Treatment Of Nonalcoholic Liver Disease Research Articles

Clinical Practice Guidelines of the Russian Scientific Liver Society, Russian Gastroenterological Association, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians and National Society for Preventive Cardiology on Diagnosis and Treatment of Non-Alcoholic Liver Disease

Aim:present clinical guidelines, aimed at general practitioners, gastroenterologists, cardiologists, endocrinologists, comprise up-to-date methods of diagnosis and treatment of non-alcoholic fatty liver disease.Key points.Nonalcoholic fatty liver disease, the most wide-spread chronic liver disease, is characterized by accumulation of fat by more than 5 % of hepatocytes and presented by two histological forms: steatosis and nonalcoholic steatohepatitis. Clinical guidelines provide current views on pathogenesis of nonalcoholic fatty liver disease as a multisystem disease, methods of invasive and noninvasive diagnosis of steatosis and liver fibrosis, principles of nondrug treatment and pharmacotherapy of nonalcoholic fatty liver disease and associated conditions. Complications of nonalcoholic fatty liver disease include aggravation of cardiometabolic risks, development of hepatocellular cancer, progression of liver fibrosis to cirrhotic stage.Conclusion.Progression of liver disease can be avoided, cardiometabolic risks can be reduced and patients' prognosis — improved by the timely recognition of diagnosis of nonalcoholic fatty liver disease and associated comorbidities and competent multidisciplinary management of these patients.

Есенціальні фосфоліпіди в терапії неалкогольної жирової хвороби печінки

Неалкогольна жирова хвороба печінки (НЖХП) — метаболічно-індуковане захворювання, що виникає внаслідок інсулінорезистентності і характеризується жировою дистрофією печінки різного ступеня за відсутності інших чинників ураження печінки. Інсулінорезистентність призводить до посиленого ліполізу жирової тканини з надмірним вивільненням жирних кислот та накопиченням їх у печінці. Клінічне значення НЖХП полягає у можливості прогресування простого стеатозу до цирозу печінки. Проведено дослідження впливу лікувального комплексу, що включає препарат есенціальних фосфоліпідів енерлів, на показники цитолізу, спектр ліпідів крові та морфоструктурні зміни печінки у хворих на НЖХП. Обстеження пацієнтів після лікування виявило зниження активності трансаміназ, підвищення вмісту фракції фосфоліпідів крові та зниження коефіцієнта атерогенності. За даними контрольного сонографічного дослідження спостерігалось зменшення розмірів лівої частки печінки.

Diet containing dehulled adlay ameliorates hepatic steatosis, inflammation and insulin resistance in rats with non-alcoholic fatty liver disease.

Dietary modification plays a vital role in the treatment of non-alcoholic liver diseases. We investigated the effects of the consumption of a different amount of dehulled adlay, which has hypolipidaemic and anti-inflammatory properties, on non-alcoholic fatty liver disease (NAFLD). We fed rats a high-fat-high-fructose liquid diet for 16 weeks to induce NAFLD. The rats were divided into three groups fed the NAFLD diet only (NN) or a diet containing 44·9 or 89·8 g/l of dehulled adlay (NA and NB groups, respectively). After 8 weeks, the NA and NB groups had lower C-reactive protein levels and improvement in insulin resistance. In addition, the NB group had lower liver weight and hepatic TAG and cholesterol concentrations than did the NN group. Compared with the NN group, the high-dose NB group had improved steatosis, lower hepatic TNF-α, IL-1β and IL-6 levels and lower adipose leptin levels. Our results suggest that a diet containing dehulled adlay can ameliorate NAFLD progression by decreasing of insulin resistance, steatosis and inflammation.

