Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5647-5653
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5647
Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study
Benjamin Terrier, Nathanael Lapidus, Stanislas Pol, Lawrence Serfaty, Vlad Ratziu, Tarik Asselah, Vincent Thibault, Jean-Claude Souberbielle, Fabrice Carrat, Patrice Cacoub
Benjamin Terrier, Patrice Cacoub, Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, F-75005 Paris, France
Benjamin Terrier, Department of Internal Medicine, Groupe Hospitalier Cochin, AP-HP, Université Paris Descartes, Paris 5, F-75014 Paris, France
Nathanael Lapidus, Fabrice Carrat, INSERM, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, F-75013 Paris, France
Nathanael Lapidus, Fabrice Carrat, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, F-75013 Paris, France
Nathanael Lapidus, Fabrice Carrat, Public Health Department, Saint-Antoine Hospital, AP-HP, F-75014 Paris, France
Stanislas Pol, Department of Hepatology, Groupe Hospitalier Cochin, AP-HP, Université Paris Descartes, Paris 5, F-75014 Paris, France
Lawrence Serfaty, Department of Hepatology, Hôpital Saint-Antoine, AP-HP, Université Pierre et Marie Curie, Paris 6, F-75012 Paris, France
Vlad Ratziu, Department of Hepatology, Groupe Hospitalier Pitié-Salpetrière, AP-HP, Université Pierre et Marie Curie, Paris 6, F-75013 Paris, France
Tarik Asselah, Department of Hepatology, Hôpital Beaujon, AP-HP, F-92110 Clichy, France
Vincent Thibault, Department of Virology, Groupe Hospitalier Pitié-Salpetrière, AP-HP, Université Pierre et Marie Curie, Paris 6, F-75013 Paris, France
Jean-Claude Souberbielle, Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, AP-HP, Université Paris Descartes, F-75015 Paris, France
Patrice Cacoub, INSERM, UMR_S 959, F-75013 Paris, France
Patrice Cacoub, CNRS, UMR 7211, F-75005 Paris, France
Patrice Cacoub, Department of Internal Medicine and Clinical Immunology, Hôpital Pitié-Salpétrière, AP-HP, 47-83 boulevard de l’Hôpital, F-75013 Paris, France
Author contributions: Terrier B, Carrat F and Cacoub P designed the research; Terrier B, Lapidus N, Pol S, Serfaty L, Ratziu V, Asselah T, Thibault V, Souberbielle JC, Carrat F and Cacoub P performed the research; Terrier B, Lapidus N, Pol S, Serfaty L, Ratziu V, Asselah T, Thibault V, Souberbielle JC, Carrat F and Cacoub P analyzed the data; Terrier B, Lapidus N, Carrat F and Cacoub P wrote the paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Patrice Cacoub, MD, Professor, Department of Internal Medicine and Clinical Immunology, Hôpital Pitié-Salpétrière, AP-HP, 47-83 boulevard de l’Hôpital, F-75013 Paris, France. patrice.cacoub@psl.aphp.fr
Telephone: +33-1-42178009 Fax: +33-1-42178033
Received: July 9, 2014
Peer-review started: July 9, 2014
First decision: August 6, 2014
Revised: August 29, 2014
Accepted: November 18, 2014
Article in press: November 19, 2014
Published online: May 14, 2015
Processing time: 313 Days and 10.7 Hours
Abstract

AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin (PegIFN/RBV) therapy could improve the efficacy of PegIFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus (HCV) infection.

METHODS: Genotype 1 or 4 HCV-infected patients with null response to previous PegIFN/RBV treatment and with hypovitaminosis D (< 30 ng/mL) prospectively received cholecalciferol 100000 IU per week for 4 wk [from week -4 (W-4) to W0], followed by 100000 IU per month in combination with PegIFN/RBV for 12 mo (from W0 to W48). The primary outcome was the rate of early virological response defined by an HCV RNA < 12 IU/mL after 12 wk PegIFN/RBV treatment.

RESULTS: A total of 32 patients were included, 19 (59%) and 13 (41%) patients were HCV genotype 1 and 4, respectively. The median baseline vitamin D level was 15 ng/mL (range: 7-28). In modified intention-to-treat analysis, 29 patients who received at least one dose of PegIFN/RBV were included in the analysis. All patients except one normalized their vitamin D serum levels. The rate of early virologic response was 0/29 (0%). The rate of HCV RNA < 12 IU/mL after 24 wk of PegIFN/RBV was 1/27 (4%). The safety profile was favorable.

CONCLUSION: Addition of vitamin D to PegIFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1 or 4 HCV infection.

Keywords: Vitamin D; Hepatitis C virus; Chronic hepatitis; Pegylated interferon; Ribavirin

Core tip: Vitamin D deficiency is commonly found in patients with chronic hepatitis C virus (HCV) infection and was shown to correlate with sustained virologic response rates to peg-interferon-alpha/ribavirin (PegIFN/RBV) therapy. The addition of vitamin D to PegIFN/RBV was well tolerated but did not improve the rate of early virologic response in previously null-responder patients with chronic genotype 1 or 4 HCV infection.