www.hivandhepatitis.com

Accelerated Liver Disease Progression in HIV-HCV Coinfected Patients May Be Due to Increased Liver Inflammation

Although results have not been not entirely consistent, several studies have shown that HIV-HCV coinfected patients tend to experience more rapid liver disease progression than HIV negative people with hepatitis C alone. A study reported in the January 11, 2008 issue of AIDS suggests a possible mechanism underlying accelerated liver disease progression in coinfected individuals.

As background, the authors noted that, "This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines."

To assess this hypothesis, the investigators used quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) assays to measure intrahepatic (within the liver) messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV monoinfected and 40 HIV-HCV coinfected patients.

Results

• Despite well preserved CD4 cell counts (median 598 cells/mm3), the HIV-HCV coinfected patients had significantly lower CD4 mRNA levels than HCV monoinfected individuals.
• Increased mRNA levels of CD3-epsilon, TCR-alpha, CD8-alpha, and CD8-beta suggested intrahepatic enrichment of CD8 T-cells in the HIV-HCV coinfected patients.
• Intrahepatic mRNA levels of the inflammatory cytokines interferon-gamma, RANTES (CCL5), macrophage inflammatory protein 1 alpha (CCL3), and interferon-inducible protein 10 (CXCL10) were significantly higher in the coinfected patients.
• mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21), and stroma-derived factor 1 (CXCL12) did not differ between the 2 groups.
• All changes were less pronounced in the subgroup of coinfected patients receiving combination antiretroviral therapy compared with untreated HIV positive individuals.