Ziel der Therapie/Definition des Behandlungserfolgs
Konsens
Kriterien eines Therapieansprechens sind:
biochemisch: ALT-Normalisierung
virologisch: HBe-Serokonversion, HBV-DNA-Negativierung im Hybridisierungsassay oder ein Abfall der HBV-DNA auf < 105 Kopien/ml in quantitativen PCR-Assays, HBsAg-Verlust
potenzielle Langzeiteffekte: Verhinderung einer hepatischen Dekompensation, die Verhinderung der Entwicklung eines HCC und ein verbessertes Überleben.
Erläuterung
Endpunkte der meisten randomisierten Therapiestudien der Hepatitis B waren dauerhafte Normalisierungen der Transaminasen und HBe-Serokonversionen. Patienten, die diese Erfolgsparameter erfüllten, zeigten eine geringere Rate hepatischer Dekompensationen, eine niedrige Rate von HCC-Entstehungen sowie ein verbessertes Langzeitüberleben [1]
[2]
[3]
[4]. Die HBV-Viruslast wurde in den Studien der 90er-Jahre zunächst nur mit Hybridisierungsassays bestimmt (Cut-Off ca. 100 000 - 200 000 Kopien/ml); sensitivere quantitative PCR-basierte Methoden sind erst seit wenigen Jahren im routinemäßigen Einsatz. Da eine dauerhaft niedrig replikative Hepatitis B mit einem milden Verlauf assoziiert ist, wird ein Abfall der HBV-DNA unter einen Wert von 105 Kopien/ml als Therapieansprechen angesehen. Das histologische Therapieansprechen, welches zur Zulassung der neuen Nukleosidanaloga gefordert wurde, ist meist nur am Ende einer Therapie bestimmt worden. Daten zum histologischen Therapieansprechen im Langzeitverlauf nach Therapieende liegen nur für einige Interferonstudien vor und fehlen bisher für die Behandlung der Hepatitis B mit Nukleosidanaloga.
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