA splicing, metabolic syndromes, fibrosis, and host defense. The role of Gal-3 has also been implicated in liver diseases. Gal-3 is activated upon a hepatotoxic insult to the liver and its level has been shown to be upregulated in fatty liver diseases, inflammation, nonalcoholic steatohepatitis, fibrosis, cholangitis, cirrhosis, and hepatocellular carcinoma (HCC). Gal-3 directly interacts with the NOD-like receptor family, pyrin domain containing 3, and activates the inflammasome in macrophages of the liver. In the chronically injured liver, Gal-3 secreted by injured hepatocytes and immune cells, activates hepatic stellate cells (HSCs) in a paracrine fashion to acquire a myofibroblast like collagen-producing phenotype. Activated HSCs in the fibrotic liver secrete Gal-3 which acts via autocrine signaling to exacerbate extracellular matrix synthesis and fibrogenesis. In the stromal microenvironment, Gal-3 activates cancer cell proliferation, migration, invasiveness, and metastasis. Clinically, increased serum levels and Gal-3 expression were observed in the liver tissue of nonalcoholic steatohepatitis, fibrotic/cirrhotic, and HCC patients. The pathological role of Gal-3 has been experimentally and clinically reported in the progression of chronic liver disease. Therefore, this review discusses the pathological role of Gal-3 in the progression of chronic liver diseases.

Association of Myosteatosis with Nonalcoholic Fatty Liver Disease, Severity, and Liver Fibrosis Using Visual Muscular Quality Map in Computed Tomography.

The association of myosteatosis measured using visual muscular quality map in computed tomography (CT) with nonalcoholic fatty liver disease (NAFLD), its severity, and fibrosis was analyzed in a large population. Subjects (n=13,452) with abdominal CT between 2012 and 2013 were measured total abdominal muscle area (TAMA) at L3 level. TAMA was segmented into intramuscular adipose tissue and skeletal muscle area (SMA), which was further classified into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The following variables were adopted as indicators of myosteatosis: SMA/body mass index (BMI), NAMA/BMI, NAMA/TAMA, and LAMA/BMI. NAFLD and its severity were assessed by ultrasonography, and liver fibrosis was measured by calculating the NAFLD fibrosis score (NFS) and fibrosis-4 index (FIB-4) scores. According to multiple logistic regression analyses, as quartiles of SMA/BMI, NAMA/BMI, and NAMA/TAMA increased, the odds ratios (ORs) for NAFLD decreased in each sex (P for trend <0.001 for all). The ORs of moderate/severe NAFLD were significantly higher in the Q1 group than in the Q4 group for SMA/BMI, NAMA/BMI, and NAMA/TAMA in men. The ORs of intermediate/high liver fibrosis scores assessed by NFS and FIB-4 scores increased linearly with decreasing quartiles for SMA/BMI, NAMA/BMI, and NAMA/TAMA in each sex (P for trend <0.001 for all). Conversely, the risk for NAFLD and fibrosis were positively associated with LAMA/BMI quartiles in each sex (P for trend <0.001 for all). A higher proportion of good quality muscle was associated with lower risks of NAFLD and fibrosis.

Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study.

Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study.

Impact of Helicobacter pylori Infection on the Pathogenesis and Management of Nonalcoholic Fatty Liver Disease.

Helicobacter pylori (H. pylori) infection is widely prevalent worldwide. H. pylori infection has been reported to be a risk factor for the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Because treatment for NAFLD, other than weight loss is limited, the treatment for H. pylori infection is well established. It is important to determine whether screening and treatment for H. pylori infection should be considered in patients with no gastrointestinal symptoms. The aim of this mini-review is to evaluate the association between H. pylori infection and NAFLD including epidemiology, pathogenesis, and the evidence for H. pylori infection as a modifiable risk factor for preventing or treating NAFLD.

Editors' Note: Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study.

