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Basic Characteristics of Mutations
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Mutation Site
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A1814C |
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Mutation Site Sentence
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Mutations affecting the initiation of translation of pre-C gene (TIM) were found in 7 (3.8%) patients, including A1814C (three ICs), T1815C (one IC), T1815A (one patient with ACH) and C1817T (two ICs). No patients with TIM had concomitant G1896A mutation. |
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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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PreC |
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Standardized Encoding Gene
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C
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Genotype/Subtype
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D;A |
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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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Morocco |
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Literature Information
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PMID
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22905181
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Title
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Variability in the precore and core promoter regions of HBV strains in Morocco: characterization and impact on liver disease progression
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Author
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Kitab B,Essaid El Feydi A,Afifi R,Trepo C,Benazzouz M,Essamri W,Zoulim F,Chemin I,Alj HS,Ezzikouri S,Benjelloun S
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Journal
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PloS one
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Journal Info
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2012;7(8):e42891
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Abstract
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BACKGROUND: Hepatitis B virus (HBV) is one of the most common human pathogens that cause aggressive hepatitis and advanced liver disease (AdLD), including liver cirrhosis and Hepatocellular Carcinoma. The persistence of active HBV replication and liver damage after the loss of hepatitis B e antigen (HBeAg) has been frequently associated with mutations in the pre-core (pre-C) and core promoter (CP) regions of HBV genome that abolish or reduce HBeAg expression. The purpose of this study was to assess the prevalence of pre-C and CP mutations and their impact on the subsequent course of liver disease in Morocco. METHODS/PRINCIPAL FINDINGS: A cohort of 186 patients with HBeAg-negative chronic HBV infection was studied (81 inactive carriers, 69 with active chronic hepatitis, 36 with AdLD). Pre-C and CP mutations were analyzed by PCR-direct sequencing method. The pre-C stop codon G1896A mutation was the most frequent (83.9%) and was associated with a lower risk of AdLD development (OR, 0.4; 95% CI, 0.15-1.04; p = 0.04). HBV-DNA levels in patients with G1896A were not significantly different from the other patients carrying wild-type strains (p = 0.84). CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were associated with higher HBV-DNA level and increased liver disease severity. Multiple logistic regression analysis showed that older age (>/= 40 years), male sex, high viral load (>4.3 log(10) IU/mL) and CP mutations C1653T, T1753V, A1762T/G1764A, and C1766T/T1768A were independent risk factors for AdLD development. Combination of these mutations was significantly associated with AdLD (OR, 7.52; 95% CI, 4.8-8; p<0.0001). CONCLUSIONS: This study shows for the first time the association of HBV viral load and CP mutations with the severity of liver disease in Moroccan HBV chronic carriers. The examination of CP mutations alone or in combination could be helpful for prediction of the clinical outcome.
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Sequence Data
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Text S1
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