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Liver disease progression in HIV/HCV co-infected patients: a role for metalloproteinases and their specific inhibitors

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Background of Study

HIV infection accelerates the rate of HCV progression to fibrosis which represents the main factor affecting the prognosis of hepatitis C as well the best indicator of disease status. There is increasing evidence that liver fibrosis is a dynamic pathology c process in which the altered balance between matrix metalloproteiases (MMPs) and their specific inhibitors (TIMPs) may play a major role.

Objective of the Study

To investigate the possible involvement of MMP-9 and TIMP-1 in the HCV liver disease progression in patients co-infected with HIV, we assessed the levels of circulating enzyme and inhibitor in a series of HIV-infected individuals with and without chronic hepatitis C.

Design

Study participants included a total of 76 HIV-infected patients, of whom 49 without HCV infection (median CD4 = 241/mmc;VL = 5 log) and 27 co-infected with HCV (median CD4 = 130/mmc; VL = 5.3 log). All but one of HIV/HCV co-infected patients had evidence of chronic hepatitis C. 11 healthy donors were used as controls. Concentrations (ng/ml) of human TIMP-1 and MMP-9 were detected in plasma samples using the Biotrak ELISA assay (Amersham). Data are expressed as median.

Results

All HIV-infected patients had plasma TIMP-1 levels significantly higher than healthy controls (1740 vs. 755), whereas MMP-9 levels were lower (23 vs. 1157) (p < 0.001). The levels of TIMP-1 were significantly higher in patients with CD4 > 300/mmc than those with CD4 < 300/mmc (p < 0.05). No statistically significant differences in the levels of MMP-9 and in the TIMP-1/MMP-9 ratio were found between HCV co-infected and not co-infected HIV+ patients (p < 0.05).

Conclusion

Our results suggest that the altered balance between MMP-9 and TIMP-1 during HIV infection may play an important role in exacerbating fibrosis progression in patients co-infected with HCV.

Author information

Correspondence to Priyo Sasongko.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Chronic Hepatitis
  • Liver Fibrosis
  • Fibrosis Progression
  • Liver Disease Progression
  • Altered Balance