Detection of residual hepatitis C virus RNA by transcription-mediated amplification in patients with complete virologic response according to polymerase chain reaction-based assays.
A considerable proportion of patients with chronic hepatitis C who achieve a virologic end-of-treatment response relapse after discontinuation of therapy. It is conceivable that polymerase chain reaction (PCR)-based assays with a lower detection limit of 100 to 1, 000 hepatitic C virus (HCV) RNA copies/mL are still too insensitive to detect residual viremia. End-of-treatment serum samples of 47 patients with a virologic relapse according to results of qualitative PCR assays (Amplicor HCV; Roche Molecular Systems, Mannheim, Germany) were tested by transcription-mediated amplification (TMA), an isothermal, autocatalytic target amplification method that has the potential to detect less than 50 HCV RNA copies/mL. Virologic sustained responders (n = 59) and nonresponders (n = 49) served as controls. In end-of-treatment serum samples of virologic sustained responders and nonresponders an almost complete concordance between PCR and TMA results was observed (98%). However, HCV RNA was detectable by TMA in end-of-treatment serum samples from 16 of 25 relapse patients (64%) who were HCV-RNA-negative according to Amplicor HCV version 1.0 (lower detection limit 1,000 copies/mL) and in 8 of 22 patients (36%) who were HCV-RNA-negative according to Amplicor HCV version 2.0 (lower detection limit 100 copies/mL). End-of-treatment alanine transaminase (ALT) levels of sustained virologic responders and TMA-negative relapsers were similar, whereas a trend toward higher ALT values was observed in TMA-positive relapsers compared with sustained virologic responders (P = 0.09). In conclusion, HCV RNA can be detected at the end of treatment by TMA in a considerable proportion of patients who were classified as virologic end-of-treatment responders with a subsequent virologic relapse according to PCR-based methods.
Sarrazin
C
C
Medizinische Klinik II, J.W. Goethe-University, Frankfurt am Main, Germany.
Teuber
G
G
Kokka
R
R
Rabenau
H
H
Zeuzem
S
S
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis*; D014158:Transcription, Genetic
D012367:RNA, Viral; D000410:Alanine Transaminase