Identification of Hepatitis B Virus DNA Polymerase Sequences to Predict Virological Response to Entecavir Therapy

Poster Presentations: Emerging / Infectious DiseasesConference Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B

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Effects of Hepatitis B Virus quasispecies and reverse Transcriptase variants on treatment responsiveness to entecavir

Poster Session - 07C. Viral Hepatitis B & D: Clinical (Therapy, New Compounds, Resistance)Background and Aims: Entecavir therapy reduces hepatitis B virus (HBV) DNA to an undetectable level in around 60–80% of patients after 1 year of treatment, but HBV DNA may remain detectable in the remaining patients. We aimed to determine whether baseline HBV reverse transcriptase (rt) sequence polymorphisms and quasispecies complexity and diversity are associated with the differences in treatment response. Methods: Pre-treatment HBV rt sequence from 305 entecavir-treated patients were determined by DNA sequencing. Sequencing data were associated with their virological outcome, as defined by optimal response (undetectable HBV DNA at year 1) or partial response (HBV DNA >60 copies/mL). Quasispecies complexity and diversity were determined using MEGA 5.0 software. Results: Seventeen rt variants were more frequently detected in the partial responders (n = 64; 21%) than in the optimal responders (all P <0.05). Multivariate analysis revealed that high baseline HBV DNA, hepatitis B e antigen (HBeAg)-positivity and rt124N were associated with partial entecavir response. Compared with the partial responders, the optimal responders had a higher quasispecies complexity at nucleotide and amino acid levels (P = 0.036 and 0.087, respectively) and higher quasispecies diversity, as reflected by a greater genetic distance at both nucleotide and amino acid levels (P = 0.019 and 0.032, respectively) and a greater number of synonymous substitutions per synonymous site (dS; P = 0.015) and number of non-synonymous substitutions per non-synonymous site (dN; P = 0.039). Conclusions: High baseline HBV DNA, HBeAg-positivity and rt124N were associated with partial entecavir response at year 1. Baseline HBV quasispecies complexity and diversity were higher in the optimal responders than in the partial responders.Link_to_subscribed_fulltex

Level of hepatitis B surface antigen and not HBV DNA level after HBeAg seroclearance is predictive of HBsAg seroclearance

Poster Presentation - Session 7B: Viral Hepatitis: Hepatitis A, B, D E Clinical (Except Therapy)Link_to_subscribed_fulltex

Reduction of hepatitis B core related antigen by long term nucleoside nucleotide analogue therapy and its correlation with intrahepatic HBV DNA reduction

Topic 11 - Hepatitis B: no. 1282Conference Theme: New Horizons from East to west in HepatologyThis journal suppl. entitled: Conference Abstracts: 24th Annual Conference of APASL, March 12-15, 2015, Istanbul, TurkeyOBJECTIVE: We aimed to investigate the reduction of hepatitis B corerelated antigen (HBcrAg) in patients with long term nucleoside/ nucleotide analogue (NA) therapy. METHODS: Forty-three patients (median age: 43 years, range: 24–63 years) who had been on continuous (median follow-up duration: 10 years; range 5–12 years) NA therapy, including lamivudine, adefovir, telbivudine, entecavir, and tenofovir, were recruited. All patients had liver biopsies at baseline and at the last follow-up. HBcrAg (detection limit: 3 log U/mL) were measured using a Lumipulse HBcrAg assay (Fujirebio, Japan). Intrahepatic total HBV DNA (ihHBV-DNA) and covalently closed circular DNA (cccDNA) were assayed by real-time PCR. RESULTS: At baseline, the median levels of HBcrAg, ihHBV-DNA, and cccDNA were 6.7 log U/mL, 286 copies/cell, and 7.3 copies/cell, respectively. Baseline level of HBcrAg correlated positively with that of ihHBV-DNA (r = 0.568, P\0.0001), and cccDNA (r = 0.559, P\0.0001). At the time of last biopsy, 12 (28 %) patients had undetectable HBcrAg (median: 3.8; range:\3–5.7 log U/mL). All patients had detectable ihHBV-DNA (median: 0.35 copies/cell), and 21 (49 %) patients had undetectable cccDNA. The median logarithmic reductions of HBcrAg, ihHBV-DNA, and cccDNA were 2.7 log U/mL, 2.81 log copies/cell, and 2.94 log copies/cell, respectively. There was a positive correlation between the logarithmic reduction of HBcrAg and ihHBV-DNA (r = 0.550, P\0.001) and cccDNA (r = 0.419, P = 0.005). CONCLUSION: The marked reduction of HBcrAg, together with the reduction in ihHBV-DNA and cccDNA, further supports the effectiveness of long-term nucleoside/tide analogue therapy in potentially eradicating HBV from chronic carriersLink_to_subscribed_fulltex

The effect of long-term Nucleoside/Tide Analogue Treatment on Intrahepatic Hbvdna and Covalently Closed Circular DNA in Chronic Hepatitis B patients

Poster Presentation - Session 7C: Viral Hepatitis: Hepatitis B & D - Clinical (Therapy, New Compounds, Resistance)Link_to_subscribed_fulltex