Long-Term Efficacy of Tenofovir Monotherapy for Hepatitis B ... : Hepatology (original) (raw)

Viral Hepatitis

Long-Term Efficacy of Tenofovir Monotherapy for Hepatitis B Virus-Monoinfected Patients After Failure of Nucleoside/Nucleotide Analogues

van Bömmel, Florian1,*; de Man, Robert A.2; Wedemeyer, Heiner3; Deterding, Katja3; Petersen, Jörg4; Buggisch, Peter4; Erhardt, Andreas5; Hüppe, Dietrich6; Stein, Kerstin7; Trojan, Jörg8; Sarrazin, Christoph8; Böcher, Wulf O.9; Spengler, Ulrich10; Wasmuth, Hermann E.11; Reinders, Jurrien G.P.2; Möller, Bernd12; Rhode, Peter13; Feucht, Heinz-Hubert14; Wiedenmann, Bertram1; Berg, Thomas1

1_Medizinische Klinik m. S. Hepatologie und Gastroenterologie Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany_

2_Man Erasmus MC, University Medical Center Rotterdam, Department of Gastroenterology & Hepatology, Rotterdam, The Netherlands_

3_Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany_

4_Department of Medicine, University of Hamburg Eppendorf, Germany_

5_Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinik Düsseldorf, Germany_

6_Gastroenterologische Schwerpunktpraxis Herne, Germany_

7_Medizinische Klinik IV für Gastroenterologie und Infektiologie, Universitätsklinikum Heidelberg, Germany_

8_Department of Internal Medicine I, Johann Wolfgang Goethe-University Hospital, Frankfurt, Germany_

9_I. Medizinische Klinik und Poliklinik, Johannes Gutenberg-Universität Mainz, Germany_

10_Department of Internal Medicine, University of Bonn, Germany_

11_Medical Department III, University Hospital Aachen, Germany_

12_Hepatologische Schwerpunktpraxis, Berlin, Germany_

13_Abteilung für Gastroenterologie, St. Marien Hospital, Hamm, Germany_

14_Laborgemeinschaft Hamburg, Germany_

*Address reprint requests to: Medizinische Klinik m. S. Hepatologie und Gastroenterologie Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Email:[email protected]; fax: +49 30 450 553903.

Received 10 February 2009; Accepted 11 August 2009

Published online 25 August 2009 in Wiley InterScience (www.interscience.wiley.com).

Supported by theGermanNetwork of Excellence(HEPNET;BMBF,Grant No.01KI0437), the European Vigilance Network excellence combating viral resistance (VIRGIL, Grant No. LSHM-CT-2004-503359), and in part by Gilead Sciences Inc.

Potential conflict of interest: Dr. van Bömmel received grants from Gilead. Dr. Buggisch is on the speakers' bureau of Gilead. Dr. Sarrazin is a consultant for and is on the speakers' bureau of Gilead and Bristol-Myers Squibb. Dr. Berg is a consultant for, advises, is on the speakers' bureau of, and received grants from Gilead.

Abstract

Tenofovir disoproxil fumarate (TDF) has demonstrated high antiviral efficacy in treatment-naive patients with chronic hepatitis B virus (HBV) infection but experience in nucleoside/nucleotide analogue (NA)-experienced patients is limited. In this retrospective multicenter study we therefore assessed the long-term efficacy of TDF monotherapy in patients with prior failure or resistance to different NA treatments. Criteria for inclusion were HBV DNA levels >4.0 log10 copies/mL at the start and a minimum period of TDF therapy for at least 6 months. In all, 131 patients (mean age 42 ± 12 years, 95 male, 65% hepatitis B e antigen [HBeAg]-positive) were eligible. Pretreatment consisted of either monotherapy with lamivudine (LAM; n = 18), adefovir (ADV; n = 8), and sequential LAM-ADV therapy (n = 73), or add-on combination therapy with both drugs (n = 29). Three patients had failed entecavir therapy. Resistance analysis in 113 of the 131 patients revealed genotypic LAM and ADV resistance in 62% and 19% of patients, respectively. The mean HBV DNA level at TDF baseline was 7.6 ± 1.5 log10 copies/mL. The overall cumulative proportion of patients achieving HBV DNA levels <400 copies/mL was 79% after a mean treatment duration of 23 months (range, 6–60). Although LAM resistance did not influence the antiviral efficacy of TDF, the presence of ADV resistance impaired TDF efficacy (100% versus 52% probability of HBV DNA <400 copies/mL, respectively). However, virologic breakthrough was not observed in any of the patients during the entire observation period. Loss of HBeAg occurred in 24% of patients and HBsAg loss occurred in 3%. No significant adverse events were noticed during TDF monotherapy. Conclusion: TDF monotherapy induced a potent and long-lasting antiviral response in NA-experienced patients with previous treatment failure. Our data may have implications for current add-on strategies. (Hepatology 2009.)