期刊
HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL
卷 15, 期 6, 页码 579-586出版社
ZHEJIANG UNIV SCH MEDICINE
DOI: 10.1016/S1499-3872(16)60064-4
关键词
hepatitis B virus; drug resistance mutation; surface protein; C-terminal truncation; oncogenic potential; hepatocellular carcinoma
资金
- National Natural Science Foundation of China [81071363]
BACKGROUND: The long-term use of nucleos(t)ide analogues causes drug resistance and mutations in the HBV reverse transcriptase (RT) region of the polymerase gene. The RT region overlaps the HBV surface gene (S gene) and therefore, the mutations in the RT region simultaneously modify S gene sequence. Certain mutations in the RT region bring about truncated S proteins because the corresponding changed S gene encodes a stop codon which results in the loss of a large portion of the C-terminal hydrophobic region of HBV surface protein. The rtA181T/sW172*, rtM204I/sW196* and rtV191I/sW182* are the most frequently reported drug-resistant mutations with C-terminal truncation, these mutations have oncogenic potential. DATA SOURCES: PubMed and Web of Science were searched using terms: hepatitis B virus, HBV drug resistance mutation'; HBV surface protein'; HBV truncation; hepatocellular carcinoma'; rtA181T/sW172*'; rtM204IfsW196*'; rtV191I/sW182*'; and relevant articles published in English in the past decades were reviewed. RESULTS: The rtA181T/sW172* and rtV191I/sW182* mutants occurred more frequently than the rtM204I/sW196* mutant both in chronic hepatitis B patients and the HBV-related hepatocellular carcinoma tissues. Although these mutations occur naturally, nucleos(t)ide analogues therapy is the main driving force. These mutations may exist alone or coexist with other HBV mutations. All these three mutants impair the virion secretion and result in HBV surface protein retention and serum HBV DNA level reduction. These mutations possess potential carcinogenic properties. The three mutations are resistant to more than one nucleos(t)ide analogue and therefore, it is difficult to treat the patients with the truncated mutations. CONCLUSIONS: Nucleos(t)ide analogues induce drug resistance and HBV S gene truncated mutations. These mutations have potential carcinogenesis.
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