The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and p...The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.展开更多
BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in ...BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia.METHODS:We undertook a one-year,prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides.The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption,the presence of co-morbidities and any medications being taken.The patients’ progression,etiological diagnosis,hospital stay and clinical and radiological severity were all recorded.RESULTS:Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%);the remaining cases were of biliary (53%),idiopathic (26%),alcoholic (11%) or other (5%) origin.Compared with these remaining cases,the patients with hypertriglyceridemia were significantly younger,had more relapses,and more often had diabetes mellitus.They usually consumed alcohol or consumed it excessively on the days before admission.Also,the ε4 allele of the APOE gene was more common in this group (P<0.05).CONCLUSION:One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and,especially,alcohol consumption.展开更多
文摘The main treatment of patients with non-alcoholic fatty liver disease(NAFLD) is life style modification including weight reduction and dietary regimen.Majority of patients are safely treated with this management and pharmacologic interventions are not recommended. However, a subgroup of NAFLD patients with non-alcoholic steatohepatitis(NASH) who cannot achieve goals of life style modification may need pharmacological therapy. One major obstacle is measurement of histological outcome by liver biopsy which is an invasive method and is not recommended routinely in these patients. Several medications, mainly targeting baseline mechanism of NAFLD, have been investigated in clinical trials for treatment of NASH with promising results. At present, only pioglitazone acting as insulin sensitizing agent and vitamin E as an antioxidant have been recommended for treatment of NASH by international guidelines. Lipid lowering agents including statins and fibrates, pentoxifylline, angiotensin receptor blockers, ursodeoxycholic acid, probiotics and synbiotics are current agents with beneficial effects for treatment of NASH but have not been approved yet. Several emerging medications are in development for treatment of NASH. Obeticholic acid, liraglutide, elafibranor, cenicriviroc and aramchol have been tested in clinical trials or are completing trials. Here in, current and upcoming medications with promising results in clinical trial for treatment of NAFLD were reviewed.
文摘目的:通过测定酒精性脂肪肝(alcoholic fatty liver,AFL)大鼠模型肝组织内甘油三酯(triglyceride,TG)、8-羟基脱氧鸟苷酸(8-hydroxy-guanin,8-OHdG)与硫代巴比妥酸反应产物(thiobarbituric acid reaction substances,TBARS)的含量及抗氧化剂维生素E(vitamin E,VE)的干预研究,探讨氧化应激(oxidative stress,OS)及脂质过氧化反应(lipid peroxidation,LPO)在AFL发病中的作用.方法:将45只Wistar大鼠随机分为空白组(Control,n=15)、模型组[(ethanol,ET),n=15]及实验组(ET+VE,n=15),空白组给予蒸馏水灌胃;AFL模型组给予鱼油2.5 mL/kg+ET灌胃;实验组采用鱼油+ET灌胃,同时加用VE 400 mg/kg灌胃.第8周取肝组织,采用比色法测定肝脏TG沉积;酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)测定肝脏8-OHdG和肝脏TBARS含量.结果:与对照组相比,AFL模型组大鼠肝脏TG沉积增加(0.72±0.09 vs 0.28±0.07,P<0.01),肝8-OHdG(1.45±0.17 vs 0.52±0.21,P<0.01)及TBARS(65.2±9.7 vs 51.2±12.9,P<0.01)含量明显升高;与模型组相比,经VE干预后,实验组大鼠肝内TG(0.53±0.11 vs 0.72±0.09,P<0.01)沉积减少,8-OHdG(0.99±0.27 vs 1.45±0.17,P<0.01)及TBARS(55.6±12.6 vs 65.2±9.7,P<0.01)含量降低.结论:AFL大鼠肝组织内TG沉积明显,肝内8-OHdG和TBARS含量明显升高,经抗氧化剂VE干预后,TG沉积减少,肝内8-OHdG和TBARS含量降低.OS损伤及LPO损伤在AFL的发病过程中具有重要作用,抗氧化剂VE可通过减轻OS及LPO损伤协同防治AFL.
基金supported by a grant from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucía(Grupo consolidado CTS-159)
文摘BACKGROUND:Hypertriglyceridemia is an unusual cause of acute pancreatitis and sometimes considered to be an epiphenomenon.This study aimed to investigate the clinical and analytical features and the APOE genotypes in patients with acute pancreatitis and severe hypertriglyceridemia.METHODS:We undertook a one-year,prospective study of patients with acute pancreatitis whose first laboratory analysis on admission to the emergency department included measurement of serum triglycerides.The APOE genotype was determined and the patients answered an established questionnaire within the first 24 hours concerning their alcohol consumption,the presence of co-morbidities and any medications being taken.The patients’ progression,etiological diagnosis,hospital stay and clinical and radiological severity were all recorded.RESULTS:Hypertriglyceridemia was responsible for 7 of 133 cases of pancreatitis (5%);the remaining cases were of biliary (53%),idiopathic (26%),alcoholic (11%) or other (5%) origin.Compared with these remaining cases,the patients with hypertriglyceridemia were significantly younger,had more relapses,and more often had diabetes mellitus.They usually consumed alcohol or consumed it excessively on the days before admission.Also,the ε4 allele of the APOE gene was more common in this group (P<0.05).CONCLUSION:One of 20 episodes of acute pancreatitis is caused by hypertriglyceridemia and it is linked to genetic (ε4 allele) and comorbid factors such as diabetes and,especially,alcohol consumption.
