Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection
Abstract
:1. Introduction
2. Pathophysiology of Liver Fibrosis in Chronic Hepatitis C Virus (HCV) Infection
2.1. Background Issues
2.2. Interplay between HCV and Liver Inflammation and Fibrosis
3. Accelerated Liver Fibrosis in Human Immunodeficiency Virus (HIV)/HCV Coinfection
3.1. Direct Effects of HIV
Markers | HIV | HCV | HCV/HIV |
---|---|---|---|
Immune cells | |||
NK | ↓ | ↓ | ↓↓ |
DC | ↓↓ | ↓ | ↓↓↓ |
CD4 T cell | ↓↓ | ↓ | ↓↓↓ |
Immune activation | |||
CD4 T cell DR/38+ | ++ | + | +++ |
CD8 T cell DR/38+ | +++ | +++ | +++ |
Macrophage (Kupffer cells) | + | ++ | +++ |
Cytokines and chemokines | |||
IP-10 | ++ | ++ | ++++ |
IL-1β | + | + | ++ |
IFN-γ | ↓ | ↓ | ↓ |
TGF-β | + | ++ | +++ |
TNF-α | ++ | + | +++ |
MIP-1α | ↓↓↓ | ↓↓ | ↓↓ |
MIP-1β | ↓↓↓ | ↓ | ↓↓ |
RANTES | +++ | + | ++ |
Microbial translocation | |||
sCD14 | ++ | + | +++ |
LPS | ++ | + | +++ |
Fibrosis mediators | |||
MMP | ++ | ++ | +++ |
TIMPs | ++ | ++ | +++ |
HA | + | ++ | +++ |
Apoptosis and ROS | |||
TRAIL/FAS | ++ | ++ | ++++ |
ROS | ++ | ++ | +++ |
Metabolic parameters | |||
Insulin resistance | ++ | + | +++ |
Adiponectin | ↓ | ↓↓ | ↓↓↓ |
Resistin | + | ++ | +++ |
Leptin | + | ++ | +++ |
3.2. HIV-Associated Dysregulation of the Immune Response and Cytokine Network
3.3. Role of Immune Activation and Microbial Translocation
4. Dysregulation of Matrix Metalloproteinases and Role of Fibrosis Biomarkers
4.1. Role of Metabolic Alterations
4.2. Role of Alcohol and Drug Use
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Mastroianni, C.M.; Lichtner, M.; Mascia, C.; Zuccalà, P.; Vullo, V. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection. Int. J. Mol. Sci. 2014, 15, 9184-9208. https://doi.org/10.3390/ijms15069184
Mastroianni CM, Lichtner M, Mascia C, Zuccalà P, Vullo V. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection. International Journal of Molecular Sciences. 2014; 15(6):9184-9208. https://doi.org/10.3390/ijms15069184
Chicago/Turabian StyleMastroianni, Claudio M., Miriam Lichtner, Claudia Mascia, Paola Zuccalà, and Vincenzo Vullo. 2014. "Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection" International Journal of Molecular Sciences 15, no. 6: 9184-9208. https://doi.org/10.3390/ijms15069184