Z Gastroenterol 2012; 50 - P4_57
DOI: 10.1055/s-0031-1295943

HBV messenger RNA (mRNA) is a strong predictive marker for HBeAg and HBsAg loss during antiviral treatment with nucleoside/nucleotide analogues (NUCs) in patients with chronic hepatitis B virus (HBV) infection

F van Bömmel 1, A Bartens 2, A Mysickova 3, A Brodzinski 1, B Fülöp 1, J Hofmann 4, D Krüger 4, T Berg 5, A Edelmann 4
  • 1Department für Innere Medizin, Dermatologie und Neurologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Leipzig
  • 2Charite Berlin Campus Virchow-Klinikum Berlin, Berlin
  • 3Max Planck Institute for Molecular Genetics, Berlin
  • 4Institute of Virology Helmut-Ruska-Haus, Charité University Medicine Berlin, Berlin
  • 5University of Leipzig, Leipzig

Aims: Treatment with NUCs can completely suppress HBV DNA levels in most patients, however there are few markers for the prediction of long term response. We studied the association of HBeAg and HBsAg loss with serum levels of circulating full-length (fl) and truncated (tr)HBV mRNA before and during NUC treatment. Methods: For specific detection and quantification of fl and trRNA species, two step real-time reverse transcription PCRs were developed (detection limit 450 and 600 copies/mL, respectively). 67 patients (45 HBeAg positive, mean HBV DNA level 7.6±8[9–2.8] log10copies/mL) receiving either tenofovir (TDF) 300mg/day (n=34) or lamivudine (LAM) 100mg/day (n=33) for ≥ 24 months were retrospectively analyzed. Levels of flRNA and trRNA were compared to levels of HBV DNA and HBsAg derived from frozen serum samples representing months 0, 3, 6, 9, and 12. Results: At treatment months 0 and 24 the mean fl and trRNA levels were 6.7±7.3 [8–2.6] and 5.9±6.5 [7.2–2.6], and 7.1±7.7 [8.5–2.7] and 5.1±5.5 [6.2–2.7] (p=n.s.), while mean HBV DNA levels decreased from 7.6±8.2 [9–3.9] to 2.9±1.6 [3.1–1.5] log10copies/mL, respectively. Patients receiving TDF showed a significantly stronger decrease in HBV DNA levels compared to patients receiving LAM (p=0.02), however there were no differences in fl, trRNA or HBsAg levels. However, in patients remaining HBeAg positive (n=30) flRNA levels remained unchanged until month 12, while in patients who achieved HBeAg loss (n=15) flRNA and tr RNA levels were already lower at baseline (p=0.02) and showed a significant decrease at months 3, 6 and 12 (p<0.001). HBV DNA and HBsAg levels were not predictive for HBeAg loss (p=n.s.). In all 4 patients achieving HBsAg loss between month 7–24, fl and trRNA levels already became undetectable until month 5. Conclusion: HBV RNA levels represent a strong predictor of HBeAg and HBsAg loss during treatment with NUCs which shloud be evaluated in further studies.

HBV RNA - HBeAg-Verlust - HBsAg-Verlust - Hepatitis B - Therapie