Degree Of Fatty Liver Disease Research Articles

An adenosine derivative prevents the alterations observed in metabolic syndrome in a rat model induced by a rich high-fat diet and sucrose supplementation.

Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake.

Comparison of Blood Biochemical Markers and Anthropometric Parameters in Different Fatty Liver Grades

Background and Aims: Obesity and hyperlipidemia, diabetes, and malnutrition are among the causes of fatty liver disease. This study compares blood biochemical markers and anthropometric parameters in different grades of fatty liver.
 Materials and Methods: In this descriptive cross-sectional study, 73 fatty liver patients were studied. The degree of fatty liver disease was divided into three grades on ultrasonography. Anthropometric parameters BMI, waist circumstance, height, weight in the fasting state were evaluated according to the standard protocols. The blood samples were taken and biochemical variables fasting blood sugar, serum glutamic-oxaloacetic transaminase (SGOT), Serum glutamic-pyruvic transaminase (SGPT), calcium, phosphorus, low density lipoprotein (LDL), cholesterol, triglyceride, and others were examined with photometric and HPLC methods.
 Results: Statistical analysis was significant between grades 1 and 3 of fatty liver (p = 0.006) and body mass index between grades 1 and 3 of fatty liver (p = 0.003). Comparing SGOT between different grades did not show any significant differences. However, comparing Bili Total indicated a significant difference between grades 1 and 2 and 1 and 3. Moreover, statistical analysis of qualitative variables, such as gender, hypertension, smoking, drug, alcohol, heart disease, stomach disease, and kidney disease, was not statistically significant between the three fatty liver groups. Median ± IQR had a significant difference for SGOT and Bili Total (p < 0.05).
 Conclusion: This study showed the significance of BMI, waist circumstance, and bilirubin factors in different grades of fatty liver. Monitoring BMI, waist circumstance, and bilirubin factors will be useful for susceptible people to non-alcoholic fatty liver disease.

The prevalence and etiology of elevated aminotransferase levels in northeastern Taiwan: A community‐based study

AbstractThe northeastern coastal regions of Taiwanare a hyperendemic area for hepatitis B (HBV) and hepatitis C (HCV) infection. We investigated the prevalence of elevated aminotransferase levels and assessed the potential influence of various risk factors among those with elevated levels. We conducted a community‐based study from October 2012 to July 2014. Blood tests included liver biochemistry, glucose, lipids, HBsAg, and anti‐HCV. The degree of fatty liver disease was evaluated by hepatic ultrasound. A total of 2981 participants were analyzed. The overall prevalence of elevated AST and ALT levels was 10.1% and 14.7%, respectively. On multiple logistic regression analysis, male gender and excess alcohol consumption were independently associated with an elevated AST level. Only male gender, BMI ≥ 27 kg/m2, excess alcohol consumption, and moderate or severe fatty liver were significantly associated with an elevated ALT. The adjusted odds ratio (95% confidence interval) for an elevated AST level was 2.27 (1.44‐3.66, P = .001) for excess alcohol consumption alone, 2.45 (1.81‐3.30, P < .001) for either HBsAg or anti‐HCV seropositivity, and 4.04 (1.90‐8.60, P < .001) for both excess drinking and a viral infection.Our results indicate that a fatty liver, especially moderate or severe, is the commonest risk factor in individuals with an elevated ALT level, with or without another identifiable cause of chronic liver disease. Viral hepatitis and excess alcohol consumption have synergic effect on an elevated AST level, someone who has viral hepatitis should avoid excess alcohol consumption.

Transient elastography in diagnosis of non-alcoholic fatty liver disease

Clinical data of 113 patients with non-alcoholic fat liver disease (NAFLD) diagnosed by liver biopsy from January 2015 to January 2017 in Taizhou People′s Hospital were retrospectively reviewed. Patients all underwent transient elastographic (TE) examination and the values of fat attenuation index (FAI) were obtained. The hepatocyt fatty changes in pathological examination were scored as 0 ( 66%, n=18). There were significant differences in AST, Glu, TC and FAI among patients with hepatocyte fatty change scores 0, 1, 2 and 3, and the FAI was significantly correlated with the degree of fatty liver disease. The areas under the ROC curve (AUCs) of FAI in patients with hepatocyte fatty change scores 1, 2 and 3 were 0.78, 0.90 and 0.96, respectively. Logistic regression analysis showed that FAI was correlated with TG, TC and BMI. The results suggest that FAI in TE can be a non-invasive, rapid and objective evaluation method for patients with NAFLD. Key words: Fatty liver, non-alcoholic; Ultrasonograph; Elasticity imaging techniques

The Association between Metabolic Syndrome Combined with Fatty Liver Disease and Gallstone Disease—Data Analysis of Health Examinations

Backgroundi¼sIn Taiwan, the prevalence rate of gallstone disease (GD) is estimated to be 5%-10% among adults. Several reports have suggested that females and old age individuals have a higher prevalence rate of GD. In addition, hyperglycemia, dyslipidemia and obesity, which are common features of metabolic syndrome, are risk factors for GD. Few studies have examined the relationship between metabolic syndrome combined with fatty liver disease and gallstone disease. Purpose: This study aimed to investigate the relationship between metabolic syndrome combined with fatty liver disease and gallstone disease. Methods: This study applied cross-sectional data analysis. Participants received physical examination at a local hospital in Kaohsiung, Taiwan, from 2011 to 2014. Fatty liver disease and gallstone disease were diagnosed by a gastroenterologist with abdominal ultrasonography. The metabolic syndrome was defined according to the standards set by Health Promotion Administration, Ministry of Health and Welfare, in 2007. Physical examination and blood test results were employed to evaluate the prevalence rate and risk factors of gallstone disease.Results: The results indicated that prevalence rate of GD was 5%. GD had a significantly higher prevalence among participants aged 40 years and older than those under 40 years old. GD prevalence rate was higher among participants with abnormalities associated with metabolic syndrome and its components than healthy participants. GD prevalence rate was significantly higher among participants with mild or moderate fatty liver combined with metabolic syndrome than those without the metabolic syndrome or with a different degree of fatty liver disease. Participants aged 40 years and older had a 2.88-fold higher risk of getting GD than those who were under 40 years old. The risk of GD increased 1.70-fold in participants with mild fatty liver disease combined with metabolic syndrome and 1.32-fold in participants with moderate fatty liver disease combined with metabolic syndrome. Conclusion: Prevalence and risk of GD is significantly higher in participants with metabolic syndrome. Awareness of GD prevalence rate and risk factors can facilitate effective GD prevention.

Screening for rare variants in the PNPLA3 gene in obese liver biopsy patients

Previous research has clearly implicated the PNPLA3 gene in the etiology of nonalcoholic fatty liver disease as a polymorphism in the gene was found to be robustly associated to the disease. However, data on the involvement of rare PNPLA3 variants in the development of nonalcoholic fatty liver disease (NAFLD) is currently limited. Therefore, we performed an extensive mutation analysis study on a cohort of obese liver biopsy patients to determine PNPLA3 variation and its correlation with fatty liver disease. We screened the entire coding region of the PNPLA3 gene in DNA samples of 393 obese liver biopsy patients with varying degrees of fatty liver disease. Mutation analysis was performed by high-resolution melting curve analysis in combination with direct sequencing. We identified several common polymorphisms as well as one rare synonymous variant (c.867G>A rs139896256), one rare intronic variant (c.979+13C>T) and 3 nonsynonymous coding variants (p.A76T, p.A104V and p.T200M) in the PNPLA3 gene. In silico analysis indicated that the p.A104V variant will probably have no functional effect, whereas for the p.A76T and p.T200M variant a possible pathogenic effect is suggested. Overall, we showed that novel variants in PNPLA3 are very rare in our liver biopsy cohort, thereby indicating that their impact on the etiology of NAFLD is probably limited. Nevertheless, for the three rare coding variants that were identified in patients with advanced liver disease, further functional characterization will be essential to verify their potential disease causality.

Rationale and Design of RNAFH Study: Effect of Rosuvastatin (10 mg/d) on Nonalcoholic Fatty Liver in Metabolic Syndrome Patients without Overt Diabetes Evaluated by 1H-Magnetic Resonance Spectroscopy

Objective. The RNAFH study (effect of rosuvastatin on nonalcoholic fatty liver disease in metabolic syndrome patients without overt diabetes evaluated by 1H-MRS) is a prospective randomized, single-center, open-label trail designed to assess the effect of rosuvastatin on the intrahepatocellular lipid (IHCL) level of nonalcoholic fatty liver disease (NAFLD). Methods. 40 NAFLD patients meeting inclusion and exclusion criteria with metabolic syndrome (MS) but without overt diabetes mellitus will be included. Patients will be randomized to 52-week treatment with either rosuvastatin (10 mg/d) or blank control. The primary end point is IHCL evaluated by 1H-MRS, which was considered to be the most accurate noninvasive method for the evaluation of NAFLD. Secondary end points include homeostasis model assessment of insulin resistance (HOMA-IR) index on behalf of insulin resistance level and lipid parameters. Safety indicators will be monitored such as liver function, renal function, muscle stability, and glucose metabolism. The aims of the present study are noteworthy in respect that (1) IHCL is a quantitative indicator for evaluating the degree of fatty liver disease and 1H-MRS is a noninvasive technique to provide this specific index precisely, (2) meanwhile the HOMA-IR index and lipid parameters will be monitored, and (3) the safety of rosuvastatin treatment for 52 weeks will be evaluated including glucose metabolism, muscle stability, liver function, and renal function.

