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| 1 | Physical activity as a treatment of non-alcoholic fatty liver disease:A systematic review显示文摘AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease(NAFLD) and potential benefits in treating insulin resistance and atherosclerosis.METHODS: Medline(EBSCOhost) and Pub Med were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged ≥ 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015.RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine(50%) studies were randomized controlled trials. Five(27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD.CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment. | Maureen Whitsett Lisa B VanWagner | 2015 | World Journal of Hepatology2015，7，16： | 281 |
| 2 | Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From “two hit theory” to “multiple hit model”显示文摘Nonalcoholic fatty liver disease(NAFLD) has become the dominant form of chronic liver disease in children and adolescents with the increasing prevalence of obesity worldwide. NAFLD represents a wide spectrum of conditions, ranging from fatty liver-which generally follows a benign, non-progressive clinical course-to non-alcoholic steatohepatitis, a subset of NAFLD that may progress to cirrhosis and end-stage liver disease or liver carcinoma. The underlying pathophysiological mechanism of 'pediatric' NAFLD remains unclear, although it is strongly associated with obesity and insulin resistance. In this review we provide a general overview on the current understanding of NAFLD in children and adolescents, which underpins practice, enabling early diagnosis and appropriate therapeutic intervention for this life-threatening liver disease. | Yan-Lan Fang Hong Chen Chun-Lin Wang Li Liang | 2018 | World Journal of Gastroenterology2018，24，27： | 100 |
| 3 | Prevalence of fatty liver disease and the economy in China: A systematic review显示文摘AIM: To investigate the relationship between the economy and the adult prevalence of fatty liver disease(FLD) in China's Mainland. METHODS: Literature searches on the Pub Med and Chinese National Knowledge Infrastructure databases were performed to identify eligible studies published before July 2014. Records were limited to crosssectional surveys or baseline surveys of longitudinal studies that reported the adult prevalence of FLD and recruited subjects from the general population or community. The gross domestic product(GDP) per capita was chosen to assess the economic status. Multiple linear regression and Loess regression were chosen to fit the data and calculate the 95%CIs. Fitting and overfitting of the models were considered in choosing the appropriate models. RESULTS: There were 27 population-based surveys from 26 articles included in this study. The pooled mean prevalence of FLD in China was 16.73%(95%CI: 13.92%-19.53%). The prevalence of FLD was correlated with the GDP per capita and survey years in the country(adjusted R2 = 0.8736, P GDP per capita = 0.00426, P years = 0.0000394), as well as in coastal areas(R2 = 0.9196, P GDP per capita = 0.00241, P years = 0.00281). Furthermore, males [19.28%(95%CI: 15.68%-22.88%)] presented a higher prevalence than females [14.1%(95%CI: 11.42%-16.61%), P = 0.0071], especially in coastal areas [21.82(95%CI: 17.94%-25.71%) vs 17.01%(95%CI: 14.30%-19.89%), P = 0.0157]. Finally, the prevalence was predicted to reach 20.21% in 2020, increasing at a rate of 0.594% per year. CONCLUSION: This study reveals a correlation between the economy and the prevalence of FLD in China's Mainland. | Jin-Zhou Zhu Qin-Yi Zhou Yu-Ming Wang Yi-Ning Dai Jiang Zhu Chao-Hui Yu You-Ming Li | 2015 | World Journal of Gastroenterology2015，21，18： | 116 |
| 4 | Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease显示文摘Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment. | Kouichi Miura Hirohide Ohnishi | 2014 | World Journal of Gastroenterology2014，20，23： | 78 |
| 5 | Risk of cardiovascular,cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease显示文摘Non-alcoholic fatty liver disease(NAFLD)has emerged as a public health problem of epidemic proportions worldwide.Accumulating clinical and epidemiological evidence indicates that NAFLD is not only associated with liver-related morbidity and mortality but also with an increased risk of coronary heart disease(CHD),abnormalities of cardiac function and structure(e.g.,left ventricular dysfunction and hypertrophy,and heart failure),valvular heart disease(e.g.,aortic valve sclerosis)and arrhythmias(e.g.,atrial fibrillation).Experimental evidence suggests that NAFLD itself,especially in its more severe forms,exacerbates systemic/hepatic insulin resistance,causes atherogenic dyslipidemia,and releases a variety of pro-inflammatory,pro-coagulant and pro-fibrogenic mediators that may play important roles in the pathophysiology of cardiac and arrhythmic complications.Collectively,these findings suggest that patients with NAFLD may benefit from more intensive surveillance and early treatment interventions to decrease the risk for CHD and other cardiac/arrhythmic complications.The purpose of this clinical review is to summarize the rapidly expanding body of evidence that supports a strong association between NAFLD and cardiovascular,cardiac and arrhythmic complications,to briefly examine the putative biological mechanisms underlying this association,and to discuss some of the current treatment options that may influence both NAFLD and its related cardiac and arrhythmic complications. | Stefano Ballestri Amedeo Lonardo Stefano Bonapace Christopher D Byrne Paola Loria Giovanni Targher | 2014 | World Journal of Gastroenterology2014，20，7： | 55 |
| 6 | Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients显示文摘AIM:To evaluate the performance of a novel non-invasive controlled attenuation parameter(CAP)to assess liver steatosis.METHODS:This was a multi-center prospective cohort study.Consecutive patients(aged≥18 years)who had undergone percutaneous liver biopsy and CAP measurement were recruited from three Chinese liver centers.Steatosis was categorized as S0:<5%;S1:5%-33%;S2:34%-66%;or S3:≥67%,according to the nonalcoholic fatty liver disease(NAFLD)activity score.The FibroScan?502 equipped with the M probe(Echosens,Paris,France)was used to capture both CAP and liver stiffness measurement values simultaneously.Receiver operating characteristic curves were plotted,and the areas under the curves were calculated to determine the diagnostic efficacy.The accuracy of the CAP values at the optimal thresholds was defined by maximizing the sum of sensitivity and specificity(maximum Youden index).RESULTS:A total of 152 patients were recruited,including 52(34.2%)patients with NAFLD and 100(65.8%)with chronic hepatitis B(CHB)virus infection.After adjustment,the steatosis grade(OR=37.12;95%CI:21.63-52.60,P<0.001)and body mass index(BMI,OR=6.20;95%CI:2.92-9.48,P<0.001)were found independently associated with CAP by multivariate linear regression analysis.CAP was not influenced by inflammation,fibrosis or aetiology.The median CAP values and interquartile ranges among patients with S0,S1,S2 and S3 steatosis were 211(181-240)dB/m,270(253-305)dB/m,330(302-360)dB/m,and 346(313-363)dB/m,respectively.The cut-offs for the CAP values in all patients with steatosis≥5%,≥34%and≥67%were 253 dB/m,285 dB/m and 310 dB/m,respectively.The areas under the curves were 0.92,0.92and 0.88 for steatosis≥5%,≥34%and≥67%,respectively.No significant differences were found in the CAP values between the NAFLD group and the CHB group in each steatosis grade.CONCLUSION:CAP appears to be a promising tool for the non-invasive detection and quantification of hepatic steatosis,but is limited by BMI. | Feng Shen Rui-Dan Zheng Yu-Qiang Mi Xiao-Ying Wang Qin Pan Guang-Yu Chen Hai-Xia Cao Ming-Li Chen Liang Xu Jian-Neng Chen Yi Cao Rui-Nan Zhang Lei-Ming Xu Jian-Gao Fan | 2014 | World Journal of Gastroenterology2014，20，16： | 55 |
| 7 | Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations显示文摘Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease in the world.Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis(NASH).NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components.Up to80%of patients with NAFLD are obese,defined as a body mass index(BMI)>30 kg/m2.However,the distribution of fat tissue plays a greater role in insulin resistance than the BMI.The large amount of visceral adipose tissue(VAT)in morbidly obese(BMI>40 kg/m2)individuals contributes to a high prevalence of NAFLD.Free fatty acids derived from VAT tissue,as well as from dietary sources and de novo lipogenesis,are released to the portal venous system.Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD.In addition,secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways,which are also activated by free fatty acids,and contribute to insulin resistance.Most NAFLD patients are asymptomatic on clinical presentation,even though some may present with fatigue,dyspepsia,dull pain in the liver and hepatosplenomegaly.Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications,anti-obesity medication and bariatric surgery.This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease.The relative contribution of visceral and liver fat to insulin resistance is discussed,and recommendations for clinical evaluation of affected individuals is provided. | Sandra Milic Davorka Lulic Davor Stimac | 2014 | World Journal of Gastroenterology2014，20，28： | 52 |
| 8 | Metabolic syndrome and non-alcoholic fatty liver disease:Asian definitions and Asian studies显示文摘BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), as conventionally recognized, is a metabolic disorder largely confined to residents of affluent industrialized Western countries. However, obesity and insulin resistance are not restricted to the West, as witnessed by their increasingly universal distribution. In particular, there has been an upsurge in metabolic syndrome in the Asia-Pacific region, although there are critical differences in the extent of adiposity between Eastern and Western populations. DATA SOURCES: An English-language literature search using PubMed (1999-2007) on obesity, metabolic syndrome and NAFLD, focusing on Asian definitions and Asian studies. RESULTS: NAFLD appears to be of long-standing insulin resistance and likely represents the hepatic manifestation