Fatty Liver Disease Group Research Articles

Pyridoxamine improves metabolic and microcirculatory complications associated with nonalcoholic fatty liver disease.

We investigated the protective effects of pyridoxamine against metabolic and microcirculatory complications in nonalcoholic fatty liver disease. Nonalcoholic fatty liver disease was established by a high-fat diet administration over 28weeks. Pyridoxamine was administered between weeks 20 and 28. The recruitment of leukocytes and the number of vitamin A-positive hepatic stellate cells were examined by in vivo microscopy. Laser speckle contrast imaging was used to evaluate microcirculatory hepatic perfusion. Thiobarbituric acid reactive substances measurement and RT-PCR were used for oxidative stress and inflammatory parameters. advanced glycation end products were evaluated by fluorescence spectroscopy. The increase in body, liver, and fat weights, together with steatosis and impairment in glucose metabolism observed in the nonalcoholic fatty liver disease group were attenuated by pyridoxamine treatment. Regarding the hepatic microcirculatory parameters, rats with high-fat diet-induced nonalcoholic fatty liver disease showed increased rolling and adhesion of leukocytes, increased hepatic stellate cells activation, and decreased tissue perfusion, which were reverted by pyridoxamine. Pyridoxamine protected against the increased hepatic lipid peroxidation observed in the nonalcoholic fatty liver disease group. Pyridoxamine treatment was associated with increased levels of tumor necrosis factor alpha (TNF-α) mRNA transcripts in the liver. Pyridoxamine modulates oxidative stress, advanced glycation end products, TNF-α transcripts levels, and metabolic disturbances, being a potential treatment for nonalcoholic fatty liver disease-associated microcirculatory and metabolic complications.

The Role of Wnt/beta-Catenin Signal Pathway in the Pathogenesis of Nonalcoholic Fatty Liver Disease and the Effect of Atorvastatin Intervention

The purpose of this study was to analyze the pathogenesis of nonalcoholic fatty liver disease in rats and study the efficacy of atorvastatin intervention. One hundred Sprague Dawley rats were selected as test system. These rats were randomly divided into 5 groups, the control group, the nonalcoholic fatty liver disease group, high-dose atorvastatin group, medium-dose atorvastatin group and low-dose atorvastatin group, each containing 20 animals. An equal dose of sodium carboxymethylcellulose was applied to the model group and the control group; while atorvastatin perfusion was given to the other 3 groups. The levels of serum aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein and malondialdehyde were compared among the groups. The serum levels of aspartate aminotransferase, alanine aminotransferase, triacylglycerol and total cholesterol of the high-fat diet model group were significantly higher; moreover, the expression levels of MMP2, MMP9, Wnt1, Wnt4, host-catenin were significantly elevated. Treatment with atorvastatin could effectively ameliorate this abnormal condition but at high doses. Atorvastatin appears to inhibit the Wnt/β-catenin signal pathway and achieve good curative effect against nonalcoholic fatty liver disease.

Assessing the risk of hepatocellular carcinoma by combining liver stiffness and the controlled attenuation parameter

Ultrasound technology can now be used for liver stiffness measurement (LSM) and for evaluating the amount of hepatic fat quantitatively known as the controlled attenuation parameter (CAP). This study aimed to determine the applicable cut-off values of LSM and the CAP for primary hepatocellular carcinoma (HCC), and to investigate their clinical usefulness for assessing HCC risk in patients with chronic liver disease. A total of 1054 patients (88 with primary HCC and 966 without HCC) whose LSM and the CAP were measured by transient elastography with clinically evident hepatitisC virus (419 patients), hepatitisB virus (377 patients), and non-alcoholic fatty liver disease (258 patients) were enrolled in this study. Subsequently, a total of 966 patients who did not have HCC initially were followed, and the usefulness of the cut-off values of LSM and CAP for HCC development were evaluated. In hepatitisC virus patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥8.0kPa and CAP ≤221dB/m than among those with other values (log-rank test 0.0239, hazard ratio 2.66, 95%CI 1.07-6.47, P= 0.0362). In non-alcoholic fatty liver disease patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥5.4kPa and CAP ≤265dB/m than among others (log-rank test 0.0040, hazard ratio 8.91, 95% CI 1.47-67.97, P= 0.0192). In the hepatitisC virus and non-alcoholic fatty liver disease groups, a combination of LSM and the CAP cut-off values would be useful for screening to identify the high-risk group for primary HCC development.

