ABSTRACT
Objective To investigate the prognostic value of platelet to lymphocyte ratio (PLR) for early virological response in Entecavir (ETV)-treated chronic hepatitis B (CHB) patients with genotype C infection.Methods Ninety-one genotype C CHB patients with HBV DNA≥1×105 copies/mL were treated with ETV (0.5 mg/d) for 10-13 days.The correlation between PLR and viral load decline was evaluated by Pearson or Spearman's rank correlation coefficient.Stepwise linear regression analysis was used to establish the prediction model of virological response.Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of PLR for early virological response in ETV-treated patients with genotype C hepatitis B virus (HBV) infection.Results After 10-13 days of ETV treatment, HBV DNA decreased ≥1×lg copies/mL from baseline in 89 cases of the 91 patients, while HBV DNA declined ≥2×lg copies/mL in 65 patients and 4 patients achieved HBV DNA<500 copies/mL.HBV DNA decline was positively correlated with baseline PLR levels (r=0.235 09, P<0.05).After adjustment for age, gender, Hepatitis B e Antigen (HBeAg), and treatment days, HBV DNA decline was still positively correlated with baseline PLR levels (r=0.220 26, P<0.05).Area under curve (AUC) of prediction model including age , baseline aspartate transaminase (AST) and HBV DNA was 0.759 (95% CI : 0.660-0.859, P<0.01).After adding PLR to the prediction model, the AUC was 0.780 (95% CI: 0.685-0.875, P<0.01).Conclusions PLR is predictive to early virological response in ETV-treated CHB patients with genotype C infection.Higher baseline PLR level indicates a better virological response.PLR monitoring should be recommended in CHB patients with antiviral treatment in clinical practice.
ABSTRACT
Objective To investigate the effect of long hairpin RNA ( lhRNA) expression vector targeting HBV X gene ( HBx) on replication of hepatitis B virus ( HBV) and gene expression.Methods Four kinds of small interference RNAs ( siRNAs) were synthesized and lhRNA expression vectors targeting HBx were constructed.Four siRNA oligonucleotides and two lhRNA expression vectors were transfected into HepG2.2.15 cells.HBsAg, HBV DNA in culture supernatants and HBx mRNA in HepG2.2.15 cells were detected by time-resolved immunofluorometric assay, real-time quantitative PCR, and reverse transcription PCR, respectively.Negative sequence group or empty vector group was taken as the control.Independent-samples t test was performed to evaluate the inhibition effect on replication of HBV and gene expression. Results Compared with the negative control, HBsAg, HBV DNA level in culture supernatants and HBx mRNA in HepG2.2.15 cells were significantly decreased after siRNA-1 and siRNA-4 transfected at high concentrations (60 nmol/L or 90 nmol/L) (P<0.05), especially the HBsAg and HBV DNA levels in the siRNA-1 transfection group, which were significantly decreased at 24, 48 and 72 h after transfection ( P<0.05 or P <0.01 ) . Two lhRNA expression vectors ( pMD-HBxlh1 and pMD-HBxlh4 ) were successfully constructed and transfected into HepG2.2.15 cells, HBsAg and HBV DNA level in transfected cells was significantly lower than those in negative control (P<0.05).Conclusion The novel siRNA-1 is confirmed to target HBx gene and lhRNA expression vector targeting HBx can effectively inhibit the replication of HBV and expression of HBV gene.