Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohep...Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms th...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration,inflammation,oxidative stress and progressive fibrosis have been proposed.Obstructive sleep apnea(OSA)may be linked with the pathogenesis and the severity of NAFLD.AIM To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure(CPAP)treatment.METHODS A Pub Med search was conducted using the terms"non-alcoholic fatty liver disease AND(obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)".Research was limited to title/abstract of articles published in English in the last 5 years;animal and child studies,case reports,commentaries,letters,editorials and meeting abstracts were not considered.Data were extracted on a standardized data collection table which included:First author,publication year,country,study design,number of patients involved,diagnosis and severity of OSA,diagnosis of NAFLD,patient characteristics,results of the study.RESULTSIn total,132 articles were initially retrieved on Pub Med search and 77 in the last five years.After removal of irrelevant studies,13 articles were included in the qualitative analysis.There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years.The proportion of males ranged from21%to 87.9%and the mean body mass index ranged from 24.0 to 49.9 kg/m2.The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA,even in the absence of coexisting comorbidities such as obesity or metabolic syndrome.Furthermore,the severity of NAFLD is associated with the increase in OSA severity.Effective CPAP treatment,although not always decisive,may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.CONCLUSION In NAFLD patients,although asymptomatic,it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which ma...Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which may progress to cirrhosis,liver cancer,and liver mortality.Common metabolic diseases,which are well established cardiovascular risk factors,have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration.Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide.First-line management focuses on lifestyle modifications.Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended.Several therapeutic interventions have been proposed.These include insulin sensitizer agents,lipid lowering drugs,antioxidants such as vitamin E and supplementation of vitamin D3.However,therapeutic strategies have been largely empirical so far,and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes.Metabolic conditions such as diabetes mellitus,obesity,hypertension and hyperlipidemia,should be strongly considered and a multidisciplinary approach should be personalized for individual patients.Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients.The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.展开更多
Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic disea...Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.展开更多
Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, ap...Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk.展开更多
文摘Non-alcoholic fatty liver disease(NAFLD) represents the most common and emerging chronic liver disease worldwide. It includes a wide spectrum of liver diseasesranging from simple fatty liver to non-alcoholic steatohepatitis(NASH),which may progress to fibrosis and more severe liver complications such as cirrhosis,hepatocellular carcinoma and liver mortality. NAFLD is strongly associated with obesity,insulin resistance,hypertension,and dyslipidaemia,and is now regarded as the liver manifestation of the metabolic syndrome. The increased mortality of patients with NAFLD is primarily a result of cardiovascular disease and,to a lesser extent,to liver related diseases. Increased oxidative stress has been reported in both patients with NAFLD and patient with cardiovascular risk factors. Thus,oxidative stress represents a shared pathophysiological disorder between the two conditions. Several therapeutic strategies targeting oxidative stress reduction in patients with NAFLD have been proposed,with conflicting results. In particular,vitamin E supplementation has been suggested for the treatment of non-diabetic,non-cirrhotic adults with active NASH,although this recommendation is based only on the results of a single randomized controlled trial. Other antioxidant treatments suggested are resveratrol,silybin,L-carnitine and pentoxiphylline. No trial so far,has evaluated the cardiovascular effects of antioxidant treatment in patients with NAFLD. New,large-scale studies including as end-point also the assessment of the atherosclerosis markers are needed.