Clinical characteristics and HBV mutation features of the patients involved in Illumina sequencing.

<p>ALT, alanine aminotransferase; AST, aspartate aminotransferase; —,not calculated; ACLF, acute on chronic liver failure; CHB-M, mild chronic hepatitis B; NS, not significant.</p><p>Clinical characteristics and HBV mutation features of the patients involved in Illumina sequencing.</p

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

<div><p>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.</p></div

The risks of CHB-M, CHB-S, and ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with ASCs, CHB-M and CHB-S respectively.

<p>ASC, asymptomatic hepatitis B surface antigen carriers; CHB-M, mild chronic hepatitis B; CHB-S, severe chronic hepatitis B; ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio;</p><p>* compared with ASCs;</p><p>** compared with CHB-M;</p><p>*** compared with CHB-S.</p><p>^a<i>P</i> < 0.01, as compared with control.</p><p>^b<i>P</i> < 0.05, as compared with control.</p><p>The risks of CHB-M, CHB-S, and ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with ASCs, CHB-M and CHB-S respectively.</p

The risks of ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with non-ACLF cases.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio.</p><p>^a<i>P</i> < 0.01, as compared with non-ACLF.</p><p>^b<i>P</i> < 0.05, as compared with non-ACLF.</p><p>The risks of ACLF cases with 7 site mutations on the basis of genotype B and genotype C as compared with non-ACLF cases.</p

Sensitivity and specificity of specific mutation patterns of hepatitis B virus for ACLF.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; —,not calculated.</p><p>^a<i>P</i><0.01, as compared with non-ACLF.</p><p>^b combinations with any 2 or more of T216C, G1896A, C1913A/G and A2159G/C.</p><p>Sensitivity and specificity of specific mutation patterns of hepatitis B virus for ACLF.</p

The associations of seven mutations in hepatitis B virus (HBV) with asymptomatic hepatitis B surface antigen carriers, mild chronic hepatitis B, severe chronic hepatitis B, acute on chronic liver failure in genotypes B and C.

<p>The associations of seven mutations in hepatitis B virus (HBV) with asymptomatic hepatitis B surface antigen carriers, mild chronic hepatitis B, severe chronic hepatitis B, acute on chronic liver failure in genotypes B and C.</p

Primers used for Illumina sequencing and direct PCR sequencing of HBV.

<p>Primers used for Illumina sequencing and direct PCR sequencing of HBV.</p

The results of stepwise multivariate regression analysis for independent risk factors associated with ACLF cases.

<p>ACLF, acute on chronic liver failure; CI, confidence interval; AOR, adjusted odds ratio.</p><p>^a<i>P</i><0.01, as compared with non-ACLF.</p><p>^b<i>P</i><0.05, as compared with non-ACLF.</p><p>The results of stepwise multivariate regression analysis for independent risk factors associated with ACLF cases.</p

The clinical data and HBV mutation profiles in 438 subjects.

<p>ALT, alanine aminotransferase; AST, aspartate aminotransferase; ASC, asymptomatic hepatitis B surface antigen carriers; CHB-M, mild chronic hepatitis B; CHB-S, severe chronic hepatitis B; ACLF, acute on chronic liver failure;</p><p>^a<i>P</i><0.01, as compared with ASC.</p><p>^b<i>P</i><0.01, as compared with CHB-M.</p><p>^c<i>P</i><0.01, as compared with CHB-S.</p><p>^d<i>P</i><0.05, as compared with ASC.</p><p>^e<i>P</i><0.05, as compared with CHB-M.</p><p>^f<i>P</i><0.05, as compared with CHB-S.</p><p>The clinical data and HBV mutation profiles in 438 subjects.</p

MOESM1 of MiR-199a-modified exosomes from adipose tissue-derived mesenchymal stem cells improve hepatocellular carcinoma chemosensitivity through mTOR pathway

Additional file 1: Figure S1. Involvement of mTOR pathway in AMSC-Exo-199a-enhanced HCC chemosensitivity