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Non-alcoholic fatty liver disease:An expanded review 被引量:63
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作者 Mark Benedict Xuchen Zhang 《World Journal of Hepatology》 CAS 2017年第16期715-732,共18页
Non-alcoholic fatty liver disease(NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing ep... Non-alcoholic fatty liver disease(NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. 展开更多
关键词 Non-alcoholic fatty liver disease Metabolic syndrome steatohepatitis Hepatocellular carcinoma STEATOSIS
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Adiponectin,a key adipokine in obesity related liver diseases 被引量:45
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作者 Christa Buechler Josef Wanninger Markus Neumeier 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第23期2801-2811,共11页
Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver i... Non-alcoholic fatty liver disease (NAFLD) comprising hepatic steatosis,non-alcoholic steatohepatitis (NASH),and progressive liver fibrosis is considered the most common liver disease in western countries.Fatty liver is more prevalent in overweight than normal-weight people and liver fat positively correlates with hepatic insulin resistance.Hepatic steatosis is regarded as a benign stage of NAFLD but may progress to NASH in a subgroup of patients.Besides liver biopsy no diagnostic tools to identify patients with NASH are available,and no effective treatment has been established.Visceral obesity is a main risk factor for NAFLD and inappropriate storage of triglycerides in adipocytes and higher concentrations of free fatty acids may add to increased hepatic lipid storage,insulin resistance,and progressive liver damage.Most of the adipose tissue-derived proteins are elevated in obesity and may contribute to systemic inflammation and liver damage.Adiponectin is highly abundant in human serum but its levels are reduced in obesity and are even lower in patients with hepatic steatosis or NASH.Adiponectin antagonizes excess lipid storage in the liver and protects from inflammation and fibrosis.This review aims to give a short survey on NAFLD and the hepatoprotective effects of adiponectin. 展开更多
关键词 Hepatic steatosis Non-alcoholic steatohepatitis ADIPONECTIN OBESITY Adipose tissue
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Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases 被引量:34
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作者 Evan J.Raff Donny Kakati +3 位作者 Joseph R.Bloomer Mohamed Shoreibah Khalid Rasheed Ashwani K.Singal 《Journal of Clinical and Translational Hepatology》 SCIE 2015年第1期9-16,共8页
Background and Aims:Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease.Diabetes mellitus (DM) is a common comorbidity among NAFLD patients.We performed this study with the sp... Background and Aims:Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease.Diabetes mellitus (DM) is a common comorbidity among NAFLD patients.We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD.Methods:Medical charts of 480 patients with ALD or NAFLD (2004-2011) managed at a tertiary center were retrospectively reviewed.NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d.ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5years.Results:Of 480 patients (307 NAFLD),200 diabetics differed from nondiabetics for:age (52±11 vs.49±11 years;p=0.004);male gender (48% vs.57%;p=0.03);metabolic syndrome (49% vs.30%;p=0.0002);NAFLD (80% vs.56%;p<0.0001);cirrhosis (70% vs.59%;p=0.005);and hepatocellular carcinoma (HCC;8% vs.3%;p=0.009).Over a 3 year median follow-up period,diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs.41%;p=0.022) and HCC (27% vs.10%;p=0.045).There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs.39%;p=0.053),and there was no difference between the two groups in survival or other liver disease complications.Conclusions:DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD.Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics. 展开更多
关键词 Diabetes mellitus steatohepatitis Nonalcoholic steatohepatitis alcoholic cirrhosis
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Alcoholic liver disease:Utility of animal models 被引量:34
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作者 Arantza Lamas-Paz Fengjie Hao +6 位作者 Leonard J Nelson Maria Teresa Vázquez Santiago Canals Manuel Gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero 《World Journal of Gastroenterology》 SCIE CAS 2018年第45期5063-5075,共13页
Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options... Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD. 展开更多
关键词 steatohepatitis CIRRHOSIS HEPATOCELLULAR carcinoma alcoholic liver disease Reactive oxygen species
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Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age? 被引量:24
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作者 Gábor Firneisz 《World Journal of Gastroenterology》 SCIE CAS 2014年第27期9072-9089,共18页
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different no... Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation &#x000b1; fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. 展开更多
关键词 Non-alcoholic fatty liver disease Nonalcoholic steatohepatitis Liver cirrhosis Hepatocellular cancer Dysfunctional adipose tissue Type 2 diabetes mellitus Insulin resistance OBESITY GENETICS Therapy
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Olive oil consumption and non-alcoholic fatty liver disease 被引量:24
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作者 Nimer Assy Faris Nassar +1 位作者 Gattas Nasser Maria Grosovski 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第15期1809-1815,共7页
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan... The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives. 展开更多
关键词 Liver steatosis Fatty liver Olive oil Fatty acids Monounsaturated Non-alcoholic steatohepatitis LIPIDS Oleic acid Non-alcoholic fatty liver disease
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Nonalcoholic fatty liver disease and vascular disease:State-of-the-art 被引量:24
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作者 Silvia Fargion Marianna Porzio Anna Ludovica Fracanzani 《World Journal of Gastroenterology》 SCIE CAS 2014年第37期13306-13324,共19页
Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases rangin... Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival. 展开更多
关键词 Intima-media thickness STEATOSIS Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Early atherosclerosis Cardiovascular risk INFLAMMATION Epicardic fat
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Clinical approaches to non-alcoholic fatty liver disease 被引量:21
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作者 Katherine JP Schwenger Johane P Allard 《World Journal of Gastroenterology》 SCIE CAS 2014年第7期1712-1723,共12页
Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwi... Non-alcoholic fatty liver disease(NAFLD)ranges from simple steatosis to nonalcoholic steatohepatitis(NASH),leading to fibrosis and potentially cirrhosis,and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions such as metabolic syndrome,obesity,cardiovascular disease and diabetes.NASH can only be diagnosed through liver biopsy,but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis,reducing the need for liver biopsy and risk to patients.Disease progression varies between individuals and is linked to a number of risk factors.Mechanisms involved in the pathogenesis are associated with diet and lifestyle,influx of free fatty acids to the liver from adipose tissue due to insulin resistance,hepatic oxidative stress,cytokines production,reduced very low-density lipoprotein secretion and intestinal microbiome.Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD.Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial.Omega 3 polyunsaturated fatty acids and statins may offer additional benefits.Bariatric surgery should be considered in morbidly obese patients.More research is needed to assess the impact of these treatments on a long-term basis.The objective of this article is to briefly review the diagnosis,management and treatment of this disease in order to aid clinicians in managing these patients. 展开更多
关键词 Non-alcoholic fatty liver disease steatohepatitis CIRRHOSIS STEATOSIS PATHOGENESIS Diagnosis Management Treatment
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Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease:A controversial issue 被引量:18
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作者 Wilhelmus J Kwanten Wim Martinet +1 位作者 Peter P Michielsen Sven M Francque 《World Journal of Gastroenterology》 SCIE CAS 2014年第23期7325-7338,共14页
Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients.The potential role of autophagy in diseas... Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients.The potential role of autophagy in disease is increasingly recognised and investigated in the last decade.Nowadays it is commonly accepted that autophagy plays a role in the hepatic lipid metabolism.Hence,dysfunction of autophagy may be an underlying cause of non-alcoholic fatty liver disease.However,controversy of the exact role of autophagy in the lipid metabolism exists:some publications report a lipolytic function of autophagy,whereas others claim a lipogenic function.This review aims to give an update of the present knowledge on autophagy in the hepatic lipid metabolism,hepatic insulin resistance,steatohepatitis and hepatic fibrogenesis. 展开更多
关键词 Non-alcoholic fatty liver disease Non-alcoholic fatty liver disease steatohepatitis Non-alcoholic steatohepatitis AUTOPHAGY Lipophagy Lipid metabolism
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Vitamin D:A new player in non-alcoholic fatty liver disease? 被引量:19
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作者 Myrto Eliades Elias Spyrou 《World Journal of Gastroenterology》 SCIE CAS 2015年第6期1718-1727,共10页
Vitamin D through its active form 1a-25-dihydroxyvtamin D[1,25(OH)2D]is a secosteroid hormone that plays a key role in mineral metabolism.Recent years have witnessed a significant scientific interest on vitamin D and ... Vitamin D through its active form 1a-25-dihydroxyvtamin D[1,25(OH)2D]is a secosteroid hormone that plays a key role in mineral metabolism.Recent years have witnessed a significant scientific interest on vitamin D and expanded its actions to include immune modulation,cell differentiation and proliferation and inflammation regulation.As our understanding of the many functions of vitamin D has grown,the presence of vitamin D deficiency has become one of the most prevalent micronutrient deficiencies worldwide.Concomitantly,non-alcoholic fatty liver disease(NAFLD)has become the most common form of chronic liver disease in western countries.NAFLD and vitamin D deficiency often coexist and epidemiologic evidence has shown that both of these conditions share several cardiometabolic risk factors.In this article we provide an overview of the epidemiology and pathophysiology linking NAFLD and vitamin D deficiency,as well as the available evidence on the clinical utility of vitamin D supplementation in NAFLD. 展开更多
