Moderate Nonalcoholic Fatty Liver Disease Research Articles

Leisure-Time Physical Activity, Time Spent Sitting and Risk of Non-alcoholic Fatty Liver Disease: A Cross-Sectional Study in Puglia.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. The increasingly sedentary lifestyle in recent years may have accelerated the development of NAFLD, independent of the level of physical activity. The purpose of this cross-sectional study was to determine the association between leisure-time physical activity (LTPA) and time spent sitting (TSS) and the likelihood of developing NAFLD in a sample of men and women aged 18-64 years, from southern Italy. The study is based on two cohort studies, a randomized clinical trial and an observational cost-benefit study. A total of 1269 participants (51.5% women) drawn from 3992 eligible subjects were enrolled in this study. Leisure-time physical activity (LTPA) and time spent sitting (TSS) were assessed using the Italian long form of the International Physical Activity Questionnaire (IPAQ-LF), designed for administration to adults aged 18 to 65 years. The association of exposures with the probability of belonging to a certain NAFLD degree of severity. The probability of having mild, moderate, and severe NAFLD tends to decrease with increasing LTPA and decreasing TSS levels. We selected a combination of participants aged 50 years and older stratified by gender. Men had a statistically significant difference in the probability of developing moderate NAFLD if they spent 70 h per week sitting and had low LTPA, while among women there was a statistically significant difference in the probability of developing mild or moderate NAFLD if they had moderate LPTA and spent 35-70 h/week sitting. The study thus showed that the amount of LTPA and the amount of TSS are associated with development and progression of NAFLD, but this relationship is not a linear one-especially in women aged ≥ 50 years old.

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

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

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

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

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

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

Development and evaluation of emulsified reference materials for magnetic resonance imaging

Hepatic steatosis is characterized by an abnormal accumulation of lipids within hepatocytes. Magnetic resonance imaging (MRI) is a widely used noninvasive method that can accurately and objectively quantify liver fat. To evaluate the accuracy of the quantitatively measured fat fraction, stable and homogenous qualified material is needed as a reference. Surfactant-free micro-emulsions of three fat fractions I, II, and III, corresponding to (9.12 ± 0.02)%, (18.32 ± 0.04)%, and (27.86 ± 0.05)%, respectively, were prepared using a high-intensity focused ultrasonic emulsification technique. The targeted fat fraction of 10%–30% covers the range of grade I moderate non-alcoholic fatty liver disease, which occurs in the early stages that require early detection. Water contents as the main component of the emulsified reference materials (RMs) were determined using the Karl Fisher titration method to evaluate the stability and homogeneity of the RMs. The water contents of fat fraction I, II, and III were (89.12 ± 1.08)%, (79.87 ± 0.81)%, and (72.71 ± 1.29)%, respectively. The RMs were stable for six months and showed good homogeneity with both standard deviations between and within units in the range of 0.3%–0.6%. The physical phantom consisted of nine vials of RMs surrounded by agarose gel. The phantom was scanned on 3 T MRI (Siemens MAGNETOM Vida, Siemens Healthineers, Erlangen, Germany). The correlation between the measured proton density fat fraction values and the fabricated fat fraction values was evaluated using linear regression analysis. The slope of the linear fitting was 0.99, and the intercept was −0.88%. These results show that the developed RMs can provide a reference value for the measured fat fraction from a medical imaging system to evaluate the effectiveness of a measurement procedure. It is also expected that the developed RMs can be utilized to harmonize the measured values across multi-site.

