Early introduction of subcutaneous hepatitis B immunoglobulin following liver transplantation for hepatitis B virus infection: A prospective, multicenter study

BACKGROUND: Subcutaneous administration of hepatitis B immunoglobulin (HBIg) is effective in preventing hepatitis B virus (HBV) recurrence after liver transplantation, but early conversion to subcutaneous administration is undocumented. METHODS: In a prospective study, patients transplanted for terminal liver disease due to HBV infection who were HBV DNA-negative at transplant were switched by week 3 posttransplantation from intravenous to subcutaneous HBIg (500 or 1000 IU weekly or fortnightly, adjusted according to serum anti-HBs trough level) if they were HBsAg- and HBV-DNA negative at time of switch. All patients concomitantly received nucleos(t)ide analogue antiviral therapy. Primary endpoint was failure rate by month 6, defined as serum anti-HBs of 100 IU/L or less or HBV reinfection despite serum anti-HBs greater than 100 IU/L. RESULTS: Of 49 patients treated, 47 (95.9%) continued treatment until month 6. All patients achieved administration by a caregiver or self-injection by week 14. No treatment failures occurred. Mean anti-HBs declined progressively to month 6, plateauing at a protective titer of approximately 290 IU/L. All patients tested for HBV DNA remained negative (45/45). Only 1 adverse event (mild injection site hematoma) was assessed as treatment-related. CONCLUSIONS: Introduction of subcutaneous HBIg administration by week 3 posttransplantation, combined with HBV virostatic prophylaxis, is effective and convenient for preventing HBV recurrence. Author Information Address:1 Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 2 Liver Transplantation Center and General Surgery 2U, Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino, Torino, Italy. 3 Unita Operativa di Chirurgia Generale e dei Trapianti di Fegato e Multiorgano, Bologna, Italy. 4 Centro Trapianti di Fegato e Pancreas, Cagliari, Italy. 5 Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 6 Chirurgia Epatobiliare e Trapianto Epatico Azienda Ospedaliera Universitaria di Padova-Unita Operativa di Chirurgia, Padova, Italy. 7 Struttura Complessa di Chirurgia Generale e dei Trapianti, Ospedale Niguarda, Milan, Italy. 8 Chirurgia Generale e Trapianto di Fegato, Bari, Italy. 9 Experimental Medicine and Surgery, Fondazione Policlinico Tor Vergata, Rome, Italy. 10 Unidad de Hepatologia, Servicio de Medicina Digestiva, Hospital Universitari i Politecnic La Fe, Valencia, Spain. 11 Servicio de Cirugia General, Aparato Digestivo y Trasplante de Organos Abdominales, Hospital Universitario Doce de Octubre, Madrid, Spain. 12 Liver Unit, Hospital Clinic de Barcelona, Barcelona, Spain. 13 Institute of Liver Studies, King's College Hospital, London, United Kingdom. 14 NIHR Liver BRU, QE Hospital and Birmingham University, Birmingham, United Kingdom. 15 AP-HP Hopital Paul-Brousse, Centre Hepato-Biliaire, Villejuif, France. 16 University Paris-Sud, UMR-S 1193, Villejuif, France. 17 Biotest AG, Dreieich, Germany.