IL‐17A, MCP‐1, CCR‐2, and ABCA1 polymorphisms in children with non‐alcoholic fatty liver disease

ObjectiveThe prevalence of non‐alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non‐alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non‐alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP‐1 (‐2518 A/G) (rs1024611), CCR‐2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL‐17A (‐197 G/A) (rs2275913) in obese Turkish children with non‐alcoholic fatty liver disease. MethodsThe study recruited 186 obese children aged 10-17 years, including 101 children with non‐alcoholic fatty liver disease and 85 children without non‐alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. ResultsNo difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non‐alcoholic fatty liver disease group compared to the non non‐alcoholic fatty liver disease group (p<0.05). The A‐allele of IL‐17A (‐197 G/A) (rs2275913) was associated with non‐alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12‐3.77, p=0.02). ConclusionsThe findings of this study suggest that there may be an association between IL‐17A (‐197 G/A) (rs2275913) polymorphism and non‐alcoholic fatty liver disease development in obese Turkish children.

Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease and chronic kidney disease share similar pathophysiologic features. Our aim was to assess the association between different stages of chronic kidney disease and mortality in patients with nonalcoholic fatty liver disease. Third National Health and Nutrition Examination Survey-linked mortality files were utilized. Nonalcoholic fatty liver disease was diagnosed by hepatic ultrasound and chronic kidney disease was defined according to the Kidney Disease Improving Global outcomes guideline. Multivariable Cox proportional hazard model was used to assess the effect of chronic kidney disease on overall and cardiovascular mortality. Total cohort included 11695 adult participants; mean age 43.3years, 48.4% male, 76.4% white, 18.6% had nonalcoholic fatty liver disease and 9.3% had chronic kidney disease. 5.6% had diabetes, 21.3% had hypertension, 4.3% had cardiovascular disease. Compared to subjects without chronic kidney disease or nonalcoholic fatty liver disease, nonalcoholic fatty liver disease patients with chronic kidney disease were more likely to be older, had less income, and higher prevalence of comorbidities (all P<0.001). Prevalence of chronic kidney disease among nonalcoholic fatty liver disease cohort was 11.31%. Compared to non-nonalcoholic fatty liver disease group, patients with nonalcoholic fatty liver disease had higher rates of stage 1, 2 and 3a chronic kidney disease, but similar rates for stage 3b, 4 and 5. Mortality rate was 18.5% in 17years. Among nonalcoholic fatty liver disease cohort, the presence of chronic kidney disease stages 2-3a (HR=2.31, 95% CI: 1.70-3.15) and stages 3b-5 (HR=4.83, 95% CI: 2.40-9.71) were independently associated with increased overall mortality. Among patients with nonalcoholic fatty liver disease, moderate to advanced stages of chronic kidney disease are associated with overall mortality. Identification of chronic kidney disease in nonalcoholic fatty liver disease has important prognostic implications.

Nutritional status and energy metabolism characteristics in patients with nonalcoholic fatty liver disease

Objective: To study the nutritional status and energy metabolic characteristics of patients with nonalcoholic fatty liver disease (NAFLD), and to provide evidence for clinical evaluation and intervention. Methods: A total of 359 NAFLD patients diagnosed on ultrasound from June 2015 to March 2017 were selected as study subjects and divided into mild, moderate to severe fatty liver disease group and 50 healthy subjects as control group. The changes of ICW, ECW, body fat, skeletal muscle, protein and visceral fat area (VFA) of patients and controls were analyzed by using body composition analyzer. The energy metabolism index was measured by the oxidation rate of resting energy expenditure(REE), respiratory quotient (RQ), and the oxidation rates of the three nutrients (CHO %, FAT %, and PRO %). According to different types of data, non-parametric tests like Kruskal-Wallis or χ(2) were used for this analysis. Results: Compared with the mild fatty liver group and the control group, the moderate and severe fatty liver group the BMI, waist circumference, waist-hip ratio were significantly elevated (P-value < 0.001), and their serum alanine aminotransferase, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, FBS levels were significantly increased (P value < 0.05). The Body composition analysis showed that there was no significant difference in skeletal muscle content between the three groups (P = 0.067). The ICW, ECW, protein, body fat content of moderate and severe fatty liver group were significantly higher than those of mild fatty liver group and control group (P < 0.01), but there was no significant difference between the mild fatty liver group and the control group. There was significant difference in the VFA between the three groups, while VFA in the moderate and severe fatty liver group was significantly increased. Metabolic results showed that the RQ of patients with moderate-severe fatty liver and mild fatty liver were 0.72 ± 0.08 and 0.78 ± 0.06, respectively, which were lower than those of the control group (0.80 ± 0.02), P = 0.004. Resting energy expenditure (REE) was not significantly different between moderate and severe fatty liver group and mild fatty liver group (P = 0.207), but both were significantly higher than those of the control group (P < 0.001). The percentages of CHO, FAT and PRO in moderate and severe fatty liver group were 19.49% ± 9.71%, 66.23% ± 12.54% and 14.22% ± 6.11% respectively. Compared with the control group, CHO % decreased, and FAT % increased. Conclusion: NAFLD patients have different extent of nutritional imbalance and energy metabolism disorders, the use of Body Composition analyzer and metabolic cart can comprehensively assess and monitor NAFLD patient's nutrition and energy metabolism status, to provide a basis for clinical intervention.

IL-17A, MCP-1, CCR-2, and ABCA1 polymorphisms in children with non-alcoholic fatty liver disease

ObjectiveThe prevalence of non-alcoholic fatty liver disease in children has risen significantly, owing to the worldwide childhood obesity epidemic in the last two decades. Non-alcoholic fatty liver disease is closely linked to sedentary lifestyle, increased body mass index, and visceral adiposity. In addition, individual genetic variations also have a role in the development and progression of non-alcoholic fatty liver disease. The aim of this study was to investigate the gene polymorphisms of MCP-1 (-2518 A/G) (rs1024611), CCR-2 (190 G/A) (rs1799864), ABCA1 (883 G/A) (rs4149313), and IL-17A (-197 G/A) (rs2275913) in obese Turkish children with non-alcoholic fatty liver disease. MethodsThe study recruited 186 obese children aged 10–17 years, including 101 children with non-alcoholic fatty liver disease and 85 children without non-alcoholic fatty liver disease. Anthropometric measurements, insulin resistance, a liver panel, a lipid profile, liver ultrasound examination, and genotyping of the four variants were performed. ResultsNo difference was found between the groups in respect to age and gender, body mass index, waist/hip ratio, or body fat ratio. In addition to the elevated ALT levels, AST and GGT levels were found significantly higher in the non-alcoholic fatty liver disease group compared to the non non-alcoholic fatty liver disease group (p<0.05). The A-allele of IL-17A (-197 G/A) (rs2275913) was associated with non-alcoholic fatty liver disease (odds ratio [OR] 2.05, 95% confidence interval: 1.12–3.77, p=0.02). ConclusionsThe findings of this study suggest that there may be an association between IL-17A (-197 G/A) (rs2275913) polymorphism and non-alcoholic fatty liver disease development in obese Turkish children.

Nonalcoholic fatty liver disease is associated with decreased lung function.

