title: New point mutations in surface and core genes of hepatitis B virus associated with acute on chronic liver failure identified by complete genomic sequencing.
abstract: The objective of this study was to identify new viral biomarkers associated with acute on chronic liver failure (ACLF) by complete genomic sequencing of HBV. Hepatitis B virus mutations associated with ACLF were screened by Illumina high-throughput sequencing in twelve ACLF cases and twelve age-matched mild chronic hepatitis B patients, which were validated in 438 chronic hepatitis B patients (80 asymptomatic carriers, 152 mild chronic hepatitis B patients, 102 severe chronic hepatitis B patients and 104 ACLF patients) by direct sequencing. The results of Illumina sequencing showed that the mutations at 7 sites (T216C, G285A, A1846T, G1896A, C1913A/G, A2159G, and A2189C) of 12 ACLF patients were significantly higher than those of 12 controls. In the validation cohorts, a significantly higher ratio of genotype B to C was found in patients with ACLF than in patients with non-ACLF. Multivariate analysis showed that T216C, G1896A, C1913A/G and A2159G/C were independent risk factors for ACLF. C216 in any combination, A/G1913 in any combination, and G/C2159 in any combination had high specificity for ACLF. In summary, T216C and A2159G/C mutations were novel factors independently associated with ACLF. Combined mutations in hepatitis B cases could play important roles in ACLF development.
authors: Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Hangdi
authors: H
authors: Xu
authors: Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors: Mingfei
authors: M
authors: Zhao
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China.
authors: Guohua
authors: G
authors: Lou
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China.
authors: Min
authors: M
authors: Zheng
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China.
authors: Qingyi
authors: Q
authors: Cao
authors: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Institute of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang, China.
authors: Zhi
authors: Z
authors: Chen
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000235:genetics* / Q000821:virology; D000328:Adult; D002874:Chromosome Mapping; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D023281:Genomics / Q000379:methods; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics* / Q000821:virology; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D017354:Point Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens