Clinical relevance of hepatitis B virus variants  

作　　者：Shan Gao Zhong-Ping Duan Carla S Coffin 

机构地区：[1]Artificial Liver Center, Beijing You’an Hospital, Capital Medical University [2]Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary

出　　处：《World Journal of Hepatology》2015年第8期1086-1096,共11页世界肝病学杂志（英文版）（电子版）

基　　金：Supported by The National Science and Technology Key Project of China on"Major Infectious Diseases such as HIV/AIDS,Viral Hepatitis Prevention and Treatment",No.2013-ZX10002002-006(Duan ZP);Speaker,advisory board and/or consulting fees from Boehringer ingelheim,Glaxo Smith Kline,Janssen Pharmaceuticals,Bristol Myers Squibb,Roche Pharmaceuticals and Gilead Sciences(Coffin CS);The Canadian Institutes for Health Research(Coffin CS)

摘　　要：The hepatitis B virus(HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs(NA) targeting the HBV polymerase(P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drugresistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene(S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.The hepatitis B virus （HBV） is a global public health problem with more than 240 million people chronicallyinfected worldwide, who are at risk for end-stage liverdisease and hepatocellular carcinoma. There are anestimated 600000 deaths annually from complications ofHBV-related liver disease. Antiviral therapy with nucleos/tide analogs （NA） targeting the HBV polymerase （P） caninhibit disease progression by long-term suppression ofHBV replication. However, treatment may fail with firstgeneration NA therapy due to the emergence of drugresistantmutants, as well as incomplete medicationadherence. The HBV replicates via an error-prone reversetranscriptase leading to quasispecies. Due to overlappingopen reading frames mutations within the HBV P cancause concomitant changes in the HBV surface gene （S ）and vice versa. HBV quasispecies diversity is associatedwith response to antiviral therapy, disease severity andlong-term clinical outcomes. Specific mutants havebeen associated with antiviral drug resistance, immuneescape, liver fibrosis development and tumorgenesis.An understanding of HBV variants and their clinicalrelevance may be important for monitoring chronichepatitis B disease progression and treatment response.In this review, we will discuss HBV molecular virology,mechanism of variant development, and their potentialclinical impact.

关 键 词：Molecular VIROLOGY Genetic heterogeneity QUASISPECIES Drug resistance Immune ESCAPE Virallymphotropism HEPATITIS B virus 

分 类 号：R512.62[医药卫生—内科学]