The association between nonalcoholic fatty liver disease and lung function has not been fully examined. The aim of this study was to clarify the association between nonalcoholic fatty liver disease and lung function in general population by performing cross-sectional and longitudinal analysis. Participants without hepatic and respiratory disease who underwent regular health exams including hepatic sonography and spirometry with at least 3years' follow-up were included. In cross-sectional analysis, the association between nonalcoholic fatty liver disease and lung function at baseline was examined with multiple regression models. The longitudinal analysis was performed by mixed linear regression models with propensity score matching. Of 11892 eligible participants (mean age, 47.7years; male, 47.2%), 3815(32.1%) had nonalcoholic fatty liver disease based on sonography. In cross-sectional analysis, the nonalcoholic fatty liver disease group had lower adjusted forced expiratory volume in 1-second (men, 3.52 vs 3.44L, P<.001; women, 2.62 vs 2.45L, P<.001) and forced vital capacity (men, 4.33 vs 4.24L, P<.001; women, 3.11 vs 2.97L, P<.001) than the control group. In longitudinal analysis, during the mean follow-up period of 6.6years, there were no significant differences in forced expiratory volume in 1-second or forced vital capacity decline rates between two groups in the propensity score-matched cohorts (n=4558). However, those with high nonalcoholic fatty liver disease fibrosis score and fibrosis-4 (men, -21.7 vs -27.4mL/y, P=.001; women, -22.4 vs -27.9mL/y, P=.016) showed significantly faster decline in forced vital capacity compared to those with low scores. Nonalcoholic fatty liver disease was associated with decreased lung function at baseline but was not associated with accelerated lung function decline in the propensity score-matched cohort. However, hepatic fibrosis was significantly associated with rapid forced vital capacity decline.

Role of γ-glutamyl transferase levels in prediction of high cardiovascular risk among patients with non-alcoholic fatty liver disease.

Background & objectives:Non-alcoholic fatty liver disease (NAFLD) is an important cause of elevated liver functions. There is evidence showing an association between NAFLD and subclinical atherosclerosis independent of traditional risk factors. We undertook this retrospective study to determine the association of Framingham cardiovascular risk scoring system with liver function tests and inflammatory markers and to find the role of liver function tests in determination of CVD risk among non-obese and non-diabetic subjects with non-alcoholic fatty liver disease.Methods:A total of 2058 patients were included in the study. Framingham cardiovascular risk scoring was done of all patients according to the age, gender, systolic blood pressure, serum total cholesterol and HDL cholesterol levels, smoking and antihypertensive medication history. Liver function test, lipid profile, insulin, uric acid, ferritin levels, etc. were determined.Results:According to the ultrasonography findings, patients were grouped as without any fatty infiltration of the liver (control group) (n=982), mild (n=473), moderate (n=363) and severe fatty liver disease (n=240) groups. In severe fatty liver disease group, the mean Framingham cardiovascular risk score was significantly higher than that of other groups. There was a positive correlation between GGT, uric acid and ferritin levels with Framingham cardiovascular score. In multivariate analysis, high GGT levels were positively associated with high-risk disease presence (OR: 3.02, 95% CI: 2.62-3.42) compared to low GGT levels independent of the age and sex.Interpretation & conclusions:Cardiovascular disease risk increases with the presence and stage of fatty liver disease. Our findings showed a positive correlation between elevated GGT levels and Framingham cardiovascular risk scoring system among non-diabetic, non-obese adults which could be important in clinical practice. Though in normal limits, elevated GGT levels among patients with fatty liver disease should be regarded as a sign of increased cardiovascular disease risk. Larger studies are warranted to elucidate the role of GGT in prediction of cardiovascular risk.

