Zusammenfassung
Einleitung: Es liegen nur wenige
europäische Daten zu einer Langzeit-Therapie mit Lamivudin sowie zu
möglichen Prädiktoren für ein anhaltendes virologisches
Ansprechen und die Entwicklung einer Resistenzmutante vor.
Patienten und Methoden: 39 Patienten (17
HBeAg+, 22 HBeAg-), wurden im Median 2,5 Jahre (0,5-4 Jahre) mit
Lamivudin behandelt. Die Patientendaten wurden retrospektiv ausgewertet.
Ergebnisse: Eine
HBsAg-/anti-HBs-Serokonversion wurde bei keinem Patienten beobachtet. Bei 14
von 17 initial HBeAg-positiven Patienten lag der HBeAg-Status zu Therapieende
vor. Dabei wurden bei 8 Patienten ein Verlust des HBeAg und bei 7 von diesen
8 Patienten eine Serokonversion zu anti-HBe beobachtet. Bei 5 von 6
Patienten mit HBeAg-Serokonversion und einer dokumentierten Nachbeobachtung
dauerte die Serokonversion nach Therapieende an. Bei den initial
HBeAg-negativen Patienten wurde ein virologisches Ansprechen (Serum HBV
DNA≤1 × 105 Kopien/ml) bei 12 von 22
Patienten nach einer medianen Therapiedauer von 2,5 Jahren beobachtet. Bei
einem von zwei initial HBeAg-negativen Patienten mit einem virologischen
Ansprechen und einer Nachbeobachtung nach Therapieende war das Ansprechen
dauerhaft. Eine Resistenz auf Lamivudin trat bei 15 von 36 Patienten mit
vorhandener HBV-DNA-Quantifizierung nach einer medianen Behandlungsdauer von 2
Jahren auf.
Schlussfolgerung: Die vorliegende
retrospektive Studie bestätigt internationale Daten zur Lamivudintherapie
für ein mitteleuropäisches Patientenkollektiv. Bei mehr als
50 % der Patienten mit chronischer Hepatitis B ließ sich
durch Lamivudin ein virologischer Therapieerfolg erzielen. Weder für
ein dauerhaftes virologisches Ansprechen noch für die Resistenzentwicklung
auf Lamivudin ließen sich Prädiktoren vor Therapie
identifizieren.
Abstract
Introduction: European data on outcome and
follow-up of long-term lamivudine treatment are sparse. Moreover, little is
known about predictors for sustained virologic response and for development of
drug resistance in patients with lamivudine monotherapy.
Patients and methods : 39 patients (17 HBeAg+, 22 HBeAg-) were treated with
lamivudine for a median duration of 2.5 years (range: 0.5-4). Outcome to
therapy and predictors for response and drug resistance were analyzed
retrospectively.
Results: None of the patients lost HBsAg.
In 14 of 17 initially HBeAg positive patients the HBeAg status was available at
the end of treatment. Loss of HBeAg was observed in 8 patients and 7 of these 8
patients seroconverted to anti-HBe. Five of 6 patients with HBeAg
seroconversion and a post-treatment follow-up period showed sustained HBeAg
seroconversion. In HBeAg negative patients virologic response (serum HBV
DNA≤1 × 105 copies/ml) was observed in 12 of
22 patients after a median treatment period of 2.5 years. Post-treatment
follow-up data were available in only 2 patients, one of which remained below
1 × 105 HBV DNA copies/ml for one year.
Resistance emerged in 15 of 36 patients with available serum HBV DNA data after
a median treatment period of 2 years.
Conclusion: The present retrospective study
confirms international data for lamivudine treatment in a central European
setting. Lamivudine therapy achieved disease control in more than
50 % of patients treated for chronic hepatitis B. Baseline
predictors could neither be identified for sustained virologic response nor for
the development of drug resistance.
Schlüsselwörter
Lamivudin-Langzeittherapie - Resistenzentwicklung - Nachbeobachtung - chronische Hepatitis B
Key words
Long-term lamivudine - post-treatment follow-up - drug resistance
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Prof. Dr. med. Stefan Zeuzem
Klinik und Poliklinik für Innere Medizin II,
Universitätskliniken des Saarlandes
Kirrberger Str.
66421 Homburg/Saar
Email: zeuzem@uniklinik-saarland.de