title: Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1.
abstract: OBJECTIVE
  Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy.
  
  
  METHODS
  Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed.
  
  
  RESULTS
  In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise.
  
  
  CONCLUSIONS
  Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.
authors.affiliation: First Department of Medicine, Johannes Gutenberg University, Mainz, Germany. tim.zimmermann@unimedizin-mainz.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Zimmermann
authors.affiliation: Center of Gastroenterology, Herne, Germany.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Hueppe
authors.affiliation: Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.affiliation: Ifi-Institute for Interdisciplinary Medicine, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.affiliation: Factum GmbH, Offenbach/Main, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pfeiffer-Vornkahl
authors.affiliation: First Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grimm
authors.affiliation: First Department of Medicine, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: Roche Pharma AG, Medical Affairs Virology, Grenzach-Wyhlen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Alshuth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005838:Genotype; D005858:Germany; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy / Q000821:virology; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D016015:Logistic Models; D015999:Multivariate Analysis; D016017:Odds Ratio; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D009842:Oligopeptides; C100416:peginterferon alfa-2a; D011092:Polyethylene Glycols; D011392:Proline; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; C486464:telaprevir