Saroglitazar for Treatment of Nonalcoholic Steatohepatitis

Numerous candidate drugs are being evaluated for the treatment of nonalcoholic fatty liver disease (NAFLD), including some for the treatment of

Study on hepatoprotective mechanisms of Veratrilla baillonii based on network pharmacology

The purpose of this study was to predict the active components, targets and signaling pathways of Veratrilla baillonii for the prevention and treatment of non-alcoholic liver diseases, preliminarily verify the active components and related targets through cell experiments, and elucidate the mechanism of V. baillonii on liver protection. The candidate active components of V. baillonii were screened by searching Chinese medicine ingredients and Chinese medicine pharmacology database and analysis platform, combined with the pharmacokinetic parameters(oral availability and drug-like principle); the target of candidate active ingredients were predicted by protein database, and the target of disease related to non-alcoholic liver disease was predicted. Cytoscape software was used to construct the network of "active component-target-disease", and the protein interaction network was constructed through the STRING database to infer the core target. GO annotation analysis, KEGG pathway analysis and enrichment analysis were conducted through DAVID bioinformatics annotation database. Finally, the core target and pathway of V. baillonii were preliminarily verified by the experimental model of H_2O_2-induced liver cell damage intervened by V. baillonii water extract(WVBF). The cell viability was detected by MTT assay and real-time unlabeled assay, and the expression of related genes was analyzed by Real-time quantitative polymerase chain reaction(PCR). Firstly, 14 active components were obtained from V. baillonii through network pharmacology. There were 287 potential targets corresponding to the components, 587 targets related to non-alcoholic liver disease, and 13 core targets after the interaction between active ingredient targets and disease targets. Secondly, GO enrichment analysis showed that these genes mainly affected 26 biological processes such as nuclear receptor activity, transcription factor activity, steroid hormone receptor activity, ubi-quitin-like protein ligase binding, protein heterodimerization activity, and transcription cofactor binding. KEGG enrichment analysis showed that PI3 K-AKT signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway, insulin signaling pathway, TNF signaling pathway and some cancer-related pathways were more enriched. Finally, TNF-α and MAPK8 were successfully verified as important targets by hepatocytes in vitro, which suggested that V. baillonii could significantly improve liver damage. TNF-α and MAPK8 were one of the targets. Based on the above results, we systematically predicted the material basis and biological mechanism of V. baillonii through multi-component, multi-target and multi-pathway regulation of nonalcoholic liver disease, and the core targets were successfully verified by cells, providing data basis and scientific basis for the in-depth development of V. baillonii.

Effectiveness of Weight Loss Interventions on Nonalcoholic Fatty Liver Disease

As there is no licensed pharmacologic therapy for the treatment of nonalcoholic fatty liver disease (NAFLD), clinical guidelines recommend counseling

Research progress of miRNA in nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease is a common, multiple liver disease, the pathogenesis is complex, the typical pathological features include liver cell lipid accumulation, sinus fibrosis and so on.MicroRNAs are single-chain non-coding miRNAs and have a wide range of effects on organisms.The research reviewed the progress of microRNA in the occurrence, development, diagnosis and treatment of nonalcoholic fatty liver disease. Key words: Fatty liver; Micro-Ribonucleic acid; Diagnosis; Review

Flavone glycosides from Sicyos angulatus and their inhibitory effects on hepatic lipid accumulation

A library of extracted natural materials (Korea Bioactive Natural Material Bank) have been screened to discover candidates for the treatment of non-alcoholic liver disease (NAFLD), and the 70% ethanol extract of Sicyos angulatus was found to inhibit hepatic lipid accumulation. Bioassay–guided fractionation of this bioactive extract yielded five previously undescribed flavonoid glycosides and one previously undescribed flavonolignan glycoside along with seven known flavonoid glycosides. The chemical structures of these compounds were elucidated by a combination of extensive spectroscopic analysis, including MS, NMR and UV techniques. Eight compounds of all isolated compounds showed inhibitory effects on the lipid accumulation induced by high concentrations of palmitic acid and glucose in HepG2 cells. Four selected compounds were tested for lipid content in a dose-dependent manner (10, 20 and 40 μM), and among those compounds, kaempferol 3-O-β-d-glucopyranosyl-7-O-α-l-rhamnopyranoside showed the strongest inhibition of hepatic lipid production in HepG2 cells. In an oil-red O staining assay, five compounds were shown to reduce hepatic lipid accumulation better than what was observed in the vehicle control group. The present study suggests a new class of chemical entities for developing bioactive agents for the treatment of diseases caused by fat accumulation in the liver.

