title: Hepatitis C treatment from "response-guided" to "resource-guided" therapy in the transition era from interferon-containing to interferon-free regimens.
abstract: Peginterferon/ribavirin has been the standard-of-care for chronic hepatitis C virus (HCV) infections: 48 weeks for genotype 1 or 4 (HCV-1/4) and 24 weeks for HCV-2/3. Response-guided therapy recommended shorter 24- and 16-week regimens for HCV-1 with lower baseline viral loads (< 400 000-800 000 IU/mL) and rapid virological response (RVR, undetectable HCV RNA at week 4) and HCV-2/3 with RVR, respectively; and extending to 72 and 48 weeks for HCV-1 slower responders and HCV-2 non-RVR patients, respectively, to improve the efficacy. The progress of directly acting antivirals (DAA), moving from interferon-containing regimens in 2011 to interferon-free regimens in 2013, has greatly improved the treatment success. Interferon-containing regimens include boceprevir or telaprevir or simeprevir or daclatasvir plus peginterferon/ribavirin, 24-48 weeks, for HCV-1 or 4. However, adding these DAA has no benefit for HCV-1 with lower baseline viral loads/RVR. Instead, 12-week sofosbuvir plus peginterferon/ribavirin attained sustained virological response rates of > 90% for HCV-1/3-6. Interferon-free regimens include two main categories: NS5B nucleotide inhibitor (sofosbuvir)-based regimens and NS3/4A inhibitor/NS5A inhibitor-based regimens (daclatasvir/asunaprevir, paritaprevir/r/ombitasvir/dasabuvir and grazoprevir/elbasvir). About 8-24 weeks interferon-free regimens could achieve sustained virological response rates of 82-99% for corresponding HCV genotypes. Although the newly DAA interferon-free regimens have high efficacy and safety, the huge budget impact increases the treatment barriers. The current recommendation should, therefore, base on the availability, indication, and cost-effectiveness in the transition era of DAA. Based on the concept of "resource-guided therapy," peginterferon/ribavirin might be applied for easy-to-treat interferon-eligible patients in resource-constrained areas. Prioritizing patients for interferon-free regimens according to "time-degenerative factors" (age and fibrosis) is justified before the regimens becoming available and affordable.
authors.affiliation: Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.|Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ming-Lung
authors.identifier: http://orcid.org/0000-0001-8145-1900
authors.initials: ML
authors.lastname: Yu
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D002219:Carbamates; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007372:Interferons; D007546:Isoquinolines / Q000008:administration & dosage; D009842:Oligopeptides / Q000008:administration & dosage; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives; D011759:Pyrrolidines; D012254:Ribavirin / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D007546:Isoquinolines; D009842:Oligopeptides; D011759:Pyrrolidines; D013449:Sulfonamides; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D007372:Interferons; D011392:Proline; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir; D000069474:Sofosbuvir
keywords: DAA; HCV; IFN; resource