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 ultrasonogr...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 type IV collagen 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.展开更多
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 ...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.展开更多
目的:探讨葛根芩连汤对非酒精性脂肪性肝炎的干预作用.方法:高脂饲料喂养SD大鼠以制备非酒精性脂肪性肝炎模型,各给药组在造模的同时进行灌胃给药,持续8 wk后取材,血清用比色法对谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨...目的:探讨葛根芩连汤对非酒精性脂肪性肝炎的干预作用.方法:高脂饲料喂养SD大鼠以制备非酒精性脂肪性肝炎模型,各给药组在造模的同时进行灌胃给药,持续8 wk后取材,血清用比色法对谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine transaminase,ALT)、总胆固醇(cholesterol total,CHO)、低密度脂蛋白((low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)、空腹血糖(fasting plasma glucose,FPG)的含量进行检测,用放免法对空腹胰岛素(fasting insulin,F I N S)的含量进行检测,并进行胰岛素抵抗指数(homeostatic model assessment of insulin resistance,HOMA-IR)计算;肝组织制成石蜡切片及冰冻切片进行HE及油红O染色,并根据"非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)活动度积分"对各组肝组织进行NASH评估.结果:与空白组比较,NASH大鼠血清中A S T、A LT、C H O、L D L的含量显著升高(P<0.05或P<0.01),H D L的含量显著降低(P<0.01),HOMA-IR指数显著升高(P<0.05),葛根芩连汤可显著抑制高脂饲料喂养SD大鼠过程中血清AST、ALT、CHO、LDL含量(P<0.01)及HOMA-IR指数的升高(P<0.05)以及HDL含量的降低(P<0.01);HE染色、油红O染色及NAFLD活动度积分结果显示,葛根芩连汤可显著抑制NASH及相关病理变化的发生发展.结论:葛根芩连汤对非酒精性脂肪性肝炎有一定的干预作用,并可改善胰岛素抵抗.展开更多
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...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.展开更多
AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were ...AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group]. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.展开更多
Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and child...Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.展开更多
Nonalcoholic fatty liver disease(NAFLD)is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world.Development of graft steatosis is a significant problem during the posttr...Nonalcoholic fatty liver disease(NAFLD)is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world.Development of graft steatosis is a significant problem during the posttransplant course,which may happen as a recurrence of pre-existing disease or de novo NAFLD.There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome,immune-suppressive medications,genetics and others.There are few studies that assessed the effects of NAFLD on graft and patient survival;most of them were limited by the duration of follow up or by the number of patients.With this review article we will try to shed light on post-liver transplantation NAFLD,significance of the disease,how it develops,risk factors,clinical course and treatment options.展开更多
基金Supported by Scholarship Funds from MSD Co.Ltd.(to Sumida Y)+3 种基金Scholarship Funds from MSD Co.Ltd.Dainippon Sumitomo Pharma Co.Ltd.(to Ioh Y)
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 type IV collagen 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.
基金Supported by The Basic Science Research Program through the National Research Foundation of South Koreafunded by the Ministry of Education,Science and Technology,No.2012R1A1A1005326
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.
文摘目的:探讨葛根芩连汤对非酒精性脂肪性肝炎的干预作用.方法:高脂饲料喂养SD大鼠以制备非酒精性脂肪性肝炎模型,各给药组在造模的同时进行灌胃给药,持续8 wk后取材,血清用比色法对谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine transaminase,ALT)、总胆固醇(cholesterol total,CHO)、低密度脂蛋白((low density lipoprotein,LDL)、高密度脂蛋白(high density lipoprotein,HDL)、空腹血糖(fasting plasma glucose,FPG)的含量进行检测,用放免法对空腹胰岛素(fasting insulin,F I N S)的含量进行检测,并进行胰岛素抵抗指数(homeostatic model assessment of insulin resistance,HOMA-IR)计算;肝组织制成石蜡切片及冰冻切片进行HE及油红O染色,并根据"非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)活动度积分"对各组肝组织进行NASH评估.结果:与空白组比较,NASH大鼠血清中A S T、A LT、C H O、L D L的含量显著升高(P<0.05或P<0.01),H D L的含量显著降低(P<0.01),HOMA-IR指数显著升高(P<0.05),葛根芩连汤可显著抑制高脂饲料喂养SD大鼠过程中血清AST、ALT、CHO、LDL含量(P<0.01)及HOMA-IR指数的升高(P<0.05)以及HDL含量的降低(P<0.01);HE染色、油红O染色及NAFLD活动度积分结果显示,葛根芩连汤可显著抑制NASH及相关病理变化的发生发展.结论:葛根芩连汤对非酒精性脂肪性肝炎有一定的干预作用,并可改善胰岛素抵抗.
基金Supported by JSPS[Grant-in-Aid for Scientific Research(C)](to Miura K)
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.
文摘AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group]. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
文摘Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease.
文摘Nonalcoholic fatty liver disease(NAFLD)is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world.Development of graft steatosis is a significant problem during the posttransplant course,which may happen as a recurrence of pre-existing disease or de novo NAFLD.There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome,immune-suppressive medications,genetics and others.There are few studies that assessed the effects of NAFLD on graft and patient survival;most of them were limited by the duration of follow up or by the number of patients.With this review article we will try to shed light on post-liver transplantation NAFLD,significance of the disease,how it develops,risk factors,clinical course and treatment options.
