Non-alcoholic Fatty Liver Disease Subjects Research Articles

Markers of atherosclerotic risk in patients with non-alcoholic fatty liver disease: A preliminary study

Introduction: The prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is rising continuously. Cardiovascular disease is one among the leading causes of morbidity and premature mortality in patients with NAFLD. Aims and Objectives: To determine the risk of atherosclerosis in NAFLD subjects diagnosed by USG at K.S.Hegde Charitable hospital. Materials and Methods:A cross-sectional study involving 203 persons diagnosed with NAFLD were included in the study. Subjects with alcoholic liver disease, renal failure, tuberculosis, hepatitis B and/or C and those on lipid lowering drug were excluded from the study. Lipid profile was measured and Atherogenic Index of Plasma (AIP) was calculated as log (TG/HDL-c). Categorization of the subjects with respect to risk of atherosclerosis was done based on serum LDL-c, non HDL-c and AIP. Statistical analysis was done using Chi Square test and p value Results: More than normal values were observed for serum total cholesterol, LDL-c, triglyceride and non HDL-c in high percentage of NAFLD subjects (76.8%, 84.7%, 70.4% and 72.4% respectively). Serum HDL-c level was low in 53.2% subjects. 51.2% of subjects had high AIP and 23.6% had moderately high AIP. Conclusion: Results of categorization of the subjects with respect to risk of atherosclerosis based on serum LDL-c, non HDL-c and AIP showed that high percentages of subjects were in moderate and high risk categories. AIP is probably a better marker to determine the risk of atherosclerosis. Keywords: Atherogenic index of plasma, NAFLD, Non-alcoholic fatty liver disease, Lipids, Cardiovascular.

Prevalence, risk factors and metabolic profile of the non-obese and obese non-alcoholic fatty liver disease in a rural community of South Asia

IntroductionSince there is a paucity of data on the epidemiology of the non-alcoholic fatty liver disease (NAFLD), particularly in rural areas in Asia, we undertook such a study among the...

Effect of angiotensin converting enzyme gene studies in nonalcoholic fatty liver disease subjects

Effect of angiotensin converting enzyme gene studies in nonalcoholic fatty liver disease subjects

Association between APOC3 polymorphisms and non-alcoholic fatty liver disease risk: a meta-analysis.

The apolipoprotein C3 (APOC3) polymorphism has been reported to predispose to non-alcoholic fatty liver disease (NAFLD). However, the results remain inconclusive. This meta-analysis aimed to provide insights into the association between APOC3 polymorphisms and NAFLD risk. Studies with terms "NALFD" and "APOC3" were retrieved from PubMed, Web of Science, CNKI and Wanfang databases up to August 1, 2019. Pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association of APOC3 polymorphisms and NAFLD risk were calculated using fixed and random-effects models. A total of twelve studies from eleven articles were included. Of them, eight studies (1750 cases and 2181 controls) reported the strong association of variant rs2854116 with NAFLD and six studies (1523 cases and 1568 controls) found the association of rs2854117 polymorphism with NAFLD. Overall, a statistically significant association between rs2854116 polymorphism of APOC3 gene and NAFLD risk was found only under dominant model. However, association of rs2854117 polymorphism with NAFLD risk was not detected under all four genetic models. In sub-group analysis of NAFLD subjects based on country, no association among them in China was detected. Besides, four studies analyze the association between the two polymorphisms and clinical characteristics in all subjects or NAFLD patients, and we also failed detect any association between the wild carriers and variant carriers. The meta-analyses suggests that the rs2854116 polymorphism but not rs2854117 polymorphism in APOC3 gene might be a risk factor for NAFLD among Asians. That is, individuals with CT+CC genotype have higher risk of developing NAFLD. However, studies with sufficient sample size are needed for the further validation.

Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P.

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography–mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (rS = 0.28), FFAs (rS = 0.42), glucose Rd (rS = −0.33) and glycerol Ra (rS = −0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (rS > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (rS = −0.31), glycine (rS = −0.44) and branched chain AA (rS = −0.32), and directly correlated with saturated (rS = 0.41) and monounsaturated FFAs (rS = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.

Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution and proinflammatory phenotype of platelets

Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and ranges from simple steatosis to nonalcoholic steatohepatitis. Recently, a platelet role in NAFLD pathogenesis and progression has been reported in mouse models and in patients. We investigated whether platelets are involved in liver and systemic inflammation processes in NAFLD. In this exploratory study we recruited 24 consecutive patients with biopsy-proven diagnosis of NAFLD and 17 healthy volunteers. We measured plasma levels of inflammatory markers by ELISA. We investigated hemostatic and inflammatory transcripts in circulating platelets and leukocytes from NAFLD patients. We analyzed platelet and neutrophil extracellular traps (NET) accumulations in liver sinusoids using CD42 and H3 citrullinated histones immunohistochemical staining on liver biopsies. NAFLD patients had increased inflammation markers and lipolysaccharides plasma levels. We found significant increase of inflammatory transcripts in circulating platelets and not in leukocytes of NAFLD subjects compared with healthy controls. We demonstrated increased intrahepatic platelet accumulation that correlated with NAFLD activity score (NAS) score and intrahepatic neutrophil extracellular traps (NET) formation in liver biopsies of NAFLD patients. NET formation was higher in livers with higher NAS and inflammation scores. The presence of low-grade systemic inflammation and proinflammatory changes of circulating platelets indicate that platelets participate on systemic inflammatory changes associated with NAFLD. Liver platelet accumulation and liver NET formation, together with low-grade endotoxemia, suggest that platelets may act to protect the liver from invading microorganisms by favoring local NET formation.

Association of apoptotic marker cytokeratin18 with blood pressure in nonalcoholic fatty liver disease patients.

Non Alcoholic fatty liver disease (NAFLD) associated with hypertension (HTN) is an emerging health issue globally. It is associated with increased levels of apoptotic marker CK18. Main objective of this study was to explore association of cytokeratin18 (CK18) with hypertension (HTN) in NAFLD patients. Descriptive cross sectional study was conducted in Mayo hospital Lahore. Hundred NAFLD subjects were enrolled from OPD of radiology department after approval from ethical review committee. Anthropometric measurements were taken and blood pressure (BP) was measured by mercury sphygmomanometer. Blood samples were drawn from each patient for CK18 levels with ELISA. Data was analyzed by SPSS 20. Continuous variables were presented as mean± SD. Association between CK18 and HTN were analyzed by regression analysis and results were presented as beta coefficient. P <0.05 was taken as significant. Mean age of studied subjects was 43.8±5.34 with height (m), weight (kg) and BMI 1.59±0.063 m, 78.2±11.17 kg, 30.5±4.07kg/m2 respectively. Systolic and diastolic blood pressures were 106±12.8, 72± 12.8mmHg. CK 18 was not significantly associated with systolic (P value 0.55) and diastolic BP (P value 0.37) most probably due to small size of study. Most of the NAFLD patients were hypertensive and have raised CK18 levels than normotensive subjects. So, raised levels of CK18 in NAFLD subjects might be helpful in early screening of HTN. However, significant association was not observed probably due to small sample size.

Liver Stiffness by Magnetic Resonance Elastography Predicts Future Cirrhosis, Decompensation, and Death in NAFLD

Magnetic resonance elastography (MRE) is the most accurate method of liver stiffness measurement (LSM) in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the role of MRE in the prediction of hard outcomes in NAFLD. Adults with NAFLD who underwent MRE between 2007 and 2019 at Mayo Clinic, Rochester were identified. Cox regression analyses were used to explore the predictive role of baseline LSM for 1) development of cirrhosis in noncirrhotic NAFLD and 2) development of liver decompensation or death in those with compensated cirrhosis. A total of 829 NAFLD subjects (54% women, median age 58 years) were identified. Of 639 subjects without cirrhosis, 20 developed cirrhosis after a median follow-up of 4 years. Baseline LSM was predictive of future cirrhosis development: age-adjusted HR= 2.93 (95% CI, 1.86-4.62, p <.0001) per 1 kPa increment (C-statistic = 0.86). Baseline LSM by MRE can be used to guide timing of longitudinal noninvasive monitoring: 5, 3 and 1 years for LSM of 2, 3 and 4-5 kPa, respectively. Of 194 subjects with compensated cirrhosis, 81 developed decompensation or death after a median follow-up of 5 years. Baseline LSM was predictive of future decompensation or death: HR = 1.32 (95% CI, 1.13-1.56, p = .0007) per 1 kPa increment after adjusting for age, sex and MELD-Na. The 1-year probability of future decompensation or death in cirrhosis with baseline LSM of 5 kPa vs 8 kPa is 9% vs 20%, respectively. In NAFLD, LSM by MRE is a significant predictor of future development of cirrhosis. These data expand the role of MRE in clinical practice beyond the estimation of liver fibrosis and provide important evidence that improves individualized disease monitoring and patient counseling.

New Insights into the Pathogenesis of Non-Alcoholic Fatty Liver Disease: Gut-Derived Lipopolysaccharides and Oxidative Stress.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The intricate NAFLD pathogenesis is summarized by the multiple-hits hypothesis, which combines all the environmental and genetic factors that promote the development of NAFLD into a single scenario. Among these, bacterial lipopolysaccharides (LPS) are derived from the overgrowth of Gram-negative bacteria and translocated mainly as a consequence of enhanced intestinal permeability. Furthermore, oxidative stress is increased in NAFLD as a consequence of reactive oxygen species (ROS) overproduction and a shortage of endogenous antioxidant molecules, and it is promoted by the interaction between LPS and the Toll-like receptor 4 system. Interestingly, oxidative stress, which has previously been described as being overexpressed in cardiovascular disease, could represent the link between LPS and the increased cardiovascular risk in NAFLD subjects. To date, the only effective strategy for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH) is the loss of at least 5% body weight in overweight and/or obese subjects. However, the dose-dependent effects of multispecies probiotic supplementation on the serum LPS level and cardiometabolic profile in obese postmenopausal women were demonstrated. In addition, many antibiotics have regulatory effects on intestinal microbiota and were able to reduce serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor alpha (TNF-α) in NASH animal models. Regarding the oxidant status, a Mediterranean diet has been reported to reduce oxidant stress, while vitamin E at high daily dosages induced the resolution of NASH in 36% of treated patients. Silymarin had the positive effect of reducing transaminase levels in NAFLD patients and long-term treatment may also decrease fibrosis and slow liver disease progression in NASH. Finally, the influence of nutraceuticals on gut microbiota and oxidant stress in NAFLD patients has not yet been well elucidated and there are insufficient data either to support or refuse their use in these subjects.

Circulating lipidomic alterations in obese and non-obese subjects with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear. To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach. A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n=66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls). Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P<0.001) but not in obese NAFLD. Additionally, SM levels were significantly associated with systemic and adipose tissue insulin resistance (SM d38:0; P=0.002 and <0.001, respectively). Five potential lipid metabolites for non-obese subjects and seven potential lipids for obese subjects were selected to predict NAFLD and NASH. These lipid combinations showed good diagnostic performance for non-obese (area under the curve [AUC] for NAFLD/NASH=0.916/0.813) and obese (AUC for NAFLD/NASH=0.967/0.812) subjects. Moreover, distinctly altered patterns of diacylglycerol (DAG), triacylglycerol (TAG) and SM levels were confirmed in the validation set depending on the histological severity of NAFLD. Non-obese and obese NAFLD subjects exhibit unique circulating lipidomic signatures, including DAGs, TAGs and SMs. These lipid combinations may be useful biomarkers for non-obese and obese NAFLD patients.

4-HNE Immunohistochemistry and Image Analysis for Detection of Lipid Peroxidation in Human Liver Samples Using Vitamin E Treatment in NAFLD as a Proof of Concept

Lipid peroxidation is a common feature of liver diseases, especially non-alcoholic fatty liver disease (NAFLD). There are limited validated tools to study intra-hepatic lipid peroxidation, especially for small specimen. We developed a semi-quantitative, fully automated immunohistochemistry assay for the detection of 4-hydroxynoneal (4-HNE) protein adducts, a marker of lipid peroxidation, for adaptation to clinical diagnostics and research. We used Hep G2 cells treated with 4-HNE to validate specificity, sensitivity, and dynamic range of the antibody. Staining and semi-quantitative automated readout were confirmed in human needle-biopsy liver samples from subjects with NAFLD and normal liver histology. The ability to detect changes in lipid peroxidation was tested in paired liver biopsies from NAFLD subjects, obtained before and after 4 weeks of treatment with the antioxidant vitamin E (ClinicalTrials.gov NCT01792115, n=21). The cellular calibrator was linear and NAFLD patients had significantly higher levels of 4-HNE adducts compared to controls (p=0.02). Vitamin E treatment significantly decreased 4-HNE (p=0.0002). Our findings demonstrate that 4-HNE quantification by immunohistochemistry and automated image analysis is feasible and able to detect changes in hepatic lipid peroxidation in clinical trials. This method can be applied to archival and fresh samples and should be considered for use in assessing NAFLD histology.

Nonalcoholic fatty liver disease is associated with COVID-19 severity independently of metabolic syndrome: a retrospective case-control study.