Lack of association between nonalcoholic fatty liver disease and intracerebral hemorrhage: A community-based cohort study

BackgroundThe association between nonalcoholic fatty liver disease (NAFLD) and intracerebral hemorrhage (ICH) remains unclear. This study aimed to investigate whether NAFLD and its severity predict incident ICH. MethodsParticipants free of other liver diseases, prior stroke, myocardial infarction, cancer, or alcohol abuse in the Kailuan cohort were enrolled in this study. Abdominal ultrasonography was used to diagnose NAFLD and assess its severity. Participants were stratified into different groups including nonfatty liver, mild, moderate and severe NAFLD. Multivariable Cox proportional hazards regression models were used to evaluate the hazard ratios (HRs) and 95% CIs of ICH events in the 11-year follow-up. ResultsA total of 77,461 participants were enrolled in our study. Among them, NAFLD was diagnosed in 23,890 (30.83 %) participants, including 15,581 (20.11 %) with mild NAFLD, 6839 (8.83 %) with moderate NAFLD and 1470 (1.90 %) with severe NAFLD. We documented 692 ICH events during 848,579 person years of follow-up. Patients with more severe NAFLD tended to be older, had higher levels of BMI, higher proportions of hypertension, diabetes and other known risk factors for cerebrovascular disease. However, there was no significant associations between NAFLD, its severity and incident ICH events. Relative to nonfatty liver participants, the HRs for participants with mild NAFLD, moderate and severe NAFLD were 0.98 (95 % CI, 0.80 to 1.20), 1.19 (95 % CI, 0.92 to 1.54) and 1.29 (95 % CI, 0.81 to 2.06), respectively. ConclusionsNAFLD and its severity did not appear to be significantly associated with ICH after adjustment for potential risk factors.

Non-alcoholic Fatty Liver in Children and Adolescents in Saudi Arabia.

Objectives This study aims to describe the disease parameters of children and adolescents diagnosed with non-alcoholic fatty liver disease (NAFLD) in Saudi Arabia. It also investigates the disease's progression and compares clinical, biochemical, and radiological parameters at baseline and follow-up of patients with NAFLD. This study was done between two groups of patients: obese and those of average body weight. Methods A retrospective cohort study was conducted between 2014 and 2018 through retrieved data from medical records. It included all children aged between six to 18 years diagnosed with NAFLD. Medical history was taken from each medical record, liver function test results, cholesterol, blood pressure readings, and body weight. Data have been restored from King Abdullah Specialist Children's Hospital (KASCH)​, Security Forces Hospital (SFH), and King Khalid University Hospital (KKUH). Results A total of 116 subjects met the inclusion criteria; 65 (56%) were male, and 81 (70%) were obese. The majority of subjects (n=112) had mild NAFLD, with (71%) obese and(29%) non-obese, followed by moderate NAFLD with 50% among obese and non-obese (N=2), and non-alcoholic steatohepatitis (NASH) with 100% non-obese (N=2). Data showed that patients' proportion of obese to non-obese is 70% (N=81) to 30%(N=35), respectively. Conclusion NAFLDwas found to affect obese children and adolescents more than non-obese, and male patients had a higher proportion of NAFLD than females. Also, obese patients had more advanced stages of NAFLD than non-obese patients. Finally, most subjects had been diagnosed with mild stage while a few had developed NASH.

PREVALENCE OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) AMONG CORONARY ARTERY DISEASE PATIENTS AND ITS ASSOCIATION WITH CAD SEVERITY

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing concern due to its potential to lead to liver transplants and its association with cardiovascular disease (CVD). However, the relationship between NAFLD and CVD remains debated, and non-invasive diagnostic methods for NAFLD are recommended. This study aimed to estimate the prevalence of NAFLD among patients with CAD and explore the association between CAD severity and the probability of developing NAFLD.&#x0D; Methodology: A cross-sectional study was conducted among CAD patients. Patients with a history of infectious liver disease, pregnant or lactating individuals, and those with excessive alcohol consumption were excluded. Coronary angiography was performed to assess CAD severity using the Gensini score. Ultrasonography and non-invasive assessments, such as the Fibrosis-4 (FIB-4) index, were used to diagnose and stage NAFLD.&#x0D; Result: The study included 156 CAD patients, with 79 (50.6%) being male. Out of total, 31 (19.8%) had severe, 79(50.6%) had moderate, and 46 (29.48%) had mild NAFLD. Male patients showed a significantly higher prevalence of severe NAFLD compared to females. There was no significant difference in the mean age of CAD patients across NAFLD severities. Severe NAFLD was associated with higher mean Gensini scores and FIB-4 values compared to mild to moderate NAFLD patients. A positive correlation was found between Gensini score and FIB4, suggesting that Gensini score could be an alternative to FIB4 in diagnosing NAFLD severity among CAD patients.&#x0D; Conclusion: The study revealed a high prevalence of NAFLD among CAD patients, with severe NAFLD being associated with higher CAD severity.

Association of neck circumference-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease: a cross-sectional study

ObjectiveThe present study aimed to establish the association of neck circumference (NC)-related indices with metabolic, atherogenic and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD).DesignCross-sectional study.SettingOutpatient clinics...

Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension.

There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10-1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10-1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07-1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03-1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Application of Scores Assessing Histological Activity and Estimated Long-Term Risk Analysis of Hepatic Decompensation of Non-Alcoholic Fatty Liver Disease in Individuals Undergoing Bariatric Surgery.

Histological scores can estimate disease staging, allowing a standardization of the assessment of non-alcoholic fatty liver disease (NAFLD). The prediction of risk of NAFLD progression is relevant to allow the planning of interventions. To analyze the application of the Iowa NAFLD decompensation risk score, the NAFLD activity score (NAS), and steatosis-activity-fibrosis score (SAF) and to assess correlations between these scores. This is a retrospective cross-sectional study enrolling 76 individuals who underwent bariatric surgery at a tertiary university hospital. Liver biopsy was performed during procedures; histological scores were then assessed. The Iowa score was calculated using age, diabetes, and platelet count. 89.5% were female and mean age was 39.1 ± 9.6 years. Mean BMI was 38.2 ± 3.7 kg/m2. Steatosis (92.1%), hepatocellular ballooning (93.4%), lobular inflammation (93.4%), and fibrosis (97.4%) were the commonest histopathological findings. According to NAS, 22.4% had definite non-alcoholic steatohepatitis (NASH). According to SAF, 89.5% had moderate or severe NAFLD. The mean risks of NAFLD decompensation at 5, 10, and 12 years were 0.8%, 2.5%, and 2.9%, respectively. The group whose risk of decompensation was above 10% comprised 2.6% and 5.3% at 10 and 12 years, respectively. The severity assessed by SAF significantly associated with definite NASH diagnosis through NAS (p < 0.001). Iowa score did not correlate with both NAS/SAF scores. The Iowa score demonstrated that individuals with obesity present with a significant long-term risk of NAFLD-related events. There were high rates of moderate/severe forms of NAFLD assessed by NAS and SAF scores. There were no significant correlations between Iowa and NAS/SAF scores.

Relationship of Helicobacter pylori Infection with Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) have become increasingly recognized, both of which affect human health globally. The association of H. pylori infection with NAFLD remains unclear. PubMed, EMBASE, and Cochrane Library databases were searched. Only a random-effects model was used. Odds ratios (ORs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for the combined estimates of raw data. Adjusted ORs (aORs) and hazard ratios (aHRs) with 95% CIs were calculated for the combined estimates of data adjusted for confounders. Thirty-four studies with 218573 participants were included. Based on unadjusted data from 26 cross-sectional studies and 3 case-control studies, H. pylori infection was significantly associated with the presence of NAFLD (OR = 1.26, 95% CI = 1.17-1.36, P < 0.001). Based on adjusted data from 15 cross-sectional studies and 1 case-control study, H. pylori infection was significantly associated with the presence of NAFLD (aOR = 1.25, 95% CI = 1.08-1.44, P < 0.001). Compared with control subjects without NAFLD, patients with moderate (OR = 1.67, 95% CI = 1.17-2.39, P = 0.005) and severe (OR = 1.71, 95% CI = 1.30-2.24, P < 0.001) NAFLD, but not those with mild NAFLD (OR = 1.14, 95% CI = 0.9-1.45, P = 0.286), had significantly higher proportions of H. pylori infection. The association of H. pylori infection with the occurrence of NAFLD was statistically significant based on adjusted data from 3 cohort studies (aHR = 1.18, 95% CI = 1.05-1.34, P = 0.007), but not based on unadjusted data from 3 cohort studies (RR = 1.41, 95% CI = 0.80-2.48, P = 0.237). H. pylori infection is associated with NAFLD, especially moderate and severe NAFLD. The impact of H. pylori eradication on the prevention of NAFLD should be further explored.