Implication of trans-11,trans-13 conjugated linoleic acid in the development of hepatic steatosis.

ScopeConjugated linoleic acids are linoleic acid isomers found in the diet that can also be produced through bacterial metabolism of polyunsaturated fatty acids. Our objective was to evaluate the contribution of fatty acid metabolites produced from polyunsaturated fatty acids by the gut microbiota in vivo to regulation of hepatic lipid metabolism and steatosis.Methods and resultsIn mice with depleted n-3 polyunsaturated fatty acids, we observed an accumulation of trans-11,trans-13 CLA and cis-9,cis-11 conjugated linoleic acids in the liver tissue that were associated with an increased triglyceride content and expression of lipogenic genes. We used an in vitro model to evaluate the impact of these two conjugated linoleic acids on hepatic lipid metabolism. In HepG2 cells, we observed that only trans-11,trans-13 conjugated linoleic acids recapitulated triglyceride accumulation and increased lipogenic gene expression, which is a phenomenon that may implicate the nuclear factors sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP).ConclusionThe trans-11,trans-13 conjugated linoleic acids can stimulate hepatic lipogenesis, which supports the conclusion that gut microbiota and related metabolites should be considered in the treatment of non-alcoholic liver disease.

Clinical study of lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease

Objective To investigate the clinical effects of lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease. Methods 120 patients with nonalcoholic fatty liver disease were selected, and they were randomly divided into control group (60 patients used glutathione alone) and observation group (60 patients received lactobacillus acidophilus on the basis of control group). The clinical efficacy, liver function index, blood lipid index and the ultrasonography grading of fatty liver before and after treatment of the two groups were compared. Results The clinical total effective rates of the control group and the observation group were 76.67%, 91.67%, respectively.The total effective rate of the observation group was significantly higher than that of the control group(χ2=10.52, P<0.05). The levels of AST, ALT and GGT of the observation group after treatment were significantly lower than those of the control group and before treatment[(36.89±7.14)U/L, (36.89±7.14)U/L, (36.89±7.14)U/L vs.(49.36±11.08)U/L, (45.91±10.24)U/L, (90.28±20.70)U/L; (36.89±7.14)U/L, (36.89±7.14)U/L, (36.89±7.14)U/L vs.(92.90±24.3)U/L, (81.11±17.37)U/L, (147.27±34.19)U/L, t=2.88, 2.54, 2.91; 3.01, 3.36; 3.18, 3.48; 3.41, 3.87; all P<0.05). The levels of TG, TC, HDL-C and LDL-C of the observation group after treatment were significantly better than those of the control group and before treatment[(1.66±0.42)mmol/L, (4.05±0.77)mmol/L, (1.69±0.60)mmol/L, (2.44±0.38)mmol/L vs.(2.13±0.80)mmol/L, (4.64±0.94)mmol/L, (1.45±0.48)mmol/L, (2.97±0.57)mmol/L; (1.66±0.42)mmol/L, (4.05±0.77)mmol/L, (1.69±0.60)mmol/L, (2.44±0.38)mmol/L vs.(2.71±1.33)mmol/L, (5.42±1.27)mmol/L, (1.08±0.36)mmol/L, (3.49±0.71)mmol/L, t=2.43, 2.13, 2.55, 2.07; 3.02, 3.41; 3.11, 3.65; 2.81, 3.30; 2.87, 3.15; all P<0.05). In the control group, normal in 6 cases, mild in 24 cases, moderate in 21 cases and severe in 9 cases as fatty liver degree; in the observation group, normal in 13 cases, mild in 30 cases, moderate in 13 cases and severe in 4 cases as fatty liver degree.The ultrasonography grading of fatty liver of the observation group after treatment were significantly better than those of control group and before treatment(U=3.74, 5.20, all P<0.05). Conclusion Lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease can efficiently promote the recovery process of liver function, regulate blood lipid levels and is helpful to improve the imaging grading. Key words: Actobacillus acidophilus; Glutathione; Nonalcoholic fatty liver disease; Clinical effects

