Hepatitis C Virus Genotypes
HCV is currently classified into eight genotypes (genotypes 1-8), which differ by at least 30% in their nucleotide sequence. 1
Genotype Classification and Diversity
The most recent guidelines from 2019 confirm eight distinct HCV genotypes, numbered 1 through 8, representing the current scientific consensus. 1
Each genotype is further subdivided into multiple subtypes (identified by lowercase letters such as 1a, 1b, etc.), which differ by greater than 15% in their nucleotide composition, with over 80 subtypes currently recognized. 1
Earlier guidelines from 2014 described seven genotypes (1-7), with genotype 7 being identified in patients from Canada and Belgium, possibly infected in Central Africa. 1
Genotype 8 was subsequently identified in India, completing the current classification of eight major genotypes. 1
Clinical Significance of Genotype Determination
Accurate determination of genotype and subtype is critical, as this directly impacts response to direct-acting antiviral (DAA) therapies. 1
Recommended methods for genotyping include Sanger sequencing of NS5B or core regions, and whole genome sequencing by next-generation sequencing (NGS), which produce accurate and reproducible results. 1
Line probe assays and 5'UTR PCR amplification are not recommended, as they may be insufficiently sensitive to distinguish between subtypes. 1
Geographic Distribution
Genotype 1 is the most prevalent worldwide, with subtype 1b predominating in Europe and 1a in the United States. 1
Genotype 3a is highly prevalent in European populations of people who inject drugs (PWID). 1
Genotype 4 is endemic in the Middle East and Africa, accounting for more than 80% of hepatitis C cases in these regions. 1
Genotypes 5 and 6 are rare in Europe, with genotype 6 more commonly found in China and Southeast Asia. 1
Genotype 7 has been identified in Central Africa (Democratic Republic of Congo). 1
Genotype 8 is found in India. 1
Important Clinical Caveats
Certain subtypes harbor natural polymorphisms conferring inherent resistance to NS5A inhibitors, including subtypes 1l (West Africa), 3b (China and Southeast Asia), 4r (Africa), 6u and 6v (China and Southeast Asia), resulting in unacceptably frequent virological failures. 1
Recombinant strains exist, most notably the 2k/1b recombinant prevalent in countries of the former USSR, where the 5' end of genotype 2k combines with the 3' end (including non-structural genes) of genotype 1b. 1
Mixed infections with two or more different HCV genotypes or subtypes occur in 1-30% of individuals, with highest rates in PWID populations. 1