New targets for Direct Acting Agents: Are we still waiting for the new commander? = New targets for Direct Acting Agents: Are we still waiting for the new commander?

다국어 초록 (Multilingual Abstract)

With the recent launch of direct acting agents (DAAs), the treatment of chronic hepatitis C has a new turning point now. Because combined treatment with DAA and pegylated interferon-alpha (PegIFN-α) or interferon-free DAA combination therapy show excellent viral responses, such therapies are likely to be adopted as standard-of-care treatment s in the future. When chronic hepatitis C is treated with a therapy including DAA available in the market, however, viral breakthrough caused by HCV-resistance mutation is observed, and antiviral activity is highly varied depending on genotype. Thus, caution should be used in drug selection, and there can be problematic drug-drug interactions with co-administered drugs for underlying concurrent co-morbid diseases of patients with chronic hepatitis C. Moreover, DAA, which has relatively fewer drug induced side effects, is expected to be applicable to difficult-to-treat patients (null responders to PegIFN-α and RBV, far advanced liver disease patients, LT recipients, HIV/HCV co-infected individuals, hemodialysis patients, immunocompromised patients), but its treatment effect on them is uncertain yet and the particular concern is interaction between DAA and various co-administered drugs. Therefore, novel antiviral approaches for treatment of chronic hepatitis C have high genetic barriers to resistance and show a powerful antiviral effect regardless of HCV genotype, and there is a synergic effect with current available DAAs, it is necessary to develop therapies that reduce drug-drug interaction through minimizing the dose of DAA. Here we introduce potential targets for novel antivirals to treat chronic HCV infection that are in preclinical and clinical development.