AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was perf...AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.展开更多
Helicobacter pylori(H.pylori)infection is widely prevalent worldwide.H.pylori infection has been reported to be a risk factor for the development of insulin resistance,nonalco-holic fatty liver disease(NAFLD),nonalcoh...Helicobacter pylori(H.pylori)infection is widely prevalent worldwide.H.pylori infection has been reported to be a risk factor for the development of insulin resistance,nonalco-holic fatty liver disease(NAFLD),nonalcoholic steatohepatitis(NASH),liver fibrosis,and cirrhosis.Because treatment for NAFLD,other than weight loss is limited,the treatment for H.pylori infection is well established.It is important to determine whether screening and treatment for H.pylori infection should be considered in patients with no gastrointestinal symptoms.The aim of this mini-review is to evaluate the association be-tween H.pylori infection and NAFLD including epidemiology,pathogenesis,and the evidence for H.pylori infection as a modifiable risk factor for preventing or treating NAFLD.展开更多
Nonalcoholic steatohepatitis(NASH)has emerged as the leading cause of chronic liver disease worldwide and is rapidly increasing in prevalence due to the obesity epidemic.There are currently no Food and Drug Administra...Nonalcoholic steatohepatitis(NASH)has emerged as the leading cause of chronic liver disease worldwide and is rapidly increasing in prevalence due to the obesity epidemic.There are currently no Food and Drug Administration(FDA)approved drugs to treat NASH,and therefore a critical need exists for novel therapies that can halt or reverse the progression to hepatic fibrosis,cirrhosis,and hepatocellular carcinoma.Clinical trials to date using single drugs to treat NASH have shown disappointing efficacy.Combination therapies to attack different targets underlying disease pathogenesis of NASH are being explored as a strategy currently.Novel RNA therapies are also being developed to target previously“undruggable”targets and are close to the maturity necessary to be viable therapeutic approaches for the treatment of NASH and fibrosis.Identifying circulating biomarkers of fibrosis could serve as a valuable,non-invasive diagnostic tool to guide clinical practice.Despite progress in translational and clinical research,one of the major reasons for the absence of effective therapeutics is our incomplete understanding of the pathophysiology that underlies the progression from steatosis to NASH and its most deadly consequence-fibrosis.Multi-omics platforms will help to drive effective precision medicine development in NASH and hepatology.展开更多
文摘AIM:To investigate the potential association of circulating zonulin with the stage of liver disease in obese children with biopsy-confirmed nonalcoholic fatty liver disease(NAFLD).METHODS:A case-control study was performed.Cases were 40 obese children with NAFLD.The diagnosis of NAFLD was based on magnetic resonance imaging(MRI)with high hepatic fat fraction(HFF≥5%),and confirmed by liver biopsy with≥5%of hepatocytes containing macrovesicular fat.Controls were selected from obese children with normal levels of aminotransferases,and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases.Controls were matched(1-to 1)with the cases on age,gender,pubertal stage and as closely as possible on body mass index-standard deviation score.All participants underwent clinical examination,laboratory testsincluding zonulin,inflammatory and metabolic parameters,and MRI for measurement of HFF and visceral adipose tissue.RESULTS:Zonulin values were significantly greater in obese subjects with NAFLD than in those without NAFLD[median(interquartile range),4.23(3.18-5.89)vs 3.31(2.05-4.63),P<0.01].In patients with NAFLD,zonulin concentrations increased significantly with the severity of steatosis and the Spearman’s coefficient revealed a positive correlation between zonulin values and steatosis(r=0.372,P<0.05);however,we did not find a significant correlation between zonulin and lobular inflammation(P=0.23),ballooning(P=0.10),fibrosis score(P=0.18),or presence of nonalcoholic steatohepatitis(P=0.17).Within the entire study population,zonulin levels were positively associated with gamma-glutamyl transferase,2-h insulin,HFF,and negatively associated with whole-body insulin sensitivity index(WBISI),after adjustment for age,gender and pubertal status.When the associations were restricted to the group of NAFLD patients,2-h insulin,hepatic fat,and WBISI retained statistical significance.CONCLUSION:Circulating zonulin is increased in children and adolescents with NAFLD and correlates with the severity of steatosis.
文摘Helicobacter pylori(H.pylori)infection is widely prevalent worldwide.H.pylori infection has been reported to be a risk factor for the development of insulin resistance,nonalco-holic fatty liver disease(NAFLD),nonalcoholic steatohepatitis(NASH),liver fibrosis,and cirrhosis.Because treatment for NAFLD,other than weight loss is limited,the treatment for H.pylori infection is well established.It is important to determine whether screening and treatment for H.pylori infection should be considered in patients with no gastrointestinal symptoms.The aim of this mini-review is to evaluate the association be-tween H.pylori infection and NAFLD including epidemiology,pathogenesis,and the evidence for H.pylori infection as a modifiable risk factor for preventing or treating NAFLD.
文摘Nonalcoholic steatohepatitis(NASH)has emerged as the leading cause of chronic liver disease worldwide and is rapidly increasing in prevalence due to the obesity epidemic.There are currently no Food and Drug Administration(FDA)approved drugs to treat NASH,and therefore a critical need exists for novel therapies that can halt or reverse the progression to hepatic fibrosis,cirrhosis,and hepatocellular carcinoma.Clinical trials to date using single drugs to treat NASH have shown disappointing efficacy.Combination therapies to attack different targets underlying disease pathogenesis of NASH are being explored as a strategy currently.Novel RNA therapies are also being developed to target previously“undruggable”targets and are close to the maturity necessary to be viable therapeutic approaches for the treatment of NASH and fibrosis.Identifying circulating biomarkers of fibrosis could serve as a valuable,non-invasive diagnostic tool to guide clinical practice.Despite progress in translational and clinical research,one of the major reasons for the absence of effective therapeutics is our incomplete understanding of the pathophysiology that underlies the progression from steatosis to NASH and its most deadly consequence-fibrosis.Multi-omics platforms will help to drive effective precision medicine development in NASH and hepatology.