Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who ...Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.展开更多
BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Unders...BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.展开更多
目的:观察滋膵降糖方联合西药治疗初发2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者的疗效及对血清胎球蛋白A(Fetuin-A)水平的影响。方法:选取初发T2DM合并NAFLD患者76例,入组后随机分组为单纯西药组(二甲双胍缓释片)、西药联合...目的:观察滋膵降糖方联合西药治疗初发2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者的疗效及对血清胎球蛋白A(Fetuin-A)水平的影响。方法:选取初发T2DM合并NAFLD患者76例,入组后随机分组为单纯西药组(二甲双胍缓释片)、西药联合中药组(二甲双胍缓释片+滋膵降糖方),治疗12周,治疗前后采用ELISA检测两组血清Fetuin-A水平,并比较两组治疗前后腰围(WC)、BMI、糖化血红蛋白(Hb A1c)、血糖(FPG/2 h PBG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及胰岛素抵抗指数(HOMAIR)、胰岛β细胞功能指数(HOMA-β)的变化。结果:(1)治疗后两组患者WC、BMI、Hb A1c、FPG、FINS、2 h PBG、TG、LDL-C、HOMA-IR均较治疗前明显下降(P<0.05);HOMA-β较治疗前明显上升(P<0.05);单纯西药组血清Fetuin-A水平较治疗前未见明显下降(P>0.05),联合组血清Fetuin-A水平较治疗前明显下降(P<0.01)。(2)治疗后两组比较,西药联合滋膵降糖方组对患者WC、Hb A1c、FPG、FINS、2 h PBG、TG改善作用明显优于单纯西药组(P<0.05);HOMA-IR明显低于单纯西药组(P<0.05);HOMA-β明显高于单纯西药组(P<0.05);血清Fetuin-A水平明显低于单纯西药组(P<0.05)。结论:滋膵降糖方协同西药可明显降低T2DM合并NAFLD患者血清Fetuin-A水平及血糖、血脂水平,改善患者胰岛素抵抗,调节糖脂代谢。展开更多
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worl...Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.展开更多
Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and...Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.展开更多
基金financially supported by Baqiyatallah University of Medical Sciences
文摘Objective:To explore demographic and metabolic factors associated with increased alanine aminotransferase(ALT)activity in non-diabetic non-alcoholic fatty liver disease(NAFLD)patients.Methods:Overall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences,Tehran,Iran awere diagnosed as NAFLD entered into analysis.Exclusion criteria were having diabetes mellitus and fasting blood glucose over126 mg/dL,active hepatitis B virus infection,having hepatitis C virus positive serology,and to be under corticosteroid therapy.ALT levels were considered pathologically high when it was over30 IU/L for men and over 19 IU/L for women.Results:Bivariate analyses using t test and chisquare test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations(P=0.003).Moreover,these patients represented significantly higher homeostatic model assessment levels(P=0.003),levels of serum insulin(P=0.002),fasting blood glucose(P<0.001),and uric acid(P=0.02).The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations.Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD(P=0.027)and insulin resistance(P=0.013)were the only variables significantly associated with abnormal ALT levels.Conclusions:This study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before.By excluding diabetic patients from our population,we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations.Further studies are needed to confirm our results.
基金Supported by the Swiss National Science Foundation,No.P2SKP3_158649,No.P3400PB_171581,and No.P3P3PB_171582(to Bluemel S)NIH grants(in part),No.R01 AA24726,No.U01 AA026939,and services provided by P30 DK120515(to Schnabl B).
文摘BACKGROUND End-stage liver disease caused by non-alcoholic steatohepatitis(NASH)is the second leading indication for liver transplantation.To date,only moderately effective pharmacotherapies exist to treat NASH.Understanding the pathogenesis of NASH is therefore crucial for the development of new therapies.The inflammatory cytokine tumor necrosis factor alpha(TNF-α)is important for the progression of liver disease.TNF signaling via TNF receptor 1(TNFR1)has been hypothesized to be important for the development of NASH and hepatocellular carcinoma in whole-body knockout animal models.AIM To investigate the role of TNFR1 signaling in hepatocytes for steatohepatitis development in a mouse model of diet-induced NASH.METHODS NASH was induced by a western-style fast-food diet in mice deficient for TNFR1 in hepatocytes(TNFR1ΔHEP)and their wild-type littermates(TNFR1fl/fl).Glucose tolerance was assessed after 18 wk and insulin resistance after 19 wk of feeding.After 20 wk mice were assessed for features of NASH and the metabolic syndrome such as liver weight,liver steatosis,liver fibrosis and markers of liver inflammation.RESULTS Obesity,liver injury,inflammation,steatosis and fibrosis was not different between TNFR1ΔHEP and TNFR1fl/fl mice.However,Tnfr1 deficiency in hepatocytes protected against glucose intolerance and insulin resistance.CONCLUSION Our results indicate that deficiency of TNFR1 signaling in hepatocytes does not protect from diet-induced NASH.However,improved insulin resistance in this model strengthens the role of the liver in glucose homeostasis.
文摘目的:观察滋膵降糖方联合西药治疗初发2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD)患者的疗效及对血清胎球蛋白A(Fetuin-A)水平的影响。方法:选取初发T2DM合并NAFLD患者76例,入组后随机分组为单纯西药组(二甲双胍缓释片)、西药联合中药组(二甲双胍缓释片+滋膵降糖方),治疗12周,治疗前后采用ELISA检测两组血清Fetuin-A水平,并比较两组治疗前后腰围(WC)、BMI、糖化血红蛋白(Hb A1c)、血糖(FPG/2 h PBG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)及胰岛素抵抗指数(HOMAIR)、胰岛β细胞功能指数(HOMA-β)的变化。结果:(1)治疗后两组患者WC、BMI、Hb A1c、FPG、FINS、2 h PBG、TG、LDL-C、HOMA-IR均较治疗前明显下降(P<0.05);HOMA-β较治疗前明显上升(P<0.05);单纯西药组血清Fetuin-A水平较治疗前未见明显下降(P>0.05),联合组血清Fetuin-A水平较治疗前明显下降(P<0.01)。(2)治疗后两组比较,西药联合滋膵降糖方组对患者WC、Hb A1c、FPG、FINS、2 h PBG、TG改善作用明显优于单纯西药组(P<0.05);HOMA-IR明显低于单纯西药组(P<0.05);HOMA-β明显高于单纯西药组(P<0.05);血清Fetuin-A水平明显低于单纯西药组(P<0.05)。结论:滋膵降糖方协同西药可明显降低T2DM合并NAFLD患者血清Fetuin-A水平及血糖、血脂水平,改善患者胰岛素抵抗,调节糖脂代谢。
文摘Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer with a high mortality rate. While chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections represent the leading risk factors worldwide, the spreading of metabolic disorders, such as diabetes, obesity and non-alcoholic fatty liver disease (NAFLD) justifies the increasing attention on their oncogenic mechanisms. This review discusses about the main pathogenic mechanisms implicated in occurrence of HCC in presence of viral and metabolic diseases. Additionally, it points to the importance of clinical surveillance for those patients considered at risk of HCC and highlights the strategical role of serum markers, such as alfa-fetoprotein (αFP) and Protein Induced by Vitamin K Absence or Antagonist II (PIVKA-II), which, in association to a strictly instrumental follow-up, contribute to the early detection of hepatic nodules with a better prognosis for affected patients.
文摘Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.
