Advances in epigenetics of nonalcoholic fatty liver desease / 复旦学报（医学版）

Nonalcoholic fatty liver disease(NAFLD)is a metabolic liver disease that ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis(NASH).NASH is characterized by persistent liver damage,inflammation,and fibrosis which significantly increases the risk of end-stage liver diseases,such as liver cirrhosis and hepatocellular carcinoma.The pathogenesis of NAFLD/NASH is not yet fully understood,but its recent epigenetic advances have provided new insights into the mechanisms of this disease.This review summarized recent progress in this area which has laid a solid foundation for elucidating the pathogenesis of NAFLD and provides potential targets for early detection,diagnosis,and treatment of this disease.

Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Dendrobii Caulis mixture on cell inflammatory response and apoptosis in diabetic rat with non-alcoholic fatty liver disease（NAFLD） and its possible mechanism. MethodForty male SD rats were randomly divided into blank group and model group of type 2 diabetes mellitus（T2DM） with NAFLD according to body weight. The model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）， which was randomly divided into the model group， Dendrobii Caulis mixture group（16.67 g·kg-1·d-1） and metformin group（100 mg·kg-1·d-1） according to blood glucose and body weight， and 10 rats in each group. Rats in each group were administered by continuous gavage for 4 weeks， the blank and model groups were given saline by gavage at 10 mL·kg-1·d-1. Fasting blood glucose（FBG）， serum insulin（INS）， glycosylated serum protein（GSP）， triglyceride（TG）， total cholesterol（TC）， high density lipoprotein（HDL-C）， low density lipoprotein（LDL-C）， alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were detected in each group of rats. The liver tissues of rats in each group were stained with hematoxylin-eosin（HE） to observe the pathological changes， and the positive expressions of nuclear transcription factor（NF）-κB， NOD-like receptor heat protein structural domain-related protein 3（NLRP3）， interleukin（IL）-1β and tumor necrosis factor（TNF）-α were observed by immunohistochemistry. Western blot and fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of B-cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， Caspase-3 and NF-κB p65， NLRP3， IL-1β， TNF-α in liver tissue of rats in each group. ResultCompared with the blank group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels were increased， INS and HDL-C levels were decreased， Bax， Caspase-3， NLRP3， IL-1β， TNF-α protein and mRNA expression were increased in model group， the ratio of p-NF-κB/NF-κB protein increased， the expression of Bcl-2 protein and mRNA decreased， and the positive immunohistochemical expression of NF-κB， NLRP3， IL-1β and TNF-α increased， and the differences were statistically significant（P<0.01）. The morphological structure of the liver was disrupted， and obvious fat vacuoles were seen. Compared with the model group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels of Dendrobii Caulis mixture group and metformin group were decreased， INS and HDL-C levels were increased， and protein and mRNA expressions of Bax， Caspase-3， NLRP3， IL-1β and TNF-α were decreased， the protein ratio of p-NF-κB/NF-κB decreased， the expression of Bcl-2 protein and mRNA increased， and the positive immunohistochemical expressions of NF-κB， NLRP3， IL-1β and TNF-α decreased， and the differences were statistically significant（P<0.01）. The liver morphology and structure were relatively complete， and the fat vacuoles were reduced. ConclusionDendrobii Caulis mixture can inhibit cell apoptosis， reduce inflammatory response and alleviate liver injury in rats with T2DM and NAFLD， the mechanism may be related to inhibiting the activation of NF-κB pathway， blocking the activation of NLRP3 inflammatory vesicles， reducing IL-1β secretion， attenuating Caspase-3 activity and reducing the ratio of Bcl-2/Bax.

