Because
treatment does not produce sustained response in a substantial proportion of patients
with chronic hepatitis C, researchers have sought
factors that can help predict early in the course of therapy which individuals
will go on to achieve sustained response,
thus sparing likely non-responders the side effects and expense of additional
futile therapy. The most common predictor is early virological response, or a
decrease in HCV RNA of at least 2 logs by Week 12.
The biological mechanisms
underlying response to antiviral therapy for chronic HCV are not fully understood.
Interferon-gamma-inducible
protein-10 (IP-10) is a chemical messenger produced by certain immune cells
that is thought to play a role in cell proliferation, angiogenesis (blood vessel
generation), and apoptosis (programmed cell death).
As
reported in the December 2006 issue of Hepatology, Swedish researchers
evaluated the association between IP-10 levels and treatment response in "difficult-to-treat"
patients with chronic genotype 1 HCV infection. In this study, IP-10 levels in
plasma from 173 patients were measured prior to treatment with pegylated interferon
alpha-2a (Pegasys) plus ribavirin.
Results
•
Significantly lower
IP-10 levels were observed in patients who achieved rapid virological response
(RVR) at 4 weeks (P < 0.0001).
•
Lower IP-10 levels
were also seen in patients who achieved sustained virological response (SVR) 24
weeks after the end of therapy (P = 0.0002).
•
This was the case even
in "difficult-to-treat" patients with body mass index (BMI) of 25 kg/m2
or greater and/or baseline HCV RNA levels of 2 million IU/mL or higher.
•
In multivariate logistic
regression analyses, a low IP-10 value was an independent predictor of both RVR
and SVR.
•
A baseline IP-10 cut-off
value of 600 pg/mL yielded a negative predictive value (NPV) of 79% for all genotype
1 patients, comparable to that observed using an HCV RNA reduction of at least
2 logs after 12 weeks (NPV 86%).
•
By combining both IP-10
and 12-week HCV RNA reduction, 30 of 38 patients potentially could have been spared
unnecessary ineffective therapy (NPV 79%).
•
In patients with both
higher BMI and higher HCV RNA, IP-10 cut-off levels of 150 and 600 pg/mL, respectively,
yielded a positive predictive value (PPV) of 71% and a NPV of 100%.
Conclusion
In
conclusion, the authors wrote, "pretreatment IP-10 levels predict RVR and
SVR in patients infected with HCV genotype 1, even in those with higher BMI and
viral load. A substantial proportion of the latter patients may achieve SVR in
spite of unfavorable baseline characteristics if their pretreatment IP-10 level
is low. Thus, pretreatment IP-10 analysis may prove helpful in decision-making
regarding pharmaceutical intervention."
Department
of Infectious Diseases, University of Goteborg, Sweden.
01/05/07
Reference M
Lagging, A I Romero, J Westin, and others. IP-10 predicts viral response and therapeutic
outcome in difficult-to-treat patients with HCV genotype 1 infection. Hepatology
4(6): 1617-1625. December 2006.
