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Altered Cytokine Levels May Explain More Rapid Liver Fibrosis Progression in HIV-HCV Coinfected Individuals

Several studies have shown that HIV positive people - especially those with low CD4 cell counts -- tend to experience more rapid liver disease progression related to chronic hepatitis C virus (HCV) infection, though the reasons for this are not fully understood.

As described in the May 2008 Journal of Viral Hepatitis, researchers conducted a study to investigate whether severe immunodeficiency in HIV-HCV coinfected individuals is associated with changes in inflammatory cytokine messenger RNA (mRNA) levels in the liver, which may play a role in fibrosis.

The investigators measured mRNA levels of the cytokines interferon gamma (IFN-gamma), tumor necrosis factor alpha (IFN-alpha), transforming growth factor beta-1 (TGF-beta-1), interleukin 4 (IL-4), IL-10, IL-12p35, and IL-12p40 using real-time PCR performed on liver specimens from 19 HCV monoinfected and 24 HIV-HCV coinfected patients.

Results

HIV-HCV coinfected patients had decreased intrahepatic mRNA levels of IFN-gamma (P = 0.09), IL-4 (P = 0.05), and IL-12p35 (P = 0.04) compared with HCV monoinfected patients.

Conversely, IL-10 was elevated in coinfected subjects (P = 0.07).

In coinfected patients, IFN-gamma mRNA levels increased linearly with increasing CD4 cell counts, by 1.23 times for every increase of 100 cells/mm3 (P = 0.02).

No other cytokines were significantly associated with CD4 cell count.

Conclusion

In conclusion, the authors wrote, "HIV-induced lymphopenia may result in hepatic inflammatory cytokine suppression" in HIV-HCV coinfected patients. In particular, "Intrahepatic IFN-gamma levels are significantly reduced in patients with advanced immunodeficiency."

They added that, "Further studies are needed to assess whether decreased IFN-gamma secretion by HCV-specific CD4+ cells may account for accelerated fibrogenesis in these patients."

4/15/08

Reference
SA Gonzalez, C Zhang, MI Fiel, and others. Hepatic inflammatory cytokine mRNA expression in hepatitis C virus-human immunodeficiency virus co-infection. Journal of Viral Hepatitis 15(5): 331-338. May 2008.


 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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