title: Efficacy of combined lamivudine and adefovir dipivoxil treatment for severe HBV graft reinfection after living donor liver transplantation.
abstract: Resistance to lamivudine and hyperimmune globulin (HBIG) may cause severe graft reinfection with progression to fulminant hepatic failure in liver transplant recipients. In this report, we describe the clinical course of a patient with perinatally acquired chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma who developed severe fibrosing cholestatic hepatitis after living donor liver transplantation because of the emergence of lamivudine and HBIG-resistant chronic hepatitis B. Immunohistochemistry demonstrated that more than 30% of hepatocytes stained positively for hepatitis B core antigen. Hepatitis B virus sequence analysis revealed several mutations in the polymerase gene (L528M, M552I, M552V) as well as in the surface gene region encoding the immunogenic major hydrophilic loop of the small surface protein (G130N, M133T, D144G). The amino acid exchange at codon 144 has already been described to escape neutralization by HBIG. Combined treatment with lamivudine and adefovir dipivoxil (ADV) was associated with a dramatic biochemical, virological and clinical response with resolution of jaundice, ascites, peripheral edema and pleural effusions. Serum bilirubin normalized, HBV DNA levels significantly decreased and liver biopsy was remarkable for the absence of viral protein. These results indicate that ADV may provide a sustained rescue treatment for aggressive courses of HBV graft reinfection in liver transplant recipients.
authors.affiliation: Department of General Surgery and Transplantation, University of Essen, Germany. susanne.beckebaum@uni-essen.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Beckebaum
authors.forename: Massimo
authors.initials: M
authors.lastname: Malagó
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.forename: Vito R
authors.initials: VR
authors.lastname: Cicinnati
authors.forename: Martin
authors.initials: M
authors.lastname: Trippler
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.forename: Nicole
authors.initials: N
authors.lastname: Lama
authors.forename: Ulrich
authors.initials: U
authors.lastname: Treichel
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Broelsch
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates
chemical_list: D000998:Antiviral Agents; D007136:Immunoglobulins; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil; C045213:hepatitis B hyperimmune globulin