Zusammenfassung
Die Höhe der Hepatitis B Virus-DNA (HBV-DNA) ist ein
entscheidender Parameter für die Progression zur Leberzirrhose
und zum hepatozellulären Karzinom [HCC].
Daher ist die dauerhafte Senkung der HBV-DNA unter die Nachweisgrenze
sensitiver Nachweisverfahren ein wichtiges Behandlungsziel. Dieses
Ziel wird mit den derzeit zur Verfügung stehenden direkt
antiviralen Medikamenten bei fast allen Patienten erreicht. Allerdings
stellt die Entwicklung von Resistenzen eine große Herausforderung
dar. Entecavir hat in dieser Hinsicht ein sehr gutes Profil – sowohl
was die antivirale Wirksamkeit als auch das Resistenzprofil bei
nicht vorbehandelten Patienten betrifft. Nach 5 Jahren dauerhafter
Behandlung mit Entecavir liegt der Anteil HBe-Antigen positiver
Patienten mit nicht nachweisbarer HBV-DNA bei über 90 %,
die Resistenzentwicklung nur bei ca. 1 %. Bei
Patienten mit Lamivudinresistenz ist das Therapieansprechen allerdings
reduziert. Patienten mit einer Lamivudinresistenz benötigen
nur noch 1 oder 2 zusätzliche Mutationen bis zur Ausbildung
einer Entecavirresistenz im Gegensatz zu 3 Mutationen bei nicht
vorbehandelten Patienten. Zusammenfassend ist Entecavir ein weiterer
wichtiger Meilenstein in der Therapie der Hepatitis B.
Abstract
The level of HBV-DNA is a crucial determinant of the progression
to liver cirrhosis or hepatocellular carcinoma. Thus the effective
suppression of HBV-DNA below the limit of detection of high sensitive
assays is a major aim of treatment. This aim will be achieved in
almost all patients with current available direct antiviral drugs.
However, the development of drug resistance remains a main challenge
for the future. Entecavir has a good profile regarding both antiviral
efficacy and resistance profile in the treatment of previously untreated
patients. After five year on Entecavir more than 90 % of
HBe-Ag positive patients had achieved HBV-DNA below 300 copies/ml
and resistance developed in only about 1 %. However, patients
in whom there had been previous resistance to lamivudine have lower
treatment responses and higher resistance rates because only one
or two additional mutations in the HBV-polymerase gene are required
for the development of entecavir resistance in contrast to three
mutations required in treatment naïve patients. In summary,
Entecavir adds a new milestone in the treatment of chronic hepatitis
B.
Schlüsselwörter
Hepatitis B - Therapie - HBV-DNA - Entecavir - Resistenz
Keywords
hepatitis B - therapy - HBV-DNA - entecavir - resistance
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Dr. med. Markus Cornberg
Klinik für Gastroenterologie, Hepatologie
und Endokrinologie, Medizinische Hochschule Hannover
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