J Gastrointestin Liver Dis, March 2016 Vol. 25 No 1: 15-24 1) First Department of Medicine, Johannes Gutenberg University, Mainz; 2) Center of Gastroenterology, Herne; 3) Center for HIV and Hepatogastroenterology, Duesseldorf; 4) If-Institute for Interdisciplinary Medicine, Hamburg; 5) Factum GmbH, Ofenbach/ Main; 6) Roche Pharma AG, Medical Afairs Virology, Grenzach-Wyhlen, Germany Address for correspondence: Tim Zimmermann, MD I. Department of Medicine Johannes Gutenberg University Langenbeckstr. 1 55101 Mainz Germany tim.zimmermann@ unimedizin-mainz.de Received: 05.08.2015 Accepted: 16.12.2015 Efects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Terapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1 Tim Zimmermann 1 , Dietrich Hueppe², Stefan Mauss³, Peter Buggisch 4 , Heike Pfeifer-Vornkahl 5 , Daniel Grimm 1 , Peter R. Galle 1 , Ulrich Alshuth 6 INTRODUCTION Hepatitis C virus (HCV) infection is a leading cause of end stage liver disease and hepatocellular carcinoma [1]. Antiviral treatment with pegylated interferon (PEG-IFN) and ribavirin (RBV) was the standard of care (SOC) until 2011 when the frst direct acting antiviral (DAA) NS3/4A protease inhibitors (PI) telaprevir and boceprevir were approved [2]. ORIGINAL PAPER ABSTRACT Background & Aims: Smoking has multiple efects on factors infuencing hepatitis C and antiviral therapy, including lipid metabolism, fbrosis, platelet count and adherence aspects. Te 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 signifcantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 – 0.96). Te efect of smoking on sustained viral response remained signifcant (p=0.028, OR 0.67 CI: 0.47 – 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a signifcant association in the univariate analysis, i.e. diabetes, fbrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the infuence 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. Te efects of smoking might be overcome by the new antiviral agents. Key words: Hepatitis C virus (HCV) – antiviral therapy – pegylated interferon alpha 2a – smoking. Abbreviations: APRI: AST to platelet ratio index; DAA: direct antiviral agent; DT: dual antiviral therapy; EoTR: end of treatment response; RVR: rapid virological response; EVR: early virological response; HCV: hepatitis C virus; IFN: interferon alpha; MPA: Matched Pair Analysis; NS: non-smokers; PEG-IFN: pegylated interferon alpha 2a; PI: protease inhibitor; RBV: ribavirin; SAE: serious adverse event; SOC: standard of care; S: smokers; SVR: sustained viral response. Available from: www.jgld.ro/wp/y2016/n1/a4 DOI: http://dx.doi.org/10.15403/jgld.2014.1121.251.a2a Nowadays, in North America and Europe, IFN-containing treatment regimens and the first generation PIs for the treatment of HCV genotype 1 infection are widely displaced by the NS5B polymerase inhibitor sofosbuvir in combination with the second generation PI simeprevir or the NS5A inhibitors daclatasvir and ledipasvir. Nevertheless, IFN/RBV in combination with DAA remains SOC for HCV genotype 1 infection in many countries worldwide. In the HCV population smoking is a frequent condition in up to 57.7% of patients, with higher rates in males than females [3, 4]. Te impact of smoking on the success of antiviral therapy has never been clarifed, although there are many related aspects which might afect treatment success. Regarding the current literature, a number of questions remain open.