Combined treatment with probiotics and fructooligosaccharides in a mouse model of nonalcoholic fatty liver disease and its possible mechanism

Objective To investigate the effectiveness of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) in the treatment of nonalcoholic fatty liver disease(NAFLD) in a mouse model and to analyze the possible mechanism. Methods Fifty male C57BL/6 mice were randomly divided into five groups and respectively given normal diet (ND group), high-fat diet (HFD group), HFD containing Lactobacillus paracasei N1115 (HFD+ L) (2.2×109 CFU/ml), HFD containing FOS (HFD+ FOS) (4 g/kg per day) and HFD containing Lactobacillus paracasei N1115 and FOS for 16 consecutive weeks. Levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum samples from each group were measured. Expression of tight-junction proteins (Claudin-1 and Occludin), p38 and phosphorylated p38 (p-p38) in intestinal tissues were analyzed. Results Compared with the HFD group, the HFD+ FOS+ L group showed decreased levels of TC, TG, LDL, LPS and DAO in serum samples, but increased serum HDL level (P<0.05). Moreover, combined treatment with Lactobacillus paracasei N1115 and FOS alleviated liver lipid deposition, significantly increased the expression of Claudin-1 and Occludin in intestine and inhibited the phosphorylation of p38 (P<0.05). Conclusion Lactobacillus paracasei N1115 combined with FOS may increase the expression of Claudin-1 and Occludin through inhibiting the phosphorylation of intestinal p38, which is conducive to maintaining the intestinal mucosal barrier integrity and alleviating NAFLD. Key words: NAFLD; Lactobacillus paracasei N1115; Fructooligosaccharides; Intestinal mucosal barrier

Exercise Strategies for the Prevention and Treatment of Non-alcoholic Fatty Liver Disease

종으로써 비알코올성 지방간은 간 조직에 중성지방이 비정상적으로 누적된 상태를 의미하는 단순 지방간(simple steatosis), 염증(inflammation)을 동반하는 지방간염(steatohepatitis), 염증과 더불어 세포 괴사(apoptosis)를 동반하는 간경변(cirrhosis)에 이르기 까지 병리학 적 진행 상태에 따라 세분화하며, 치료하지 않고 방치할 경우 궁극적 으로 간암으로까지 진행되어 조기 사망을 일으킬 수 있는 질환이다. 비알코올성 지방간은 당뇨(diabetes), 고혈압(hypertension), 심혈관 질환(cardiovascular disease) 등 대사질환의 독립적인 위험인자로 밝 혀지고 있어 그로 인한 이차적인 심각성이 부각되고 있는 실정이다. 비알코올성 지방간 질환은 비만(obesity)과 당뇨환자의 증가와 더 불어 그 유병률이 세계적으로 급격한 증가 추세에 있으며, 우리나라 의 경우 비알코올성 지방간의 유병률이 약 20-30% 정도로 추정되고 있으나 이에 따른 체계적인 치료지침은 없는 실정이다. 비알코올성

Diagnosis and treatment of non-alcoholic fatty liver disease

非酒精性脂肪性肝病(NAFLD)是代谢综合征累及肝脏的临床病理表现,疾病谱包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)以及肝硬化和肝细胞癌(HCC).随着肥胖及2型糖尿病的流行以及慢性病毒性肝炎的有效控制,NAFLD现已成为慢性肝病的主要原因,与肝脏及肝外残疾和死亡密切相关.然而,至今广大群众和临床医生对NAFLD这一新的慢性非传染性流行病并没有充分的认识.而2006年以来相继出台的众多NAFLD诊疗指南和专家共识则又使临床医生无所适从,目前我国NAFLD的规范化诊疗以及NAFLD患者科学管理仍困难重重.为此,2013年中国医师协会脂肪性肝病专家委员会发布的《脂肪性肝病诊疗规范化的专家建议》[1],但临床医生对这些文献的理解和执行情况并不乐观. 关键词：脂肪肝;诊断;治疗

