Alavian SM et al. sistent with the SOC for all patients including GT1 cases and leave triple therapies (PegIFNα / RBV / Boceprevir or PegIFNα / RBV / Teleprevir) for specific patient categories which includes protease inhibitors. 3. On Treatment Management With Stan- dard of Care; The Evidence for “Cure” Achievement 3.1. Treatment Options for HCV; the Historical Perspec- tive HCV life cycle is believed to be dependent on series of intra-cytosolic events in host cells. RNA is first replicated and then translated to proteins. The biochemical nature of cascade of events leading to HCV RNA replication and ultimately translation and poly protein processing is partly altered by immunologic interventions. Although interferon alpha does not seem to have direct antiviral ef- fect on HCV, its bounding to Jack-Stat receptor is proven to stop HCV gene transcription and replication based on in-vitro and in-vivo studies (18). Interferon alpha (IFNα) was introduced as an anti -HCV agent in 1959. HCV mono- therapy with IFNα for 24 to 48 weeks resulted in 10% to 20% of virological response (1991) and this modest effica- cy brought up the need for more investigations. Adding ribavirin (RBV) to IFNα (1998) resulted in improved re- sponse rates up to 30% to 40 %. Since 2000, Pegylated IFNα plus RBV has been considered as a more efficacious and preferred regimen which results in over 54% to 63% sus- tained virological response in various genotypes (19-21). Currently there are two approved PegIFNα formulations available for the treatment of chronic hepatitis C. These include PegIFNα-2a (Pegasys®) and PegIFNα-2b (PegIn- tron®). PegIFNα-2a is usually given at the dose 180mcg subcutaneously once weekly (QW) and PegIFNα-2b at 1.5 mcg/kg subcutaneously once weekly. Both medications are administered together with weight based ribavirin (Copegus® or Rebetol®) at the dose of 800-1200 mg and 600-1400 mg PO daily based on HCV GT,respectively. Apart from both above mentioned PegIFNα which are read- ily available in Iran, there is a another Pegylated IFNα-2a known as Pegaferon® (Iranian branded with different pe- gylation sites) which is administered at 180 mcg SC once weekly together with RBV at 800-1200 mg PO daily. Also there are other older available medicines such as inter- feron alpha-2a (Roferon®), interferon alpha-2b (Intron- A®) , consensus interferon (Infergen®) and PD-feron (an Iranian branded conventional IFN) which are adminis- tered at 3-4.5 m-IU/three times weekly, 3m-IU TIW, 9mcg TIW as monotherapy, and 4.5 mega units 3thimes weekly, respectively (19). The efficacy and safety of the two FDA ap- proved brands of PegIFNα were evaluated and compared together in a large phase 3b randomized clinical trial en- gaging 118 academic centers in US and Canada. 3070 GT 1, treatment naive patients were enrolled and randomized to receive one of the following regimens. Arm1: Pegylated 426 HCV; the Rising Concerns and Growing Hopes IFNα-2a, 180 mcg/W + 1000-1200 mg RBV/d, arm2: PegIFNα- 2b, 1.5mcg/kg/W + 800-1400 mg RBV/d and arm3: PegIFNα- 2b, 1mcg/kg/W + 800-1400 mg RBV/d. All patients received 48 weeks of treatment with PegIFNα and equivalent dose of RBV. The primary endpoints were SVR achievement and safety and secondary endpoints, the predictability and relapse rate (22). Results showed that the three arms had same SVR rates (39% to 41%) and were not different in terms of adverse events. However, PegIFNα-2b regimen resulted in lower relapse and higher predictability of re- sponse. The results of this elegant study which is known as IDEAL trial (22), re-confirms what is currently stated in practice guidelines for the use of PegIFNα-2a or 2b with no specific privilege of one over the other. The results of two single arm multi-centered trials we conducted to as- sess the efficacy and safety of the locally manufactured PegIFNα-2a in hepatitis-C, showed the SVR of 67% for GT 1, 95% for GT 2 and 3 and 77.8% for all genotypes (23, 24). However, we wish to be able to design and run random- ized clinical trials comparing the efficacy and safety of the locally manufactured PegIFNα-2a with the branded PegIFNα-2a and 2b to arrive at more interesting and de- pendable data in this respect. 3.2. Adherence to Hepatitis C Virus Therapy One of the main predictive factors for response to HCV treatment is the patient’s adherence to therapy. There are number of studies showing that adherence is generally high (70-98%) at the prime of the treatment journey. pa- tients adherence is higher for PegIFNα than for RBV and decreases by time for both drugs (25). There are issues like literacy, financial hurdles and socioeconomic prob- lems such as improper living status which are proven to hamper patients abilities to sufficiently adhere to the prescribed treatment protocols. One of the major bar- riers to adherence is the side effects of the prescribed regimens. Patients often start to feel uncomfortable with these medicines so their compliance declines. The most prevalent side effects with SOC regimens include consti- tutional symptoms not just restricted to headache, pyrex- ia, myalgia, weight loss, pruritus, fatigue and depression (22). Timely management of the occurred adverse effects seen with these medications would make patients more motivated to keep up with the therapy throughout the course. We recommend treating physicians to fully de- scribe the treatment journey and the possible untoward effects of the prescribed medications to their hepatitis C patients. Patients are expected to remain more adherent to the suggested treatments when they know for what reason (HCV virus eradication and preventing further liv- er damages) they need to have all those weekly injections and daily capsules to ensure they have received whatever therapy schedule you suggest them. Refilling patients pill boxes for them, creating easy-to-follow dosing and refill schedules, filling in log books, and helping them set alarms to remind them to take their medications may all Hepat Mon. 2012