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TRANSPLANTATION

Tenofovir Therapy for Lamivudine Resistance Following Liver Transplantation

Assistant Professor of Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH

Jose Nery, MD

Associate Professor of Surgery, Department of Surgery, University of Miami, Miami, FL

Daryl TY Lau, MD

Associate Professor of Medicine, Department of Medicine, The University of Texas Medical Branch, Galveston, TX

Christopher B O'Brien, MD

Associate Professor of Medicine, Department of Medicine, University of Miami

Robert Duncan, MD

Professor of Epidemiology, University of Miami

Norah J Shire, MPH

Epidemiologist, Division of Digestive Diseases, University of Cincinnati

Phillip Ruiz, MD PhD

Professor of Pathology and Immunology, Department of Pathology and Surgery, University of Miami

Caio Nery, MD

Associate Professor of Surgery, Department of Surgery, University of Miami

Marzia Montalbano, MD

Research Assistant of Surgery, Department of Surgery, University of Miami

Halim Muslu, MD

Hepatology Fellow, Department of Medicine, University of Miami

Kamran Safdar, MD

Assistant Professor of Medicine, Department of Medicine, University of Miami

Eugene R Schiff, MD

Professor of Medicine, Department of Medicine, University of Miami

Andreas G Tzakis, MD PhD

Professor of Surgery, Department of Surgery, University of Miami

Juan R Madariaga, MD PhD

Associate Professor of Surgery, Department of Surgery, University of Miami

Reprints: Guy W Neff MD, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, MSB Room 6560, Cincinnati, OH 45267-0595, fax 513/558-1744, Guy.Neff{at}uc.edu

BACKGROUND: Resistant hepatitis B virus (HBV) strains develop in 30% of liver transplant recipients treated with lamivudine within 2 years from the time of transplantation.

OBJECTIVE: To assess safety and outcomes of tenofovir salvage therapy for patients with lamivudine resistance in a retrospective cohort of liver-transplanted patients.

METHODS: Medical records were retrospectively evaluated for patients who received tenofovir. Data collected included demographics, HBV serologic information prior to and during tenofovir therapy, drug-related complications, and creatinine clearance. Criteria for lamivudine resistance included elevation of liver chemistries along with reappearance of hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA.

RESULTS: Sixteen patients showed resistance to lamivudine at 10–85 months (median 26) following liver transplantation. Tenofovir 300 mg/day orally was added in 8 patients 1–66 months after the development of viral lamivudine resistance and continued for 14–26 months (median 19.3). All 8 patients experienced HBV DNA viral suppression, with 7 currently nondetectable. No adverse events were reported, and creatinine clearance was not impaired.

CONCLUSIONS: Our results suggest that tenofovir safely and markedly decreases replication of lamivudine-resistant HBV variants after liver transplantation and is another potential option for the treatment of HBV lamivudine resistance.

Key Words: adefovir, hepatitis B virus, hepatitis C virus, lamivudine, liver transplantation, tenofovir disoproxil fumarate

Published Online, October 26, 2004. www.theannals.com, DOI 10.1345/aph.1E280

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