 Accelerated
Liver Disease Progression in HIV-HCV Coinfected Patients May Be Due to Increased
Liver Inflammation
By
Liz Highleyman 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.
Conclusion
Based
on these findings, the authors wrote, "The accelerated liver disease observed
in HIV-HCV coinfected patients might reflect enhanced intrahepatic inflammatory
responses rather than increased local transcription of directly profibrogenic
cytokines."
01/11/08
Reference
T Kuntzen, C Tural,
B Li, and others. Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis
C virus co-infection: infiltrating cells, cytokines, and influence of HAART. AIDS
22(2):203-10. January 11, 2008.
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