Non-alcoholic Fatty Liver Disease In Males Research Articles

Value of serum high density lipoprotein-cholesterol in risk assessment of non-alcoholic fatty liver disease

Objective To investigate the value of high density lipoprotein-cholesterol (HDL-C) in the diagnosis and risk assessment of non-alcoholic fatty liver disease (NAFLD). Methods A cross-sectional study and multistage stratified random sampling method were performed in epidemiological survey. According to inclusion and exclusion criteria, a total of 3 312 individuals were enrolled and divided into NAFLD group (913 cases) and non-NAFLD group (2 399 cases). The serum lipid levels were compared between the two groups. Receiver operating characteristic (ROC) curve was performed to evaluate the value of HDL-C in the diagnosis of NAFLD. The binary logistic regression models were established based on HDL-C level.The differences in liver function indexes were compared among the research objects with different HDL-C levels.T test and Mann-Whitney U test were performed for statistical analysis. Results The serum levels of total cholesterol, triglyceride and low density lipoprotein-cholesterol (LDL-C) of NAFLD group were all higher than those of non-NAFLD group ((5.24±0.92) mmol/L vs.(4.98±0.92) mmol/L, (1.95±1.41) mmol/L vs.(1.13±0.68) mmol/L, (3.31±0.84) mmol/L vs.(3.09±0.84) mmol/L), and the differences were statistically significant (t=-7.29, -22.38 and -6.84, all P<0.01). However the serum HDL-C level of NAFLD group was lower than that of non-NAFLD group((1.30±0.33) mmol/L vs.(1.64±0.40) mmol/L), and the difference was statistically significant (t=24.93, P<0.01). The incidence of hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia and hyper-low-density lipoprotein cholesterolemia of NAFLD group was 48.0%(438/913), 44.8%(409/913), 31.0%(283/913) and 82.8%(756/913), respectively, which were significantly higher than that of non-NAFLD group (36.8%, 882/2 399; 13.2%, 317/2 399; 10.5%, 251/2 399; 71.8%, 1 723/2 399), and the differences were statistically significant (χ2=34.65, 385.43, 206.18 and 42.37, all P<0.01). Using the cut-off values of HDL-C≤1.66 mmol/L in female and≤1.33 mmol/L in male, the area under curve (AUC) values for NAFLD diagnosis were 0.720(95% confidence interval (CI) 0.693 to 0.747) and 0.708 (95%CI 0.679 to 0.737), respectively, the sensitivity was 79.1% and 76.6%, and the specificity was 55.0%and 54.6%. The results of binary logistic regression models based on HDL-C level indicated that prevalence of NAFLD in female with low HDL-C was 4.584 times (95%CI 3.530 to 5.940, P<0.01) higher than that in female with high HDL-C; the prevalence of NAFLD in male with low HDL-C was 3.898 times (95%CI 3.020 to 5.030, P<0.01) higher than that of male with high HDL-C. The alanine aminotransferase (ALT), aspartate transaminase (AST), gamma glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) levels of low HDL-C group were all higher than those of high HDL-C group (20.10 U/L, 14.40 U/L to 29.40 U/L vs. 16.80 U/L, 12.70 U/L to 23.00 U/L; 19.20 U/L, 16.00 U/L to 23.70 U/L vs. 19.00 U/L, 16.00 U/L to 22.17 U/L; 22.00 U/L, 14.00 U/L to 34.00 U/L vs. 15.00 U/L, 11.00 U/L to 23.00 U/L and 71.00 U/L, 59.00 U/L to 85.00 U/L vs. 66.00 U/L, 55.00 U/L to 82.00 U/L), and the differences were statistically significant (Z=-10.53, -2.20, -14.19 and -5.87, all P<0.05). Conclusion The serum HDL-C level is negatively correlated with the risk of NAFLD level, and the NAFLD risk of individuals with low HDL-C level is significantly higher than individuals with high HDL-C level. Key words: Cholesterol, HDL; Non-alcoholic fatty liver disease; Risk factors; Anti-inflammation effects

Assessment of Liver Fatty Acid Binding Protein (L-FABP) as a Diagnostic Marker in Non-Alcoholic Fatty Liver Disease

