Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience H. L. Tillmann, 1,2 J. Hadem, 2 L. Leifeld, 3 K. Zachou, 4 A. Canbay, 5 C. Eisenbach, 6 I. Graziadei, 7 J. Encke, 6 H. Schmidt, 8,  W. Vogel, 7 A. Schneider, 2 U. Spengler, 3 G. Gerken, 5 G. N. Dalekos, 4 H. Wedemeyer 2 and M. P. Manns 2 1 Medical Clinic and Policlinic II, University Leipzig, Leipzig, Germany; 2 Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; 3 Medical Clinic and Policlinic I, Universita ¨t Bonn, Bonn, Germany; 4 Academic Liver Unit, Medical School, University of Thessaly, Faculty of Health Sciences, Larissa, Greece; 5 Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany; 6 Department of Internal Medicine IV, University of Heidelberg, Heidelberg, Germany; 7 Clinical Department of Gastroenterology and Hepatology, University Hospital Innsbruck, Innsbruck, Austria; and 8 Medical Clinic, Gatroenterolog, Charite ´ Campus Mitte, Berlin, Germany Received December 2004; accepted for publication April 2005 SUMMARY. Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine ther- apy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by po- lymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivu- dine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough. Keywords: fulminant hepatitis, hepatitis B, lamivudine, severe acute hepatitis, therapy. INTRODUCTION Acute hepatitis B virus (HBV) infection may take a severe course, which can eventually lead to fulminant hepatic failure in about 1% of all cases with acute hepatitis B [1]. Liver transplantation is currently the only therapeutic option to prevent death, which would occur otherwise in approximately 70% of patients [2–6]. Outcome of HBV-in- duced liver failure is worse than for most other etiologies for acute liver failure as recently reported [6]. No specific ther- apy is currently established for severe acute hepatitis or fulminant hepatic failure due to HBV infection. Moreover, about 20% of patients transplanted for fulminant hepatitis B suffer from recurrent hepatitis B infection [7]. This rate of recurrence can be reduced by application of hepatitis B immunoglobulin (HBIg) from the time of transplantation [7]. In patients transplanted for chronic hepatitis B it has been shown that the recurrence rate of HBV is further reduced by the combination of HBIg with lamivudine [8]. In case of resistance against lamivudine we would nowadays use adefovir dipivoxil. For chronic hepatitis B, there are currently three-licensed treatment options: either interferon-alpha, lamivudine or  Present address: Division of Transplant Hepatology, Universita ¨tsk- linikum Mu ¨ nster, Albert-Schweitzer-Str. 33, 48149 Mu ¨ nster, Ger- many. Abbreviations: HBV, hepatitis B virus; HBIg, hepatitis B immuno- globulin; ALT, Alanine-aminotransferase; PCR, polymerase chain reaction. Correspondence: Hans L. Tillmann, Medizinische Klinik and Poli- klinik II, Universita ¨t Leipzig, Philipp-Rosenthal Str. 27, 04103 Leipzig, Germany. E-mail: hans.tillmann@medizin.uni-leipzig.de Journal of Viral Hepatitis, 2006, 13, 256–263 doi:10.1111/j.1365-2893.2005.00695.x Ó 2006 Blackwell Publishing Ltd