title: Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy.
abstract: Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Carl Neuberg Strasse 1, D-30625 Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Potthoff
authors.forename: H L
authors.initials: HL
authors.lastname: Tillmann
authors.forename: C
authors.initials: C
authors.lastname: Bara
authors.forename: K
authors.initials: K
authors.lastname: Deterding
authors.forename: K
authors.initials: K
authors.lastname: Pethig
authors.forename: S
authors.initials: S
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Haverich
authors.forename: K H W
authors.initials: KH
authors.lastname: Böker
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D015075:2-Aminopurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000821:virology; D000077595:Famciclovir; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000821:virology; D008297:Male; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir