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
The review presents the data accumulated for more than 20 years of research of torque teno virus(TTV).Its molecular genetic structure,immunobiology,epidemiology,diagnostic methods,possible replication sites,and pathog...The review presents the data accumulated for more than 20 years of research of torque teno virus(TTV).Its molecular genetic structure,immunobiology,epidemiology,diagnostic methods,possible replication sites,and pathogenicity factors are described.TTV is a virus that is frequently detectable in patients with different viral hepatitides,in cases of hepatitis without an obvious viral agent,as well as in a healthy population.There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection.There are sufficient histological signs of liver damage,which confirm that the virus can undergo a replicative cycle in hepatocytes.Along with this,cytological hybridization in TTV-infected cells has shown no substantial cytopathic(cell-damaging)effects that are characteristic of pathogenic hepatotropic viruses.Studying TTV has led to the evolution of views on its role in the development of human pathology.The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses,including the viruses of the known types of hepatitides.The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a nonpathogenic virus.It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body’s immune status.The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses.Fortunately,the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties.The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study.展开更多
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.
文摘The review presents the data accumulated for more than 20 years of research of torque teno virus(TTV).Its molecular genetic structure,immunobiology,epidemiology,diagnostic methods,possible replication sites,and pathogenicity factors are described.TTV is a virus that is frequently detectable in patients with different viral hepatitides,in cases of hepatitis without an obvious viral agent,as well as in a healthy population.There is evidence suggesting that biochemical and histological changes occur in liver tissue and bile duct epithelium in TTV monoinfection.There are sufficient histological signs of liver damage,which confirm that the virus can undergo a replicative cycle in hepatocytes.Along with this,cytological hybridization in TTV-infected cells has shown no substantial cytopathic(cell-damaging)effects that are characteristic of pathogenic hepatotropic viruses.Studying TTV has led to the evolution of views on its role in the development of human pathology.The first ideas about the hepatotropism of the virus were gradually reformed as new data became available on the prevalence of the virus and its co-infection with other viruses,including the viruses of the known types of hepatitides.The high prevalence of TTV in the human population indicates its persistence in the body as a virome and a nonpathogenic virus.It has recently been proposed that the level of TTV DNA in the blood of patients undergoing organ transplantation should be used as an endogenous marker of the body’s immune status.The available data show the polytropism of the virus and deny the fact that TTV can be assigned exclusively to hepatitis viruses.Fortunately,the rare detection of the damaging effect of TTV on hepatic and bile duct epithelial cells may be indirect evidence of its conditionally pathogenic properties.The ubiquity of the virus and the variability of its existence in humans cannot put an end to its study.