Application research of MR quantitative analysis in the relationships between LFF and the NAFLD,and between PFF and the NAFLD / 中国医学装备

Objective:To explore the application of magnetic resonance(MR)quantitative analysis technique of fat in analyzing the relationships between liver fat fraction(LFF)and pancreatic fat fraction(PFF)and the severity of nonalcoholic fatty liver disease(NAFLD),and between them and liver function.Methods:A total of 185 patients who received MR whole-liver mDIXON sequence scan were selected,and their LFF and PFF were measured.They were divided into NAFLD group(160 cases)and control group(25 cases)according to the fat fraction(FF)of liver.The body mass index(BMI),alanine aminotransferase(ALT),triglycerides(TG),fasting blood glucose(FBG),low-density lipoprotein(LDL-c),high-density lipoprotein(HDL-c),LFF and PFF between two groups were compared.Spearman analysis method was adopted to analyze the correlation between LFF and various indicators,and between PFF and various indicators.Logistic regression analysis was used to analyze the influencing factors of NAFLD severity.Results:In 160 patients of NAFLD group,72 cases were mild degree(LFF WAS 5.1%-14.0%),and 76 cases were moderate degree(LFF was 14.1%-28.0%),and 12 cases were severe degree(LFF>28.0%).There were significant differences in LFF,PFF and BMI between NAFLD group and control group(tLFF=17.259,tPFF=9.058,tBMI=7.430,P<0.05),and the differences of ALT,TG,FBG,LDL-c and HDL-c between two groups also were significant(t=6.591,t=3.957,t=3.267,t=2.112,t=-3.727,P<0.05),respectively.There were significant differences in LFF,PFF,BMI,ALT,TG,FBG,LDL-c and HDL-c among mild group,moderate group and severe group of patients(F=21.944,F=16.391,F=5.872,F=30.240,F=3.984,F=3.863,F=3.398,F=1.214,P<0.05),respectively.BMI,ALT,TG and FBG appeared positive correlation with LFF and PFF of NAFLD patients(r=0.31,r=0.52,r=0.33,r=0.35,r=0.30,r=0.36,r=0.27,r=0.29,P<0.05),and HDL-c appeared negative correlation with them(r=-0.16,r=-0.3,P<0.05),respectively.Multivariate Logistic regression analysis showed that HDL-c was an independent protective factor of the severity of NAFLD(OR=0.004,P<0.05),and LFF,PFF,BMI,ALT,TG,LDL were independent risk factors of the severity of NAFLD(OR=2.252,OR=1.988,OR=1.404,OR=1.196,OR=1.025,OR=5.150,P<0.05),respectively.Conclusion:LFF and PFF are closely related to the severity of NAFLD and the indicators of liver function,and the increases of LFF and PFF are independent risk factors of the aggravation of NAFLD.The MR quantitative analyses of LFF and PFF values have a certain guiding significance in clinical monitoring for NAFLD severity and liver function.

Lipid-lowering effect of drug pair Scutellariae Radix-Coptidis Rhizoma based on lipomics / 中国中药杂志

This study investigated the mechanism of action of Scutellariae Radix-Coptidis Rhizoma(SR-CR) in intervening in non-alcoholic fatty liver disease(NAFLD) in rats based on lipidomics. Thirty-six SD rats were divided into a control group, a model group, SR-CR groups of different doses, and a simvastatin group, with six rats in each group. Rats in the control group were fed on a normal diet, while those in the remaining groups were fed on a high-lipid diet. After four weeks of feeding, drug treatment was carried out and rats were sacrificed after 12 weeks. Serum liver function and lipid indexes were detected using kits, and the pathomorphology of liver tissues was evaluated by hematoxylin-eosin(HE) staining and oil red O staining. Changes in lipid levels in rats were detected using the LC-MS technique. Differential lipid metabolites were screened by multivariate statistical analysis, and lipid metabolic pathways were plotted. The changes in lipid-related protein levels were further verified by Western blot. The results showed that compared with the control group, the model group showed increased levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.01), and decreased levels of γ-glutamyl transferase(γ-GT) and high-density lipoprotein cholesterol(HDL-c)(P<0.01), which were significantly recovered by the intervention of SR-CR. HE staining and oil red O staining showed that different doses of SR-CR could reverse the steatosis in the rat liver in a dose-dependent manner. After lipidomics analysis, there were significant differences in lipid metabolism between the model group and the control group, with 54 lipids significantly altered, mainly including glycerolipids, phosphatidylcholine, and sphingolipids. After administration, 44 differential lipids tended to normal levels, which indicated that SR-CR groups of different doses significantly improved the lipid metabolism level in NAFLD rats. Western blot showed that SR-CR significantly decreased TG-synthesis enzyme 1(DGAT1), recombinant lipin 1(LPIN1), fatty acid synthase(FASN), acetyl-CoA carboxylase 1(ACC1), and increased the phosphorylation level of ACC1. These changes significantly decreased the synthesis of TG and increased the rate of its decomposition, which enhanced the level of lipid metabolism in the body and finally achieved the lipid-lowering effect. SR-CR can improve NAFLD by inhibiting the synthesis of fatty acids and TG.

