Pegylated interferon based therapy with second-wave direct-acting antivirals in genotype 1 chronic hepatitis C

Liver Int. 2015 Jan;35 Suppl 1:11-7. doi: 10.1111/liv.12715.


Within the last few years, treatment of chronic hepatitis C infection has progressed beyond regimens containing the first-wave direct-acting antiviral agents (DAAs) boceprevir and telaprevir, which had high pill burdens as well as low efficacy and safety in treatment-experienced patients. Triple therapy regimens with newer second-wave DAAs combined with pegylated interferon (PEG-IFN) and ribavirin (RBV), have shown rates of sustained virological response never before achieved with previous regimens in treatment-naïve genotype 1 (HCV-1) patients. Additionally, increased response rates have been found with quadruple agent therapy in prior non-responders, partial-responders, and relapsers, including those with cirrhosis. This review will focus on the second-wave DAAs including protease inhibitors (PI), nucleotide inhibitors, and NS5B inhibitors combined with PEG-IFN and RBV for both treatment-naïve and treatment-experienced genotype 1 hepatitis C virus (HCV-1) infected patients. The current standard of care for treatment-naïve HCV-1 is the second-wave PI, sofosbuvir, plus PEG-IFN/RBV and sofosbuvir plus the second-wave nucleotide inhibitor simeprevir with or without RBV in treatment-experienced HCV-1 patients. These recommendations could change, especially for treatment-experienced patients based on the positive results obtained with the newest quadruple therapy studies.

Keywords: direct-acting antiviral agents; genotype 1 HCV; hepatitis C; hepatitis C therapy; pegylated interferon based therapies.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination / methods*
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Heterocyclic Compounds, 3-Ring / therapeutic use
  • Humans
  • Interferon-alpha / therapeutic use*
  • Polyethylene Glycols / therapeutic use*
  • Protease Inhibitors / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Simeprevir
  • Sofosbuvir
  • Sulfonamides / therapeutic use
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use
  • Viral Nonstructural Proteins / antagonists & inhibitors*


  • Antiviral Agents
  • Heterocyclic Compounds, 3-Ring
  • Interferon-alpha
  • Protease Inhibitors
  • Recombinant Proteins
  • Sulfonamides
  • Viral Nonstructural Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Simeprevir
  • Uridine Monophosphate
  • NS-5 protein, hepatitis C virus
  • peginterferon alfa-2a
  • Sofosbuvir