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

Am J Gastroenterol. 2004 Dec;99(12):2359-64. doi: 10.1111/j.1572-0241.2004.40047.x.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

MeSH terms

  • Adult
  • Aged
  • Female
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Injections, Subcutaneous
  • Interleukin-11 / administration & dosage
  • Interleukin-11 / therapeutic use*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Pilot Projects
  • Platelet Count
  • Polymerase Chain Reaction
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use*
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Interleukin-11
  • Recombinant Proteins
  • oprelvekin