Chronic kidney disease in nonalcoholic fatty liver disease at primary healthcare centers in Korea.

The prevalence rates of nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are expected to increase with the rising trends in diabetes and obesity associated with aging populations. Considering the impacts of coexistent NAFLD and CKD on morbidity and mortality rates, screening strategies for groups at high-risk of CKD are needed in community-dwelling individuals with NAFLD. The aims of this study were to determine the prevalence and distribution of CKD in NAFLD, as well as the risk factors for CKD and the correlation with liver fibrosis in asymptomatic individuals with NAFLD at primary healthcare centers in Korea. This retrospective cross-sectional study used data from 13 health-promotion centers in 10 Korean cities. Liver steatosis and stiffness were assessed using ultrasonography and magnetic resonance elastography (MRE), respectively. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73m2, and urine albumin-to-creatinine ratio or proteinuria. CKD was categorized into four stages: no CKD, mild, moderate, and severe. Comparisons according to the CKD stages in NAFLD were performed using Student's t-test or the chi-square test. Multivariable logistic regression analyses were performed to identify the risk factors for CKD and the correlation with liver fibrosis in NAFLD. The prevalence of CKD was 12.4% in NAFLD. Albuminuria (16.2%) and proteinuria (8.0%) were more prevalent in NAFLD. NAFLD (odd ratio = 1.27, 95% CI = 1.09-1.48, P = 0.003) was independently associated with CKD of at least mild stage. However, there was no significant association between CKD of at least moderate stage and NAFLD after adjusting for age and a metabolically unhealthy status. CKD was associated with significant liver fibrosis as measured by MRE in NAFLD. The presence of NAFLD and liver fibrosis were independent risk factors for CKD, but NAFLD was not an independent risk factor for the later stages of CKD.

Association of complement components with the risk and severity of NAFLD: A systematic review and meta-analysis.

It is generally believed that complement system is strongly associated with the risk of nonalcoholic fatty liver disease (NAFLD). However, complement system contains a variety of complement components, and the relationship between complement components and the risk and severity of NAFLD is inconsistent. The aim of this meta-analysis was to evaluate the association of complement components with the risk and severity of NAFLD. We searched PubMed, Embase, Cochrane Library, Google Scholar, Scopus, and ZhiWang Chinese databases from inception to May 2022 for observational studies reporting the risk of NAFLD with complement components. Random-effects meta-analysis was used to obtain pooled estimates of the effect due to heterogeneity. We identified 18 studies with a total of 18560 included subjects. According to recent studies, levels of complement component 3 (C3) (mean difference (MD): 0.43, 95% confidence interval (CI) 0.26-0.60), complement component 4 (C4) (MD: 0.04, 95% CI 0.02-0.07), complement component 5(C5) (MD: 34.03, 95% CI 30.80-37.27), complement factor B (CFB) (MD: 0.22, 95% CI 0.13-0.31) and acylation stimulating protein (ASP) (standard mean difference (SMD): 5.17, 95% CI 2.57-7.77) in patients with NAFLD were significantly higher than those in the control group. However, no statistical significance was obtained in complement factor D (CFD) levels between NAFLD and non-NAFLD (MD=156.51, 95% CI -59.38-372.40). Moreover, the levels of C3, C5, CFB, and ASP in patients with moderate and severe NAFLD were significantly higher than those in patients with mild NAFLD. Except for C4 and CFD, the included studies did not explore the changes in the severity of NAFLD according to the concentration of C4 and CFD. This meta-analysis demonstrates that an increase in complement components including C3, C5, CFB, and ASP is associated with an increased risk and severity of NAFLD, indicating that they may be good biomarkers and targets for the diagnosis and treatment of NAFLD. PROSPERO [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42022348650.

Severity of Nonalcoholic Fatty Liver Disease is Associated With Cardiovascular Outcomes in Patients With Prehypertension or Hypertension: A Community-Based Cohort Study.

BackgroundIt is unclear whether more severe non–alcoholic fatty liver disease (NAFLD) combined with prehypertension or hypertension is associated with a higher risk of cardiovascular events (CVEs). To evaluate the relationship between the severity of NAFLD and CVEs among patients with prehypertension or hypertension.MethodsIn this prospective community–based Kailuan cohort, participants without cardiovascular disease and alcohol abuse, or other liver diseases were enrolled. NAFLD was diagnosed by abdominal ultrasonography. Prehypertension was defined as systolic blood pressure (BP) of 120–139 mmHg or diastolic BP of 80–89 mmHg. Participants with NAFLD were divided into mild, moderate, and severe subgroups. Follow–up for CVEs including myocardial infarction, hemorrhagic stroke, and ischemic stroke. The Cox proportional hazards model was used to estimate hazard ratios and 95% CIs of CVEs according to the severity of NAFLD and hypertensive statutes. The C-statistic was used to evaluate the efficiency of models.ResultsA total of 71926 participants (mean [SD] age, 51.83 [12.72] years, 53794 [74.79%] men, and 18132 [25.21%] women) were enrolled in this study, 6,045 CVEs occurred during a median of 13.02 (0.65) years of follow–up. Compared with participants without NAFLD, the hazard ratios of CVEs for patients with mild, moderate, and severe NAFLD were 1.143 (95% CI 1.071–1.221, P < 0.001), 1.218 (95% CI 1.071–1.221, P < 0.001), and 1.367 (95% CI 1.172–1.595, P < 0.001), respectively. Moreover, participants with prehypertension plus moderate/severe NAFLD and those with hypertension plus moderate/severe NAFLD had 1.558–fold (95% CI 1.293–1.877, P < 0.001) and 2.357–fold (95% CI 2.063–2.691, P < 0.001) higher risks of CVEs, respectively, compared with those with normal BP and no NAFLD. Adding a combination of NAFLD and BP status to the crude Cox model increased the C–statistic by 0.0130 (0.0115–0.0158, P < 0.001).ConclusionsOur findings indicated that the increased cardiovascular risk with elevated BP is largely driven by the coexistence of moderate/severe NAFLD, suggesting that the severity of NAFLD may help further stratify patients with prehypertension and hypertension.

The association of pericardial fat and peri-aortic fat with severity of nonalcoholic fatty liver disease

Visceral adipose tissue (VAT) is associated with central obesity, insulin resistance and metabolic syndrome. However, the association of body-site specific adiposity and non-alcoholic fatty liver disease (NAFLD) has not been well characterized. We studies 704 consecutive subjects who underwent annual health survey in Taiwan. All subjects have been divided into three groups including normal (341), mild (227) and moderate and severe (136) NAFLD according to ultrasound finding. Pericardial (PCF) and thoracic peri-aortic adipose tissue (TAT) burden was assessed using a non-contrast 16-slice multi-detector computed tomography (MDCT) dataset with off-line measurement (Aquarius 3DWorkstation, TeraRecon, SanMateo, CA, USA). We explored the relationship between PCF/TAT, NAFLD and cardiometabolic risk profiles. Patients with moderate and mild NAFLD have greater volume of PCF (100.7 ± 26.3vs. 77.1 ± 21.3 vs. 61.7 ± 21.6 ml, P < 0.001) and TAT (11.2 ± 4.1 vs. 7.6 ± 2.6 vs. 5.5 ± 2.6 ml, P < 0.001) when compared to the normal groups. Both PCF and TAT remained independently associated with NAFLD after counting for age, sex, triglyceride, cholesterol and other cardiometabolic risk factors. In addition, both PCF and TAT provided incremental prediction value for NAFLD diagnosis. (AUROC: 0.85 and 0.87, 95%, confidence interval: 0.82–0.89 and 0.84–0.90). Both visceral adipose tissues strongly correlated with the severity of NAFLD. Compared to PCF, TAT is more tightly associated with NAFLD diagnosis in a large Asian population.