Dr. Xiao et al. investigated the association of nonalcoholic fatty liver disease (NAFLD) and fibrosis with incident dementia and cognition among participants in the Rotterdam Study, a prospective cohort study that included 3,975 patients with available fatty liver index (FLI), 4,577 patients with abdominal ultrasound, and 3,300 patients with liver stiffness assessments. NAFLD was defined as FLI ≥60 or steatosis on ultrasound and fibrosis as liver stiffness ≥8.0 kPa. Over 5 or more years of follow-up, NAFLD and liver fibrosis were not associated with an increased risk of incident dementia, and NAFLD was not associated with impaired cognitive function. Of interesting, NAFLD diagnosis was associated with a significantly decreased risk of incident dementia in the first 5 years of follow-up after FLI assessment. In response, Dr. Gupta notes the current lack of a biological model for linking NAFLD to protection from dementia, seeks evidence for weight loss–induced NAFLD regression, and wonders what phenomena might be occurring in these patients before vs after 5 years of follow-up to explain the study observations. Responding to these comments, the authors note that weight loss is the hallmark of NAFLD regressions, citing studies where regressions occurred even with slight weight reductions. They also note the interesting observation in several dementia cohorts (including theirs) of weight loss occurring in the years before dementia onset. By excluding the initial years of follow-up to address confounding by these intertwined mechanisms of weight loss and dementia, they note that the apparent beneficial effect of NAFLD disappeared. They posit that the presence of NAFLD may simply reflect the absence of weight loss rather than any true protective effect against dementia, but note the need for further studies to clarify these questions. This correspondence highlights the challenges of disentangling the complex interplay between weight loss and the natural history of NAFLD and dementia. Dr. Xiao et al. investigated the association of nonalcoholic fatty liver disease (NAFLD) and fibrosis with incident dementia and cognition among participants in the Rotterdam Study, a prospective cohort study that included 3,975 patients with available fatty liver index (FLI), 4,577 patients with abdominal ultrasound, and 3,300 patients with liver stiffness assessments. NAFLD was defined as FLI ≥60 or steatosis on ultrasound and fibrosis as liver stiffness ≥8.0 kPa. Over 5 or more years of follow-up, NAFLD and liver fibrosis were not associated with an increased risk of incident dementia, and NAFLD was not associated with impaired cognitive function. Of interesting, NAFLD diagnosis was associated with a significantly decreased risk of incident dementia in the first 5 years of follow-up after FLI assessment. In response, Dr. Gupta notes the current lack of a biological model for linking NAFLD to protection from dementia, seeks evidence for weight loss–induced NAFLD regression, and wonders what phenomena might be occurring in these patients before vs after 5 years of follow-up to explain the study observations. Responding to these comments, the authors note that weight loss is the hallmark of NAFLD regressions, citing studies where regressions occurred even with slight weight reductions. They also note the interesting observation in several dementia cohorts (including theirs) of weight loss occurring in the years before dementia onset. By excluding the initial years of follow-up to address confounding by these intertwined mechanisms of weight loss and dementia, they note that the apparent beneficial effect of NAFLD disappeared. They posit that the presence of NAFLD may simply reflect the absence of weight loss rather than any true protective effect against dementia, but note the need for further studies to clarify these questions. This correspondence highlights the challenges of disentangling the complex interplay between weight loss and the natural history of NAFLD and dementia.

Reader Response: Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study.

Xiao et al.1 observed that nonalcoholic fatty liver disease (NAFLD) is associated with a reduced risk of dementia and cognitive decline for the first 5 years of the disease, which is possibly driven by weight loss before the onset of dementia. The biology of any illness is the outcome of a meticulously orchestrated parallel activation of multiple physiologic processes constituting the cause-effect-adaptive continuum that pushes or pulls the patient toward or away from any disease, including dementia.2

Author Response: Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study.

We appreciate the interest of Dr. Gupta in our recent study, in which we demonstrated that fatty liver disease did not increase the risk of dementia for different follow-up durations nor was it associated with impaired cognitive function.1

Association of iron status with non-alcoholic fatty liver disease and liver fibrosis in US adults: a cross-sectional study from NHANES 2017-2018.

Aims: Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder resulting in a high risk of adverse prognosis, and its presence has been considered a cause or an outcome of metabolic syndrome. But the relative factors and mechanism of NAFLD are still unclear. The aim of this study is to explore the association between iron status indicators and NAFLD as well as liver fibrosis. Methods: This study evaluated whether serum iron status indicators are independently related to the risk of NAFLD. The independent variable was each one of the iron status indicators (iron intake, ferritin, iron, unsaturated iron binding force (UIBC), total iron binding capacity (TIBC), transferrin saturation, transferrin receptor, hemoglobin, and mean cell hemoglobin), and the dependent variables were NAFLD and advanced liver fibrosis. A multivariable logistic regression analysis and subgroup analysis were performed to evaluate the association between iron status indicators and NAFLD as well as liver fibrosis. Results: A total of 3727 patients were included. After adjusting for other covariates in multiple logistic regression models, the serum ferritin, UIBC, TIBC, and hemoglobin had a significant positive association with the NAFLD (odds ratio [OR] = 1.16, 95% confidence interval [CI]: 1.09, 1.23; 1.31, 95% CI: 1.06, 1.62; 1.82, 95% CI: 1.23, 2.67; 2.67, 95% CI: 1.48, 4.82, separately), and the risk of NAFLD diagnosed by VCTE or ALT/AST further increased in the fourth quartile group of serum ferritin (diagnosed by VCTE OR = 1.93, 95% CI: 1.49, 2.50; diagnosed by ALT/AST OR = 5.76, 95% CI: 3.96, 8.38). Moreover, the main positive correlation between serum ferritin and NAFLD was found in females, participants aged >41 years, with no diabetes. Conclusion: Our results indicated that iron status indicators were closely associated with the occurrence of advanced liver fibrosis, which may indicate that iron status indicators could be potential biomarkers of NAFLD and advanced liver fibrosis.

