Long-term interleukin 10 therapy in chronic hepatitis C patients has a proviral and anti-inflammatory effect

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Abstract

An imbalance in Th1 and Th2 cytokine production is implicated in disease progression of HCV. Our aim was to determine the effect of IL-10 administration in patients with HCV-related liver disease. Thirty patients with advanced fibrosis who had failed antiviral therapy were enrolled in a 12-month treatment regimen with SQ IL-10 given daily or thrice weekly. Liver biopsies were performed before and after therapy. Serum and PBMC were collected for HCV RNA, ALT, and functional T-cell analysis. IL-10 led to significant improvement in serum ALT (mean ALT: day 0 = 142 ± 17 vs. month 12 = 75 ± 10; P < .05). Hepatic inflammation score decreased by at least 2 in 13 of 28 patients (mean decrease from 4.6 ± 0.3 to 3.7 ± 0.3, P < .05) and 11 of 28 showed a reduction in fibrosis score (mean change from 5.0 ± 0.2 to 4.5 ± 0.3, P < .05). Serum HCV RNA levels increased by 0.5 log during therapy (mean HCV RNA day 0: 12.3 ± 3.0 Meq/mL; 12 months: 38 Meq/mL; P < .05) and returned to baseline at the end of follow-up (11.0 ± 2.4 Meq/ml). Five patients developed viral loads of greater than 120 Meq/mL and two of these developed an acute flare in serum ALT. IL-10 caused a decrease in the number of HCV-specific CD4+ and CD8+ IFN-γ secreting T cells and alterations in PBMC cytokine production towards a Th2 dominant profile. These changes parallel the improvement in ALT and rise in HCV RNA. In conclusion, long-term rIL-10 therapy appears to decrease disease activity, but also leads to increased HCV viral burden via alterations in immunologic viral surveillance. (Hepatology 2003;38:859–868).

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