Insulin-Like Growth Factor-I Might be a Predictor for Severe Non-Alcoholic Fatty Liver Disease in Morbidly Obese Patients.

The aim of the study was to compare the IGF-1 levels, metabolic and clinical parameters among the ultrasonographically classified non-alcoholic fatty liver disease (NAFLD) groups and determine the factors that may predict the NAFLD severity in patients with morbid obesity. This study was conducted on 316 morbidly obese patients (250 F/66 M). The data of patients before and 1st-year after bariatric surgery were recorded. According to the ultrasonographically NAFLD screening, patients with normal hepatic features were classified as Group 1(n=57), with mild and moderate NAFLD were classified as Group 2(n=219), and with severe NAFLD were classified as Group 3(n=40). IGF-1 standard deviation scores (SDSIGF1) were calculated according to age and gender. Parameters that could predict the presence and severity of NAFLD were evaluated. IGF-1 levels were significantly associated with Group 3 than Group 1(p=0.037), and the significance remained between the same groups when IGF-1 levels were standardized as SDSIGF1(p=0.036). Decreased levels of SDSIGF1 explained 5% of severe NAFLD than the normal group (p=0.036). Liver Diameter, FPG, ALT, AST, and GGT were also found as significant predictors for severe NAFLD. There were significant differences between pre-and postop values in all groups (p<0.001). This study showed that IGF-1 might be considered a sgnificant predictor of severe NAFLD in morbidly obese patients. It is crucial in clinical practice to determine predictive factors of NAFLD that could support the diagnosis accompanied by non-invasive imaging methods.

The Negative Association Between NAFLD Severity and CKD in a Non-Diabetic Gouty Population.

Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors. We aim to evaluate the association between NAFLD and CKD in a non-diabetic gouty population. The retrospective cross sectional study was performed on 1049 non-diabetic gouty participants, who were hospitalized between 2014 and 2020, across 4 districts in Shandong, China. Demographic and clinical characteristics of the study population were collected. The odds ratios (OR) and corresponding 95% confidence intervals (CI) about the NAFLD severity determined by ultrasonography were obtained by multiple logistic regression analysis. An unexpectedly inverse relationship was found between NAFLD severity and the risk of CKD in people with gout. Multivariate logistic regression analysis demonstrated that a higher degree of NAFLD severity is independently associated with a lower risk of CKD in people with gout, after adjusted for age, sex, smoking, gout duration, and metabolic risk factors including obesity, hypertension, hyperglycemia, hyperuricemia, and dyslipidemia, with OR 0.392 (95% CI 0.248-0.619, p<0.001), 0.379 (95% CI 0.233-0.616, p<0.001) and 0.148 (95% CI 0.043-0.512, p=0.003) in participants with mild, moderate, and severe NAFLD, respectively, compared to those without NAFLD. We also observed a weakened association of serum uric acid (SUA) with metabolic risk factors and NAFLD under circumstances of CKD in people with gout (r=-0.054, p=0.466). In conclusion, the presence and severity of NAFLD were negatively associated with the risk of CKD in the non-diabetic gouty population.

Non-alcoholic Fatty Liver Disease Is Associated With Cardiovascular Outcomes in Subjects With Prediabetes and Diabetes: A Prospective Community-Based Cohort Study.