Systemic TM4SF5 overexpression in ApcMin/+ mice promotes hepatic portal hypertension associated with fibrosis

Mutation of the gene for adenomatous polyposis coli (APC), as seen in ApcMin/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding ApcMin/+ with TM4SF5-overexpressing transgenic (TgTM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (ApcMin/+:TgTM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in ApcMin/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in ApcMin/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old TgTM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver. [BMB Reports 2022; 55(12): 609-614].

Improved glycaemic control in patients with type 2 diabetes has a beneficial impact on NAFLD, independent of change in BMI or glucose lowering agent

Background and aimThe current focus of the treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) is lifestyle intervention with the aim of significant weight loss alongside aggressive cardiovascular risk reduction. NAFLD is tightly associated with type 2 diabetes (T2D) and obesity. In patients with T2D, glucose lowering agents that promote weight loss have shown a beneficial impact on NAFLD. However, it remains unclear as to whether glucose lowering can improve NALFD in patients with T2D, independent of weight loss. Methods and resultsIn a retrospective analysis of data from 637 people with T2D, we examined the longitudinal impact of optimizing glycaemic control with DPP-IV inhibitors, GLP-1RAs and SGLT2 inhibitors on Fatty liver index (FLI) and Fibrosis score 4 (Fib-4) adjusting for changes in BMI and choice of glucose lowering regimen over a 12-month period.Multiple linear regression analysis demonstrated a significant correlation between the change in glycated haemoglobin and change in FLI after adjustment for change in BMI, age, sex, and drug class (R = 0.467, p = 0.031). The greatest reduction in FLI was observed in patients with the largest reduction in glycated haemoglobin (p < 0.0001). The probability of improvements in FLI with optimization of glycaemic control was similar with all 3 glucose lowering agents, despite differences in weight reduction. Similar relationships were observed examining the changes in glycaemic control and Fib-4. ConclusionsImprovements in glucose control that are independent of weight loss are associated with improvement in NAFLD and should form an integral part of the management patients with co-existent NAFLD and T2D.

Antisense oligonucleotide is a promising intervention for liver diseases.

As the body's critical metabolic organ, the liver plays an essential role in maintaining proper body homeostasis. However, as people's living standards have improved and the number of unhealthy lifestyles has increased, the liver has become overburdened. These have made liver disease one of the leading causes of death worldwide. Under the influence of adverse factors, liver disease progresses from simple steatosis to hepatitis, to liver fibrosis, and finally to cirrhosis and cancer, followed by increased mortality. Until now, there has been a lack of accepted effective treatments for liver disease. Based on current research, antisense oligonucleotide (ASO), as an alternative intervention for liver diseases, is expected to be an effective treatment due to its high efficiency, low toxicity, low dosage, strong specificity, and additional positive characteristics. In this review, we will first introduce the design, modification, delivery, and the mechanisms of ASO, and then summarize the application of ASO in liver disease treatment, including in non-alcoholic fatty liver disease (NAFLD), hepatitis, liver fibrosis, and liver cancer. Finally, we discuss challenges and perspectives on the transfer of ASO drugs into clinical use. This review provides a current and comprehensive understanding of the integrative and systematic functions of ASO for its use in liver disease.

Association between Sarcopenic Obesity Status and Nonalcoholic Fatty Liver Disease and Fibrosis.

