No beneficial effects of amantadine in treatment of chronic hepatitis C patients

van Soest, Hanneke; van der Schaar, Peter J.; Koek, Ger H.; de Vries, Richard A.; van Ooteghem, Nancy A.; van Hoek, Bart; Drenth, Joost P.H.; Vrolijk, Jan M.; Lieverse, Rob J.; Houben, Peter; van der Sluys Veer, Annet; Siersema, Peter D.; Schipper, Marguerite E.I.; van Erpecum, Karel J.; Boland, Greet J.

doi:10.1016/j.dld.2009.10.006

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Volume 42, Issue 7 , Pages 496-502, July 2010

No beneficial effects of amantadine in treatment of chronic hepatitis C patients☆

Hanneke van Soest
- Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
Peter J. van der Schaar
- Dept. of Gastroenterology and Hepatology, Atrium Medical Center Heerlen, The Netherlands
Ger H. Koek
- Dept. of Gastroenterology and Hepatology, University Hospital Maastricht, The Netherlands
Richard A. de Vries
- Dept. of Gastroenterology and Hepatology, Rijnstate Hospital Arnhem, The Netherlands
Nancy A. van Ooteghem
- Dept. of Gastroenterology and Hepatology, St Lucas Andreas Hospital Amsterdam, The Netherlands
Bart van Hoek
- Dept. of Gastroenterology and Hepatology, Leiden University Medical Center, The Netherlands
Joost P.H. Drenth
- Dept. of Gastroenterology and Hepatology, University Hospital Nijmegen, The Netherlands
Jan M. Vrolijk
- Dept. of Gastroenterology and Hepatology, Erasmus Medical Center Rotterdam, The Netherlands
Rob J. Lieverse
- Dept. of Gastroenterology and Hepatology, Gelre Ziekenhuizen Apeldoorn, The Netherlands
Peter Houben
- Dept. of Gastroenterology and Hepatology, Ziekenhuis Zeeuws Vlaanderen, The Netherlands
Annet van der Sluys Veer
- Dept. of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis Amsterdam, The Netherlands
Peter D. Siersema
- Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
Marguerite E.I. Schipper
- Dept. of Pathology, University Medical Center Utrecht, The Netherlands
Karel J. van Erpecum
- Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
- Corresponding author at: Dept. of Gastroenterology and Hepatology F 02. 618, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Tel.: +31 88 7557004; fax: +31 88 7555533.
Greet J. Boland
- Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht, The Netherlands
- Dept. of Virology, University Medical Center Utrecht, The Netherlands

Received 11 January 2009; accepted 28 October 2009. published online 17 December 2009.

Abstract

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-naïve patients.

Methods

297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5μg/kg/week up to 26 weeks and thereafter, 1.0μg/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 γGT levels were independent predictors for sustained viral response.