of the metabolic syndrome. With insulin resistance as a common factor, the disease is associated with atherosclerosis and cardiovascular risk. All features of the metabolic syndrome and related events are assessed for practical management of NAFLD, although the criteria for the diagnosis of obesity and central obesity differ across racial groups. CONCLUSIONS: The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension and ultimately metabolic syndrome, puts a very large population at risk of developing NAFLD in the coming decades. The simultaneous identification and appropriate treatment of the components of metabolic syndrome are crucial to reduce hepatic as well as cardiovascular morbidity and mortality. | Fan, Jian-Gao Peng, Yong-De | 2007 | Hepatobiliary & Pancreatic Diseases International2007，6，6： | 42 |
| 9 | Non-alcoholic fatty liver disease in 2015显示文摘There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. | Monjur Ahmed | 2015 | World Journal of Hepatology2015，7，11： | 41 |
| 10 | Gut microbiota dysbiosis in patients with nonalcoholic fatty liver disease显示文摘BACKGROUND:Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease(NAFLD)This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD.METHODS:Forty-seven human feces samples(25 NAFLD patients and 22 healthy subjects) were collected and 16 S r DNA amplicon sequencing was conducted on Hiseq 2000 platform Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value<0.01.RESULTS:NAFLD patients harbored lower gut microbiota diversity than healthy subjects did.In comparison to the control group,the Proteobacteria(13.50%) and Fusobacteria(2.76%) phyla were more abundant in NAFLD patients.Additionally,the Lachnospiraceae(21.90%),Enterobacteriaceae(12.02%),Erysipelotrichaceae(3.83%),and Streptococcaceae(1.39%) families,as well as the Escherichia_Shigella(10.84%)Lachnospiraceae_Incertae_Sedis(7.79%),and Blautia(4.95%)genera were enriched in the NAFLD group.However,there was a lower abundance of Prevotella in the NAFLD group than that in the control group(5.83% vs 27.56%,P<0.01)The phylum Bacteroidetes(44.63%) also tended to be more abundant in healthy subjects,and the families Prevotellaceae(28.66%) and Ruminococcaceae(26.44%) followed the same trend.Compared to those without non-alcoholic steatohepatitis(NASH),patients with NASH had higher abundance of genus Blautia(5.82% vs 2.25%;P=0.01) and the corresponding Lachnospiraceae family(24.33% vs 14.21%;P<0.01).Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella(12.53% vs 1.97%;P<0.01) and the corresponding Enterobacteriaceae family(13.92% vs 2.07%;P<0.01) compared to those with F0/F1 fibrosis.CONCLUSIONS:NAFLD patients and healthy subjects harbor varying gut microbiota.In contrast to the results of previous research on children,decreased levels of Prevotella might be detrimental for adults with NAFLD.The increased level of the genus Blautia,the family Lachnospiraceae,the genus Escherichia_Shigella,and the family Enterobacteriaceae may be a primary contributor to NAFLD progression. | Feng Shen Rui-Dan Zheng Xing-Qiang Sun Wen-Jin Ding Xiao-Ying Wang Jian-Gao Fan | 2017 | Hepatobiliary & Pancreatic Diseases International2017，16，4： | 46 |
| 11 | Current guidelines for the management of non-alcoholic fatty liver disease:A systematic review with comparative analysis显示文摘The current epidemic of non-alcoholic fatty liver disease(NAFLD) is reshaping the field of hepatology all around the world.The widespread diffusion of metabolic risk factors such as obesity,type2-diabetes mellitus,and dyslipidemia has led to a worldwide diffusion of NAFLD.In parallel to the increased availability of effective anti-viral agents,NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries,and a similar trend is expected in Eastern Countries in the next years.This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis,management,and treatment of NAFLD.Different scientific societies from Europe,America,and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD.These guidelines are consistent with the key elements in the management of NAFLD,but still,show significant difference about some critical points.We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences.We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions.Differences were noted in: the definition of NAFLD,the opportunity of NAFLD screening in high-risk patients,the noninvasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis,in the follow-up protocols and,finally,in the treatment strategy(especially in the proposed pharmacological management).These difference have been discussed in the light of the possible evolution of the scenario ofNAFLD in the next years. | Simona Leoni Francesco Tovoli Lucia Napoli Ilaria Serio Silvia Ferri Luigi Bolondi | 2018 | World Journal of Gastroenterology2018，24，30： | 42 |
| 12 | Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘It is estimated that 30%of the adult population in Japan is affected by nonalcoholic fatty liver disease(NAFLD).Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography(US)and computed tomography(CT),but the sensitivity of these imaging techniques is low in cases of mild steatosis.Alanine aminotransferase levels may be normal in some of these patients,warranting the necessity to establish a set of parameters useful for detecting NAFLD,and the more severe form of the disease,nonalcoholic steatohepatitis(NASH).Although liver biopsy is currently the gold standard for diagnosing progressive NASH,it has many drawbacks,such as sampling error,cost,and risk of complications.Furthermore,it is not realistic to perform liver biopsies on all NAFLD patients.Diagnosis of NASH using various biomarkers,scoring systems and imaging methods,such as elastography,has recently been attempted.The NAFIC score,calculated from the levels of ferritin,fasting insulin,and typeⅣcollagen 7S,is useful for the diagnosis of NASH,while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis.This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH. | Yoshio Sumida Atsushi Nakajima Yoshito Itoh | 2014 | World Journal of Gastroenterology2014，20，2： | 45 |
| 13 | Radiologic evaluation of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a frequent cause of chronic liver diseases,ranging from simple steatosis to nonalcoholic steatohepatitis(NASH)-related liver cirrhosis.Although liver biopsy is still the gold standard for the diagnosis of NAFLD,especially for the diagnosis of NASH,imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy.Ultrasonography is a well-established and costeffective imaging technique for the diagnosis of hepatic steatosis,especially for screening a large population at risk of NAFLD.Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis,operator-dependent,and rather qualitative.Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard.However,computed tomography may be effective in specific clinical situations,such as evaluation of donor candidates for hepatic transplantation.Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice,especially for longitudinal followup of patients with NAFLD.Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis.This article will review current imaging methods used to evaluate hepatic steatosis,including the diagnostic accuracy,limitations,and practical applicability of each method.It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. | Seung Soo Lee Seong Ho Park | 2014 | World Journal of Gastroenterology2014，20，23： | 41 |
| 14 | Non-alcoholic fatty liver disease: What the clinician needs to know显示文摘Non-alcoholic fatty liver disease(NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. | Mariana Verdelho Machado Helena Cortez-Pinto | 2014 | World Journal of Gastroenterology2014，20，36： | 45 |
| 15 | Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD)is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis.The pathogenesis of NAFLD and nonalcoholic steatohepatitis(NASH)has not been fully elucidated.The'two-hit'hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH.It should be better regarded as a multiple step process,with accumulation of liver fat being the first step,followed by the development of necroinflammation and fibrosis.Adipose tissue,which has emerged as anendocrine organ with a key role in energy homeostasis,is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins.These adipocyte-specific or enriched proteins,termed adipokines,have been shown to have a variety of local,peripheral,and central effects.In the current review,we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD.We particularly focus on adiponectin,leptin and ghrelin,with a brief mention of resistin,visfatin and retinol-binding protein 4 among adipokines,and tumor necrosis factor-α,interleukin(IL)-6,IL-1,and briefly IL-18 among proinflammatory cytokines.We update their role in NAFLD,as elucidated in experimental models and clinical practice. | Sanja Stojsavljevi? Marija Gomer?i? Pal?i? Lucija Virovi? Juki? Lea Smir?i? Duvnjak Marko Duvnjak | 2014 | World Journal of Gastroenterology2014，20，48： | 42 |
| 16 | Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis显示文摘Nonalcoholic fatty liver disease(NAFLD)/nonalcoholic steatohepatitis(NASH) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing worldwide. It is currently the most common chronic liver disease. NASH can progress to liver cirrhosis and hepatocellular carcinoma, and may result in liver-related death. Currently, the principal treatment for NAFLD/NASH is lifestyle modification by diet and exercise. However, pharmacological therapy is indispensable because obese patients with NAFLD often have difficulty maintaining improved lifestyles. The pathogenesis of NAFLD/NASH has not been completely elucidated. However, insulin resistance, inflammatory cytokines, and oxidative stress are thought to be important in the development and/or progression of the disease. Currently, insulin sensitizers(thiazolidinediones) and antioxidants(vitamin E) seem to be the most promising therapeutic agents for NAFLD/NASH, and lipid-lowering drugs, pentoxifylline, angiotensin receptor blockers, and n-3 polyunsaturated fatty acids also have promise. However, there is a lack of consensus regarding the most effective and appropriate pharmacotherapy for NAFLD/NASH. Animal experiments suggest that herbal medicines and natural products may be promising therapeutic agents for NAFLD/NASH, but their efficacy and safety are yet to be investigated in human studies. In this paper, we review the existing and potential pharmacological therapies for NAFLD/NASH. | Yoshihisa Takahashi Keiichiro Sugimoto Hiroshi Inui Toshio Fukusato | 2015 | World Journal of Gastroenterology2015，21，13： | 41 |
