173 Original article Insights into the role of HCV Plus-/Minus strand RNA, IFN-γ and IL-29 in relapse outcome in patients infected with HCV Amir Mohammad Alborzi, 1 Taravat Bamdad, 1 Parivash Davoodian, 2 Tayebeh Hashempoor, 3 Abdol Azim Nejatizadeh 4 and Javad Moayedi 3 Summary Background and Objectives: Approximately one- third of hepatitis C virus (HCV) infected patients who complete antiviral therapy with undetectable serum HCV RNA at the end of therapy (ETR), will experience relapse. The reasons for the failure of treatment have not been elucidated. It was showed that HCV RNA can persist and replicate in extra hepatic sites, e.g. in peripheral blood mononuclear cells (PBMCs), but the relevance of its presence with relapse over time is still unknown. Moreover, interferon-gamma (IFN-γ) and IFN-lambdas [IFN- λ1, interleukin-29 (IL-29)], possess potent antiviral activity. We studied if the presence of plus-/minus strand RNA in PBMCs of patients and the serum level of IFN-γ and IL-29, which is the most abundant IFN-lambdas in serum, can be considered as predictive factors in relapse outcomes. Methods: Patients were screened for plus-/minus strand RNA at ETR and after 6 months. Also, we measured the serum level of IFN-γ and IL-29 and compared the result with those who developed a sustained virological response (SVR). Results: Levels of IL-29 and IFN-γ serum were significantly higher in SVR at ETR and 6 months later compared to those of the relapsed patients, but there was no difference between the two groups regarding the presence or absence of plus-/minus HCV strand in PBMCs. Conclusions: Our novel findings showed that the serum level of IL-29 and IFN-γ are predictive of relapse outcomes to HCV treatment, but there was no association between the presence of plus-/minus HCV RNA in PBMCs of patients with an outcome of therapy at ETR and later. (Asian Pac J Allergy Immunol 2015;33:173-81) Keywords: IL-29, IFN-γ, Relapsed, HCV Introduction Endogenous interferon (IFN) specifically IFNα, play a pivotal role in host defense against a viral infection and has been one of the therapeutic options for the treatment of chronic hepatitis C virus (HCV) infection. 1 For years, treatment with pegylated IFN (PEG-IFN)-α plus ribavirin, combination therapy has been the standard of care for patients with chronic hepatitis C (CHC) fostering sustained virological response (SVR) in nearly half of the patients with HCV infection. 2 The mechanisms of virus elimination by antiviral therapy remain unclear. Several reports showed that in addition of viral factors (HCV genotypes and viral load), a number of baseline host-related factors (i.e. age, gender, race, body mass index, pre- treatment ALT level, stage of fibrosis, insulin resistance and genetic factors) may have an impact on antiviral treatment outcome. 3-5 One of the factors that may play an important role in re-infection of the liver and in the high rate of unsuccessful treatment and relapse in patients with CHC is active HCV replication in peripheral blood mononuclear cells (PBMC). 6 It is generally accepted that the presence of minus strand HCV RNA in hepatocytes and PBMCs may be an indicator of continued From 1. Department of virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran 2. Infectious and Tropical Disease Research Center, Hormozgan University of Medical Sciences (HUMS), Bandar Abbas, Hormozgan, Iran 3. Professor Alborzi Clinical Microbiology Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran 4. Research Center for Molecular Medicine, Hormozgan University of Medical Sciences (HUMS), Bandar-Abbas, Hormozgan, Iran Corresponding author: Taravat Bamdad E-mail: bamdad_t@modares.ac.ir Submitted date: 30/9/2014 Accepted date: 21/1/2015