关键词 steatohepatitis Non-alcoholic FATTY LIVER DISEASE
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Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial 被引量:19
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作者 Tisha R Joy Charles A McKenzie +5 位作者 Rommel G Tirona Kelly Summers Shannon Seney Subrata Chakrabarti Neel Malhotra Melanie D Beaton 《World Journal of Gastroenterology》 SCIE CAS 2017年第1期141-150,共10页
AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (10... AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% &#x000b1; 0.4% vs 7.9% &#x000b1; 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 &#x000b1; 3.5 &#x003bc;g/mL vs 3.9 &#x000b1; 2.7 &#x003bc;g/mL, P = 0.06) and triglyceride levels (1.26 &#x000b1; 0.43 mmol/L vs 2.80 &#x000b1; 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mm 展开更多
关键词 SITAGLIPTIN Randomized controlled trial Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis FIBROSIS Magnetic resonance imaging Hepatic steatosis Insulin resistance Platelet aggregation
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Non-invasive diagnosis of alcoholic liver disease 被引量:16
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作者 Sebastian Mueller Helmut Karl Seitz Vanessa Rausch 《World Journal of Gastroenterology》 SCIE CAS 2014年第40期14626-14641,共16页
Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patient... Alcoholic liver disease(ALD)is the most common liver disease in the Western world.For many reasons,it isunderestimated and underdiagnosed.An early diagnosis is absolutely essential since it(1)helps to identify patients at genetic risk for ALD;(2)can trigger efficient abstinence namely in non-addicted patients;and(3)initiate screening programs to prevent life-threateningcomplications such as bleeding from varices,spontaneous bacterial peritonitis or hepatocellular cancer.The two major end points of ALD are alcoholic liver cirrhosis and the rare and clinically-defined alcoholic hepatitis(AH).The prediction and early diagnosis of both entities is still insufficiently solved and usually relies on acombination of laboratory,clinical and imaging findings.It is not widely conceived that conventional screeningtools for ALD such as ultrasound imaging or routine laboratory testing can easily overlook ca.40%of manifest alcoholic liver cirrhosis.Non-invasive methods such as transient elastography(Fibroscan),acoustic radiation force impulse imaging or shear wave elastography have significantly improved the early diagnosis of alcoholiccirrhosis.Present algorithms allow either the exclusion or the exact definition of advanced fibrosis stages in ca.95%of patients.The correct interpretation of liver stiffness requires a timely abdominal ultrasound and actual transaminase levels.Other non-invasive methods such as controlled attenuation parameter,serum levels of M30 or M65,susceptometry or breath tests are under current evaluation to assess the degree of steatosis,apoptosis and iron overload in these patients.Liver biopsy still remains an important option to rule out comorbidities and to confirm the prognosis namely for patients with AH. 展开更多
关键词 alcoholic hepatitis alcoholic steatohepatitis alcoholic liver disease NON-INVASIVE Liver stiffness Serum marker STEATOSIS
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Probiotics in hepatology 被引量:19
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作者 Jan Lata Jana Jurankova +1 位作者 Marcela Kopacova Petr Vitek 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第24期2890-2896,共7页
The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established ... The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established as well as potential pathogens. Furthermore, it influences the motility and perfusion of the intestinal wall, stimu- lates the intestinal immune system and therefore also the so-called common mucosal immune system, reducing bacterial translocation and producing vitamins. Immune homeostasis at mucosal level results from a controlled response to intestinal luminal antigens. In liver cirrhosis, there are many changes in its function, mostly an increase in bacterial overgrowth and translocation. In this review, probiotics and their indications in hepatology are generally discussed. According to recent knowledge, these preparations are indicated in clinical practice only for cases of hepatic encephalopathy. Probiotics are able to decrease the permeability of the intestinal wall, and decrease bacterial translocation and endotoxemia in animal models as well as in clinical studies, which is extremely important in the prevention of complications of liver cirrhosis and infection after liver transplantation. Probiotics could limit oxidative and inflammatory liver damage and, in some situations, improve the histological state, and thus non-alcoholic steatohepatitis could be considered as another possible indication. 展开更多