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common liver disease worldwide, it causes chronic hepatitis, which leads to cirrhosis and hepatocellular carcinoma. We aimed to assess the value of liver fatty acid binding protein (L-FABP) in the diagnosis of non-alcoholic fatty liver disease in comparison to ultrasonography. Patients and Methods: Ninty subjects were enrolled in this study who attended the Hepatology, Gastroenterology and Internal medicine clinics in Benha University Hospitals between January 2017 and January 2018 and divided into group I included 70 consecutive patients with non-alcoholic fatty liver disease who were diagnosed by ultrasound with or without elevated liver enzymes and group II included 20 healthy control subjects without NAFLD (by ultrasound) with normal liver enzymes. Serum levels of L-FABP were determined by enzyme-linked immunosorbent assay. Results: NAFLD patients were slightly older than healthy subjects as mean age in group I was (37.74 ± 11.7) while in group II was (36.5 ± 11.31). There was a slight increase in NAFLD in males, there was a high prevalence of NAFLD in the urban population. L-FABP levels in NAFLD patients were higher than in the control group (levels were 188.6 ± 34.94 and 137.7 ± 13.05 ng/l respectively). A strong correlation was found between L-FABP and ALT, AST, BMI and glucose levels. Analysis of ROC curve revealed that at a level 151.1 ng/sensitivity, specificity, PPV, NPV and accuracy were 83.3%, 71.8%, 31.3%, 96.6% and 73.3% respectively with AUC 0.839 and at a level 189.5 ng/sensitivity, specificity, PPV, NPV and accuracy were 90%, 90%, 95.4%, 95.4%, 88.9% with AUC was 0.950. Conclusion: Serum L-FABP could be used as a new diagnostic biomarker for detecting NAFLD.

Risk factors differentially associated with non-alcoholic fatty liver disease in males and females with metabolic syndrome.

non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in western countries. This study aimed to investigate putative risk factors differentially related with NAFLD in obese males and females diagnosed with metabolic syndrome (MetS), stratified using the non-invasive hepatic steatosis index (HSI). a cross-sectional analysis of the PREDIMED Plus study was performed of 278 participants with MetS (141 males and 137 females) of the Navarra-Nutrition node. Subjects were categorized by HSI tertiles and gender. Baseline clinical, biochemical variants and adherence to a Mediterranean diet and physical activity were evaluated. multivariate analyses showed that females had 4.54 more units of HSI (95% CI: 3.41 to 5.68) than males. Both sexes showed increased levels of triglycerides, TG/HDL cholesterol ratio and triglyceride glucose index across the HSI tertiles. Physical activity exhibited a negative statistical association with HSI (males: r = -0.19, p = 0.025; females: r = -0.18, p = 0.031). The amount of visceral fat showed a positive association with HSI in both sexes (males: r = 0.64, p < 0.001; females: r = 0.46, p < 0.001). Adherence to the Mediterranean diet was lower in those subjects with higher HSI values (males: r = -0.18, p = 0.032; females r= -0.19, p = 0.027). females had a poor liver status, suggesting gender differences related to NAFLD. Adherence to a Mediterranean diet and physical activity were associated with beneficial effects on cardiovascular disease features. Thus, reducing the risk of hepatic steatosis in subjects with MetS and obesity.

Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.

The association between missing teeth and non-alcoholic fatty liver disease in adults.

Long-term oral chronic inflammatory process is closely related to systemic inflammation, which is a main mechanism involved in non-alcoholic fatty liver disease (NAFLD). Tooth loss could reflect the accumulation of oral local inflammation, implying that number of missing teeth may associate with NAFLD. This study evaluated the association between missing teeth and presence of NAFLD in a general population. A cross-sectional study of 24,470 adults was carried out from the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. The self-reported number of missing teeth (excluding third molars) was recorded and classified into four categories: 0, 1-2, 3-5, and ≥6. The NAFLD was diagnosed by the liver ultrasonography. Associations were analysed by adjusted multivariable logistic regression. The multivariable-adjusted odds ratios (95% confidence interval) of NAFLD across the categories of missing teeth were as follows: in males, 1.00 (reference), 1.04 (0.93-1.16), 1.06 (0.90-1.24), and 1.40 (1.09-1.81) (p for trend=0.04); in females, 1.00 (reference), 0.98 (0.83-1.15), 1.11 (0.90-1.37), and 1.07 (0.77-1.48) (p for trend=0.45). The number of missing teeth was associated with a higher presence of NAFLD in males but not females.

