Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver ...Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.展开更多
Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and c...Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.展开更多
AIM: To examine the association of daily alcohol intake,types of alcoholic beverage consumed, drinking patterns and obesity with alcoholic liver disease in China.METHODS: By random cluster sampling and a 3-year follow...AIM: To examine the association of daily alcohol intake,types of alcoholic beverage consumed, drinking patterns and obesity with alcoholic liver disease in China.METHODS: By random cluster sampling and a 3-year follow-up study, 1 270 alcohol drinkers were recruited from different occupations in the urban and suburban areas of Xi'an City. They were examined by specialists and inquired for information on: Medical history and family medical history, alcohol intake, types of alcoholic beverage consumed, drinking patterns by detailed dietary questionnaires. Routine blood tests and ultrasonography were done.RESULTS: Multivariate analysis showed that: (1) The risk threshold for developing alcoholic liver disease was ingestion of more than 20 g alcohol per day, keeping on drinking for over 5 years in men. The highest OR was at the daily alcohol consumption ≥160 g, the occurrencerate of ALD amounted to 18.7% (P<0.01). No ALD occurred when ingestion of alcohol was less than 20 g per day. (2) 87.9% of all drank only at mealtimes. The cumulative risk of developing ALD was significantly higher in those individuals who regularly drank alcohol without food than in those who drank only at mealtimes, especially for those who regularly drank hard liquors only and multiple drinks (P<0.05). (3) The alcohol consumption in those with BMI ≥25 was lower than in those with BMI<25, but the risk increased to 11.5%, significantly higher than that of general population, 6.5% (P<0.01). (4) Abstinence and weight reduction could benefit the liver function recovery.CONCLUSION: In the Chinese population the ethanol risk threshold for developing ALD is 20 g per day, and this risk increases with increased daily intake. Drinking 20 g of ethanol per day and for less than 5 years are safe from ALD. Drinking alcohol outside mealtimes and drinking hard liquors only and multiple different alcohol beverages both increase the risk of developing ALD. Obesity also increases the risk, Abstinence and weight reduction will directly affect the prognosis of A展开更多
基金supported by the intramural program of the NIAAA(Bin Gao),U01 AA022614,and R01 DK099205(Tatiana Kisseleva)and AA011576 and AA017729(Gyongyi Szabo).
文摘Chronic liver injury with any etiology can progress to fibrosis and the end-stage diseases cirrhosis and hepatocellular carcinoma.The progression of liver disease is controlled by a variety of factors,including liver injury,inflammatory cells,inflammatory mediators,cytokines,and the gut microbiome.In the current review,we discuss recent data on a large number of cytokines that play important roles in regulating liver injury,inflammation,fibrosis,and regeneration,with a focus on interferons and T helper(Th)1,Th2,Th9,Th17,interleukin(IL)-1 family,IL-6 family,and IL-20 family cytokines.Hepatocytes can also produce certain cytokines(such as IL-7,IL-11;and IL-33),and the functions of these cytokines in the liver are briefly summarized.Several cytokines have great therapeutic potential,and some are currently being tested as therapeutic targets in clinical trials for the treatment of liver diseases,which are also described.
基金supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.
文摘Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease worldwide.Inflammatory processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some extent.Here,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and NASH.Multiple cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease inflammation.In addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous system.We point out that inflammation also plays important roles in promoting liver repair and controlling bacterial infections.Understanding the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.
基金Supported by the Scientific Foundation of Ministry of Health of China,No.98-1-236
文摘AIM: To examine the association of daily alcohol intake,types of alcoholic beverage consumed, drinking patterns and obesity with alcoholic liver disease in China.METHODS: By random cluster sampling and a 3-year follow-up study, 1 270 alcohol drinkers were recruited from different occupations in the urban and suburban areas of Xi'an City. They were examined by specialists and inquired for information on: Medical history and family medical history, alcohol intake, types of alcoholic beverage consumed, drinking patterns by detailed dietary questionnaires. Routine blood tests and ultrasonography were done.RESULTS: Multivariate analysis showed that: (1) The risk threshold for developing alcoholic liver disease was ingestion of more than 20 g alcohol per day, keeping on drinking for over 5 years in men. The highest OR was at the daily alcohol consumption ≥160 g, the occurrencerate of ALD amounted to 18.7% (P<0.01). No ALD occurred when ingestion of alcohol was less than 20 g per day. (2) 87.9% of all drank only at mealtimes. The cumulative risk of developing ALD was significantly higher in those individuals who regularly drank alcohol without food than in those who drank only at mealtimes, especially for those who regularly drank hard liquors only and multiple drinks (P<0.05). (3) The alcohol consumption in those with BMI ≥25 was lower than in those with BMI<25, but the risk increased to 11.5%, significantly higher than that of general population, 6.5% (P<0.01). (4) Abstinence and weight reduction could benefit the liver function recovery.CONCLUSION: In the Chinese population the ethanol risk threshold for developing ALD is 20 g per day, and this risk increases with increased daily intake. Drinking 20 g of ethanol per day and for less than 5 years are safe from ALD. Drinking alcohol outside mealtimes and drinking hard liquors only and multiple different alcohol beverages both increase the risk of developing ALD. Obesity also increases the risk, Abstinence and weight reduction will directly affect the prognosis of A
