BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursod...BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults.Damage to cholangiocytes triggers the development of intrahepatic...Primary biliary cholangitis(PBC)is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults.Damage to cholangiocytes triggers the development of intrahepatic cholestasis,which progresses to cirrhosis in the terminal stage of the disease.Accumulating data indicate that damage to biliary epithelial cells[(BECs),cholangiocytes]is most likely associated with the intracellular accumulation of bile acids,which have potent detergent properties and damaging effects on cell membranes.The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen,which is controlled by the bicarbonate(HCO3-)buffer system“biliary HCO3-umbrella”.The impaired production and entry of HCO3-from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506.Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC,we propose a hypothesis explaining the pathogenesis of the first morphologic(ductulopenia),immunologic(antimitochondrial autoantibodies)and clinical(weakness,malaise,rapid fatigue)signs of the disease in the asymptomatic stage.This review focuses on the consideration of these mechanisms.展开更多
Helicobacter pylori(H.pylori)infection occurs in almost half of the world's population,most of whom are merely carriers of this microorganism.H.pylori is shown to be detected more frequently in patients with diabe...Helicobacter pylori(H.pylori)infection occurs in almost half of the world's population,most of whom are merely carriers of this microorganism.H.pylori is shown to be detected more frequently in patients with diabetes mellitus(DM)than in the general population,which is accompanied by a significantly increased risk of developing H.pylori-associated diseases.In addition,eradication therapy shows a low efficiency for H.pylori infection in patients with DM.There is a relationship between the level of chronic hyperglycemia and a higher detection rate of H.pylori as well as a lower efficiency of eradication therapy in patients with DM.The exact mechanisms of these phenomena are unknown.The authors make a hypothesis that explains the relationship between chronic hyperglycemia and the increased detection rate of H.pylori,as well as the mechanisms contributing to the improved survival of this bacterium in patients with DM during eradication therapy.展开更多
Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic ...Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.展开更多
文摘BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults.Damage to cholangiocytes triggers the development of intrahepatic cholestasis,which progresses to cirrhosis in the terminal stage of the disease.Accumulating data indicate that damage to biliary epithelial cells[(BECs),cholangiocytes]is most likely associated with the intracellular accumulation of bile acids,which have potent detergent properties and damaging effects on cell membranes.The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen,which is controlled by the bicarbonate(HCO3-)buffer system“biliary HCO3-umbrella”.The impaired production and entry of HCO3-from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506.Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC,we propose a hypothesis explaining the pathogenesis of the first morphologic(ductulopenia),immunologic(antimitochondrial autoantibodies)and clinical(weakness,malaise,rapid fatigue)signs of the disease in the asymptomatic stage.This review focuses on the consideration of these mechanisms.
文摘Helicobacter pylori(H.pylori)infection occurs in almost half of the world's population,most of whom are merely carriers of this microorganism.H.pylori is shown to be detected more frequently in patients with diabetes mellitus(DM)than in the general population,which is accompanied by a significantly increased risk of developing H.pylori-associated diseases.In addition,eradication therapy shows a low efficiency for H.pylori infection in patients with DM.There is a relationship between the level of chronic hyperglycemia and a higher detection rate of H.pylori as well as a lower efficiency of eradication therapy in patients with DM.The exact mechanisms of these phenomena are unknown.The authors make a hypothesis that explains the relationship between chronic hyperglycemia and the increased detection rate of H.pylori,as well as the mechanisms contributing to the improved survival of this bacterium in patients with DM during eradication therapy.
文摘Knowledge of the etiological and pathogenetic mechanisms of the development of any disease is essential for its treatment.Because the cause of primary biliary cholangitis(PBC),a chronic,slowly progressive cholestatic liver disease,is still unknown,treatment remains symptomatic.Knowledge of the physicochemical properties of various bile acids and the adaptive responses of cholangiocytes and hepatocytes to them has provided an important basis for the development of relatively effective drugs based on hydrophilic bile acids that can potentially slow the progression of the disease.Advances in the use of hydrophilic bile acids for the treatment of PBC are also associated with the discovery of pathogenetic mechanisms of the development of cholangiocyte damage and the appearance of the first signs of this disease.For 35 years,ursodeoxycholic acid(UDCA)has been the unique drug of choice for the treatment of patients with PBC.In recent years,the list of hydrophilic bile acids used to treat cholestatic liver diseases,including PBC,has expanded.In addition to UDCA,the use of obeticholic acid,tauroursodeoxycholic acid and norursodeoxycholic acid as drugs is discussed.The pathogenetic rationale for treatment of PBC with various bile acid drugs is discussed in this review.Emphasis is made on the mechanisms explaining the beneficial therapeutic effects and potential of each of the bile acid as a drug,based on the understanding of the pathogenesis of the initial stages of PBC.