The association of sleep duration and sleep quality with non-alcoholic fatty liver disease in a Taiwanese population

ObjectiveThe association of sleep duration/quality with nonalcoholic fatty liver disease (NAFLD) is inconclusive. Several important covariates were not adjusted concomitantly in some studies, and the severity of NAFLD was not considered. Furthermore, the gender impact of sleep duration or sleep quality on NAFLD remains unclear. We thus aimed to examine the association of sleep duration and quality with NAFLD by gender in a Taiwanese population. MethodsA total of 6663 subjects aged 18 years or more were enrolled. The severity of NAFLD was divided into mild, moderate, and severe degrees based on ultrasound findings. The sleep duration was classified into three groups: short (<6h), normal (6–8h), and long (>8h). Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and poor sleep quality was defined as a global PSQI score greater than 5. ResultsAfter adjustment for potential confounders, multinomial logistic regression showed that poor sleep quality was negatively associated with both mild and moderate-to-severe NAFLD in males, but sleep duration was not independently related to NAFLD. In females, sleep condition was not related to NAFLD. ConclusionsPoor sleep quality but not sleep duration was associated with a lower risk of not only moderate to severe but also mild NAFLD in males. In females, the association of sleep quality and duration with the risk of NAFLD was insignificant.

Serum Lipid Abnormalities and Nonalcoholic Fatty Liver Disease in Adult Males

BackgroundDyslipidemia is a risk factor for nonalcoholic fatty liver disease (NAFLD). The aim of our study was to determine the associations of serum lipid indexes with NAFLD in adult males. Materials and MethodsIn this cross-sectional study, 830 patients with NAFLD and 2,357 healthy individuals were assessed. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were compared between patients with NAFLD and controls. The associations of dyslipidemia indexes with NAFLD occurrence were assessed by univariate analysis, and multivariate analysis was performed to identify independent dyslipidemia factors predictive of NAFLD. ResultsOf the 3,187 study subjects, NAFLD occurred in 830 (26.04%), there were 504 (60.72%) patients with mild disease and 326 (39.28%) patients with moderate-to-severe disease. Although the frequency of normal TC, TG, LDL-C and high-density lipoprotein cholesterol levels in patients with NAFLD was similar to the controls, the frequencies of patients with NAFLD with marginally high and high TC, TG and LDL-C levels were significantly different when compared with controls. Interestingly, the association of the number of abnormal serum lipid indexes and NAFLD was highly significant with 2 abnormalities (odds ratio = 1.977; 95% CI: 1.436-2.722; P < 0.001) and ≥3 abnormalities (odds ratio = 3.505; 95% CI: 2.466-4.982; P < 0.001). ConclusionsA significant positive association was found between dyslipidemia characteristics and NAFLD in adult males.

Gender differences in the association of non-alcoholic fatty liver disease and metabolic syndrome with erosive oesophagitis: a cross-sectional study in a Taiwanese population

ObjectivesAlthough metabolic syndrome correlates with erosive oesophagitis, few studies have examined the association between non-alcoholic fatty liver disease (NAFLD), associated with obesity and insulin resistance as metabolic syndrome, and erosive...

Elevated transaminase levels among overweight adolescents in eastern China.

We aim to investigate the prevalence and correlates of suspected nonalcoholic fatty liver disease (NAFLD) among adolescents in eastern China. The study uses data from the annual health examination among all students finishing high school who applied for university entrance in Changzhou City between 2012 and 2014 (n=19162). Suspected NAFLD was defined as overweight plus elevated alanine aminotransferase levels (males >25.8U/L; females >22.1U/L). The prevalence of suspected NAFLD was 6.9% (11.1% in males and 2.6% in females). Students from medium and high socio-economic status (SES) schools had a higher prevalence of suspected NAFLD than those from low SES schools. Prehypertension had similar odds ratios (ORs, above four) for suspected NAFLD in both genders. The positive association between impaired fasting glucose/diabetes and suspected NAFLD was stronger in females than males. Compared with those born in autumn, these born in spring (OR 1.39; 95% CI, 1.16-1.67) and winter (OR 1.24; 95% CI, 1.04-1.49) had increased odds to have suspected NAFLD in males but not in females. Suspected NAFLD was prevalent among urban university applicants especially in males and those of high SES. Prehypertension was positively related to suspected NAFLD. Season of birth was related to suspected NAFLD in males but not in females.

Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of very low-density lipoprotein-triglyceride (VLDL-TG) kinetics is not fully understood. The objective of the study was to determine VLDL-TG, glucose, and palmitate kinetics during fasting and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD−). Twenty-seven nondiabetic, upper-body obese (waist to hip ratio > 0.9, body mass index > 28 kg/m2) men, 18 NAFLD+, and nine NAFLD− determined by magnetic resonance spectroscopy were enrolled.14C-labeled VLDL-TG and 3H-labeled glucose and palmitate tracers were applied in combination with indirect calorimetry and breath samples to assess kinetics and substrate oxidations postabsorptively and during a hyperinsulinemic-euglycemic clamp. Dual-X-ray absorptiometry and magnetic resonance imaging assessed body composition. Liver fat content was greater in NAFLD+ than NAFLD− men (21.0% vs 3.7%), even though body composition, metabolites (except triglycerides), and insulin were similar in the groups. Insulin suppression of VLDL-TG secretion (P = .0001), oxidation (P = .0003), and concentration (P= .008) as well as percentage decreases were lower in NAFLD+ than NAFLD− men (secretion: 31.9% ± 17.2% vs 64.7% ± 19.9%; oxidation: −9.0% ± 24.7% vs 46.5% ± 36.6%; concentration: 11.9% ± 20.7% vs 56.2% ± 22.9%, all P < .001). Likewise, lower insulin suppression of very low-density lipoprotein particle size was present in NAFLD+ than NAFLD− men (P = .0002). Conversely, insulin suppression of endogenous glucose production was similar in the groups. Compared with endogenous glucose production, the inability of NAFLD+ men to suppress VLDL-TG kinetics to compensate for the increased liver fat content seems to be an early pathophysiological manifestation of male NAFLD+. These data suggest therapeutic targets reducing liver fat content may ameliorate metabolic abnormalities associated with NAFLD and presumably diabetes.

Dietary patterns are associated with prevalence of fatty liver disease in adults.

Previous studies have indicated that higher levels of food consumption are associated with fatty liver disease (FLD), but few studies have investigated the relationship between this disease and different dietary patterns. The aim of this cross-sectional study was to examine the association between dietary patterns and FLD in adults. Dietary intakes of participants in the Tianjin were assessed via questionnaire. Factor analysis was used to identify dietary patterns, and FLD was defined as having a FLD diagnosis using liver ultrasonography. Relationships between dietary patterns and FLD were assessed using multiple logistic regression analysis. Female participants in the highest quartile of high-carbohydrate/sweet pattern scores had a 2.19-fold greater risk (95% confidence interval (CI), 1.40-3.46) of developing non-alcoholic FLD (NAFLD) than those in the lowest quartile after adjusting for confounding factors. No significant differences were found between any dietary pattern and NAFLD in males. In males, a significantly increasing trend of alcoholic FLD (AFLD) prevalence was associated with increasing high-protein/cholesterol pattern scores (P for trend = 0.03; odds ratio (OR), 2.08; 95% CI, 1.15-3.81) while an increased high-carbohydrate/sweet pattern score appeared protective against AFLD (P for trend = 0.02; OR, 0.55; 95% CI, 0.29-1.00). Our study demonstrates that high-protein/cholesterol pattern scores are associated with higher prevalence of AFLD in males. We also show high-carbohydrate/sweet pattern scores are associated with higher prevalence of NAFLD in females; but, interestingly, this pattern shows a favorable effect on AFLD in males.

Plasminogen activator inhibitor-1 is independently associated with non-alcoholic fatty liver disease whereas leptin and adiponectin vary between genders.

