**4. Past therapy**

Over the past several years, more so recently, treatment options for HCV have exponentially grown. Treatment for HCV began with the FDA approval of interferon (IFN) in 1991, followed by combined IFN and RBV in 1998, and later with peg-IFN in 2001. The regimen of peg-IFN and RBV once stood as the standard of care, and still does in many nations, until recently. DAAs, which target nonstructural proteins involved in replication and infection of HCV, were first approved in 2011.

Peg-IFN and RBV historically have been shown to result in SVR rates of 75% in patients with genotypes 2 or 3, but only of 40% in patients with genotype 1 [16]. The duration of therapy often depended on both patient's genotype and their response to therapy as measured by HCV RNA viral load following initiation of treatment [17]. In one-third of all patients being treated with peg-IFN and RBV, adverse side effects were noted. These ranged from an influenza-like illness, characterized by fatigue, headache, fever, and rigors as well as complaints of depres‐ sion, irritability, or insomnia. In addition to the side effects, therapy with peg-IFN was a tedious experience. Treatment often included weekly subcutaneous injections of peg-IFN in addition to daily oral RBV for up to 48 weeks. In addition to this, patients required at least monthly appointments for the first 12 weeks for monitoring of side effects and blood work, including HCV viral load monitoring. The tedious schedule and weekly subcutaneous injections lead many to either not enroll for therapy or undergo incomplete treatment.

As it stands now, the time of weekly injections and unfavorable side effects are gone. In 2014, new IFN-free regimens became available. The previous peg-IFN and RBV therapy or even triple therapy involving TEL or BOC is quickly becoming extinct. In 2015 onward, IFNcontaining regimens will be replaced by all-oral, IFN-free therapies. Additionally, RBV-free regimens are also becoming widely available, and RBV will likely go the way of peg-IFN due to its unfavorable side effect of anemia.
