Sustained virological response in a patient with chronic hepatitis C treated by monotherapy with the NS3-4A protease inhibitor telaprevir.
Here, we describe for the first time a case of sustained virological response (SVR) achieved in a patient with chronic hepatitis C (CH-C) by monotherapy with a NS3-4A protease inhibitor, telaprevir, without interferon therapy. A 59-year-old treatment-naïve Japanese man was enrolled in a phase II trial of telaprevir by repeat oral administration at a dose of 750mg every 8h for 24 weeks. At the start of treatment, he exhibited a low-level viremia with genotype 1b of the hepatitis C virus (HCV). After the first week of treatment with telaprevir, serum HCV RNA was undetectable, and negativity remained until the end of treatment. Moreover, he was evaluated as having a SVR after the post-treatment 24-week follow-up program. Two characteristics may explain the strong antiviral activity of telaprevir in the present case. First, although pre-treatment PCR-direct sequencing and cloning for the N-terminal in the NS3 region showed a protease inhibitor-resistant variant (T54A) in 1 of 32 independent clones, the T54A substitution has only a low-level resistance to protease inhibitors and his viral load was low. Second, when compared to a consequence sequence of 35 treatment-naïve patients with HCV genotype 1b, R130K and Q195K substitutions were unique to the present case. Although it is presently unknown whether the R130K and Q195K substitutions are related to SVR, this case suggests that long-term telaprevir monotherapy may be effective in CH-C patients with genotype 1 and a low viral load.
Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. fumitakas@toranomon.gr.jp
Fumitaka
F
Suzuki
Yoshiyuki
Y
Suzuki
Norio
N
Akuta
Hitomi
H
Sezaki
Hiromi
H
Yatsuji
Yasuji
Y
Arase
Miharu
M
Hirakawa
Yusuke
Y
Kawamura
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Satoshi
S
Saito
Kenji
K
Ikeda
Mariko
M
Kobayashi
Sachiyo
S
Watahiki
Rie
R
Mineta
Satomi
S
Iwasaki
Hiromitsu
H
Kumada
D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D016174:Hepacivirus / Q000201:enzymology* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000627:therapeutic use*; D016415:Sequence Alignment; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C486464:telaprevir