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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.

plos one

New Point Mutations in Surface and Core Genes of Hepatitis B Virus Associated with Acute on Chronic Liver Failure Identified by Complete Genomic Sequencing