[Therapy of recurrent hepatitis B infection after liver transplantation. A retrospective analysis of 200 liver transplantations based on hepatitis B associated liver diseases].
BACKGROUND
Before introduction of passive immunoprophylaxis and new antiviral nucleoside analogues the course of hepatitis B recurrence after liver transplantation could hardly be influenced. The result was a inferior graft survival. In the present retrospective analysis of the efficacy of hepatitis B therapy after liver transplantation was analysed retrospectively.


METHODS
Between 1988 and 1998 in total 179 patients were transplanted due to hepatitis B related liver failure at our centre. All patients received passive immunoprophylaxis with hepatitis B immunoglobulin. In case of reinfection after 1993 an antiviral therapy with famciclovir 1500 mg daily was initiated (n = 26), since 1996 lamivudine (100-150 mg daily) was used (n = 12). In case of viral breakthrough under famciclovir treatment or prophylaxis therapy was switched to lamivudine (n = 22). In case of ineffectiveness of lamivudine an antiviral combination therapy with lamivudine and interferon (n = 4) or lamivudine and famciclovir (n = 4) was initiated. Before availability of antiviral agents or in case of viral breakthrough in total 12 patients were retransplanted due to acute or chronic reinfection.


RESULTS
With passive immunoprophylaxis reinfection rate was 33%, 43% and 44% after 1, 3 and 5 years respectively. Without antiviral treatment 52% of patients died within the first year after reinfection. Antiviral therapy with lamivudine or famciclovir improved the one year survival after reinfection to 79%. Suppression of viral replication was more effective with lamivudine. Under lamivudine 26 patients (76%) became HBV-DNA negative, 9 patients HBsAg negative (26%). In contrast no patient became HBsAg negative during famciclovir therapy. Lamivudine was effective also after famciclovir breakthrough in 94% of patients. In case of lamivudine resistant reinfection viral replication could be suppressed with an antiviral combination therapy up to negative HBV-DNA in the hybridization assay. Severe side effects were not observed during any of the antiviral therapies. The graft survival after retransplantation for hepatitis B reinfection was 42% and 25% after one and 3 years.


CONCLUSIONS
Whereas it is generally accepted, that passive immunoprophylaxis lowers the reinfection rate it could be shown in the present study, that antiviral treatment lowers mortality of hepatitis B reinfection. The major problem of lamivudine and famciclovir is viral resistance formation. In this case an antiviral combination therapy might be useful, whereas retransplantation for hepatitis B reinfection should be considered carefully due to inferior graft survival rates.
Seehofer
D
D
Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Humboldt-Universität zu Berlin. daniel.seehofer@charite.de
Rayes
N
N
Bechstein
W O
WO
Naumann
U
U
Neuhaus
R
R
Berg
T
T
Hopf
U
U
Langrehr
J M
JM
Steinmüller
T
T
Platz
K P
KP
Müller
A R
AR
Neuhaus
P
P
D015075:2-Aminopurine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D005260:Female; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007116:Immunization, Passive; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir