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| Pathogenesis of Hepatitis C Virus (HCV) in HIV Positive Patients |
| Presentation Time: Sunday, 2:00 p.m. - 2:15 p.m. |
KATHLEEN A. STELLRECHT, A. MCELHONE, K. PROVIDENCE;
Albany Medical Center, Albany, NY. |
| Presentation Number: 456 |
| Background: Rapid progression of chronic hepatitis C occurs in HIV patients by unknown mechanisms. Previously, HIV viral loads correlated with liver pathology (r = 0.45, p = 0.02), suggesting that HIV had a direct effect. Cytokines are integral to the manifestations of HIV disease and also, mediate liver damage. Tumor necrosis factor-alpha (TNFα) and TNFα receptor II (sTNFαRII) levels, which correlate with HIV viral loads, are involved in fibrosis. Transforming growth factor-beta (TGF-β) inhibits hepatocyte proliferation and stimulates extracellular matrix protein production. The role of these cytokines in HCV disease in coinfected patients was studied. Methods: Plasma TNFα, sTNFαRII and TGF-β levels were measured in 52 HCV PCR positive patients (24 HCV mono-infected and 28 HIV coinfected patients). Liver biopsies were scored by Knodell methodology and evaluated for apoptosis using the ApopTag kit. Results: TNFα levels were higher in coinfected versus mono-infected patients (6.6 vs 3.9 pg/ml, p =.04). Linear regression revealed a correlation between sTNFαRII and histology in the HIV negative group (r = 0.40 , p =.04), suggesting a role for the immune response in liver disease in this population. In coinfected patients, HIV viral load correlated with liver histology, TNFα, and sTNFαRII levels, but these cytokines did not correlate with liver pathology. Increased apoptosis was demonstrated in the mono-infected as compared to the coinfected patients (62 vs 28 cells/cm2, p=0.02). However, this difference was not maintained when controlling for liver pathology. Furthermore, in coinfected patients, apoptosis correlated with liver damage (r = 0.42, p=0.024) and TGF-β levels (r0 .62 , p < 0.01). In a multiple regression analysis, HIV viral load, apoptosis and TGF-β associated independently with liver pathology (r=0.7, p = 0.03). Conclusion: Our studies have indicated a HCV pathogenesis is immune mediated in mono-infected patients, but not in HIV coinfected patients. HIV appears to directly affect liver disease. This effect maybe cytokine driven. |
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