Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirr...Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.展开更多
Hepatocellular carcinoma(HCC)remains to be one of the top causing cancer-related deaths today.The majority of HCC cases are reported to be the result of chronic hepatitis B virus(HBV)infection.Current treatments for H...Hepatocellular carcinoma(HCC)remains to be one of the top causing cancer-related deaths today.The majority of HCC cases are reported to be the result of chronic hepatitis B virus(HBV)infection.Current treatments for HBV-related HCC revolve around the use of drugs to inhibit viral replication,as a high level of viral load and antigen in circulation often presents a poor patient prognosis.However,existing therapies are inefficient in the complete eradication of HBV,often resulting in tumour recurrence.The involvement of microRNAs(miRNAs)in important processes in HBV-related HCC makes it an important player in the progression of HCC in chronic hepatitis B infected patients.In this review,we discuss the key aspects of HBV infection and the important viral products that may regulate cancerrelated processes via their interaction with miRNAs or their closely related protein machinery.Conversely,we also look at how miRNAs may go about regulating the virus,especially in vital processes like viral replication.Apart from miRNAs acting as either oncogenes or tumour-suppressors,we also look at how miRNAs may function as biomarkers that may possibly serve as better candidates than those currently employed in the diagnosis of HBV infection or HBV-related HCC.A summary of the roles of miRNAs in HBV-related HCC will hopefully lead to a gain in understanding of the pathogenesis process and pave the way for new insights in medical therapy.展开更多
AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH fe...AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined.The activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3.The infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.RESULTS:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in PBC.CD3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC.The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in AIH.CD20+cells were mainly found in the portal tracts and,occasionally,at the interface in both diseases.Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in PBC.No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH.While most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with AIH.CONCLUSION:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.展开更多
文摘Chronic active hepatitis(CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma.The histological end points of CAH are chronic inflammation,fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers.The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis,inflammation and cytokine production and liver scaring(fibrosis).The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components.The viral and cellular factors that contribute to liver injury are discussed in this article.Liver injury caused by the viral infection affects many cellular processes such as cell signaling,apoptosis,transcription,DNA repair which in turn induce radical effects on cell survival,growth,transformation and maintenance.The consequence of such perturbations is resulted in the alteration of bile secretion,gluconeogenesis,glycolysis,detoxification and metabolism of carbohydrates,proteins,fat and balance of nutrients.The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.
文摘Hepatocellular carcinoma(HCC)remains to be one of the top causing cancer-related deaths today.The majority of HCC cases are reported to be the result of chronic hepatitis B virus(HBV)infection.Current treatments for HBV-related HCC revolve around the use of drugs to inhibit viral replication,as a high level of viral load and antigen in circulation often presents a poor patient prognosis.However,existing therapies are inefficient in the complete eradication of HBV,often resulting in tumour recurrence.The involvement of microRNAs(miRNAs)in important processes in HBV-related HCC makes it an important player in the progression of HCC in chronic hepatitis B infected patients.In this review,we discuss the key aspects of HBV infection and the important viral products that may regulate cancerrelated processes via their interaction with miRNAs or their closely related protein machinery.Conversely,we also look at how miRNAs may go about regulating the virus,especially in vital processes like viral replication.Apart from miRNAs acting as either oncogenes or tumour-suppressors,we also look at how miRNAs may function as biomarkers that may possibly serve as better candidates than those currently employed in the diagnosis of HBV infection or HBV-related HCC.A summary of the roles of miRNAs in HBV-related HCC will hopefully lead to a gain in understanding of the pathogenesis process and pave the way for new insights in medical therapy.
基金Supported by Primary Biliary Cirrhosis Subdivision of Intrac-table Hepatobiliary Diseases Study Group of Japan(Chairman,Hirohito TsubouchiDepartment of Human and Environmental Sciences,Graduate School of Medical and Dental Sciences,Ka-goshima University,Kagoshima,Japan)
文摘AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH features.METHODS:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined.The activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3.The infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions.RESULTS:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in PBC.CD3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC.The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in AIH.CD20+cells were mainly found in the portal tracts and,occasionally,at the interface in both diseases.Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in PBC.No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH.While most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with AIH.CONCLUSION:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.