AimCoronavirus disease 2019 (COVID-19) is a recently encountered disease that was declared a pandemic by WHO in 2020. Obesity and other components of the metabolic syndrome may aggravate the severity of COVID-19. Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome. The aim of this study was to investigate a possible association between MAFLD and COVID-19 severity.MethodsWe performed a retrospective, case-control study, enrolling 71 consecutive COVID-19 patients who were divided into two groups according to the presence or absence of fatty liver by computed tomography scan. All medical records of eligible patients were reviewed including demographic, clinical, laboratory parameters and data regarding the presence of NAFLD and COVID-19 severity.ResultsNAFLD was identified in 22/71 (31%) of the study group. Out of 71, thirteen suffered from severe COVID-19. NAFLD patients had more severe COVID-19 compared with non-NAFLD subjects, 8/22 (36.3%) vs. 5/49(10.2%), (P < 0.005), respectively. Multiple logistic regression analysis showed that NAFLD subjects were more likely to have severe COVID-19 disease (odds ratio 3.57, 95% confidence interval: 1.22, 14.48, P = 0.0031).ConclusionNAFLD represents a high risk for severe COVID-19 irrespective to gender, and independent of metabolic syndrome specifically in male gender. Moreover, obesity, hypertension and metabolic syndrome were also significantly associated with severe COVID-19.

Moderate alcohol consumption is not associated with subclinical cardiovascular damage but with hepatic fibrosis in non-alcoholic fatty liver disease.

Moderate alcohol consumption is believed to be associated with reduced mortality from cardiovascular disease (CVD) in the general population. This cross-sectional study aimed to comprehensively examine the association between alcohol consumption and subclinical cardiovascular damage or hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). Subjects with NAFLD without a history of heart disease were extracted from 977 consecutive examinees who completed health checkups and optional cardiovascular examinations. Subclinical cardiovascular damage was assessed by coronary artery calcification (CAC), carotid artery ultrasound, and brachial-ankle pulse wave velocity (ba-PWV). CAC scores were classified into three grades (0, ≤100, and >100) by Agatston's method. Alcohol consumption was divided into three groups [Non-drinking (G0); Light (G1), 0.1-6.9 drinks/week; Moderate (G2), 7-20.9 drinks/week for men and 7-13.9 drinks/week for women]. Noninvasive markers (FIB-4, Fibrosis-4; NFS, NAFLD fibrosis score) were calculated for assessment of hepatic fibrosis and classified into low and intermediate-high grade. The overall mean age was 60.2 years and males were 200 (74.6%) among 268 subjects with NAFLD. Number (%) of G0, G1, and G2 were 102 (38.1%), 103 (38.4%), and 63 (23.5%). Binary logistic regression analysis showed no significant difference between G0 and G1, or G0 and G2 in any of the above subclinical cardiovascular damages (CAC score >0, or CAC score >100, carotid plaque+, intima-media thickness ≥1.1mm, and ba-PWV >1400cm/s). However, only G2 had a significant association with intermediate-high grade of FIB-4 or NFS [odds ratio (95% confidence intervals), p value: 1.871 (1.209-2.893), p=0.005; 2.910 (1.715-4.939), p=0.000], compared to G0. Non-heavy drinking might not reduce the risk of CVD in NAFLD subjects. On the contrary, even moderate drinking could promote hepatic fibrosis. Thus, NAFLD drinkers should not be recommended for even a moderate amount of alcohol.

Doppler perfusion index in adolescents with non-alcoholic fatty liver disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) as a multi-factorial disorder is the most common cause of abnormal liver function tests in adolescents. Objectives: The present study aimed to assess Doppler perfusion index (DPI) in adolescents with NAFLD as compared with healthy subjects. Patients and Methods: Thirty-seven adolescents with NAFLD and 25 healthy individuals were enrolled in the study. Hemodynamic indices were measured using a color Doppler ultrasound machine. Severity of fatty liver disease and steatosis grade were assessed using FibroScan. The measured indices were peak systolic velocity (PSV), resistive index (RI), end-diastolic velocity (EDV), time-averaged mean velocity (TAMV), time-averaged peak velocity (TAPV), portal venous blood flow (PVBF) volume, hepatic arterial blood flow (HABF) volume, and DPI. Results: The mean of DPI in the case and control groups was 0.31±0.11 and 0.31±0.09, respectively (P=0.972). HABF volume was significantly lower in the case group as compared with the control group (103.8 versus 153.3 respectively, P=0.015). PSV, TAMV, mean velocity, and PVBF volume were significantly lower in the case group as compared with the control group (P&lt;0.05). Patients with a higher steatosis grade indicated a significantly lower mean of PSV and TAMV portal than controls (P&lt;0.05). Conclusion: DPI was similar in adolescents with NAFLD and healthy subjects and was not associated with severity of fatty liver disease and steatosis grade. In addition, the percentage of steatosis would be increased with increased liver span.

Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Lean non-alcoholic fatty liver disease (NAFLD) is a potentially metabolically unhealthy state that refers to NAFLD occurring in non-overweight/nonobese subjects. Yet its global epidemiology and metabolic characteristics are not extensively elucidated. PubMed, EMBASE, Web of Science and Cochrane databases were searched for eligible studies until January 2020. Random-effects/fixed-effects models were used to estimate the global prevalence of lean NAFLD and to compare clinical characteristics among lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD subjects. "Lean" NAFLD was defined by ethnic-specific body mass index measurements in the normal range. Meta-regression and subgroup analyses were performed to determine potential sources of heterogeneity. A total of 33 observational studies were included with 205307 individuals from 14 countries. The global prevalence of lean NAFLD was 4.1% (95% confidence interval [CI]: 3.4-4.8%). In lean subjects, the prevalence of NAFLD was 9.7% (95% CI: 7.7-11.8%). The prevalence of lean NAFLD with diabetes, hypertension, metabolic syndrome, dyslipidemia, or central obesity was 0.6% (95% CI: 0.4-0.9%), 1.8% (95% CI: 1.2-2.5%), 1.4% (95% CI: 1.0-1.9%), 2.8% (95% CI: 1.9-3.7%), and 2.0% (95% CI: 1.6-2.4%), respectively. The prevalence of lean NAFLD showed an upward trend between 1988 and 2017. Asian individuals had the highest prevalence of lean NAFLD (4.8%, 95% CI: 4.0-5.6%). Middle-aged people (45-59years old) had the highest prevalence of lean NAFLD (4.4%, 95% CI: 3.2-5.5%). The prevalence of metabolic complications in lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD groups increased sequentially. Lean NAFLD occurs with metabolic complications and is not an uncommon condition. The highest prevalence of lean NAFLD occurs in middle-aged individuals of Asian countries.

Genetic susceptibility of increased intestinal permeability is associated with progressive liver disease and diabetes in patients with non-alcoholic fatty liver disease

Background and aimIncreased intestinal permeability plays a key role in the pathogenesis of fat deposition in the liver. The aim of our study was to assess whether a single nucleotide polymorphism of protein tyrosine phosphatase non-receptor type 2 (PTPN2) (rs2542151 T→G), involved in intestinal permeability, may be associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods and resultsWe recruited a prospective cohort of NAFLD subjects and matched controls. Clinical data, PTPN2 genotype and laboratory data were collected for each patient. Results were stratified according to liver histology and diabetes. We enrolled 566 cases and 377 controls. PTPN2 genotype distribution did not significantly differ between patients and controls. In the entire population, patients with PTPN2 rs2542151 T→G (dominant model) have a higher prevalence of diabetes; 345 patients (60.9%) underwent liver biopsy: 198 (57.4%) had steatohepatitis and 75 (21.7%) had advanced fibrosis. At multiple logistic regression analysis PTPN2 rs2542151 T→G was associated with T2DM (OR 2.14, 95% CI 1.04–4.40, P = 0.03). Patients who underwent liver biopsy, rs2542151 T→G of PTPN2 was independently associated with severe steatosis (OR 2.00, 95% CI 1.17–3.43, p = 0.01) and severe fibrosis (OR 2.23, 95% CI 1.06–4.72, P = 0.03). ConclusionOur study shows that NAFLD patients with rs2542151 T→G of PTPN2 have a higher severity of fatty liver disease and a higher prevalence of T2DM. These results suggest that individual genetic susceptibility to intestinal permeability could play a role in liver disease progression.

The Effect of Three Mediterranean Diets on Remnant Cholesterol and Non-Alcoholic Fatty Liver Disease: A Secondary Analysis.

