Virological and Clinical Response to Interferon-Free Regimens in Patients with HCV-Related Mixed Cryoglobulinemia: Preliminary Results of a Prospective Pilot Study

Curr Drug Targets. 2017;18(7):772-785. doi: 10.2174/1389450117666160208145432.

Abstract

Mixed Cryoglobulinemia (MC) is the most frequent extrahepatic manifestation of Hepatitis C virus (HCV) infection. MC is an autoimmune /B-cell lymphoproliferative disorder characterized by circulating immune-complexes, named cryoglobulins. MC patients exhibit symptoms due to a systemic vasculitis of small/medium size vessels (mixed cryoglobulinemia syndrome, MCS) in a percentage going from 5 to 30%. The first-line therapeutic option in MCS patients is the etiologic treatment and, in the past fifteen years, antiviral therapy with Pegylated-Interferon (Peg-IFN) plus Ribavirin (RBV) represented the standard of care. Lately, the arrival of direct acting antivirals (DAAs) significantly modified the cure of HCV infection, consenting the use of IFN-free regimens. Here we report a review of the literature about the role of antiviral treatment, following its evolution, in treating HCVrelated MC. Furthermore, we report the results, after 8 weeks of treatment, of a preliminary pilot prospective study, counting 17 patients with HCV-related MC with or without MCS, treated with new generation DAAs in IFN-free regimens. After 8 weeks of DAA administration, all the subjects were HCV RNA negative. Moreover, in 6/17 (35%) patients cryoglobulins disappeared and, on the whole, in all patients a decrease of the cryocrit values was observed (p<0.05). Furthermore, three MCS-HCV patients (30%) resulted to be complete clinical responders and 5 subjects (50%) partial clinical responders. Therefore, IFN-free anti-HCV treatment appears to be safe and effective in MC patients from virological and clinical points of view, thus supporting the importance of HCV eradication in leading MC remission.

Keywords: Antiviral treatment; HCV; direct-acting antiviral (DAA); efficacy; interferon-free (IFN-free); mixed cryoglobulinemia; safety.

Publication types

  • Review

MeSH terms

  • Aged
  • Anilides / administration & dosage
  • Anilides / pharmacology
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Carbamates / administration & dosage
  • Carbamates / pharmacology
  • Cryoglobulinemia / drug therapy*
  • Cryoglobulinemia / virology*
  • Cyclopropanes
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Lactams, Macrocyclic
  • Macrocyclic Compounds / administration & dosage
  • Macrocyclic Compounds / pharmacology
  • Male
  • Middle Aged
  • Pilot Projects
  • Proline / analogs & derivatives
  • Prospective Studies
  • RNA, Viral / drug effects
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacology
  • Sulfonamides
  • Treatment Outcome
  • Valine

Substances

  • Anilides
  • Antiviral Agents
  • Carbamates
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Macrocyclic Compounds
  • RNA, Viral
  • Sulfonamides
  • ombitasvir
  • Proline
  • Valine
  • Ritonavir
  • paritaprevir