Pretreatment expression of the perforin gene by circulating CD8(+) T lymphocytes predicts biochemical response to interferon-alpha in patients with chronic hepatitis C.
It would be of great value to be able to predict, before the initiation of treatment, which patients with hepatitis C virus-induced chronic hepatitis will be cured by interferon-alpha (IFN-alpha). Competitive RT-PCR was used to evaluate spontaneous expression of the perforin gene, a marker of cytotoxic cell activation, by circulating mononuclear cells in 17 patients undergoing IFN-alpha treatment. IFN-alpha increased perforin gene expression (p < 0.003), but this was not correlated with outcome. In contrast, pretreatment perforin gene expression levels were higher in the 8 patients with a sustained biochemical response after treatment than in the 9 non-responsive patients (p = 0.01). This factor predicted favorable clinical outcome with a sensitivity of 75% and a specificity of 89%. Thus, pretreatment immunological status has a major influence on the ability of IFN-alpha to cure chronic hepatitis C, and the evaluation of perforin gene expression may help to select patients that will benefit from IFN-alpha treatment.
Balian
A
A
Hôpital Antoine-Béclère, Insitut Paris-Sud sur les Cytokines, 92140 Clamart, France. axel.balian@abc.ap-hop-paris.fr
Naveau
S
S
Zou
W
W
Durand-Gasselin
I
I
Bouchet
L
L
Foussat
A
A
Galanaud
P
P
Chaput
J C
JC
Emilie
D
D
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016174:Hepacivirus / Q000187:drug effects; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data; D014779:Virus Replication / Q000187:drug effects
D017931:DNA Primers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054353:Perforin; D000410:Alanine Transaminase