Animal Models of Nonalcoholic Fatty Liver Disease：A Review / 中国实验方剂学杂志

Nonalcoholic fatty liver disease （NAFLD） is a metabolic stress-induced liver injury characterized by excessive lipid accumulation in hepatocytes， which is closely related to insulin resistance and genetic susceptibility. It falls into the category of "liver lump" in traditional Chinese medicine （TCM）. NAFLD affects about 25% of the population worldwide and has become a major burden of the world health care system. However， its exact pathogenesis remains unclear. Conducting the basic research on NAFLD is of great clinical significance and social value. As an important tool for NAFLD research， animal model plays a particularly important role in clarifying the pathophysiological mechanism of NAFLD. In recent years， the modeling methods for NAFLD in China and abroad have been constantly updated， and in particular， certain progress has been made in the duplication of TCM syndrome models. By consulting and sorting out the relevant literature published in recent years in China and abroad， the author summarized the replication methods of NAFLD animal models. This paper reviewed the advantages and disadvantages of models established via dietary induction （high-fat feed， high-fat and high-fructose feed， high-fat and high-cholesterol feed， and methionine choline-deficient feed）， models with genetic defects ［leptin-deficiency （Lepob/Lepob）， autosomal recessive diabetes gene homozygous deficiency （ob/ob）， Alms1 gene （foz/foz） mutation， and FATZO mice］ and exposure to special diets， and models for TCM syndromes （liver depression and spleen deficiency syndrome， phlegm-dampness syndrome， blood stasis syndrome， combined phlegm and stasis syndrome， and qi stagnation and blood stasis syndrome）， in order to provide reference for the preparation of more scientific， reasonable， economical， and convenient animal models of NAFLD， thus laying a foundation for in-depth study of the pathogenesis， prevention， and treatment of NAFLD.

Effect of Modified Taohe Chengqitang Combined with Colon Hydrotherapy on Inflammatory Factors and Insulin Resistance in Patients with Severe Nonalcoholic Fatty Liver Disease / 中国实验方剂学杂志

Objective::To define the clinical efficacy of modified Taohe Chengqitang combined with colon hydrotherapy in patients with severe nonalcoholic fatty liver disease (NAFLD) accompanied by phlegm-heat stagnation syndrome and its mechanism. Method::Totally 100 patients with severe NAFLD by phlegm-heat stagnation syndrome were enrolled in the study.They were all given Shanzha Xiaozhi capsule.According to the random number table, the patients were randomly divided into the observation group (50 patients, colon hydrotherapy combined with traditional Chinese medicine) and the control group (50 patients, Shanzha Xiaozhi capsule alone). The observation period was 4 weeks.The therapeutic effect of colon hydrotherapy was verified through determinations of the liver function, blood lipid, insulin resistance index (IRI), controlled attenuation parameter (CAP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) before and after treatment.The mechanism of colon hydrotherapy combined with modified Taohe Chengqitang was preliminarily analyzed based on changes of IR, TNF-α and IL-6. Result::Alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptadase (γ-GT), total cholesterol (TCH), triglyceride (TG), fasting plasma glucose (FPG), fasting insulins (FINS), IRI, CAP, TNF-αand IL-6 of NAFLD patients in both of two groups were significantly lower than those before treatment (P<0.01). ALT, AST, γ-GT, TCH, TG, FPG, IRI, CAP, TNF-α and IL-6 in observation group were significantly lower than those in the control group after treatment (P<0.01). FINS in observation group was significantly lower than that in the control group (P<0.05). Conclusion::Colon hydrotherapy combined with modified Taohe Chengqitang is an effective method for treating NAFLD accompanied by phlegm-heat stagnation syndrome.Its mechanism may be mainly correlated with the reduction of IRI, serum TNF-α and IL-6.The course of colon hydrotherapy, the therapeutic mechanism and the long-term efficacy need to be further studied in the future.