Increased microalbuminuria prevalence among patients with nonalcoholic fatty liver disease

Aim: To determine the prevalence of microalbuminuria, that is an indirect predictor of coronary artery disease, among non-obese and non-diabetic patients with fatty liver disease. Material and method: This retrospective study was carried out on non-obese (body mass index (BMI) < 30) and non-diabetic 290 female and 189 male, totally 479 cases. All subjects underwent liver ultrasonography scanning to determine the presence and stage of fatty liver disease. Results: The subjects were grouped according to the ultrasound findings as follows: 182 (37.9%) cases without any fat accumulation in liver were regarded as control group; and among remaining cases, 124 (25.8%) had mild, 93 (19.4%) had moderate, and 80 (16.7%) had severe fatty liver disease. There was not any statistically significant difference between groups in regards to the age, gender, liver function tests, renal function tests or glomerular filtration rate. However urinary protein/creatinine ratio was statistically significantly higher in severe nonalcoholic fatty liver disease (NAFLD) group than the other three groups. In moderate and severe NAFLD groups, microalbuminuria was statistically significantly more common compared with the control and mild NAFLD groups. Regarding the results of multiple logistic regression analysis, presence of fatty liver disease increased the risk of microalbuminuria for 1.87 times independently from increased BMI and increased HOMA-IR values. Conclusion: We have determined that microalbuminuria is more prevalent among NAFLD cases compared with control cases and microalbuminuria prevalence was increasing with the advanced stages of NAFLD although two main etiologic factors of microalbuminuria, type 2 diabetes, and obesity were excluded.

Cytokeratin 18-Aspartate396 apoptotic fragment for fibrosis detection in patients with non-alcoholic fatty liver disease and chronic viral hepatitis

BackgroundThe combination of non-invasive markers for the detection of fibrosis in patients with chronic liver diseases is still a matter of debate. AimsTo test the performance of cytokeratin18-Aspartate396 alone or in combination with transient elastography as a marker of fibrosis, compared to liver biopsy as gold standard. MethodsIn 259 prospectively enrolled patients with chronic liver diseases, clinical, biochemical, and histological features were assessed. Serum cytokeratin18-Aspartate396 and Fibroscan were performed within 6 months prior to liver biopsy. ResultsCytokeratin18-Aspartate396 levels predicted both significant and advanced fibrosis in non-alcoholic fatty liver disease group, correctly identifying 83.7% and 80.8% of cases, respectively. Liver stiffness performed best in predicting severe fibrosis in patients with chronic viral infection, correctly identifying 78.7% of chronic hepatitis B and 88.6% of chronic hepatitis C subjects. The combination of cytokeratin18-Aspartate396 and liver stiffness improved their diagnostic performance for the detection of significant and advanced fibrosis in non-alcoholic fatty liver disease group, only (sensitivity=78.3%, specificity=90.7%; sensitivity=91.7%, specificity=71.6%, respectively). ConclusionCytokeratin18-Aspartate396 and liver stiffness can improve the non-invasive prediction of significant and advanced fibrosis in patients with non-alcoholic fatty liver disease, while in hepatitis B and C virus infected patients their combined use had no advantage over the diagnostic accuracy of transient elastography alone.

The relationship between insulin resistance, metabolic syndrome and nonalcoholic fatty liver disease in non-obese non-diabetic Turkish individuals: A pilot study.

Nonalcoholic fatty liver disease is related to obesity, metabolic syndrome, and insulin resistance. Nonalcoholic fatty liver disease and metabolic syndrome may also be encountered in non-obese, non-diabetic individuals, and there are no published data about the prevalence of these conditions in non-obese, non-diabetic Turkish subjects. We aimed to determine the difference between non-obese, non-diabetic nonalcoholic fatty liver disease patients and healthy controls in terms of insulin resistance and metabolic syndrome in Turkish subjects. Non-obese, non-diabetic individuals (n=219) were enrolled. The cohort was divided into two groups according to presence of steatosis in ultrasonography: nonalcoholic fatty liver disease group (n=143) and healthy control group (n=76). Insulin resistance and metabolic syndrome were analyzed and compared between the two groups. The prevalences of metabolic syndrome (32.2% vs. 5.3%, respectively; p<0.001) and insulin resistance (46.2% vs. 9.2%, respectively; p<0.001) were significantly higher in the nonalcoholic fatty liver disease group. According to multiple logistic regression analysis, age (odds ratio 1.534; p=0.0032), insulin resistance (odds ratio 1.074; p<0.001), and serum ALT levels (odds ratio 1.102; p<0.001) were independently associated with nonalcoholic fatty liver disease. Insulin resistance and metabolic syndrome are not rare in non-obese, non-diabetic Turkish subjects with nonalcoholic fatty liver disease. Ultrasonographically detected fatty liver was independently associated with insulin resistance, irrespective of the presence of metabolic syndrome.

