A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy.

Abstract

To evaluate the effects of recombinant human interleukin (rhIL)-11 on liver histology in patients with chronic hepatitis C virus (HCV) infection and advanced liver disease who had failed antiviral therapy. This was an open-label study of rhIL-11 (Neumega), Wyeth Laboratories, Collegeville, PA) at a dose of 5 microg/kg administered by subcutaneous injection daily for 12 wk. The primary efficacy endpoint was the change in the Knodell Histology Activity Index (HAI) between pre- and posttreatment liver biopsies. Secondary efficacy endpoints included changes in plasma alanine transaminase (ALT) concentrations and in the number of platelets. The Knodell HAI improved in 11 (55%) of the 20 subjects enrolled, with the mean score improving from 7.3 to 5.9 (p= 0.006). Eight subjects (40%) experienced significant improvement as defined by a decrease of at least two points in the HAI. IL-11 treatment was also associated with a decrease in ALT levels from a mean level of 113 IU/L at baseline to 65 IU/L at week 12 (p < 0.001). Platelet levels increased from a mean of 143 x 10(3)/microl at baseline to 198 x 10(3)/mul at week 12 of treatment (p < 0.001). Overall, rhIL-11 was well tolerated and no serious adverse events (AEs) were reported. The most common AE was edema of the lower extremities, which occurred in all subjects. The findings from this pilot study suggest that rhIL-11 may be beneficial for patients with hepatic inflammation and advanced liver disease associated with chronic HCV infection. Larger clinical trials are warranted to further evaluate the long-term antiinflammatory and antifibrotic effects of rhIL-11.