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is an emerging liver disease and currently the most common cause of incidental abnormal liver tests.The pathogenesis of NAFLD is multifactorial and many mechanisms that cause fatty liver infiltration,inflammation,oxidative stress and progressive fibrosis have been proposed.Obstructive sleep apnea(OSA)may be linked with the pathogenesis and the severity of NAFLD.AIM To study the association between NAFLD and OSA considering also the efficacy of continuous positive airway pressure(CPAP)treatment.METHODS A Pub Med search was conducted using the terms"non-alcoholic fatty liver disease AND(obstructive sleep apnea OR obstructive sleep disorders OR sleep apnea)".Research was limited to title/abstract of articles published in English in the last 5 years;animal and child studies,case reports,commentaries,letters,editorials and meeting abstracts were not considered.Data were extracted on a standardized data collection table which included:First author,publication year,country,study design,number of patients involved,diagnosis and severity of OSA,diagnosis of NAFLD,patient characteristics,results of the study.RESULTSIn total,132 articles were initially retrieved on Pub Med search and 77 in the last five years.After removal of irrelevant studies,13 articles were included in the qualitative analysis.There was a total of 2753 participants across all the studies with a mean age between 42 and 58 years.The proportion of males ranged from21%to 87.9%and the mean body mass index ranged from 24.0 to 49.9 kg/m2.The results of this review showed an increased prevalence of NAFLD in patients with diagnosis of OSA,even in the absence of coexisting comorbidities such as obesity or metabolic syndrome.Furthermore,the severity of NAFLD is associated with the increase in OSA severity.Effective CPAP treatment,although not always decisive,may stabilize or slow NAFLD progression with benefits on metabolic and cardiovascular functions.CONCLUSION In NAFLD patients,although asymptomatic,it is recommended to systematically perform polysomnography in order to early and better treat them before the development of potentially life threatening systemic dysfunctions.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common and emerging form of chronic liver disease worldwide.It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis,which may progress to cirrhosis,liver cancer,and liver mortality.Common metabolic diseases,which are well established cardiovascular risk factors,have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration.Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide.First-line management focuses on lifestyle modifications.Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended.Several therapeutic interventions have been proposed.These include insulin sensitizer agents,lipid lowering drugs,antioxidants such as vitamin E and supplementation of vitamin D3.However,therapeutic strategies have been largely empirical so far,and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes.Metabolic conditions such as diabetes mellitus,obesity,hypertension and hyperlipidemia,should be strongly considered and a multidisciplinary approach should be personalized for individual patients.Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients.The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.
文摘Lysosomal acid lipase(LAL)plays a key role in intracellular lipid metabolism.Reduced LAL activity promotes increased multi-organ lysosomal cholesterol ester storage,as observed in two recessive autosomal genetic diseases,Wolman disease and Cholesterol ester storage disease.Severe liver steatosis and accelerated liver fibrosis are common features in patients with genetic LAL deficiency.By contrast,few reliable data are available on the modulation of LAL activity in vivo and on the epigenetic and metabolic factors capable of regulating its activity in subjects without homozygous mutations of the Lipase A gene.In the last few years,a less severe and non-genetic reduction of LAL activity was reported in children and adults with non-alcoholic fatty liver disease(NAFLD),suggesting a possible role of LAL reduction in the pathogenesis and progression of the disease.Patients with NAFLD show a significant,progressive reduction of LAL activity from simple steatosis to non-alcoholic steatohepatitis and cryptogenic cirrhosis.Among cirrhosis of different etiologies,those with cryptogenic cirrhosis show the most significant reductions of LAL activity.These findings suggest that the modulation of LAL activity may become a possible new therapeutic target for patients with more advanced forms of NAFLD.Moreover,the measurement of LAL activity may represent a possible new marker of disease severity in this clinical setting.
文摘Congenital analbuminemia is a rare autosomic recessive inherited disorder characterized by low plasma albumin and hypercholesterolemia, which may increase cardiovascular risk. Patients are essentially asymptomatic, apart from ease of fatigue, minimal ankle oedema and hypotension. There is no accepted strategy for safely treating both hypercholesterolemia and analbuminemia in order to eventually decrease the atherosclerotic risk. We report a case of congenital analbuminemia(1.0 g/dL) in a 38-year-old male with hypercholesterolemia(range: 406-475 mg/dL) and severe arterial dysfunction [no brachial artery flow-mediated dilation(FMD)]. Long-term, cholesterol-lowering treatment with atorvastatin was associated with the appearance of peripheral edema. Twomonths of infusion with albumin improved FMD(7%) and reduced serum cholesterol(273 mg/dL), supporting the hypothesis of a compensatory role of hypercholesterolemia. Statin treatment, together with periodical albumin infusions, may contribute to the safe reduction of cardiovascular risk.