Background: Elevated fasting remnant cholesterol (REM-C) levels have been associated with an increased cardiovascular risk in patients with metabolic syndrome (Mets) and Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to estimate the effect of different diets on REM-C levels in patients with MetS, as well as the association between NAFLD and REM-C. Methods: This is a secondary analysis of the MEDIDIET study, a parallel-arm Randomized Clinical Trial (RCT). We examined 237 people with MetS who underwent Liver Ultrasound (LUS) to assess the NAFLD score at baseline, 3-, and 6-months follow-up. Subjects were randomly assigned to the Mediterranean diet (MD), Low Glycemic Index diet (LGID), or Low Glycemic Index Mediterranean diet (LGIMD). REM-C was calculated as [total cholesterol–low density lipoprotein cholesterol (LDL-C)–high density lipoprotein cholesterol (HDL-C)]. Results: REM-C levels were higher in subjects with moderate or severe NAFLD than in mild or absent ones. All diets had a direct effect in lowering the levels of REM-C after 3 and 6 months of intervention. In adherents subjects, this effect was stronger among LGIMD as compared to the control group. There was also a significant increase in REM-C levels among Severe NAFLD subjects at 3 months and a decrease at 6 months. Conclusions: fasting REM-C level is independently associated with the grade of severity of NAFLD. LGIMD adherence directly reduced the fasting REM-C in patients with MetS.

MRI-determined liver fat correlates with risk of metabolic syndrome in patients with nonalcoholic fatty liver disease.

Little is known about that the relationship between hepatic fat content (HFC) and metabolic syndrome (MetS). We aimed to determine whether HFC correlated with MetS in patients with nonalcoholic fatty liver disease (NAFLD). HFC was measured by MRI-determined proton density fat fraction (MRI-PDFF) for 131 suspected NAFLD subjects. Patients with NAFLD defined as MRI-PDFF ≥5% were stratified into two groups based on whether they were above or below the median MRI-PDFF value; the MRI-PDFF value for the control group was <5%. The primary outcome was the presence of MetS. Logistic regression models were used to obtain the associations between the severity of liver fat and MetS, and the corresponding odds ratios (ORs) and 95% confidence intervals (CIs) were recorded. Compared to NAFLD patients with low-HFC (n = 48) and the control group (n = 35), NAFLD patients with high-HFC (n = 48) had significantly greater prevalence of central obesity, hypertension, hyperglycemia, and hypertriglyceridemia (all P < 0.05). NAFLD patients with high-HFC had a higher prevalence of MetS than NAFLD patients with low-HFC (79.2% vs. 56.2%, P < 0.05). The multivariate-adjusted OR for the prevalence of MetS comparing NAFLD patient with low-HFC and high-HFC to the control group were 4.56 (95% CI: 0.54-38.79, P = 0.165) and 22.91 (95% CI: 1.80-292.21, P = 0.016), respectively (Ptrend = 0.014). Increased hepatic fat quantitatively measured by MRI-PDFF had a significant dose-relationship with the presence of MetS, and the amount of liver fat may affect cardiovascular risk.

Prevalence and Profile of Nonalcoholic Fatty Liver Disease in Lean Adults: Systematic Review and Meta-Analysis.

Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C‐reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long‐term hepatic and extrahepatic outcomes in individuals with lean NAFLD.

Neck Circumference is an Effective Supplement for Nonalcoholic Fatty Liver Disease Screening in a Community-Based Population.

Background Accumulating evidence has shown that neck circumference (NC) is associated with obesity-related metabolic abnormalities. Nonalcoholic fatty liver disease (NAFLD) is regarded as a liver manifestation of metabolic syndrome. This study aimed to investigate the relationship between NC and liver fat content (LFC) and NAFLD. Methods A total of 1698 subjects (577 men and 1121 women) from the Shanghai community were enrolled. All the subjects underwent NC measurement and biochemical measurements. LFC was calculated using the parameters from abdominal ultrasound images. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. Results Subjects with NAFLD based on the LFC measurement had higher values of NC, liver enzyme profiles, homoeostasis model assessment-insulin resistance index, and LFC than those without NAFLD (all P < 0.05), irrespective of sex. NC showed an upward trend with the increase of LFC in both men and women (both P < 0.05). An elevated NC could identify 55.22% of men and 50.29% of women with NAFLD based on quantitative ultrasonography. The positive correlation between NC and LFC remained significant even after adjustment for central obesity (both P < 0.05). After adjusting for confounding factors, the risk of NAFLD in subjects with an elevated NC was 1.52-fold higher in men (P=0.036) and 2.31-fold higher in women (P < 0.001). Conclusions There was a significant and positive correlation between NC and LFC. The risk of NAFLD increased significantly in subjects with an elevated NC.