Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and mo...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry.Here we summarise the current knowledge about autoimmune liver diseases(AILDs)and SARS-CoV-2,focusing on:(1)The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs;(2)the role of SARS-CoV-2 in inducing liver damage and triggering AILDs;and(3)the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver.Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine.Although SARSCoV-2 infection can lead to the development of several autoimmune diseases,few reports correlate it to the appearance of de novo manifestation of immunemediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)or AIH/PBC overlap syndrome.Different case series of an AIHlike syndrome with a good prognosis after SARS-CoV-2 vaccination have been described.Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established,these reports suggest that this association could be more than coincidental.展开更多
The harmful use of alcohol is a worldwide problem.It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability;it is a causal factor of 60 types of diseases and...The harmful use of alcohol is a worldwide problem.It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability;it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others.Liver is the main organ responsible for metabolizing ethanol,thus it has been considered for long time the major victim of the harmful use of alcohol.Ethanol and its bioactive products,acetaldehyde-acetate,fatty acid ethanol esters,ethanol-protein adducts,have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver.A similar mechanism has been postulated for the alcohol-related pancreatic damage.Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the"necrosis-fibrosis"sequence that finally leads to atrophy and fibrosis,morphological hallmarks of alcoholic chronic pancreatitis.Even if less attention has been paid to the upper and lower gastrointestinal tract,ethanol produces harmful effects by inducing:(1)direct damaging of the mucosa of the esophagus and stomach;(2)modification of thesphincterial pressure and impairment of motility;and(3)alteration of gastric acid output.In the intestine,ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system.Notably,disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage.This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver,pancreas and gastrointestinal tract.展开更多
Traditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continual...Traditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continually diversifying cells. This heterogeneity enables the survival of different clones under particular conditions allowing growth at metastatic locations or resistance to chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this traditional understanding of cancer suggesting that only CSCs can self-renew and promote tumor growth. CSCs are relatively refractory to conventional therapies, thus explaining why anti-cancer therapies are far from curative and why relapses of cancer are frequent. The identification of the CSC component of a tumor might, thus, open new therapeutic perspective based on the selective targeting of this small population of cells. In this review we examine the current scientific evidence supporting the existence of CSC in gastric tumors and analyze the main unsolved questions of this difficult field of cancer research.展开更多
Although the prevalence of gastric cancer(GC) progressively decreased during the last decades,due to improved dietary habit,introduction of food refrigeration and recovered socio-economic level,it still accounts for 1...Although the prevalence of gastric cancer(GC) progressively decreased during the last decades,due to improved dietary habit,introduction of food refrigeration and recovered socio-economic level,it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs,that rises many relevant concerns taking into account its worldwide variability,natural history,diagnostic tools,therapeutic strategies,and cost-effectiveness. Intestinal-type,the most frequent GC histotype,develops through a multistep process triggered by Helicobacter pylori(H. pylori) and progressing from gastritis to atrophy,intestinal metaplasia(IM),and dysplasia. However,the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore,it remains unclear who should be screened,when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries,at high prevalence of GC and the high-risk subjects in western countries,at low prevalence of GC.As far as concern surveillance,currently,we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach,the patients at higher risk,the best timing and the cost-effectiveness.Anyway,patients with corpus atrophic gastritis,extensive incomplete IM and dysplasia should enter a surveillance program.At present,screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.展开更多
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry.Here we summarise the current knowledge about autoimmune liver diseases(AILDs)and SARS-CoV-2,focusing on:(1)The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs;(2)the role of SARS-CoV-2 in inducing liver damage and triggering AILDs;and(3)the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver.Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine.Although SARSCoV-2 infection can lead to the development of several autoimmune diseases,few reports correlate it to the appearance of de novo manifestation of immunemediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)or AIH/PBC overlap syndrome.Different case series of an AIHlike syndrome with a good prognosis after SARS-CoV-2 vaccination have been described.Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established,these reports suggest that this association could be more than coincidental.
文摘The harmful use of alcohol is a worldwide problem.It has been estimated that alcohol abuse represents the world’s third largest risk factor for disease and disability;it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others.Liver is the main organ responsible for metabolizing ethanol,thus it has been considered for long time the major victim of the harmful use of alcohol.Ethanol and its bioactive products,acetaldehyde-acetate,fatty acid ethanol esters,ethanol-protein adducts,have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver.A similar mechanism has been postulated for the alcohol-related pancreatic damage.Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the"necrosis-fibrosis"sequence that finally leads to atrophy and fibrosis,morphological hallmarks of alcoholic chronic pancreatitis.Even if less attention has been paid to the upper and lower gastrointestinal tract,ethanol produces harmful effects by inducing:(1)direct damaging of the mucosa of the esophagus and stomach;(2)modification of thesphincterial pressure and impairment of motility;and(3)alteration of gastric acid output.In the intestine,ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system.Notably,disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage.This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver,pancreas and gastrointestinal tract.
基金Supported by grants from the Italian Ministry of University and Research(MURST)to the Department of Clinical and Experimental Medicine,University Fedefico Ⅱ,Naples,Italy
文摘Traditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continually diversifying cells. This heterogeneity enables the survival of different clones under particular conditions allowing growth at metastatic locations or resistance to chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this traditional understanding of cancer suggesting that only CSCs can self-renew and promote tumor growth. CSCs are relatively refractory to conventional therapies, thus explaining why anti-cancer therapies are far from curative and why relapses of cancer are frequent. The identification of the CSC component of a tumor might, thus, open new therapeutic perspective based on the selective targeting of this small population of cells. In this review we examine the current scientific evidence supporting the existence of CSC in gastric tumors and analyze the main unsolved questions of this difficult field of cancer research.
文摘Although the prevalence of gastric cancer(GC) progressively decreased during the last decades,due to improved dietary habit,introduction of food refrigeration and recovered socio-economic level,it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs,that rises many relevant concerns taking into account its worldwide variability,natural history,diagnostic tools,therapeutic strategies,and cost-effectiveness. Intestinal-type,the most frequent GC histotype,develops through a multistep process triggered by Helicobacter pylori(H. pylori) and progressing from gastritis to atrophy,intestinal metaplasia(IM),and dysplasia. However,the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore,it remains unclear who should be screened,when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries,at high prevalence of GC and the high-risk subjects in western countries,at low prevalence of GC.As far as concern surveillance,currently,we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach,the patients at higher risk,the best timing and the cost-effectiveness.Anyway,patients with corpus atrophic gastritis,extensive incomplete IM and dysplasia should enter a surveillance program.At present,screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC.