There are no data regarding the association between sarcopenic obesity status and nonalcoholic fatty liver disease (NAFLD) and NAFLD-associated liver fibrosis. Therefore, we aimed to investigate the relationship between sarcopenic obesity status (sarcopenia only, obesity only, and sarcopenic obesity) and NAFLD and liver fibrosis in Korean adults. In total, 2,191 subjects completed a health checkup program, including abdominal ultrasonography and FibroScan. Subjects were classified into the following four categories: optimal body composition (nonobese and nonsarcopenic), sarcopenia only (nonobese), obesity only (nonsarcopenic), and sarcopenic obesity. Sarcopenic obesity was stratified by the skeletal muscle mass index and body fat using bioelectrical impedance analysis. NAFLD was diagnosed by ultrasonography, and liver fibrosis was assessed using transient elastography in subjects with NAFLD. The prevalence of NAFLD and liver fibrosis significantly increased according to the sarcopenic obesity status. In the logistic regression analysis, after adjusting for multiple risk factors, the odds ratio (OR) for the risk of NAFLD was largest in the sarcopenic obesity group (OR, 3.68; 95% confidence interval [CI], 2.94 to 4.60), followed by the obesity only (OR, 2.25; 95% CI, 1.67 to 3.03) and sarcopenia only (OR, 1.92; 95% CI, 1.30 to 2.84) groups, when compared with the optimal group. Additionally, liver fibrosis was independently associated with sarcopenic obesity status (OR 4.69, 95% CI 1.95 to 11.29; OR 4.17, 95% CI 1.56 to 11.17; OR 3.80, 95% CI 0.86 to 16.75, respectively). These results demonstrated that sarcopenic obesity was independently associated with NAFLD and liver fibrosis and increased the risk of NAFLD and liver fibrosis more than obesity or sarcopenia alone.

Risk Factors of Nonalcoholic Fatty Liver Disease and Liver Fibrosis in Non-Obese Patients with Obstructive Sleep Apnea.

Liver injury in non-obese obstructive sleep apnea (OSA) patients has received much attention in recent years. This study aimed to investigate risk factors of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis in non-obese patients with OSA. A retrospective study was conducted in the Sleep Center of the First Affiliated Hospital of Fujian Medical University. All consecutive non-obese patients with suspected sleep apnea admitted to the center were enrolled. The clinical characteristics of patients with simple snoring and with different severity OSA were compared. Multivariate logistic regression models were used to analyze the risk factors of NAFLD and liver fibrosis. A total of 410 patients were enrolled. The levels of triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased with the aggravation of OSA (All p<0.05). Among non-obese patients with OSA, 17 (5%) were diagnosed with liver fibrosis and 228 (65%) with NAFLD; Apnea‑hyponea index (AHI) was an independent predictor for NAFLD and liver fibrosis [OR (95% CI): 1.02 (1.00-1.03), 1.04 (1.00-1.07), both p<0.05]; hypertriglyceridemia was an independent predictor for NAFLD [OR (95% CI): 1.13 (1.12-1.99), p<0.05]. NAFLD and liver fibrosis were common in non-obese OSA patients and the severity of OSA was an independent risk factor for them.

Associations of phthalates with NAFLD and liver fibrosis: A nationally representative cross-sectional study from NHANES 2017 to 2018.

Although phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis. Data of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis. After adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: β, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis. All in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

Cardiometabolic profile of 15057 elderly Spanish workers: association of sociodemographic variables and tobacco consumption

BackgroundAging of the world population is one of the most significant demographic changes of our time. Populations older than 60 years are heterogeneous, and age is an independent cardiovascular risk factor aggravated by frailty, obesity, and diabetes, and influenced by several factors, including sex and socioeconomic status. The objective of this study was to calculate cardiovascular risk in workers of both sexes over 60 years of age and to assess whether there are difference s by sex, social class, smoking, and type of job.MethodsA cross-sectional study was carried out in 15,057 elderly Spanish workers from different autonomous communities in Spain and with different labor occupations. Anthropometric, sociodemographic, clinical, and laboratory values were determined. People were classified according to age from 60 to 64 years inclusive and from 65 to 69 years, smokers and non-smokers, and both blue-collar and white-collar workers. Subsequently, a multivariate analysis was carried out.ResultsMen, blue-collar workers, smokers, and aging were factors that influenced cardiovascular risk: with an OR of 3.27 (95% CI: 2.64–4.05) in people 65 years of age or older versus the younger group, and an OR of 3.15 (95% CI: 2.69–3.69) in smokers versus non-smokers. A stronger independent association was found between smoking, age, and cardiovascular risk. The risk of developing non-alcoholic fatty liver and liver fibrosis was much higher in men than in women, with an OR of 4.06 (95% CI: 3.66–4.50) for the former and an OR of 2.10 (95% CI: 1.95–2.26) for the BARD index.ConclusionsThe highest risk groups were observed in male subjects with a history of smoking and blue-collar workers and, as such, should be considered for cardiovascular risk screening programs.