Z Gastroenterol 2010; 48 - P593
DOI: 10.1055/s-0030-1264032

Efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy in a European multicenter cohort of nucleos(t)ide experienced patients with chronic hepatitis B virus (HBV)-infection

F van Bömmel 1, RA De Man 2, P Ferenci 3, JG Reijnders 2, JP Bronowicki 4, A Brodzinski 1, B Fülöp 1, H Wedemeyer 5, K Deterding 5, A Erhardt 6, D Hüppe 7, M Bourlière 8, C Sarrazin 9, J Trojan 9, P Buggisch 10, J Petersen 10, U Spengler 11, K Stein 12, A Pariente 13, M Schuchmann 14, HE Wasmuth 15, K Rutter 3, HH Feucht 16, M Joachim 1, T Berg 1
  • 1Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Leipzig, Germany
  • 2Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands
  • 3Department of Internal Medicine III, Medical University of Vienna, Wien, Austria
  • 4Service d'Hépato-Gastroentérologie, CHU de Nancy, Nancy, France
  • 5Medizinische Hochschule Hannover, Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Germany
  • 6Universitätsklinikum der Heinrich-Heine-Universität, Klinik für Gastroenterologie, Hepatologie und Infektiologie, Düsseldorf, Germany
  • 7Gastroenterologische Gemeinschaftspraxis, Herne, Germany
  • 8Service d'Hépatogastroentérologie, CHU de Nancy, Nancy, France
  • 9Johann Wolfgang Goethe University Medical Centre, Department of Internal Medicine, Frankfurt am Main, Germany
  • 10IFI-Institut, Asklepios Klinik St. Georg, Hamburg, Germany, Hamburg, Germany
  • 11Zentrum für Innere Medizin, Universität Bonn, Bonn, Germany
  • 12Innere Medizin IV, Universitätsklinikum Heidelberg, Heidelberg, Germany
  • 13Unité d' Hépatogastroentérologie, Pau, France
  • 14Universitätsklinikum Mainz, I. Department of Internal Medicin, Mainz, Germany
  • 15Medizinische Klinik III, RWTH Aachen, Aachen, Germany
  • 16Laborgemeinschaft Hamburg, Hamburg, Germany

Aims: The nucleotide analogue tenofovir disoproxil fumarate (TDF) was shown to be an effective treatment for treatment-naïve patients up to three years of treatment (Marcellin & Heathcote et al, AASLD 2009). The aim of this multicenter cohort study is to study the long term outcome of TDF treatment in patients with previous failure to nucleos(t)ide analogues.

Methods: Data from all HBV monoinfected patients treated with TDF monotherapy in 21 European centers were retrospectively analyzed. Inclusion criteria were: age ≥18 years, HBV DNA ≥105 copies/mL and treatment with TDF ≥6 months. HBV DNA (Roche Monitor, LLD 400 copies/mL), ALT and creatinine levels were measured at baseline and every 3 months. Mean changes in glomerular filtration rate (eGFR, estimated by Cockroft-Gault formula) over a period of 48 months were compared to a group of age-matched of 92 asymptomatic HBsAg carriers.

Results: Of 352 patients screened, 203 patients were eligible for the retrospective analysis (m/f 154/49, mean±SD age 45±12 years [range 18–76], 141 HBeAg positive, mean HBV DNA 6.9±1.5 [range 4–10] log copies/mL). All patients were treated with TDF 300mg/day monotherapy for a mean duration of 30±16 [6–90] months; data were available from 199, 143, 99, and 79 patients who had evaluations at 12, 24, 36 and 48 months of treatment, respectively. HBV DNA suppression <400 copies/mL was achieved in 177 out of the 195 patients (90%) during the observation. The overall probability of achieving complete HBV DNA suppression was 92% after 24 months of observation (Kaplan-Meier analysis). At baseline, the mean eGFR in patients treated with TDF and in a control of untreated HBsAg carriers group was 114±26 [22–237] and 102±36 [78–156]mL/min, respectively (p=0.8). By month 48, patients in the TDF group had a significantly greater decrease in eGFR as compared to the control group (–16±36 [–48– +23] and –9.6±36 [–21– +22]mL/min, respectively, p=0.03). One patient required a dose reduction after 15 months of TDF treatment following a change in creatinine from 0.8 to 1.18mg/dl.

Conclusion: TDF monotherapy was well tolerated and induced a potent antiviral response in nucleos(t)ide analogue experienced patients with previous treatment failure.