Despite advances in treating HCV, even with the optimal delivery of the current interferon-based regimen for HCV, only about 50% of treated patients with genotype 1/4 successfully clear the virus (Mauss et al.
2011). The success of the current treatment is multi-factorial and depends on a combination of several host, viral, and treatment factors. Inhibitors,research,lifescience,medical Viral Sorafenib Tosylate clinical trial factors consist of HCV genotype, pretreatment viral load, and presence of viral quasi-species (Timm and Roggendorf 2007). Host factors include presence of co-morbidities such as obesity, cirrhosis, ethnic background, gender, and age (Bondini and Younossi 2006; Chen et al. 2007; Neumann-Haefelin et al. 2007; Sharma et al. 2007). Finally, treatment-related factors affecting response Inhibitors,research,lifescience,medical include adequate duration of treatment, patient adherence and, importantly, optimal management of PEG-IFN and RBV-related side effects (Mulhall and Younossi 2005; Sharma et al. 2007). Consequently, there are two main areas of focus to develop future treatment regimens for HCV. One of them focuses on new therapeutics that can potentially
increase the rates for sustained virological response (SVR) by developing regimens that would include direct acting antiviral agents (DAA). The other, equally important area, is to optimize treatment regiments and reduce its side-effect profile. Despite diligent Inhibitors,research,lifescience,medical efforts by clinicians and clinical investigators, successful management of treatment-associated side effects remains
a substantial problem and contributes significantly to treatment discontinuation or dose reduction (10 and 35%, respectively) (Manns et al. 2001; Dan et al. 2006). research use depression disorder is one Inhibitors,research,lifescience,medical of the least tangible, and one of the most difficult IFN-related side effects to quantify in the treatment of HCV. IFN-α-induced depression is markedly similar to major depressive disorder (MDD) and may be manifested as depressed mood, irritability, emotional lability, agitation, fatigue, apathy, Inhibitors,research,lifescience,medical anhedonia, anorexia, psychomotor retardation, sleep disturbance, sexual dysfunction, memory impairment, and diminished ability to concentrate (Valentine et al. 1998). Due to the variability of the symptoms and lack of unification in their measurements, studies on IFN-α-induced depression also produce variable results with incidence rates ranging from 16 to 45% in patients receiving treatment (Fattovich et al. 1996; Hauser et al. 2002; Dieperink et al. 2003). The most common risk factors Cilengitide for IFN-α-induced depression are related either to treatment regimen itself (i.e., higher dose and longer duration of medication) (Capuron and Ravaud 1999; Hauser et al. 2002; Dieperink et al. 2003; Capuron and Miller 2004) or to intrinsic factors predisposing patients to the development of DSM-IV symptom criteria for MDD. The most common risk factor of latter kind is pre-existing psychiatric problems or previously diagnosed MDD.