Figure 1

Adverse effects of HIV on HCV replication and liver fibrosis. HIV-associated systemic immune dysfunction and microbial translocation are the critical factors that drive HCV replication and fibrosis in HIV/HCV co-infected individuals. Depletion of CD4⁺T cells in conjunction with Th17 cells causes microbial translocation that dispenses their products in the blood circulation. Activation of Kupffer cells via TLR4 produces numerous fibrotic mediators including TGF-β, TIMP-1 and type-1 collagen. Taken together both systemic immune dysfunction and microbial translocation contribute to enhanced HCV replication and liver fibrosis.