title: Asunaprevir-containing regimens for the treatment of hepatitis C virus infection.
abstract: Chronic hepatitis C virus (HCV) infection has been a tremendous health burden worldwide with an annual mortality of 300,000 people due to decompensated cirrhosis or hepatocellular carcinoma. A combination of interferon (IFN), ribavirin (RBV), and/or direct-acting antivirals (DAAs) can eradicate HCV in a various proportion of infected patients. Unfortunately, IFN-based therapy is associated with significant adverse effects, contraindications, and limited tolerability, leading to lower adherence or even treatment discontinuation. With the rapid evolution of newer DAAs or host-targeting agents, emerging HCV therapy is moving towards an IFN- and RBV-free strategy. To this end, a recently developed NS3 protease inhibitor, asunaprevir (ASV), in combination with other DAAs as IFN/RBV-containing or -free regimen, has shown promising results with fewer adverse effects. In this review, preclinical profiles and clinical proof-of-concept studies of ASV, including viral resistance, host polymorphism, and role of ASV in future HCV therapy are reviewed and discussed.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Sheng-Shun
authors.initials: SS
authors.lastname: Yang
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D055808:Drug Discovery; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D007546:Isoquinolines; D011480:Protease Inhibitors; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C571889:asunaprevir
keywords: NS3 protease inhibitor; asunaprevir; direct-acting antivirals; hepatitis C virus; interferon; ribavirin