• Quantitation of large, middle and small hepatitis B surface proteins in HBeAg-positive patients treated with peginterferon alfa-2a.

      Rinker, Franziska; Bremer, Corinna M; Schröder, Kathrin; Wiegand, Steffen B; Bremer, Birgit; Manns, Michael P; Kraft, Anke R; Wedemeyer, Heiner; Yang, Lei; Pavlovic, Vedran; et al. (Wiley, 2019-11-13)
      BACKGROUND & AIMS: Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive versus active chronic infection. Interferon alfa may convert HBeAg-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. METHODS: HBs proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as hepatitis B e antigen (HBeAg) seroconversion 24 weeks post-treatment. RESULTS: Mean total HBs levels were significantly lower in responders versus nonresponders at all time points (P<.05) and decreased steadily during the initial 24 weeks' treatment (by 1.16 versus 0.86 ng/mL in responders/nonresponders, respectively) with unchanged relative proportions. Genotype B had a twofold higher proportion of LHBs than genotype C (13% versus 6%). HBV DNA, HBeAg, HBsAg, and HBs protein levels predicted response equally well but not optimally (area under the ROC curve values >0.70). CONCLUSIONS: HBs proteins levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients.
    • Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection.

      Marcellin, Patrick; Wong, Dave; Sievert, William; Buggisch, Peter; Petersen, Jörg; Flisiak, Robert; Manns, Michael; Kaita, Kelly; Krastev, Zahari; Lee, Samuel S; et al. (Wiley-Blackwell, 2019-05-28)
      Background & Aims Tenofovir disoproxil fumarate (TDF) is a first‐line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well‐described cohort of CHB patients. Methods Hepatitis B e antigen (HBeAg)‐negative and HBeAg‐positive patients from two randomised, double‐blind trials (ClinicalTrials. gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open‐label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety, and tolerability. Results Of 641 randomised and treated patients, 585 (91%) entered the open‐label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg‐negative patients and 78/80 (98%) of HBeAg‐positive patients with available data achieved hepatitis B virus (HBV) DNA <69 IU/mL, while 88/106 (83%) and 60/77 (78%) patients achieved ALT normalisation, respectively. Of the 23 patients with HBeAg status available at Year 10, 12 (52%) and six (27%) experienced HBeAg loss and seroconversion, respectively. No resistance to TDF was documented up to Year 10. In the period between Year 8 and Year 10, the safety profile of TDF was similar to previous reports, with few patients experiencing renal‐ or bone‐related adverse events. Conclusions Over 10 years, TDF had a favourable safety profile, was well tolerated, and resulted in continued maintenance of virological suppression with no documented resistance.