Serum levels of interferon-gamma-inducible protein 10 and response to peginterferon therapy in HBeAg-positive chronic hepatitis B

Background & Aims: Serum levels of interferon-gamma inducible protein 10 (IP-10) are a marker for immune activity, and may predict response to peginterferon (PegIFN) therapy in chronic hepatitis B. Methods: IP-10 was measured at baseline and on-treatment week 12 in 210 HBeAg-positive patients treated with PegIFN for 52 weeks. Response to treatment was assessed at 6 months post-treatment and defined as HBeAg loss, combined response (HBeAg loss with HBV DNA <10,000 c/ml) or HBsAg loss. Results: Median baseline IP-10 levels were 158 pg/ml. Higher baseline IP-10 was associated with more HBV DNA, HBeAg and HBsAg decline from week 4 onwards, and IP-10 was higher in patients who achieved HBeAg loss (p = 0.001) and combined response (p = 0.052). A combination of high IP-10 (>150 pg/ml) with absence of precore (PC) and core promoter (BCP) mutants strongly predicted combined response and HBsAg loss: 48% of patients with high IP-10 and no detectable mutants achieved a combined response (p <0.001). A minimal non-significant decline from baseline was observed to week 12 (0.015 log pg/ml, p = 0.52 compared to baseline), but decline was somewhat more pronounced in patients who achieved HBeAg loss (0.05 log pg/ml, versus an increase of 0.05 in patients without HBeAg loss, p = 0.04). Conclusions: Higher pre-treatment IP-10 levels are associated with an increased probability of HBeAg loss after PegIFN therapy. A combination of high baseline IP-10 and absence of PC and BCP mutants identified patients with the highest probability of combined response and HBsAg loss. There appears little use for on-treatment quantification of IP-10 for prediction of response to PegIFN. (c) 2013 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.