BackgroundThere have been no studies of the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular events (CVEs) in patients with pre-diabetes (pre-DM), and diabetes mellitus (DM). We performed a community-based cohort study to evaluate the relationship between NAFLD and CVEs in patients with glucose metabolism disorder.MethodsWe enrolled 71,852 participants from the Kailuan study who had not experienced CVEs, after excluding alcohol abuse and other liver diseases. NAFLD was assessed using abdominal ultrasonography. Besides, participants were categorized by glucose metabolism status [normal glucose regulation (NGR), pre-DM, and DM]. All subjects were followed up for the occurrence of CVEs.ResultsDuring a median of 13.01 (0.64) years of follow-up, 6,037 CVEs occurred. NAFLD was present in 22,525 (31.3%), and compared with participants without NAFLD, those with NAFLD had a 12.3% [95% confidence interval (CI) 1.059–1.191, P < 0.001] higher risk of CVEs, after adjustment for potential confounders. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.104 (95% CI 1.035–1.179, P < 0.001), 1.149 (95% CI 1.055–1.251, P < 0.001), and 1.235 (95% CI 1.059–1.441, P < 0.001), respectively. Moreover, participants with pre-DM plus NAFLD and participants with DM plus NAFLD had 1.267-fold (95% CI 1.151–1.395, P < 0.001) and 1.829-fold (95% CI 1.666–2.008, P < 0.001) higher risks of CVEs, respectively, compared with those with NGR and no NAFLD. The addition of the combination of NAFLD and glucose metabolism status to the crude Cox model increased the C-statistic by 0.0066 (0.0053–0.0080, P < 0.001).ConclusionsNAFLD is associated with higher risks of CVEs. Moreover, NAFLD is an independent predictor of CVEs in patients with pre-DM and DM, suggesting that NAFLD may provide greater risk predictive value for patients with glucose metabolism disorder.

Association between Non-alcoholic Fatty Liver Disease and the Severity of Coronary Artery Stenosis in Eastern Chinese Population

Background: The present study aimed to investigate the relationship of non-alcoholic fatty liver disease (NAFLD) with the severity and extent of coronary stenotic lesions calculated by the Gensini score. In addition, the ability of Fibrosis-4 (FIB4) score to differentiate coronary artery calcification (CAC) and its severity is assessed. Methods: The current retrospective study was performed on a total of 342 patients examined between January and December 2016 in an affiliated hospital of Jiaxing University, Zhejiang, China. The study used liver ultrasonography for the assessment of NAFLD. Furthermore, the FIB4 and Gensini scores were used to predict hepatic fibrosis risk and the severity of coronary stenotic lesions. Results: The present study revealed that the serum levels of triglycerides, fasting glucose, alanine aminotransferase, and uric acid were significantly higher in patients with NAFLD than in participants without NAFLD (P &lt; 0.001, P &lt; 0.001, P = 0.032, and P = 0.002). Moreover, cases with NAFLD had a higher percentage of diabetes mellitus and hypertension (P &lt; 0.001 and 0.001) than those without NAFLD. It was noted that the level of high-density lipoprotein was lower in patients with NAFLD than in participants without NAFLD (P = 0.006). In addition, we observed that the Gensini score was higher in patients with NAFLD than in participants without NAFLD (P = 0.033). It was found that 27.3%, 25.8%, 45.7%, and 56.3% of the participants had NAFLD in control, single, double, and multi lesion groups, respectively, and the difference was statistically significant (P = 0.008). The number of diseased vessels in patients with severe NAFLD was higher than in the control group (P &lt; 0.001). It was also evident that the number of affected vessels significantly increased (P = 0.010 and P = 0.001) with the stages of NAFLD predicted by the FIB4 and Gensini scores. Furthermore, the Gensini score in patients with moderate and severe NAFLD was higher than in the control group (P = 0.013 and P = 0.019). We also conducted univariate logistic regression analyses to examine the relationship of CAC with FIB4 scores, and it was not significant (P = 0.191). Conclusions: The present study showed a positive relationship between NAFLD severity and coronary stenotic lesions in the eastern Chinese population. Furthermore, it was found that the higher the degree of FIB4 score, the higher the risk of CAC in patients with NAFLD. Therefore, assessing NAFLD severity using the FIB4 score may be useful for differentiating the patients at a higher risk of CAC. However, further prospective studies are required to establish the link between the FIB4 score and CAC.