Electroacupuncture combined with lifestyle control on obese nonalcoholic fatty liver disease: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD).@*METHODS@#A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymology [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)], glycolipid metabolism and insulin sensitivity [fasting plasma glucose (FPG), fasting serum lisulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)] and anthropological parameters [body weight (BW), body mass index (BMI), fat percentage (FP), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)] in the two groups were observed before and after treatment.@*RESULTS@#①Compared before treatment, hepatic CAP, LSM, serum ALT, AST and GGT after treatment were obviously reduced in the two groups (<0.05, <0.01). After treatment, CAP and ALT in the observation group were lower than the control group (<0.05). ②Compared before treatment, FINS, HOMA-IR, LDL-C, TC and TG after treatment were obviously reduced in the two groups (<0.05, <0.01),while the levels of HDL-C were increased (<0.05). Compared before treatment, FPG after treatment in the observation group was reduced (<0.05). Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (<0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (<0.01). After treatment, WC and WHR in the observation group were lower than the control group (<0.05).@*CONCLUSION@#Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.

Influence of increased physical activity without body weight loss on hepatic inflammation in patients with nonalcoholic fatty liver disease

BACKGROUND@#Physical activity (PA) that includes an accumulated exercise regimen that meets or exceeds a certain intensity reduces intrahepatic fat, leading to the improvement of nonalcoholic fatty liver disease (NAFLD) in afflicted patients. However, whether an increase in comprehensive PA, including activities of daily living, contributes to ameliorating the pathophysiology of NAFLD remains unclear. This study aimed to examine whether PA improves liver function in patients with NAFLD.@*METHODS@#The study included 45 patients with NAFLD who underwent follow-up examinations at least 6 months-but no later than 1 year-after their baseline examinations. The patients were interviewed about their daily activities and exercise habits to determine whether they had engaged in at least 3 metabolic equivalents (METs) per day during the previous 6 months; the quantity of PA, expressed in Ekusasaizu (Ex) units, was calculated as METs multiplied by hours. Patients who had achieved at least a 1-Ex increase in PA per week compared to baseline at the time of their follow-up interview (the PA increase group) were compared to those whose PA was the same or lower at the time of follow-up (the PA non-increase group).@*RESULTS@#There were no significant changes in all blood and biochemical parameters in the PA non-increase group at the time of follow-up when compared with baseline levels. In the PA increase group, aspartate aminotransferase, alanine aminotransferase, and γ-guanosine triphosphate levels were all significantly lower at follow-up than they were at baseline. Body weight did not change significantly from baseline to follow-up in both groups.@*CONCLUSIONS@#In the present study, hepatic inflammation improvement was accompanied by increased PA but not decreased body weight. Increasing PA may be effective for the improvement of hepatic inflammation even without body weight loss. Our results indicate the effectiveness of PA monitoring for the management of NAFLD.@*TRIAL REGISTRATION@#UMIN-CTR, UMIN000038530.

