Yesterday’s post “Understanding HCV Treatment Failures with Sofusbuvir” provided a summary of why patients with hepatitis C virus (HCV) genotype 3 may not respond to therapy. Now a terrific article (Hepatology 2015; 61: 471-80, editorial, titled “Mutant Ninja Viruses” 421-23) looks at why some patients with the favorable HCV genotype 2 may fail to respond.

By using extensive genotyping data and sequencing, the authors were able to determine why some patients with genotype 2 did not respond to combination therapy with ribavirin/sofusbuvir.  These patients were characterized by as genotype 2 based on Siemens VERSANT HCV Genotype INNO-LiPA 2.0 Assay.  This assay “looks at conserved sequences in the 5′ region of the virus.” However, these patients were genotyped as well using a technique to examine the 3′ region of the virus.  From among more than 2000 samples, the two assays gave divergent results in 0.5% of the cases with the 5′ end indicating genotype 2 and the 3′ end indicating genotype 1.

What is happening?

• Detailed analyses of these discordant viruses showed that they were hybrid viruses with a crossover point located in the NS2/NS3 region.
• In patients with these hybrid viruses, only 3 of 11 responded to therapy, indicating that they behave like genotype 1 patients.

Bottomline: “These novel viruses are true viral Ninjas hiding a challenging array of ‘difficult-to-cure’ genotype 1 enzymes under an ‘easy-to-cure’ genotype 2 coat.