Alterations of adipocytokine levels and clinical parameters in non-alcoholic fatty liver disease (NAFLD) are crucial for the prognosis and complications of the diseases. However, the key adipocytokines independently associated with NAFLD have not been identified, and we aimed to investigate them. This study was conducted on a consecutive series of 210 Taiwanese NAFLD patients and 420 sex- and age-matched controls. Fatty liver was diagnosed by magnetic resonance spectroscopy. The enrolled subjects' body mass indexes, homeostasis model of assessment-insulin resistance, uric acid, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, blood pressure, metabolic syndrome (yes/no), alanine aminotransferase, aspartate aminotransferase-to-platelet ratio indexes, leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were analyzed to determine their association with NAFLD. Univariate analysis showed that all of the aforementioned factors were associated with NAFLD, whereas multivariate analysis revealed that only PAI-1 (odds ratio: 1.39, P = 0.039) was independently associated with NAFLD. Subgroup analysis showed that females consistently had higher leptin (P < 0.001) and adiponectin (P < 0.001) levels than males, whereas their PAI-1 levels were similar. Males with NAFLD had higher leptin but lower adiponectin levels than their subgroup counterparts (all P < 0.001). Among the female subgroups, hyperleptinemia and hypoadiponectinemia were only observed in the NAFLD patients ≥ 45 years. PAI-1 is independently associated with NAFLD after adjusting for other factors, including leptin and adiponectin. Male and female NAFLD patients show distinct patterns of leptin and adiponectin alterations; special attention is required when evaluating these alterations in female NAFLD patients < 45 years.

Influence of lifestyle-related diseases and age on the development and progression of non-alcoholic fatty liver disease.

Although non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, the clinical association between non-alcoholic steatohepatitis (NASH) and lifestyle-related diseases such as obesity, type 2 diabetes mellitus (DM), hypertension (HT) and dyslipidemia (DL) has not been clarified. We studied the influence of lifestyle-related diseases and age on the development and progression of NAFLD. We enrolled 550 patients with biopsy-proven NAFLD (284 men, 266 women; average age, 52 and 62 years, respectively). The effect of lifestyle-related diseases and age (≤49 vs ≥50 years) on the frequency of NASH and advanced fibrosis (≥stage 3) was studied. Prevalence of obesity, DM, HT and DL in male and female NASH patients was 75%/67%, 53%/54%, 66%/77% and 85/79%, respectively. DM patients had a higher frequency of NASH in the older male NAFLD group and a higher frequency of advanced fibrosis in the older female NASH group. With the increasing number of complicating lifestyle-related diseases, the rate of NASH increased in male NAFLD patients. In both sexes, aging resulted in the development of NASH and progression of liver fibrosis. Multivariate logistic regression analysis revealed that age and DM were significantly associated with the development of NASH in male NAFLD patients and progression of fibrosis in female NASH patients. Age is strongly associated with the development and progression of NASH. Type 2 DM may play the most crucial role among lifestyle-related diseases in the development and progression of NASH.

The value of neck circumference (NC) as a predictor of non-alcoholic fatty liver disease (NAFLD)

AimsTo analyze the correlation between neck circumference (NC) and non-alcoholic fatty liver disease (NAFLD) and compare the predictive value of NC for NAFLD with that of other simple anthropometric measures and other biochemical profiles. Methods2761 subjects, undergoing a medical check-up at the Changhai Hospital between October 01, 2012 and November 30, 2012, were recruited to the study. NC, other simple anthropometric measures, and biochemical profiles were analyzed. ResultsNC in NAFLD subjects with or without elevated ALT were 38.94 ± 2.62 cm and 37.21 ± 3.06 cm respectively, which was significantly higher than that in subjects with other metabolic disorders (NC: 35.33 ± 3.03 cm) and in normal controls (NC: 32.60 ± 2.37) (both P < 0.001). NC in women with NAFLD increased by 1 cm and fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR) increased by 1.87 mIU/L and 1.43, respectively. Compared with other anthropometric measures, neck circumference-height ratio (NHtR) had a significant impact both on the incidence of NAFLD. After adjustment for sex, abdominal obesity and other influencing factors, the incidence of NAFLD still tended to positively correlate with NC. Optimal cut-off points of NC and NHtR for predicting NAFLD in males were 37.25 cm and 0.224, respectively, and such points in females were 32.90 cm and 0.208, respectively. ConclusionNC was wider in NAFLD patients than in healthy subjects and other metabolic disorder sufferers. NC and NHtR could be used as simple predictive tools for NAFLD.

