Clinical utility of complex mutations in the core promoter and proximal precore regions of the hepatitis B virus genome  

作　　者：Young Min Park 

机构地区：[1]Hepatology Center,Department of Internal Medicine,Bundang Jesaeng General Hospital,Seongnam-si,Kyungki-do 463-774,South Korea [2]Biomedical Research Center,Bundang Jesaeng General Hospital,Seongnam-si,Kyungki-do 463-774,South Korea

出　　处：《World Journal of Hepatology》2015年第1期113-120,共8页世界肝病学杂志（英文版）（电子版）

摘　　要：The core promoter and proximal precore regions are the most complex portions of the hepatitis B virus(HBV) genome. These regions cooperatively regulate viral replication and differentially regulate the synthesis of the viral proteins E,core,and X. Multiple mutations in these regions are associated with the persistency of viral infection and the development of cirrhosis and hepatocellular carcinoma(HCC). In South Korea,nearlyall HBVs are classified as HBV genotype C2; the majority of these viruses have the basal core promoter double mutation,a precore stop mutation,or both. These mutations may play a role in the alteration of viral and clinical features,and abundant and complex mutations are particularly prevalent in the core promoter and proximal precore regions. We previously demonstrated that the accumulation of ≥ 6 mutations at eight key nucleotides located in these regions(G1613A,C1653 T,T1753 V,A1762 T,G1764 A,A1846 T,G1896 A,and G1899A) is a useful marker to predict the development of HCC regardless of advanced liver disease. In addition,certain mutation combinations were predominant in cases with ≥ 4 mutations. In cases with ≤ 5 mutations,a low Hepatitis B e antigen titer(< 35 signal to noise ratio) was indicative of HCC risk. Viral mutation data of the single HBV genotype C2 suggest that the combined effect of the number and pattern of mutations in the core promoter and proximal precore regions is helpful in predicting HCC risk.The core promoter and proximal precore regions arethe most complex portions of the hepatitis B virus（HBV） genome. These regions cooperatively regulateviral replication and differentially regulate the synthesisof the viral proteins E, core, and X. Multiple mutationsin these regions are associated with the persistencyof viral infection and the development of cirrhosis andhepatocellular carcinoma （HCC）. In South Korea, nearlyall HBVs are classified as HBV genotype C2; the majorityof these viruses have the basal core promoter doublemutation, a precore stop mutation, or both. Thesemutations may play a role in the alteration of viral andclinical features, and abundant and complex mutationsare particularly prevalent in the core promoter andproximal precore regions. We previously demonstratedthat the accumulation of ≥ 6 mutations at eight keynucleotides located in these regions （G1613A, C1653T,T1753V, A1762T, G1764A, A1846T, G1896A, andG1899A） is a useful marker to predict the developmentof HCC regardless of advanced liver disease. In addition,certain mutation combinations were predominant incases with ≥ 4 mutations. In cases with ≤ 5 mutations,a low Hepatitis B e antigen titer （〈 35 signal to noiseratio） was indicative of HCC risk. Viral mutation data ofthe single HBV genotype C2 suggest that the combinedeffect of the number and pattern of mutations in thecore promoter and proximal precore regions is helpful inpredicting HCC risk.

关 键 词：Hepatitis B VIRUS Point mutation HEPATITISB VIRUS X protein HEPATOCELLULAR carcinoma Cancerscreening 

分 类 号：R512.62[医药卫生—内科学]