A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C
| Autor: | Valeer Desmet, Christine Vander Stichele, Dirk Sprengers, Stéphanie Dincq, Erik Depla, Frederik Nevens, Geert Maertens, Yves Horsmans, Tania Roskams, Frank Hulstaert, Hans Van Vlierberghe, Emmanuel Quinaux, A. Elewaut, Geert Leroux-Roels |
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| Předmět: |
Male
medicine.medical_specialty Hepatitis C virus Hepacivirus Pilot Projects medicine.disease_cause Placebo Gastroenterology Fibrosis Internal medicine Biopsy Medicine Humans Viral Structural Proteins Hepatology medicine.diagnostic_test biology business.industry Alanine Transaminase Hepatitis C Chronic Middle Aged biology.organism_classification medicine.disease Ishak Score Vaccination Alanine transaminase Immunology Antibody Formation biology.protein RNA Viral Female business |
| Zdroj: | Ghent University Academic Bibliography |
| Popis: | New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype 1) were randomized to receive 20 mug of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty-four patients (12 men, 12 women; mean age, 52 y; 18 interferon-based treatment failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent a biopsy before and after 2 courses of E1, 17 months later. Liver histology was scored by 2 blinded pathologists according to the Ishak and Metavir systems. Postinjection reactions were similar to placebo (alum only). Nine of 24 patients (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%) showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak and Metavir fibrosis scores. Plasma HCV-RNA levels remained unchanged, whereas ALT levels showed a trend toward a decrease during treatment. All but 3 patients developed a significant de novo E1-specific T-cell response. The increase in anti-E1 antibody levels correlated with the decrease in total Ishak score and with the relative decreases in both Ishak fibrosis score and ALT level (all P < or =.01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study. |
| Databáze: | OpenAIRE |
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