Hepatitis C treatment from “response‐guided” to “resource‐guided” therapy in the transition era from interferon‐containing to interferon‐free regimens

• Published in: Journal of gastroenterology and hepatology Vol. 32; no. 8; pp. 1436 - 1442
• Main Author: Yu, Ming‐Lung
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.08.2017
• Subjects: Antiretroviral drugs; Antiviral agents; Antiviral Agents - administration & dosage; DAA; Drug Administration Schedule; Drug Therapy, Combination; Fibrosis; Genotypes; HCV; Hepatitis; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C - virology; Humans; IFN; Imidazoles - administration & dosage; Interferon; Interferons; Isoquinolines - administration & dosage; Oligopeptides - administration & dosage; Proline - administration & dosage; Proline - analogs & derivatives; resource; Response rates; Ribavirin; Ribavirin - administration & dosage; Ribonucleic acid; RNA; Sofosbuvir - administration & dosage; Sulfonamides - administration & dosage; Time Factors; Viral Load; IFN; HCV; DAA; resource
• ISSN: 0815-9319; 1440-1746; 1440-1746
• DOI: 10.1111/jgh.13747

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.