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OBJECTIVE:Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease.METHODS:We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease.RESULTS:The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl).CONCLUSIONS:In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed.

Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity

Increased intestinal permeability seems to play a major role in non-alcoholic liver disease development and progression. To investigate the prevalence of altered intestinal permeability in children with non-alcoholic fatty liver disease, and to study its potential association with the stage of liver disease. We performed a case-control study examining intestinal permeability in children using the lactulose-mannitol bowel permeability test. Overall, 39 consecutive patients (30 males, median age 12 years) and 21 controls (14 males, median age 11.8 years) were included. The lactulose/mannitol ratio resulted impaired in 12/39 patients (31%) and none of the controls. Intestinal permeability was higher in children with non-alcoholic fatty liver disease (lactulose/mannitol ratios: 0.038±0.037 vs. 0.008±0.007, p<0.05). Within the non-alcoholic fatty liver disease group, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only (0.05±0.04 vs. 0.03 vs. 0.03, p<0.05). Pathological lactulose/mannitol ratio correlated with portal inflammation (p=0.02), fibrosis (p=0.0002), and ballooning of hepatocytes (p=0.003). Blood lipopolysaccharides levels were higher in children with steatohepatitis (2.27±0.68 vs. 2.80±0.35, p<0.05). Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with the severity of the disease.

Apoptotic and anti-apoptotic seromarkers for assessment of disease severity of non-alcoholic steatohepatitis

Background and study aimsThis study aimed to find out non-invasive markers for the assessment of severity of non-alcoholic steatohepatitis (NASH) in an attempt to decrease the need for liver biopsy. It also aimed to evaluate the key role of apoptosis in the pathogenesis of the disease and the suggested role of anti-apoptotic factors in therapeutic modalities and disease prognosis. Patients and methodsThe serum levels of soluble Fas (s. Fas), s. Fas ligand, cytokeratin 18 (CK-18) fragment and Bcl-2 were measured in 80 patients and 15 non-hepatic subjects as control. The patients were divided based on histological examination of liver biopsy into three groups. Group I included 40 patients with NASH, group II had 40 patients with non-alcoholic fatty liver disease (NAFLD) non-NASH and group III had 15 non-hepatic subjects as control. Apoptosis of hepatocytes was assessed by morphological examination using a light microscope and expressed as number per square millimetre. ResultsThere was a significant increase in the serum levels of s. Fas, s. Fas ligand and CK-18 fragments in the NASH group. The anti-apoptotic protein Bcl-2 showed significantly low levels in NASH patients. Apoptosis of hepatocytes was significantly higher in the NASH group. The degree of apoptosis was inversely correlated with the level of Bcl-2. A significant correlation between both s. Fas and CK-18 fragment with liver histology with regard to lobular inflammation and ballooning was found. ConclusionsIncreased serum levels of s. Fas and CK-18 fragment in the NASH group and its correlation with the severity of disease suggested the key role of apoptosis in NASH pathogenesis which can be used for the assessment of the severity of NASH. A high level of anti-apoptotic Bcl-2 in NAFLD suggests its protective role in disease progress.

Relationship between fatty liver disease and intracranial main artery stenosis.