Association of Liver Histology with Sonological Grading and Liver Stiffness Measured by Fibroscan in Patients with NAFLD

Background: Non-alcoholic fatty liver disease (NAFLD) is theterm for a range of situations caused by a build-up of fat inthe liver. It's usually seen in people who are obese.Objective: In this study our main goal is to evaluate theassociation of liver histology with sonological grading and liverstiffness measured by Fibroscan in patients with NAFLD.Methods: This cross-sectional study was done at Departmentof Hepatology, Bangabandhu Sheikh Mujib Medical Universityfrom July 2007 to June 2009. Total 45 patients of fatty liverdisease were studied. All collected data was recorded in astructured questionnaire and was analyzed by SPSS version20. Values were expressed either as mean + SD or infrequency or in percentages.Results: During the study majority of the patients were 30-50years old (73.33 %), which indicates that the patients weresomewhat younger and out of 45 of study population 21(46.7%) patients was grade I fatty liver, 23(51.1%) were gradeII fatty liver and only one (2.2%) was grade III fatty liver. Thisstudy also showed that correlation between fibroscan of liverand grading of fibrosis in liver histology reveals significantassociation.

Association between hepatic steatosis and the development of hepatocellular carcinoma in patients with chronic hepatitis B

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake. METHODS: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors. RESULTS: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9–8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122–8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404–7.228; P=0.47). CONCLUSIONS: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

Psoralen and isopsoralen improve lipid metabolism disorder via inhibition of NF-κB activation in LO2 cells / 中国中药杂志

The aim of this paper was to investigate the mechanism and effect of psoralen and isopsoralen in the treatment of lipid accumulation in LO2 cells. Human LO2 cells nonalcoholic fatty liver models were established by using palmitic acid( PA). Then psoralen and isopsoralen were administered for intervention. Intracellular triglyceride( TG) and total cholesterol( TC) content,the cell supernatant alanine aminotransferase( ALT) and aspartate aminotransferase( AST) levels were determined by enzyme method. Cell supernatant proinflammatory cytokines( IL-6,TNF-α) and chemokines( IL-8,MCP-1) were determined by ELISA method. Western blot method was conducted to detect the protein expression of intracellular nuclear factor( NF-κB) p65 phosphorylation( p-p65),nonphosphorylated protein( p65),and transforming factor TGF-β1. Result showed that as compared with the model group,intracellular TG and TC levels,the cell supernatant ALT and AST levels,proinflammatory cytokines and chemokines were decreased( P < 0. 01,P <0. 05); the p-p65/p65 ratio and TGF-β1 protein expression were also significantly decreased( P< 0. 01,P< 0. 05) in psoralen intervention group. As compared with the model cells,intracellular TG content had no significant changes,but all the other indexes were reduced( P<0. 01,P<0. 05) in the cells of isopsoralen intervention group. Psoralen exhibited better effect than isopsoralen( P< 0. 01,P<0. 05). It is concluded that psoralen could improve the adipogenesis of LO2 cells induced by PA; both psoralen and isopsoralen are effective in ameliorating LO2 cells injury induced by PA,reducing inflammation via inhibiting the activation of NF-κB and down-regulating the expression of TGF-β1.

Analysis on risk factors of nonalcoholic fatty liver disease complicated with hypertension in the enterprise retirees / 中国基层医药

Objective To observe and explore the risk factors of nonalcoholic fatty liver diseas(NAFLD) complicated with hypertension in the enterprise retirees .Methods A total of 209 NAFLD patients diagnosed by ultrasound combined with questionnaire were collected in the enterprise retirees,and they were divided into the NAFLD with hypertension group(100 cases)and NAFLD without hypertension group (109 cases)after combined with physical examination results and past medical history.The relevant data of the two groups were retrospectively analyzed,and the risk factors of NAFLD complicated with hypertension disease were analyzed.Results The levels of age(t =1.69,P <0.05),body mass index(BMI)(t =0.36,P <0.05),waist circumference(t =0.64,P <0.05), total cholesterol(TC)(t =2.31,P <0.05),total bilirubin(TBS)(t =6.83,P <0.05),serum creatinine(Scr)(t =2. 20,P <0.05)in NAFLD complicated with hypertension group were higher than those in NAFLD group,and the differ-ences were statistically significant(P <0.01 or P <0.05).The logistic regression analysis showed that TC(OR =4.2)was the independent influencing factor of NAFLD with hypertension.Conclusion NAFLD is closely associated with hypertension,NAFLD can be incorporated into chronic disease management system with high blood pressure in order to improve the value of the disease in the elderly,and it is conducive to the further study of NAFLD and the management of other chronic disease.

