All-trans retinoic acid for treatment of chronic hepatitis C

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Liver International 28 (3) , 347–354 doi:10.1111/j.1478-3231.2007.01666.x

Abstract

CLINICAL STUDIES

All-trans retinoic acid for treatment of chronic hepatitis C

Wulf O. Böcher11 I Department of Internal Medicine, Johannes Gutenberg

University Hospital, Mainz, Germany, Christian Wallasch22 GPC Biotech (former

AXXIMA Biotech), München, Germany, Höhler33 Department of Internal

Medicine, Prosper Hospital, Recklinghausen, Germany and R. Galle11 I

Department of Internal Medicine, Johannes Gutenberg University Hospital, Mainz,

Germany1 I Department of Internal Medicine, Johannes Gutenberg University

Hospital, Mainz, Germany

2 GPC Biotech (former AXXIMA Biotech), München, Germany

3 Department of Internal Medicine, Prosper Hospital, Recklinghausen, Germany

Correspondence

Wulf O. Böcher, MD, I Department of Internal Medicine, Johannes Gutenberg

University Hospital, Langenbeckstrasse 1, 55131 Mainz, Germany

Tel: +49 6131 172666

Fax: +49 6131 176621

e-mail: boecher@...

Abbreviations

ATRA, all-trans retinoic acid; EVR, early virological response; GI-GPx,

gastrointestinal glutathione peroxidase; PegIFN-α, pegylated interferon-alpha;

SVR, sustained virological response.

Abstract

Background/Aims: In vitro studies in the subgenomic hepatitis C virus (HCV)

replicon system have identified all-trans retinoic acid (ATRA) as a potential

therapeutic against hepatitis C. Thus, the antiviral potential of this drug

should be assessed in vivo.

Methods: Twenty highly treatment experienced serotype 1 patients with

non-response to conventional or pegylated interferon-α (Peg-/IFN-α) and

ribavirin were randomly assigned to 12 weeks of monotherapy with ATRA (group A)

or a combination of ATRA and PegIFN-α2a (group . HCV RNA was assessed by bDNA

assay and if negative by highly sensitive polymerase chain reaction.

Results: During treatment, five of 10 patients in group A had a drop of

viraemia>1log, while in group B after 8 weeks five of 10 dropped>2log, and three

of 10 cleared HCV RNA from serum. Viraemia relapsed after treatment cessation.

ATRA was rather well tolerated, with transient headache, dry skin and mucosa

representing the most common side effects.

Conclusions: The viral load reduction under ATRA monotherapy, although limited

and transient, supports the antiviral activity of ATRA. However, the rapid loss

of HCV RNA in three of 10 previous non-responders under ATRA and PegIFN-α2a

treatment demonstrates a strong additive or synergistic ATRA effect and calls

for a controlled trial to assess the therapeutic potential of this drug.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1478-3231.2007.01666.x

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[Guest guest]

Liver International 28 (3) , 347–354 doi:10.1111/j.1478-3231.2007.01666.x

Abstract

CLINICAL STUDIES

All-trans retinoic acid for treatment of chronic hepatitis C

Wulf O. Böcher11 I Department of Internal Medicine, Johannes Gutenberg

University Hospital, Mainz, Germany, Christian Wallasch22 GPC Biotech (former

AXXIMA Biotech), München, Germany, Höhler33 Department of Internal

Medicine, Prosper Hospital, Recklinghausen, Germany and R. Galle11 I

Department of Internal Medicine, Johannes Gutenberg University Hospital, Mainz,

Germany1 I Department of Internal Medicine, Johannes Gutenberg University

Hospital, Mainz, Germany

2 GPC Biotech (former AXXIMA Biotech), München, Germany

3 Department of Internal Medicine, Prosper Hospital, Recklinghausen, Germany

Correspondence

Wulf O. Böcher, MD, I Department of Internal Medicine, Johannes Gutenberg

University Hospital, Langenbeckstrasse 1, 55131 Mainz, Germany

Tel: +49 6131 172666

Fax: +49 6131 176621

e-mail: boecher@...

Abbreviations

ATRA, all-trans retinoic acid; EVR, early virological response; GI-GPx,

gastrointestinal glutathione peroxidase; PegIFN-α, pegylated interferon-alpha;

SVR, sustained virological response.

Abstract

Background/Aims: In vitro studies in the subgenomic hepatitis C virus (HCV)

replicon system have identified all-trans retinoic acid (ATRA) as a potential

therapeutic against hepatitis C. Thus, the antiviral potential of this drug

should be assessed in vivo.

Methods: Twenty highly treatment experienced serotype 1 patients with

non-response to conventional or pegylated interferon-α (Peg-/IFN-α) and

ribavirin were randomly assigned to 12 weeks of monotherapy with ATRA (group A)

or a combination of ATRA and PegIFN-α2a (group . HCV RNA was assessed by bDNA

assay and if negative by highly sensitive polymerase chain reaction.

Results: During treatment, five of 10 patients in group A had a drop of

viraemia>1log, while in group B after 8 weeks five of 10 dropped>2log, and three

of 10 cleared HCV RNA from serum. Viraemia relapsed after treatment cessation.

ATRA was rather well tolerated, with transient headache, dry skin and mucosa

representing the most common side effects.

Conclusions: The viral load reduction under ATRA monotherapy, although limited

and transient, supports the antiviral activity of ATRA. However, the rapid loss

of HCV RNA in three of 10 previous non-responders under ATRA and PegIFN-α2a

treatment demonstrates a strong additive or synergistic ATRA effect and calls

for a controlled trial to assess the therapeutic potential of this drug.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1478-3231.2007.01666.x

_________________________________________________________________

Helping your favorite cause is as easy as instant messaging. You IM, we give.

http://im.live.com/Messenger/IM/Home/?source=text_hotmail_join