Retrospektive Kohortenstudie zur Lamivudintherapie bei Patienten mit chronischer Hepatitis B

 

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Hintergrund und Fragestellung: Lamivudin, ein Nukleosidanalogon mit spezifischer, antiviraler Wirkung gegen das Hepatitis-B-Virus, steht seit 1999 zur Behandlung der chronischen Hepatitis B als Alternative zu der bisherigen Standardtherapie mit Interferon-α (IFN-α) zur Verfügung. Da bislang nur wenige Daten aus Europa vorliegen, untersuchten wir Wirksamkeit und Verträglichkeit einer Lamivudintherapie in einem mitteleuropäischen Patientenkollektiv und verglichen unsere Erfahrungen mit den Ergebnissen der vorliegenden, internationalen Studien.

Patienten und Methodik: Im Rahmen einer retrospektiven, multizentrischen Kohortenuntersuchung wurden die Daten, Krankheits- und Therapieverläufe von 95 Patienten mit chronischer Hepatitis B (medianes Alter: 40,4 Jahre, Männer: 87 Patienten, Frauen: 8 Patienten, HBeAg-positiv: 47 Pat.; Anti-HBe-positiv: 48 Pat.), die zwischen 1997 und 1999 Lamivudin (100 - 300 mg/d per os, mediane Therapiedauer: 52 Wochen) erhielten, analysiert.

Ergebnisse: Unter Lamivudintherapie wurde ein virologisches Ansprechen mit HBeAg-/Anti-HBe-Serokonversion bei 22/47 (47 %) der HBeAg-positiven Patienten erzielt. Als positive Prädiktoren für ein Ansprechen auf eine Therapie konnten eine Erhöhung der GPT (> dem Dreifachen des oberen Normbereichs: p = 0,03) sowie eine niedrige HBV-DNS-Konzentration im Serum (<= 100 pg/ml: p = 0,08) vor Therapie identifiziert werden. Bei sechs von neun Patienten mit einer Nachbeobachtung bei erfolgter HBeAg-/Anti-HBe-Serokonversion wurde ein dauerhaftes virologisches Ansprechen beobachtet. Desweiteren konnte ein virologisches Ansprechen mit Negativierung der HBV-DNS bei 35/48 (73 %) der Anti-HBe-positiven Patienten unter Lamivudintherapie erzielt werden. Während der Behandlung wurden lediglich leichtgradige, reversible Nebenwirkungen beobachtet.

Folgerungen: In unserer retrospektiven Kohortenstudie waren die virologischen Ansprechraten auf eine Lamivudintherapie mit den Ergebnissen der vorliegenden, internationalen Studien vergleichbar. Lamivudin stellt somit eine kostengünstige und nebenwirkungsarme Alternative zu einer IFN-α Therapie dar.

Lamivudin in the treatment of chronic hepatitis B - a retrospective analysis in German centers

Background and Aims: Lamivudine, a nucleoside analogue with specific antiviral activity against the hepatitis B virus, is now available as an alternative therapeutic option to standard interferon-α treatment in chronic hepatitis B. Larger studies with lamivudine treatment in chronic hepatitis B were mainly performed in North America and Asia. Data on treatment responses in European patients are sparse. Therefore, we evaluated the efficacy and safety of lamivudine therapy in Central European patients and compared the data with the results from international trials.

Patients and Methods: In this retrospective, multicenter, cohort study, 95 patients with chronic hepatitis B (median age: 40.4 years, male: 87 patients, female: 8 patients, HBeAg positive: 47 patients, anti-HBe positive: 48 patients), who were treated with lamivudine (100 - 300 mg/d per os) between 1997 to 1999, were enrolled.

Results: During lamivudine treatment a virologic response with HBeAg to anti-HBe seroconversion was achieved in 22/47 (47 %) of the HBeAg positive patients. Pretreatment ALT levels (> threefold the upper limit of normal; p = 0.03) and HBV-DNA serum concentration (<= 100 pg/ml; p = 0.08) were identified as positive predictors for virologic responses. The virologic response was sustained in six of nine patients who had a follow-up period (median 26 weeks). In anti-HBe positive patients a virologic response with undectable HBV-DNA levels was achieved in 35/48 (73 %) patients during lamivudine treatment. Side effects during lamivudine therapy were generally mild and reversible.

Conclusions: In this retrospective cohort study virologic end-of-treatment responses to lamivudine monotherapy in patients with chronic hepatitis B were comparable with yet reported international trials. Thus, lamivudine represents a cost-effective and well tolerable option in addition to IFN-α in the treatment of chronic hepatitis B.

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Korrespondenz

Prof. Dr. med. Stefan Zeuzem

Medizinische Klinik II

Theodor-Stern-Kai 7

60590 Frankfurt

Phone: 069/6301-5212 oder -5297

Fax: 069/6301-4807

Email: Zeuzem@em.uni-frankfurt.de