关键词 Intestinal microflora PROBIOTICS Liver en-cephalopathy Non-alcoholic steatohepatitis Liver cirrhosis
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Alcoholic liver disease and hepatitis C:A frequently underestimated combination 被引量:18
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作者 Sebastian Mueller Gunda Millonig Helmut K Seitz 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第28期3462-3471,共10页
Alcoholic liver disease(ALD) and hepatitis C virus(HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world.This review discusses the epide... Alcoholic liver disease(ALD) and hepatitis C virus(HCV) infection represent, either alone or in combination, more than two thirds of all patients with liver disease in the Western world.This review discusses the epidemiology and combined impact of ALD and HCV on the progres sion of liver disease.ALD and HCV affect the progres sion of liver disease to liver cirrhosis and hepatocellular carcinoma(HCC) in a synergistic manner.Thus, the risk for HCC increases f ive times with a daily alcohol con sumption of 80 g;in the presence of HCV it is increased 20fold, and a combination of both risk factors leads to a more than 100fold risk for HCC development.Alcohol consumption also decreases the response to interferon treatment which is probably due to a lack of compliance than a direct effect on HCV replication.Several molecu lar mechanisms are discussed that could explain the synergistic interaction of alcohol and HCV on disease progression.They include modulation of the immune response and apoptosis, increased oxidative stress via induction of CYP2E1 and the hepatic accumulation of iron.Thus, both HCV and alcohol independently cause hepatic iron accumulation in > 50% of patients probably due to suppression of the liversecreted systemic iron hormone hepcidin.A better understanding of hepcidin regulation could help in developing novel therapeutic approaches to treat the chronic disease in the future.For now, it can be generally concluded that HCVinfect ed patients should abstain from alcohol and alcoholicsshould be encouraged to participate in detoxification programs. 展开更多
关键词 alcoholic liver disease Chronic hepatitis C STEATOSIS steatohepatitis FIBROSIS CIRRHOSIS Reactiveoxygen species Hepatocellular carcinoma Iron accu-mulation
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Hepatic stellate cells and innate immunity in alcoholic liver disease 被引量:18
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作者 Yang-Gun Suh Won-Il Jeong 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第20期2543-2551,共9页
Constant alcohol consumption is a major cause of chronic liver disease, and there has been a growing concern regarding the increased mortality rates worldwide. Alcoholic liver diseases (ALDs) range from mild to more s... Constant alcohol consumption is a major cause of chronic liver disease, and there has been a growing concern regarding the increased mortality rates worldwide. Alcoholic liver diseases (ALDs) range from mild to more severe conditions, such as steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is enriched with innate immune cells (e.g. natural killer cells and Kupffer cells) and hepatic stellate cells (HSCs), and interestingly, emerging evidence suggests that innate immunity contributes to the development of ALDs (e.g. steatohepatitis and liver fibrosis). Indeed, HSCs play a crucial role in alcoholic steatosis via production of endocannabinoid and retinol metabolites. This review describes the roles of the innate immunity and HSCs in the pathogenesis of ALDs, and suggests therapeutic targets and strategies to assist in the reduction of ALD. 展开更多
关键词 alcoholic liver disease Hepatic stellate cell Natural killer cell Kupffer cell ENDOCANNABINOID Ste-atosis steatohepatitis FIBROSIS
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Experimental models of non-alcoholic fatty liver disease in rats 被引量:17
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作者 Otto Kucera Zuzana Cervinkova 《World Journal of Gastroenterology》 SCIE CAS 2014年第26期8364-8376,共13页
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and i... Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease. 展开更多
关键词 Animal model High-fat diet Methionine- and choline-deficient diet Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Otsuka-Long-Evans-Tokushima fatty rats Zucker rats
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Non-alcoholic fatty liver disease and thyroid dysfunction:A systematic review 被引量:16
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作者 Ahad Eshraghian Alireza Hamidian Jahromi 《World Journal of Gastroenterology》 SCIE CAS 2014年第25期8102-8109,共8页
Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic ... Thyroid hormones are totally involved in the regulation of body weight, lipid metabolism, and insulin resistance. Therefore it is anticipated that thyroid hormones may have a role in the pathogenesis of non alcoholic fatty liver disease(NAFLD) and non alcoholic steatohepatitis(NASH). In this study, we reviewed the current literature on the association between thyroid dysfunction and NAFLD/NASH. A search for English language medical literature reporting an association between thyroid dysfunction and NAFLD/NASH in humans was conducted across PubMed, ISI Web of Science, and Scopus in August, 2013. Out of 140 studies initially identified through the search, 11 relevant articles were included in the final review. Thyroid dysfunctions in the form of overt or subclinical hypothyroidism are prevalent among patients with NAFLD/NASH. Hypothyroidism appears to be an independent risk factor for NAFLD/NASH in some studies; however, other newly published studies failed to find such anassociation. The results of the studies on the role of thyroid abnormalities in NAFLD/NASH are inconsistent, and further research is recommended to determine the relationship between hypothyroidism and NAFLD/NASH and the underlying mechanisms. 展开更多
