Over the past few decades, non-alcoholic fatty liver disease(NAFLD) has become one, if not the most common,cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early ...Over the past few decades, non-alcoholic fatty liver disease(NAFLD) has become one, if not the most common,cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis(NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.展开更多
In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failu...In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.展开更多
With the support by the National Natural Science Foundation of China,Dr.Li Bin and colleagues at the Institut Pasteur of Shanghai,in collaboration with Dr.Zheng Songguo and colleagues,have published their study entitl...With the support by the National Natural Science Foundation of China,Dr.Li Bin and colleagues at the Institut Pasteur of Shanghai,in collaboration with Dr.Zheng Songguo and colleagues,have published their study entitled'Inflammation negatively regulates FOXP3and regulatory T-cell function via DBC1'in PNAS(2015,112(25):E3246—3254).Regulatory T cells(Treg)are actively engaged in the prevention of autoimmunity and mitigation of aber-展开更多
基金Supported by European Union Seventh Framework Program(FP7/2007-2013)under grant agreement,No.Health-F2-2009-241762,for the project FLIPItalian National Grant MIUR(Art.13 D.LGS 297/99-Progetto Nutrizione e Salute)an in house grant from Fondazione Italiana Fegato,ONLUS
文摘Over the past few decades, non-alcoholic fatty liver disease(NAFLD) has become one, if not the most common,cause of chronic liver disease affecting both adults and children. The increasing number of cases at an early age is the most worrying aspect of this pathology, since it provides more time for its evolution. The spectrum of this disease ranges from liver steatosis to steatohepatitis, fibrosis and in some cases, hepatocellular carcinoma. NAFLD may not always be considered a benign disease and hepatologists must be cautious in the presence of fatty liver. This should prompt the use of the available experimental models to understand better the pathogenesis and to develop a rational treatment of a disease that is dangerously increasing. In spite of the growing efforts, the pathogenesis of NAFLD is still poorly understood. In the present article we review the most relevant hypotheses and evidence that account for the progression of NAFLD to non-alcoholic steatohepatitis(NASH) and fibrosis. The available in vitro and in vivo experimental models of NASH are discussed and revised in terms of their validity in translational studies. These studies must be aimed at the discovery of the still unknown triggers or mediators that induce the progression of hepatic inflammation, apoptosis and fibrosis.
基金Supported by Novo Nordisk Foundation and the University of Copenhagen
文摘In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal syndrome.Patients with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver transplantation.As a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.
文摘With the support by the National Natural Science Foundation of China,Dr.Li Bin and colleagues at the Institut Pasteur of Shanghai,in collaboration with Dr.Zheng Songguo and colleagues,have published their study entitled'Inflammation negatively regulates FOXP3and regulatory T-cell function via DBC1'in PNAS(2015,112(25):E3246—3254).Regulatory T cells(Treg)are actively engaged in the prevention of autoimmunity and mitigation of aber-