Efficacy of Short-term Metformin Treatment on Nonalcoholic Fatty Liver Disease in Obese Children / 中山大学学报(医学科学版)

[Objective] To observe the efficacy of metformin treatment on non-alcoholic fatty liver disease (NAFLD) in obese children.[Methods] A retrospective analysis was performed of 10 patients over 10 years old with NAFLD from July 10,2013 to August 23,2016.These patients were treated with metformin in pediatric endocrinology outpatient department of the First Affiliated Hospital of Sun Yat-sen University.The changes of liver ultrasonography,hepatic enzymes,blood lipids,blood glucose,insulin,HOMA-IR,BMI,and waist circumference height ratio were compared before and after treatment with metformin.[Results] There were 10 cases of NASH,including 5 boys and 5 girls.The short-term treatment of metformin reduced the levels of ALT,AST,and HOMA-IR for all 10 patients (P ＜ 0.01).ALT,gradually decreased with the course of treatment.Fasting insulin and waist circumference to height ratio also improved with the treatment (P ＜ 0.05);the changes of TG,BMI,and fast glucose were not obvious (P ＞ 0.05).[Conclusion] Metformin can effectively reduce liver enzymes and improve insulin sensitivity in children with NASH in short term,the improvement of TG and BMI in short term is not obvious.

Preliminarily genetic characterizations of nonalcoholic fatty liver disease mongolian gerbil / 中国比较医学杂志

Non-alcoholic fatty liver disease (NAFLD) has become one of the major metabolic diseases.In view of the defects of traditional animal models, this study was the first to establish the NAFLD model of Mongolian gerbil (Meriones unguiculatus) with simple feed formula which is similar to human (from simple fatty liver to steatohepatitis, fibrosis,Liver cirrhosis).This study discussed the mechanism of rapid fatty liver deposition in Mongolian gerbil, revealed its molecular mechanism,main regulatory target and network function of fatty liver susceptibility.We provide a new animal model of NAFLD with relatively clear background and less time-consuming for clinical treatment and new drug development.The theoretical and practical basis for the breeding of inbred strain NAFLD gerbil was established.

Prevalence of nonalcoholic fatty liver disease in an adult population in a rural community of Haryana, India.

Background: Though nonalcoholic fatty liver disease (NAFLD) is increasingly becoming prevalent in the Indian population, knowledge regarding the burden and risk factors of NAFLD is limited, more so from rural areas. This study was thus conducted to estimate the prevalence of NAFLD among adults in a rural community of Haryana, India and to measure the association of diet, physical activity, and other selected risk factors with NAFLD. Materials and Methods: The present study was conducted in a rural community of Haryana, India among resident adults ≥35 years of age. Eight out of 28 villages were selected by probability proportion to size sampling. The number of eligible and consenting participants randomly selected from each village was 27. Out of 216 participants thus recruited, 184 participants reported for undergoing ultrasonography (USG) of the liver, anthropometry, blood pressure recording, and blood sample collection. Finally, 176 participants were analyzed. Results: Prevalence of NAFLD was 30.7%. There was no significant difference in the calorie intake and average total physical activity between participants with and without NAFLD. On multivariate analysis, hypertension [adjusted odds ratio (OR): 2.3, 95% confidence interval (CI): 1.1-5.0, P 0.03] and an increased waist circumference (adjusted OR: 4.9, 95% CI: 1.5-7.0, P < 0.001) were independently associated with NAFLD. A normal high-density lipoprotein (HDL) level was protective against NAFLD (adjusted OR: 0.4, 95% CI: 0.2-0.8, P 0.001). Conclusions: The high prevalence of NAFLD is already a public health problem, even in the rural parts of India. Urgent public health interventions are required to prevent its development by controlling the cardiometabolic risk factors associated with it.

