Necessity for reassessment of patients with serogroup 2 hepatitis C virus (HCV) and undetectable serum HCV RNA.
We encountered a patient positive for anti-hepatitis C virus (HCV) whose serum HCV RNA was undetectable with the Roche AmpliPrep/Cobas TaqMan HCV assay (CAP/CTM) version 1 but showed a high viral load with the Abbott RealTime HCV assay (ART). Discrepancies in the detectability of serum HCV RNA were investigated among 891 consecutive patients who were positive for anti-HCV. Specific nucleotide variations causing the undetectability of HCV RNA were determined and confirmed by synthesizing RNA coding those variations. Serum samples with the discrepancies were also reassessed by CAP/CTM version 2. Among the 891 anti-HCV-positive patients, 4 patients had serum HCV RNA levels that were undetectable by CAP/CTM version 1 despite having levels of >5 log IU/ml that were detected by ART. All four patients had HCV genotype 2a and high titers of anti-HCV. Sequencing of the HCV 5' noncoding regions revealed 2 common variations, A at nucleotide (nt) 145 and T at nt 151. Synthesized RNAs of the HCV 5' noncoding region with standard (NCR145G151C) and variant nucleotides at nt 145 and nt 151 were quantified with CAP/CTM. RNAs of NCR145G151C and NCR145G151T were quantifiable with CAP/CTM version 1, while those of NCR145A151T and NCR145A151C went undetected. The substitution from G to A at nt 145 specifically conferred this undetectability, while this undetectability was reverted in synthesized HCV RNA with correction of this variation. Reassessment of these samples by CAP/CTM version 2 resulted in similar levels of HCV RNA being detected by ART. We conclude that HCV patients with undetectable HCV RNA by CAP/CTM version 1 should be reassessed for viral quantification.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yuki
Y
Moritou
Fusao
F
Ikeda
Yasuto
Y
Takeuchi
Hiroyuki
H
Seki
Shintaro
S
Nanba
Yoshiaki
Y
Iwasaki
Kazuhide
K
Yamamoto
D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006526:Hepatitis C / Q000175:diagnosis* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood* / Q000235:genetics; D044967:Serum / Q000821:virology*; D019562:Viral Load
D018937:Hepatitis C Antibodies; D012367:RNA, Viral