Matrix Metalloproteinase-9 and Tissue Inhibitors of Matrix Metalloproteinase-1 in Plasma of Patients Co-infected with HCV and HIV

Background: Accelerated progression of hepatic fibrosis has been shown in patients co-infected with hepatitis C virus (HCV) and HIV. Liver fibrosis is a dynamic process in which the altered balance between matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) may play a major role.

Method: The involvement of MMP-9 and TIMP-1 in HCV liver disease progression in patients co-infected with HIV was evaluated. Plasma concentrations of human MMP-9 and TIMP-1 were assessed in 76 HIV-infected patients; 27 were co-infected with HCV and 49 were HCV negative. 18 healthy donors were included as controls.

Results: Patients with HIV infection exhibited a striking increase in TIMP-1 levels; this is more evident in patients with advanced CD4 depletion. There was no elevation in the plasma concentrations of the MMP-9. The highest levels of TIMP-1 were found in the HIV/HCV co-infected patients. The values of TIMP-1 in HIV-infected patients with chronic HCV hepatitis were significantly higher than in HIV-positive individuals without HCV infection, even including those with low CD4 count. No significant differences were seen in the MMP-9 levels.

Conclusion: These findings suggest that the altered balance between circulating MMP-9 and TIMP-1 during HIV infection may play an important role in exacerbating liver fibrosis progression in patients co-infected with HCV.