A study on the association between nonalcoholic fatty liver disease and the levels of sex hormones among patients with type 2 diabetes mellitus / 预防医学

Objective To explore the association between non -alcoholic fatty liver disease(NAFLD)and the levels of sex hormones among patients with type 2 diabetes mellitus(T2DM).Methods The prevalence of NAFLD in 256 patients in Shaoxing Central Hospital from Match 2010 to October 2013 with type 2 diabetes were calculated.According to with or without NAFLD,the T2DMpatients were divided into NAFLD group and non -NAFLD group.The levels of sex hormones, glucose and lipid were detected.The difference between the two groups was compared and the relationship between NAFLD and sex hormone were explored.Results The prevalence rate of NAFLD in patients with type 2 diabetes was 56.25%, but the prevalence of NAFLD was not different between different genders.Patients with NAFLD have obvious sex hormone disorder,and testosterone(T)in NAFLD group were lower than those in non -NAFLD group and estradiol (E2 )in NAFLD group were higher than those in non -NAFLD group among males.E2 in NAFLD group were lower than those in non -NAFLD group among females.Further logisitic regression analysis showed that T and E2 were protective factors of NAFLD in males and females,while E2 was the risk factors of NAFLD in males.Conclusion For patients with NAFLD in type 2 diabetes,the dominant sex hormone is a protective factor for the formation of NAFLD.

Effects total glucosides paeony on downregulating the expression ERKI/2, TLR4 and TRL9 in rats with nonalcoholic fatty liver disease / 中国药学杂志

OBJECTIVE: To investigate total glucosides paeony (TGP) on the expression phosphorylated extracellelar signal regulated kinase 1/2(p-ERK1/2), Toll-like receptors 4(TLR4) and Toll-like receptors 9(TLR9) in rats with nonalcoholic fatty liver disease (NAFLD) induced by fructose and high-fat feed. METHODS: SD rats were divided into normal group and test groups. The rats in test groups were fed with fructose and high-fat feed for 10 weeks totally to induce the test model. After 6 weeks the model was established, the rats were divided into four groups randomly, the model group (NAFLD), the metformin group (Met, 200 mg · kg-1), the low-dose TGP group(TGP-L, 100 mg · kg-1) and the high-dose TGP group(TGP-H, 200 mg · kg-1) (n=10). Four weeks later all the rats were killed and checked the indexes such as serum fasting blood glucose(FBG), fasting insulin(Fins), insulin sensitivity index (ISI), total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), free fatty acids (FFA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutathione S-transferase (GST) and liver index. The expression p-ERK1/2, TLR4 and TLR9 were inspected by Western-blot. RESULTS: Compared with the normal group, the rats in test groups were with the high levels serum FBG, insulin, TC, LDL-C, TG, FFA, ALT, AST, GST, liver index, p-ERK1/2, TLR4 and TLR9 (P 0.05). CONCLUSION: By downregulating the expression ERK1/2, TLR4 and TRL9, TGP can improve abnormal glucose and lipid metabolism and insulin resistance, enhance insulin sensitivity and ameliorate liver function in rats with NAFLD induced by fructose and high-fat feed.

Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

BACKGROUND/AIMS: Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD. METHODS: A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day. RESULTS: The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001). CONCLUSIONS: Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.

Nonalcoholic Steatohepatitis / 대한간학회지

No abstract available.

The Prevalence of Metabolic Syndrome in Patients with Nonalcoholic Fatty Liver Disease / 대한간학회지

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD. We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. METHODS: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons who visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. RESULTS: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance was the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. CONCLUSIONS: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis.