Hepatitis D and hepatocellular carcinoma  

作　　者：Zaigham Abbas Minaam Abbas Sarim Abbas Lubna Shazi 

机构地区：[1]Department of Hepatogastroenterology,Sindh Institute of Urology and Transplantation [2]University of Cambridge [3]LiverS tomach Clinic,Akber Centre

出　　处：《World Journal of Hepatology》2015年第5期777-786,共10页世界肝病学杂志（英文版）（电子版）

摘　　要：Hepatitis D virus(HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins,small and large hepatitis D antigens,surrounded by hepatitis B surface antigen.Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis.In spite of some controversy in the epidemiological studies,HDV infection does increase the risk of hepatocellular carcinoma(HCC) compared to hepatitis B virus(HBV) monoinfection.Hepatic decompensation,rather than development of HCC,is the first usual clinical endpoint during the course of HDV infection.Oxidative stress as a result of severe necroinflammation may progress to HCC.The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription(STAT)3 and the nuclear factor kappa B pathway.Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases.HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter.This enhances the expression of clusterin in infected cells,increasing cell survival potential.Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage.The targeted inhibition of STAT3 and cyclophilin,and augmentation of peroxisome proliferatoractivated receptor γ have a potential therapeutic role in HCC.Hepatitis D virus （HDV） is a defective circular shapesingle stranded HDV RNA virus with two types ofviral proteins, small and large hepatitis D antigens,surrounded by hepatitis B surface antigen. Superinfectionwith HDV in chronic hepatitis B is associated with amore threatening form of liver disease leading to rapidprogression to cirrhosis. In spite of some controversyin the epidemiological studies, HDV infection doesincrease the risk of hepatocellular carcinoma （HCC）compared to hepatitis B virus （HBV） monoinfection.Hepatic decompensation, rather than developmentof HCC, is the first usual clinical endpoint during thecourse of HDV infection. Oxidative stress as a result ofsevere necroinflammation may progress to HCC. Thelarge hepatitis D antigen is a regulator of various cellularfunctions and an activator of signal transducer andactivator of transcription （STAT）3 and the nuclear factorkappa B pathway. Another proposed epigenetic mechanismby which HCC may form is the aberrant silencing oftumor suppressor genes by DNA Methyltransferases. HDVantigens have also been associated with increased histoneH3 acetylation of the clusterin promoter. This enhancesthe expression of clusterin in infected cells, increasing cellsurvival potential. Any contribution of HBV DNA integrationwith chromosomes of infected hepatocytes is not clearat this stage. The targeted inhibition of STAT3 andcyclophilin, and augmentation of peroxisome proliferatoractivatedreceptor γ have a potential therapeutic role inHCC.

关 键 词：Hepatitis D Hepatocellular carcinoma NECROINFLAMMATION Epigenetic processes CIRRHOSIS Oxidative stress 

分 类 号：R512.64[医药卫生—内科学]