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World J Gastroenterol. Jun 7, 2013; 19(21): 3199-3206
Published online Jun 7, 2013. doi: 10.3748/wjg.v19.i21.3199
Sofosbuvir and ABT-450: Terminator of hepatitis C virus?
Qing-Lei Zeng, Ji-Yuan Zhang, Zheng Zhang, Li-Feng Wang, Fu-Sheng Wang
Qing-Lei Zeng, Fu-Sheng Wang, The Institute of Translational Hepatology, Beijing 302 Hospital, Peking University, Beijing 100039, China
Ji-Yuan Zhang, Zheng Zhang, Li-Feng Wang, Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China
Author contributions: Zeng QL and Zhang JY contributed equally to this work; Zeng QL and Zhang JY contributed to the study idea, study design, literature search, manuscript writing and final revision of the article; Zhang Z and Wang LF contributed to the manuscript writing and the final revision of the article; Wang FS contributed to the study design, manuscript writing and the final revision of the article.
Supported by Grants from the National Key Basic Research Program of China, No. 2009CB522507, No. 2012CB519005; and Beijing Nova Program of China, No. Z12110702512071
Correspondence to: Fu-Sheng Wang, MD, PhD, The Institute of Translational Hepatology, Beijing 302 Hospital, Peking University, 100 Xisihuan Middle Road, Beijing 100039, China.
Telephone: +86-10-66933332 Fax: +86-10-66933332
Received: February 20, 2013
Revised: March 31, 2013
Accepted: April 17, 2013
Published online: June 7, 2013

Combination therapy with peginterferon (pegIFN)-α and ribavirin (RBV) has been the standard of care (SOC) for chronic hepatitis C. Unfortunately, not all patients can achieve a sustained virologic response (SVR) with this regimen. SVR rates are approximately 80% in patients with hepatitis C virus (HCV) genotype 2, 3, 5 and 6 and 40%-50% in patients with genotype 1 and 4. Therefore, strategies to improve SVR rates have been an important issue for clinical physicians. Several direct acting antiviral agents (DAAs) have significantly higher SVR rates when combined with pegIFN-α and RBV than pegIFN-α and RBV alone. Treatments containing DAAs have several advantages over the previous SOC, including higher specificity and efficacy, shorter treatment durations, fewer side effects, and oral administration. Based on these advantages, treatment with pegIFN-α and RBV plus telaprevir or boceprevir has become the current SOC for patients with genotype 1 HCV infection. However, many patients are either not eligible for therapy or decline treatment due to coexisting relative or absolute contraindications as well as an inability to tolerate the hematological side effects and adverse events caused by the new SOC. These factors have contributed to the advent of pegIFN-α-free regimens. The newest therapeutic regimens containing sofosbuvir and ABT-450 have shown promising results. In this review, we summarize the development of anti-HCV agents and the clinical efficacy of sofosbuvir and ABT-450-based therapies as well as the potential for future HCV studies.

Keywords: Sofosbuvir, ABT-450, Hepatitis C virus, Antiviral therapy, Sustained virologic response

Core tip: We are entering an era in which the development of antiviral agents and successful treatment of chronic hepatitis C is rapidly escalating. In this review, we have summarized the history of anti-hepatitis C virus (HCV) agents from interferon-α (IFN-α) to the latest sofosbuvir- and ABT-450-based therapies. Although a new generation of direct acting anti-HCV agents has largely improved the sustained virologic response rates of patients, many unmet needs and questions remain, such as IFN-free regimens for difficult to treat patients, avoidance of cross-resistance, the role of interleukin-28B status as well as the management of some advanced and co-infected patients.