HCV genotype-3h, a difficult-to-diagnose sub-genotype in the DAA era

Antivir Ther. 2018;23(7):605-609. doi: 10.3851/IMP3228. Epub 2018 Mar 5.


Background: No data are available on the clinical presentation and virological pattern in the case of failure of interferon (IFN)-free regimens in patients with genotype-3h. In this paper authors identified the virological and clinical characteristics of patients with genotype-3h treated with suboptimal or not indicated IFN-free regimens for the misclassification of HCV genotype.

Methods: A total of 87 consecutive patients with failure to an IFN-free regimen were re-tested for HCV genotype by HCV NS5B sequencing; the 26 patients identified as harbouring HCV-3 were enrolled.

Results: Of the 26 patients enrolled, 4 (15.4%) harboured sub-genotype-3h and 22 (84.6%) 3a. All patients were Italian. Patients with genotype-3a infection were younger (median age 56 years, range 47-78) compared to those with genotype-3h infection (median 74 years, range 65-79; P<0.006). With regard to the failed direct-acting antiviral (DAA)-regimens, three of the four patients with genotype-3h (75%) had been treated with an ineffective​ DAA regimen (paritaprevir, ombitasvir, dasabuvir ± ribavirin for 3 months) more frequently than those with genotype-3a (13.6%; P=0.02), because of previous erroneous identification of HCV-1 genotype. NS5A resistance-associated substitutions (RASs) were observed in 10 (45.4%) genotype-3a-infected patients and in 2 (50%) with genotype-3h. NS5B RASs were observed in only two genotype-3a-infected patients and in none of the 3h-infected patients.

Conclusions: This is the first time genotype-3h has been identified in Italian patients failing an IFN-free regimen, in the majority of cases because of a misclassification of the HCV genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Anilides / therapeutic use
  • Antiviral Agents / therapeutic use*
  • Carbamates / therapeutic use
  • Drug Administration Schedule
  • Drug Resistance, Viral / genetics*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Genotype*
  • Hepacivirus / classification
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Isoenzymes / genetics
  • Macrocyclic Compounds / therapeutic use
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Recurrence
  • Ribavirin / therapeutic use
  • Sulfonamides / therapeutic use
  • Treatment Failure
  • Uracil / analogs & derivatives
  • Uracil / therapeutic use
  • Viral Load / drug effects
  • Viral Nonstructural Proteins / genetics*


  • ABT-267
  • ABT-333
  • Anilides
  • Antiviral Agents
  • Carbamates
  • Isoenzymes
  • Macrocyclic Compounds
  • NS-5 protein, hepatitis C virus
  • Sulfonamides
  • Viral Nonstructural Proteins
  • Ribavirin
  • Uracil
  • paritaprevir