The aim of this study was to evaluate the relationship between fatty liver disease (FLD) and cerebrovascular disease. We conducted a cross-sectional study of 76 consecutive healthy subjects who participated in a two-day hospitalized health checkup program. The maximal intima-media thickness (IMT) of the common carotid artery and bifurcation of the carotid artery as well as the plaque score (PS) were evaluated on carotid artery ultrasonography. Fluid attenuated inversion recovery brain MRI was used to determine the presence of asymptomatic cerebral lesions and periventricular hyperintensity. Brain MR angiography was used to evaluate the degree of intracranial main artery stenosis (ICAS). FLD was diagnosed based on the ultrasonographic pattern. The PS and IMT did not differ between the FLD (n=24) and non-FLD (n=52) groups. There was a tendency toward a higher percentage of multiple lacunar lesions in the non-FLD group than in the FLD group. ICAS was significantly more frequent in subjects in the FLD group than those in the non-FLD group (25.0% vs. 5.8%). A logistic regression analysis revealed that age and FLD were significant determinants of ICAS. Our study findings suggest a significant association between ICAS and FLD.

The impact of weight changes on nonalcoholic Fatty liver disease in adult men with normal weight.

BackgroundAlthough it is known that losing weight has an effect on the treatment of non-alcoholic fatty liver disease, the studies that show how losing weight affects the non-alcoholic fatty liver disease for the normal weight male adults are limited so far. In this study, we set body mass index as criteria and investigated how the weight changes for 4 years makes an impact on the risk of non-alcoholic fatty liver disease for the male adults who have the normal body mass index.MethodsFrom January to December of 2004, among the normal weight male adults who had general check-up at the Health Promotion Center of Ulsan University Hospital, 180 people (average age, 47.4 ± 4.61 years) who were diagnosed with fatty liver through abdominal ultrasonography were included in this study and were observed according to the variety of data and ultrasonography after 4 years (2008). People who had a history of drinking more than 140 g of alcohol per week or who had a past medical history were excluded from the analysis. The weight change of subjects was calculated using the formula 'weight change = weight of 2008 (kg) - weight of 2004 (kg)' and classified into three groups, loss group (≤-3.0 kg), stable group (-2.9 to 2.9 kg), and gain group (≥3.0 kg). The odds for disappearance of non-alcoholic fatty liver disease in those three different groups were compared.ResultsAmong 180 subjects, compared with stable group (67.2%, 121 subjects), loss group (11.7%, 21 subjects) showed 18.37-fold increase in the odds of disappearance of non-alcoholic fatty liver disease (95% confidence interval [CI], 4.34 to 77.80) and gain group (21.1%, 38 subjects) showed 0.28-fold decrease in the odds of disappearance of non-alcoholic fatty liver disease (95% CI, 0.10 to 0.83).ConclusionEven for the normal weight people, losing weight has an effect on the improvement of non-alcoholic fatty liver disease.

Hepatic Glucose Uptake Is Increased in Association with Elevated Serum γ-Glutamyl Transpeptidase and Triglyceride

Subjects with fatty liver disease (FLD) can show increased hepatic 2-deoxy-2-((18)F)fluoro-D-glucose (FDG) uptake, but the role of hepatic inflammation has not been explored. We investigated whether hepatic inflammatory response, as implicated by elevated serum markers, is associated with increased liver FDG uptake in FLD. Liver sonography and FDG positron emission tomography was performed in 331 asymptomatic men with nonalcoholic FLD (NAFLD), 122 with alcoholic FLD (AFLD), and 349 controls. Mean standard uptake value (SUV) of liver FDG uptake was compared to cardiac risk factors and serum markers of liver injury. Hepatic FDG mean SUV was increased in NAFLD (2.40 ± 0.25) and AFLD groups (2.44 ± 0.25) compared to controls (2.28 ± 0.26; both P < 0.001). Both FLD groups also had higher serum γ-glutamylranspeptidase (GGT), triglyceride (TG), hepatic transaminases, and LDL. High GGT and TG levels were independent determinants of increased FDG uptake for both FLD groups. Hepatic mean SUV significantly increased with high compared to low GGT for NAFLD (2.48 ± 0.28 vs. 2.37 ± 0.24), AFLD (2.51 ± 0.27 vs. 2.39 ± 0.23), and control groups (2.39 ± 0.22 vs. 2.26 ± 0.26). High TG increased hepatic mean SUV in AFLD and control groups. Furthermore, serum GGT and TG levels significantly correlated to hepatic mean SUV in all three groups. Hepatic FDG uptake is closely associated with elevated TG and GGT regardless of the presence of FLD. Thus, inflammation response may play a major role in increased hepatic glucose uptake.