关键词 Non alcoholic fatty liver disease Thyroid dysfunction HYPOTHYROIDISM Non alcoholic steatohepatitis Risk factor PATHOPHYSIOLOGY
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Visceral fat and insulin resistance as predictors of non-alcoholic steatohepatitis 被引量:17
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作者 Abhasnee Sobhonslidsuk Sutipong Jongjirasiri +3 位作者 Ammarin Thakkinstian Naruemon Wisedopas Pongamorn Bunnag Gobchai Puavilai 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第26期3614-3618,共5页
AIM: To examine whether visceral fat is associated with non-alcoholic steatohepatitis (NASH), to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic seve... AIM: To examine whether visceral fat is associated with non-alcoholic steatohepatitis (NASH), to assess for parameters associated with visceral adiposity and to investigate for factors associated with fibrotic severity in NASH. METHODS: Thirty NASH and 30 control subjects underwent biochemical tests, anthropometric assessment, bioelectrical impedance, dual energy X-ray absorptiometry and abdominal fat study by CT scan. Liver biopsies were graded according to the Brunt criteria. RESULTS: NASH subjects had elevated blood pressure, body mass index, waist circumference and waist-to-hip ratio. A greater number of diabetes rnellitus, impaired glucose tolerance test and HOMA-IR 〉 3.5 were found in NASH patients. HOMA-IR 〉 2.8 (OR 20.98, 95% CI 3.22-136.62; P 〈 0.001) and visceral fat area 〉 158 cm^2 (OR 18.55, 95% CI 1.60-214.67; P = 0.019) were independent predictors for NASH. Advanced stage of NASH was found in 15 (50%) patients. HOMA-IR 〉 3.5 (OR 23.12, 95% CI 2.00-266.23; P = 0.012) and grading of portal inflammation (OR 7.15, 95% CI 1.63-31.20; P = 0.009) were determined as independent risk factors for advanced stage of NASH. CONCLUSION: Obesity (especially central obesity) and metabolic syndrome are common in Thai NASH. Insulin resistance and elevated visceral fat are risk factors for the presence of NASH. The advanced stage of thedisease is related to insulin resistance. 展开更多
关键词 Non-alcoholic steatohepatitis Visceral fat Insulin resistance Metabolic syndrome OBESITY
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Non-alcoholic Fatty Liver Disease in South Asians:A Review of the Literature 被引量:16
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作者 Sital Singh Gabriela N.Kuftinec Souvik Sarkar 《Journal of Clinical and Translational Hepatology》 SCIE 2017年第1期76-81,共6页
Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and f... Non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)are national and global epidemics.The disease is characterized by a spectrum of liver steatosis(fat deposition),inflammation(in NASH)and fibrosis.NAFLD and specifically NASH can lead to cirrhosis,which carry risks of progression to portal hypertension and hepatocellular carcinoma(HCC).NASH is also associated with higher mortality from cardiovascular causes.Most of the data for NAFLD has been obtained from the perspective of developed nations,although the disease is increasing and threatening to reach epidemic proportions across the world.Emerging data is notable for high prevalence of NAFLD in South Asian populations,presumably resulting from a combination of underlying genetic polymorphisms and changes in socio-economic status.It is also notable that an‘Asian Paradox'has been defined for NAFLD based upon the observation of lower than predefined body mass index(BMI),otherwise termed as"lean NAFLD",among this population.Yet,data remains limited in regards to the characteristics of NAFLD/NASH in this population.In this article,we present a review of the literature and discuss the prevalence,associated risk factors and burden of HCC in South Asians with NAFLD. 展开更多
关键词 Non-alcoholic fatty liver disease(NAFLD) Non-alcoholic steatohepatitis(NASH) South Asia
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Genetic factors that affect nonalcoholic fatty liver disease: A systematic clinical review 被引量:13
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作者 Tyler J Severson Siddesh Besur Herbert L Bonkovsky 《World Journal of Gastroenterology》 SCIE CAS 2016年第29期6742-6756,共15页
AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and spec... AIM: To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.METHODS: The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.RESULTS: We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFN&#x003bb;4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.CONCLUSION: Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management. 展开更多
关键词 Genetic polymorphisms Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis PNPLA3 TM6SF2 FTO CIRRHOSIS Iron metabolism
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