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Basic Characteristics of Mutations
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Mutation Site
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A1762T |
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Mutation Site Sentence
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A1762T + G1764A in combination with PC mutation G1896A. |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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BCP;PreC |
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Standardized Encoding Gene
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C
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Genotype/Subtype
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C |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Liver Diseases
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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- |
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Location
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China |
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Literature Information
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PMID
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29322851
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Title
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Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases
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Author
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Zang H,Xu Z,Liu Y,Li X,Rong Y,Jiang L,You S,Hu J,Zhao J,Xu D,Xin S
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Journal
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Scandinavian journal of gastroenterology
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Journal Info
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2018 Mar;53(3):319-328
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Abstract
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OBJECTIVE: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined. MATERIALS AND METHODS: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis. RESULTS: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF patients within six months after the disease onset (OR 1.704, p = .041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p < .001), while C1913A led to a significant decrease of core protein expression (p < .05). CONCLUSION: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.
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Sequence Data
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EU939536-EU939681
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