Prevalence of hepatitis C virus subgenotypes 1a and 1b in Japanese patients: ultra-deep sequencing analysis of HCV NS5B genotype-specific region.
BACKGROUND
Hepatitis C virus (HCV) subgenotypes 1a and 1b have different impacts on the treatment response to peginterferon plus ribavirin with direct-acting antivirals (DAAs) against patients infected with HCV genotype 1, as the emergence rates of resistance mutations are different between these two subgenotypes. In Japan, almost all of HCV genotype 1 belongs to subgenotype 1b.


RESULTS
To determine HCV subgenotype 1a or 1b in Japanese patients infected with HCV genotype 1, real-time PCR-based method and Sanger method were used for the HCV NS5B region. HCV subgenotypes were determined in 90% by real-time PCR-based method. We also analyzed the specific probe regions for HCV subgenotypes 1a and 1b using ultra-deep sequencing, and uncovered mutations that could not be revealed using direct-sequencing by Sanger method. We estimated the prevalence of HCV subgenotype 1a as 1.2-2.5% of HCV genotype 1 patients in Japan.


CONCLUSIONS
Although real-time PCR-based HCV subgenotyping method seems fair for differentiating HCV subgenotypes 1a and 1b, it may not be sufficient for clinical practice. Ultra-deep sequencing is useful for revealing the resistant strain(s) of HCV before DAA treatment as well as mixed infection with different genotypes or subgenotypes of HCV.
Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan.
Shuang
S
Wu
Tatsuo
T
Kanda
Shingo
S
Nakamoto
Xia
X
Jiang
Tatsuo
T
Miyamura
Sueli M
SM
Nakatani
Suzane Kioko
SK
Ono
Azusa
A
Takahashi-Nakaguchi
Tohru
T
Gonoi
Osamu
O
Yokosuka
D000328:Adult; D000368:Aged; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction