Low IP-10 Levels Predict Better Virological Response to Interferon-Based Therapy

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Low IP-10 Levels Predict Better Virological Response to Interferon-

Based Therapy

By Liz Highleyman

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