| 17 | Gut microbiota and host metabolism in liver cirrhosis显示文摘The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulatingthe activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probioticstreated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients. | Makoto Usami Makoto Miyoshi Hayato Yamashita | 2015 | World Journal of Gastroenterology2015，21，41： | 44 |
| 18 | Prevalence of and risk factors for non-alcoholic fatty liver disease in a Chinese population: An 8-year follow-up study显示文摘AIM: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease(NAFLD) in a Chinese population.METHODS: A total of 1948 adults from China was followed for 8 years. A cross-sectional study was performed to investigate the prevalence of NAFLD at baseline, and then the participants were followed for 8 years to investigate risk factors for the development of NAFLD.RESULTS: A total of 1948 participants were enrolled at baseline, of whom 691 were diagnosed with NAFLD. During the 8-year follow-up, 337 baseline NAFLD-free participants developed NAFLD. They had a greaterincrease in body mass index(BMI), serum uric acid, fasting plasma glucose, very low-density lipoprotein cholesterol and a considerable decrease in high-density lipoprotein cholesterol. 123 participants who had NAFLD at baseline lost NAFLD during the 8-year follow-up period. They had a greater decrease in BMI, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase.CONCLUSION: NAFLD is prevalent in Chinese population with a rapidly increasing tendency. It can be reversed when patients lose their weight, control their hyperlipidemia and hyperglycemia, and reduce the liver enzyme levels. | Zhen-Ya Lu Zhou Shao Ya-Li Li Muhuyati Wulasihan Xin-Hua Chen | 2016 | World Journal of Gastroenterology2016，22，13： | 42 |
| 19 | Treatment options for alcoholic and non-alcoholic fatty liver disease: A review显示文摘Alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are serious health problems worldwide.These two diseases have similar pathological spectra,ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma.Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver(simple steatosis),a small percentage develops progressive liver disease.Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available.The treatment for ALD remains as it was 50 years ago:abstinence,nutritional support and corticosteroids(or pentoxifylline as an alternative if steroids are contraindicated).As for NAFLD,the treatment modality is mainly directed toward weight loss and co-morbidity management.Therefore,new pathophysiology directed therapies are urgently needed.However,the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy.Hence,a combination therapy towards multiple targets would eventually be required.In this review,we delineate the treatment options in ALD and NAFLD,including various new targeted therapies that are currently under investigation.We hope that soon we will be having an effective multi-therapeutic regimen for each disease. | Sukhpreet Singh Natalia A Osna Kusum K Kharbanda | 2017 | World Journal of Gastroenterology2017，23，36： | 45 |
| 20 | Noninvasive evaluation of nonalcoholic fatty liver disease: Current evidence and practice显示文摘With the increasing number of individuals with diabetes and obesity,nonalcoholic fatty liver disease(NAFLD) is becoming increasingly prevalent,affecting one-quarter of adults worldwide. The spectrum of NAFLD ranges from simple steatosis or nonalcoholic fatty liver(NAFL) to nonalcoholic steatohepatitis(NASH). NAFLD, especially NASH, may progress to fibrosis, leading to cirrhosis and hepatocellular carcinoma. NAFLD can impose a severe economic burden,and patients with NAFLD-related terminal or deteriorative liver diseases have become one of the main groups receiving liver transplantation. The increasing prevalence of NAFLD and the severe outcomes of NASH make it necessary to use effective methods to identify NAFLD. Although recognized as the gold standard, biopsy is limited by its sampling bias, poor acceptability, and severe complications, such as mortality, bleeding, and pain. Therefore, noninvasive methods are urgently needed to avoid biopsy for diagnosing NAFLD. This review discusses the current noninvasive methods for assessing NAFLD,including steatosis, NASH, and NAFLD-related fibrosis, and explores the advantages and disadvantages of measurement tools. In addition, we analyze potential noninvasive biomarkers for tracking disease processes and monitoring treatment effects, and explore effective algorithms consisting of imaging and nonimaging biomarkers for diagnosing advanced fibrosis and reducing unnecessary biopsies in clinical practice. | Jiang-Hua Zhou Jing-Jing Cai Zhi-Gang She Hong-Liang Li | 2019 | World Journal of Gastroenterology2019，25，11： | 42 |
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