Comparison of the effects of fenofibrate and polyene phosphatidylcholine in the treatment of non-alcoholic fatty liver disease

Objective To investigate the clinical effects of fenofibrate and polyene phosphatidylcholine in treatment of non-alcoholic fatty liver disease.Methods 86 patients with non-alcoholic fatty liver disease were randomly divided into two groups.45 cases in therapy group received 0.2g of fenofibrate once a day,and the others in control group received 456mg of polyene phosphatidylcholine for three times per day.All of the patients were treated for 12 weeks.Liver function,blood fat,clinical effect and liver B ultrasonic were analyzed before treatment and after 12 weeks.Results The improvement of liver function,blood fat,and liver ultrasonic imaging in therapy group was better than that in the control group.The cure rate was 82.2％ in therapy group and 63.4％ in control group.There was a statistical significance between the two groups ( x2 =3.874,P ＜ 0.05).Conclusion Fenofibrate had significant therapeutic effect in treatment of non-alcoholic fatty liver disease with lower costs and lower side effects. Key words: Fenofibrate; Non-alcoholic fatty liver

Effects of calorie restriction on SIRT1 expression in liver of nonalcoholic fatty liver disease: experiment with rats

To investigate the molecular mechanisms of calorie restriction (CR) in treatment of nonalcoholic fatty liver disease (NAFLD). 25 male Wistar rats were randomly divided into 2 groups: normal control group (NC, n = 7) fed with regular diet and high fat diet-NAFLD model group (HFM, n = 18) fed with high-fat diet. Two months later, the rats in Group HFM were further divided into 2 subgroups: continuous high-fat feeding group (HF, n = 9) and normal diet feeding with 60% calorie restriction group (CR, n = 9). The rats were sacrificed after 1 month calorie restriction. By the end of experiment, body weight (BW), visceral fat mass (VF), fasting plasma glucose (FPG), fasting serum insulin (FINS), blood lipids (BL), including total cholesterol (TC) and triglyceride (TG), and hepatoultrastructure changes were examined to evaluate the effect of different feeding protocols on the experimental animals. The mRNA expression of the longevity gene SIRT1 in the liver was detected by RT-PCR. Western blot analysis was performed to determine the expression of SIRT1 protein in each group. Electron microscopy showed that the rats in group HF displayed obviously abnormal hepatoultrastructure, and the ultramicropathology changes of liver cell were improved obviously in Group CR. The VF, FINS, FPG, TC, and TG of the Group HF were 15.1 g +/- 4.1 g, 29.22 mU/L +/- 7.28 mU/L, 6.2 mmol/L +/- 1.46 mmol/L, 2.61 mmol/L +/- 0.29 mmol/L, and 1.35 mmol/L +/- 0.21 mmol/L respectively, all significantly higher than those in Group NC (9.0 g +/- 0.4 g, 13.09 mU/L +/- 1.18 mU/L, 4.4 mmol/L +/- 0.57 mmol/L, 1.41 mmol/L +/- 0.28 mmol/L, and 0.67 mmol/L +/- 0.10 mmol/L respectively, all P < 0.01). The mRNA expression of SIRT1 in the liver of Group HF was significantly lower than that of Group NC (P < 0.05), and the mRNA expression of SIRT1 in the liver of Group CR was significantly higher than those of Group HF and Group NC (both P < 0.01). The protein expression of SIRT1 of Group HF was significantly lower than that of Group NC (P < 0.01), and that of Group CR was significantly higher than that of Group HF, however, still significantly lower than that of Group NC (both P < 0.01). The BW and VF, FINS, FPG, TC, and TG of Group CR were all significantly lower than those of Group HF (all P < 0.01). CR can reverse NAFLD significantly. The increased expression of SIRT1 in liver induced by CR may be an important molecular mechanism involved in the improvement of NAFLD by CR.

Metformin vs. Vitamin E or Diet for NAFLD Treatment

Currently, no specific therapy can be recommended for treatment of nonalcoholic fatty liver disease (NAFLD). Moreover, few randomized controlled trials