The likelihood of having a serum PSA level of ≥2.5 ng/mL according to the degree of fatty liver disease in a screened population

We sought to investigate the impact of fatty liver disease (FLD) on prostate cancer (PCa) screening by estimating the odds of having a prostate-specific antigen (PSA) value over the cutoff used to prompt for the recommendation of prostate biopsy. Between 2007 and 2013, 18 533 native Korean men eligible to receive a serum PSA test, liver profiles, and abdominal ultrasonography were recruited. Logistic regression was used to estimate the odds of an abnormal PSA (≥2.5 ng/mL) in these men (age 45-75 years, PSA≤10 ng/mL) in relation to FLD. The FLD status was categorized as normal, mild, moderate, and severe grade by abdominal sonography. A total of 16 563 men (89.4%) were included in the study after applying the inclusion criteria. Liver profiles were negatively correlated with the serum PSA level. After controlling for age and obesity, there was a statistically significant trend towards a lower likelihood of having a serum PSA level of ≥2.5 ng/mL with severe FLD, having a 34.7% lower likelihood (odds ratio 0.653, 95% confidence interval 0.477-0.88; p<0.01) compared to men in the normal group. Severe FLD is an independent predictor of a lower likelihood of having abnormal PSA level. Further studies are needed to better define these results in clinical biopsy practice.

Is There Any Relation Between the Degree of Fatty Liver Disease and Severity of Lower Urinary Tract Symptoms?

To evaluate the association between the degree of fatty liver disease and severity of lower urinary tract symptoms (LUTS) in healthy middle-aged males. A total of 1943 Korean men aged between 40 and 70 years who had participated in the voluntary health checkup program from January 2012 to December 2014 were enrolled. LUTS were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Abdominal ultrasonography was performed to assess nonalcoholic fatty liver disease (NAFLD). Trend test was performed to investigate the association between the degree of fatty liver disease and LUTS severity. Differences between the two groups were analyzed by chi-square test, and we adjusted for confounding factors with analysis of covariance and logistic regression test. The mean age was 51.79 ± 7.03 years, and 1026 (52.8%) subjects were determined to have NAFLD. Differences in categorical variables, between NAFLD grades and IPSS grades, were analyzed by Trend test, and no significant difference was observed (Pearson chi-square, P = .155; likelihood ratio, P = .151; linear-by-linear association, P = .527). After adjustment for age, body mass index, metabolic syndrome, C-reactive protein, prostate-specific antigen, prostate volume with analysis of covariance, and multiple logistic regression test, no significant associations were found between IPSS and NAFLD. No significant associations were found between NAFLD and LUTS in middle-aged men, and the degree of NAFLD was not significantly associated with the severity of LUTS in trend. The role of NAFLD, in comparison with age, might be too small to change the LUTS.

Association study of PNPLA2 gene with histological parameters of NAFLD in an obese population

The prevalence of non-alcoholic fatty liver disease (NAFLD) and the closely associated metabolic syndrome is high and is related to risk factors such as obesity and type2 diabetes. A genetic basis for NAFLD has been suggested, but only few causal genes have been identified. The most significant association reported to date is the robust association of the PNPLA3 I148M variant with susceptibility to NAFLD. We therefore hypothesized that the PNPLA2 gene might also be involved in NAFLD pathogenesis, because of its close sequence similarity with PNPLA3 and its possible involvement in ectopic fat accumulation. In this study, we investigated the association of PNPLA2 polymorphisms with the development of non-alcoholic fatty liver disease in a prospectively recruited Belgian obese population comprising 633 individuals with varying degrees of fatty liver disease. We selected 3 PNPLA2 SNPs for genotyping, including 2tagSNPs that cover most information on common genetic variation in the selected region. After performing linear regression analysis, we found that 2 of the analyzed PNPLA2 SNPs were associated with anthropometric and metabolic parameters. In our subcohort of patients that underwent liver biopsy (n=372/633 or 58.7%), we assessed the influence of the PNPLA2 variants on the severity of histologically determined liver damage, but we did not find convincing evidence for association. Although we found evidence for moderate association between PNPLA2 tagSNPs and anthropometric and metabolic parameters in our cohort, no evidence for association between polymorphisms in the PNPLA2 gene and the presence and severity of NAFLD was identified.

Association of Doppler Wave Pattern of Hepatic Veins and Fatty Liver Disease Degree

The objective of this study was to document the progressive effects of fatty infiltration of the liver on hepatic veins (HVs) by measuring Doppler waveforms in groups of rats and dogs. All of the groups underwent hepatic B-mode and duplex Doppler sonography. B-mode fatty infiltration was classified into four degrees corresponding to increasing grades of hepatic echogenicity for all groups: (0) absent, (1) mild, (2) moderate and (3) severe fatty infiltration. Histograms were obtained in all dogs to standardise each grade of hepatic echogenicity and an increasing distribution of grey-levels was found according to the grade of fatty infiltration of the liver in obese dogs. The Doppler sonography spectra of HVs were classified into three groups: normal or triphasic waveforms, biphasic waveforms, and monophasic or flat waveforms. Obese dogs (60%) and rats (100%) with fatty infiltration of the liver presented biphasic or flat right HV Doppler waveforms more often than control dogs and rats, and these differences were statistically significant (p = 0.002 for dogs and p = 0.0028 for rats). None of the control dogs and rats had monophasic waveforms. These findings suggest there is an association between wave form pattern of hepatic veins and the degree of fatty liver disease.

Expression of genes encoding mitochondrial proteins can distinguish nonalcoholic steatosis from steatohepatitis.

In patients without substantial alcohol use, triglyceride accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) that may progress to nonalcoholic steatohepatitis (NASH). The differential diagnosis between NAFLD and NASH can be accomplished only by morphological examination. Although the relationship between mitochondrial dysfunction and the progression of liver pathologic changes has been described, the exact mechanisms initiating primary liver steatosis and its progression to NASH are unknown. We selected 16 genes encoding mitochondrial proteins which expression was compared by quantitative RT-PCR in liver tissue samples taken from patients with NAFLD and NASH. We found that 6 of the 16 examined genes were differentially expressed in NAFLD versus NASH patients. The expression of hepatic HK1, UCP2, ME2, and ME3 appeared to be higher in NASH than in NAFLD patients, whereas HMGCS2 and hnRNPK expression was lower in NASH patients. Although the severity of liver morphological injury in the spectrum of NAFLD-NASH may be defined at the molecular level, expression of these selected 6 genes cannot be used as a molecular marker aiding histological examination. Moreover, it is still unclear whether these differences in hepatic gene expression profiles truly reflect the progression of morphological abnormalities or rather indicate various metabolic and hormonal states in patients with different degrees of fatty liver disease.

Studies on the Fatty Liver Diseases of Sciaenops ocellatus Caused by Different Ether Extract Levels in Diets

An experiment was conducted to study fatty liver disease caused by different ether extract levels in diets of juvenile Sciaenops ocellatus. Juvenile S. ocellatus (n=1,260; initial body weight approximately 2.73 g) were divided into nine treatment groups (triplicate groups per treatment) and fed in aquatic cases by a recirculated filtered rearing system; the temperature of the aquatic cases was maintained at 23.2±2.0° for 8 weeks. Nine kinds of diets containing different protein (38, 42, 46%) and ether extract levels (4, 8, 12%) were used. Results showed that the relative growth ratio and survival ratio of the fish fed on medium lipid diets (8%) or high ether extract diets (12%) were significantly lower than those of the fish fed on low ether extract diets (4%) (p < 0.05). There was a positive correlation between the ether extract contents in hepatopancreas of fish and the ether extract contents of diets. At the end of the experimental period, the fish of the nine experimental groups suffered from different degrees of fatty liver disease and serious illness, and death occurred in a large number of fish fed on medium (8%) and high ether extract diets (12%) from the third test week; mortality was highest in the fifth test week. The ill S. ocellatus showed symptoms of loss of appetite, lack of movement, black skin, and weight loss and eventually died. The main pathological change in ill fish was fatty liver disease. Their hepatopancreas were swollen and pale, accompanied by fatty degeneration, fatty necrosis of hepatocytes, and atrophy of the pancreas. Ultrastructural changes showed the presence of many lipid droplets and granules in the mitochondria, endoplasmic reticulum, and cell plasm of hepatocytes. Study results indicated that all the nine kinds of diets with different lipid or protein levels could cause nutritional fatty liver disease in juvenile S. ocellatus. The pathological severity and serious level of fatty liver disease in the tested fish positively correlated with the contents of the ether extract, but not with those of protein, in test diets. The increase in the level of ether extract in test diets was responsible for the direct cause of illness or death in juvenile S. ocellatus.