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


 
 
 
 
 
 Background & Aims: 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.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.
 
 
 
 
 
 
 
 
 
 
 

Hepatitis C virus infection and tobacco smoking - joint health effects and implications for treatment of both: A systematic review

“…77,78 Approaches to address both will have multiple benefits to both patients and the health system and increases the likelihood that DAAs reduce morbidity and mortality rates better than delivering DAAs alone. 79 Tobacco smokers may face many challenges due to lack of access to care, poor adherence to therapy, and HCV reinfection due to risks such as injecting drug use. However, smokers living with HCV can be assisted to quit smoking with both pharmacotherapy and behavioural interventions where close monitoring of adherence and compliance to treatment is promoted.…”

Smoking impairs molecular response, and reduces overall survival in patients with chronic myeloproliferative neoplasms: A retrospective cohort study

“…The effects of smoking on MR and OS in patients with MPNs have not been investigated before, but in CML no effect of smoking on MR was observed in patients treated with imatinib 18 . However, in patients with hepatitis C treated with PEG‐IFN‐α2 and ribavirin, sustained viral response rates were lower in smokers compared with non‐smokers, and an in‐vitro study has shown down‐regulation of interferon receptors induced by smoking products 29,30 . Moreover, in patients with multiple sclerosis, smoking was associated with a reduced treatment response to PEG‐IFN‐β, possibly due to treatment‐induced neutralising antibodies 31,32 .…”

Prospective Longitudinal Substance Use Patterns in Patients Preparing for Hepatitis C Treatment

“…Recent estimates indicate that 57%-67% of people with hepatitis C virus (HCV) smoke cigarettes (Basseri et al, 2010; Chew et al, 2015; Shuter et al, 2016; Zimmermann et al, 2016), 65%-73% consume alcohol (Drumright et al, 2011; North et al, 2014; Taylor, Denniston, Klevens, McKnight-Eily, & Jiles, 2016; Tsai, Ford, Li, & Zhao, 2012), and 57%-65% use illicit drugs (Sims et al, 2016; Whitehead, Hearn, Trenz, Burrell, & Latimer, 2014). Alcohol use and smoking independently accelerate progression to HCV-related liver disease and cancer (Jeng et al, 2009; Lok et al, 2009; Soeda et al, 2012).…”

“…Cigarette smoke contains several cytotoxic chemicals metabolized in the liver that cause chronic inflammation leading to cell death and contribute to viability and replication of HCV (Costiniuk et al, 2016; Zhao, Li, & Taylor, 2013). Alcohol use and smoking are independent risk factors for suboptimal HCV treatment outcomes (Choi, 2012; Zimmermann et al, 2016; Osna, Ganesan, & Kharbanda, 2015). Clinical guidelines recommend abstaining from alcohol, and several studies have advised clinicians to recommend smoking cessation for patients with HCV (Kertesz et al, 2014; Shuter et al, 2016).…”