Assessment of the Relationship between Non-Alcoholic Fatty Liver Disease and CAD using MSCT

BackgroundSome risk factors for atherosclerosis are followed by non-alcoholic fatty liver disease (NAFLD). We wanted to use Multislice computed tomography (MSCT) as technique for searching relationship between NAFLD and coronary artery disease (CAD). ObjectiveThe relationship between NAFLD and CAD was investigated using MSCT. MethodsA total of 372 individuals with or without cardiac symptoms who had undergone MSCT angiography were included in the study. The patients were divided into two groups according to the presence of NAFLD. Coronary artery segments were visually evaluated via MSCT angiography. Based on the coronary artery stenosis degree, those with no or minimal plaques were considered normal, whereas those who had stenosis of less than 50% and at least one plaque were considered to have non-obstructive coronary artery disease (non-obsCAD). The patients who had at least one plaque and coronary artery stenosis of 50% or more were considered to have obstructive coronary artery disease (obsCAD). NAFLD was determined according to the MSCT protocol, using the liver density. ResultsAccording to the liver density, the number of patients with non-alcoholic fatty liver disease (group 1) was 204 (149 males, 54.8%) and with normal liver (group 2) was 168 (95 males, 45.2%). There were 50 (24.5%) non-obsCAD and 57 (27.9%) obsCAD cases in Group 1, and 39 (23.2%) non-obsCAD and 23 (13.7%) obsCAD cases in Group 2. ConclusionsThe present study using MSCT demonstrated that the frequency of coronary artery disease in patients with NAFDL was significantly higher than that of patients without NAFDL.

Measurement of the coronary flow velocity reserve in patients with non-alcoholic fatty liver disease

Endothelial dysfunction is an early and reversible feature in the pathogenesis of atherosclerosis. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. This study was designed to evaluate the carotid intima-media thickness and myocardial microvascular circulation in patients with non-alcoholic fatty liver disease. Twenty-four patients with non-alcoholic fatty liver disease and 28 healthy subjects were studied. According to the pathology of liver biopsies, patients with non-alcoholic fatty liver disease were divided into non-alcoholic fatty liver and nonalcoholic steatohepatitis groups. Coronary diastolic peak flow velocities were measured at baseline, and then dipyridamole infusion was measured by transthoracic Doppler echocardiography. The ratio of hyperemic to baseline diastolic peak velocities was calculated and the intima-media thicknesss of the carotid arteries were measured. Baseline average diastolic peak and diastolic mean flow velocities were similar between non-alcoholic fatty liver disease patients and healthy subjects. However, hyperemic average diastolic peak and diastolic mean flow velocities were significantly lower in the patient groups compared to those in the controls (p=0.005 and p=0.002). Coronary flow velocity reserve was 1.65 ± 0.36 and 2.67 ± 0.81 in patients and healthy subjects, respectively (p < 0.001). The intima-media thickness was similar between the patients with non-alcoholic fatty liver disease and healthy subjects. The comparison of patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis within the non-alcoholic fatty liver disease group with respect to coronary flow velocity reserve and intima-media thickness yielded no statistical differences. The present study showed that coronary flow velocity reserve, which establishes coronary microvascular and endothelial functions noninvasively, is significantly impaired in patients with non-alcoholic fatty liver disease. The impaired coronary flow velocity reserve-like early atherosclerotic changes may have value in the prediction of coronary artery disease in patients with non-alcoholic fatty liver disease.