Background: Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial. Aims: We aimed to examine whether such policy enhances sustained viral response in treatment-naive... Show moreBackground: Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial. Aims: We aimed to examine whether such policy enhances sustained viral response in treatment-naive patients. Methods: 297 naive hepatitis C patients were randomized for treatment with amantadine 200 mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 mu g/kg/week up to 26 weeks and thereafter, 1.0 mu g/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24. Results: 49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p = 0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response. Conclusion: Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects. (C) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Show less
Background: Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune... Show moreBackground: Five to ten percent of immunocompetent persons fail to develop a protective immune response to hepatitis B vaccination, and are defined non-responders (NR). We investigated the immune response to intradermal hepatitis B vaccination after pre-treatment of the skin with the TLR7 agonist imiquimod. Methods: Twenty-one non-responders (anti-HBs <10 IU/l after at least 6 intramuscular hepatitis B vaccinations) were randomly assigned to the control group (N=11) or the experimental group (N=10). Participants in both groups received 3 intradermal (ID) vaccinations with 5 mu g HBsAg (0.125 mL) at 0, 1 and 6 months. In the experimental group, the dermal site of injection was pre-treated with 250 mg imiquimod ointment. Anti-HBs antibodies were determined at 0, 1, 2, 6 and 7 months. Results: In both study groups, 70% of the participants developed a protective immune response (anti-HBs >= 10 IU/l), after the 3rd intradermal vaccination. Conclusion: The application of imiquimod on the skin prior to intradermal vaccination did not enhance the humoral response to hepatitis B vaccine. However, irrespective of imiquimod application, 70% of the NR who had not responded to 6 previous intramuscular vaccinations, developed a protective immune response with high affinity antibodies after 3 ID hepatitis B vaccinations with 5 mu g HBsAg. (C) 2010 Elsevier Ltd. All rights reserved. Show less