Non-alcoholic fatty liver disease and risk of in-stent restenosis after bare metal stenting in native coronary arteries

In-stent restenosis (ISR) remains the most common complication of percutaneous coronary intervention. Due to shared risk factors, it is postulated that non-alcoholic fatty liver disease (NAFLD) patients have an increased risk of ISR. This study aimed to determine the association between NAFLD and ISR in patients after bare metal stenting. This study included a cohort of 210 consecutive patients (150 men and 60 women) undergoing follow-up angiography. The primary end-point was angiographic ISR. Multivariate logistic regression analysis was used to identify independent risk factors for ISR. The cumulative ISR rate during follow-up was analyzed by Kaplan-Meier method. Subgroup analyses were also done for different gender. The ISR rate was 29.5%. Patients with NAFLD had a significantly higher prevalence of ISR than patients without NAFLD (43.3 vs. 16.0%, P < 0.001). In logistic regression analysis, NAFLD was associated with increased ISR, independent of low-density lipoprotein cholesterol, body mass index (adjusted odds ratio: 2.688, 95% confidence intervals: 1.285-5.537, P < 0.001). Male NAFLD patients had a higher prevalence of ISR than patients without NAFLD (48.4 vs. 15.3%, P < 0.001), while the prevalence of ISR in female patients with and without NAFLD were comparable (7.7 vs. 17.0%, P = 0.404). Kaplan-Meier analysis showed a significant association between NAFLD and ISR in all patients (log-rank P = 0.008) and in male subgroup (log-rank P = 0.033), but not in female subgroup (log-rank P = 0.313). This preliminary study suggests that NAFLD could independently associate with a high prevalence of ISR, especially in male patients.

Letter: gender‐associated cell‐free microRNA profiles in non‐alcoholic fatty liver disease

Sirs; The study by Schwimmer et al. suggested the existence of a gender phenomenon in non-alcoholic fatty liver disease (NAFLD).1 First, the majority of children diagnosed with NAFLD were male. Second, NAFLD boys had significantly higher levels of serum alanine aminotransferases (ALT) than NAFLD girls. This ALT trend, however, was also seen in non-NAFLD children who were obese and overweight. Therefore, ALT alone was likely inadequate, if at all involved, in explaining the biology underlying the gender-skewed prevalence of NAFLD in their study and others.2 We have identified miRNA profiles in fasting serum from NAFLD patients (n = 5) recruited to the National Institutes of Health (NIH) Clinical Research Center between January 2009 and December 2012, compared with age and race matched controls with no NAFLD (n=5) using nCounter® (Nanostring). Male NAFLD patients also had significantly (P < 0.05) upregulated expressions of the hsa-miR-432-5p, hsa-miR-578, and hsa-miR-155-5p compared to female NAFLD patients (See Figure 1). The hsa-miR-432-5p and hsa-miR-301b levels were significantly (P < 0.05) higher in NAFLD male patients compared to male controls. In contrast, female NAFLD patients did not have significantly different miRNA levels compared to female controls. Thus, our pilot study showed empirical evidence for a male NAFLD-associated miRNA profile. Figure 1 MicroRNA Expressions in Male NAFLD versus Female NAFLD Patients. The male NAFLD-associated miRNA species found above are linked to inflammatory cytokines.3 Our findings also add to the literature suggesting the intriguing involvement of oestrogen and endocrine/metabolic signaling in NAFLD pathogenesis. In mice, oestrogen withdrawal leads to alterations in the peroxisome proliferator-activated receptor (PPAR) genes, which are the predicted targets of hsa-miR-142, which in turn is a target of hsa-miR-155. 4,5,6 We suggest that these male NAFLD miRNA profiles provide a starting point not only for the development of biomarkers for male NAFLD screening, but also for understanding the molecular basis of a gender-unique NAFLD pathogenesis.

Hematocrit is associated with fibrosis in patients with nonalcoholic steatohepatitis

Hematocrit levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) and related to hypoxia and hyperlipidemia. This study was conducted to investigate the association between elevated hematocrit and liver histology in patients with NAFLD. We examined 215 consecutive adults with biopsy-proven NAFLD (108 with steatosis alone, 107 with nonalcoholic steatohepatitis) and 110 controls. The stage of fibrosis was measured using a four-point scale. All underwent anthropometric and metabolic profiling. Hematocrit and related hematologic variables such as blood viscosity and red blood cell count were also measured. NAFLD morbidity was found to be positively correlated with hematocrit levels. After adjusting for age, smoking, diabetes, BMI, homeostasis model assessment of insulin resistance, triglycerides, and obstructive sleep apnea, patients with hematocrit levels in the highest quartile were seen to have had an odds ratio of 3.05 (95% confidence interval 2.12-4.36, P=0.015) for NAFLD in males. Hematocrit levels increased significantly (P<0.001) in steatosis (42.4±4.6%) compared with control groups (38.2±4.2%), and in nonalcoholic steatohepatitis (45.1±5.2%) compared with steatosis patients. On multivariate analysis, hematocrit levels were found to be strongly and independently associated with fibrosis (β=0.205, P=0.030). Moreover, hematocrit levels increased with the severity of hepatic fibrosis (P<0.05). Our results indicate that hematocrit levels are significantly increased and independently associated with fibrosis in NAFLD patients. Therefore, hematocrit levels may have potential interest as a clinical marker of NAFLD severity.

Risk factors analysis of nonalcoholic fatty liver disease in Chinese men

To explore risk factors of nonalcoholic fatty liver disease (NAFLD) in men in order to provide a theoretical basis for developing more effective NAFLD prevention and control strategies. One-hundred-and-two male patients (37.3+/-11.4 years old) hospitalized with NAFLD at the Dongnan Affiliated Hospital of Xiamen University between January 2009 and December 2010 were enrolled in the study, along with 23 age-matched healthy men (34.4+/-16.7 years old) to serve as the control group. The correlation(s) of body mass index (BMI; overweight defined as more than or equal to 22.717 kg/m2), waist circumference (WC), waist-to-hip ratio (WHR; central obesity defined as more than or equal to 0.866), fasting plasma glucose (FPG), triglyceride (TG), and total cholesterol (TC) with NAFLD was analyzed by univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to select proper thresholds for classification. BMI, WC, WHR, FPG, TG, and TC were significantly different between the cases and controls (P less than 0.01). BMI, WC, WHR, TG and TC were identified as risk factors of NAFLD in these male cases (P less than 0.01). Relative to WC, TG and TC, both BMI and WHR had significant predictive value for NAFLD (odds ratio (OR) = 10.819 and 10.588, respectively). In addition, BMI had the highest diagnostic value for the prediction of NAFLD (area under the curve (AUC) = 0.931) followed by WHR (AUC = 0.879). BMI, WC, WHR, TG, and TC are risk factors of NAFLD in Chinese men. BMI and WHR are effective anthroposomatology indices of NAFLD and may be useful factors on which to base future prevention and early diagnosis strategies for NAFLD in males.

An Increased Circulating Angiotensin II Concentration is Associated with Hypoadiponectinemia and Postprandial Hyperglycemia in Men with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a condition associated with type 2 diabetes (T2D). Insulin resistance, a common pathogenesis of NAFLD and T2D, is partially caused by alterations in angiotensin II (Ang II) and is accompanied by hypoadiponectinemia. We aimed to investigate whether the circulating Ang II and adiponectin concentrations are related to hyperglycemia in male NAFLD patients. Thirty-five controls and 85 NAFLD patients without prior known T2D were enrolled. All participants were non-smoking men who performed 75-g oral glucose tolerance tests. According to the American Diabetes Association (ADA) criteria, the NAFLD patients were divided into the euglycemia and hyperglycemia groups. The NAFLD patients with hyperglycemia were further divided into the isolated impaired fasting glucose (I-IFG) and postprandial hyperglycemia subgroups. The fasting serum Ang II and adiponectin concentrations were measured. Among the 85 NAFLD patients, 40 (47%) had hyperglycemia, including I-IFG (18%) and postprandial hyperglycemia (29%). The serum Ang II concentrations in the euglycemia and hyperglycemia groups were significantly higher than those observed in the control and euglycemia groups, respectively; whereas the serum adiponectin concentrations were significantly lower. The serum Ang II concentrations were significantly higher in the postprandial hyperglycemia subgroup than in the I-IFG subgroup. The serum Ang II and adiponectin concentrations were found to be independent predictors of hyperglycemia in the NAFLD patients. The serum Ang II concentration was significantly associated with the serum adiponectin and 2-hour postprandial glucose concentrations in the NAFLD patients. An increased circulating Ang II concentration is associated with hypoadiponectinemia and postprandial hyperglycemia in male NAFLD patients and may be involved in the pathogenesis of T2D in NAFLD patients.

Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease

To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m(2)). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6 mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m(2) to 25.0 ± 3.3 kg/m(2), WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r(s) = 0.90) and liver histology (P = 0.03, r(s) = 0.73). Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.