December 16, 2001
This study is interesting because it deals with a basic problem in HIV/HCV co-infection: What is the mechanism of liver damage in co-infection? Why is the disease more severe for people who are co-infected than for those with only hepatitis C? Is the mechanism of liver cell damage and fibrosis different in mono-infected patients than in co-infected patients? At this moment we do not know the answers to these questions and have very little data, but ongoing research is trying to answer these questions.
Knowing the exact mechanism of liver damage is vital for the development of better and more specific therapies, not only for viral clearance but also for the treatment of fibrosis. This study is basically a study of the levels of different cytokines in co-infected patients and the relationship with HIV viral load, hepatic histology and the proposal for a "model of liver damage in HIV."
Dr. Stellrecht and her group collected data on 52 patients who had liver biopsies -- 24 mono-infected and 28 co-infected. They then measured levels of TNFa and TNFa receptor II (sTNFaRII), which have been shown to correlate with HIV levels and the pathogenesis of fibrosis, via the activation of TGF-b.
The baseline data for the co-infected patients was as follows: median CD4+ T-cell counts of 363, 64 percent on NRTIs, only four percent on protease inhibitors and 28 percent not on any HIV therapy. This is important because a significant number of these patients could have higher HIV PCR, as well as a very different immune status, when compared to patients who were treated. The results of the liver histology in the co-infected cases was less severe than in the mono-infected, with a mean Knodell score of 6.22. This is very unusual; all the cohort studies show that liver biopsy findings are worse with co-infection, unless you have an additional variable to explain this, such as alcohol ingestion among mono-infected patients, for example.
The results: HIV PCR correlated with the severity of the Knodell score. TNFa levels were higher in the HIV/HCV group, as compared to the HCV group. The study also showed a correlation between HIV levels and sTNFaRII levels but not with the severity of the histology. (This could have been because of the cohort's low Knodell scores.) Also, apoptosis was correlated to liver damage, with increased apoptosis in the mono-infected as opposed to the co-infected patients.
The conclusion of this study is that there may be different mechanisms for liver damage among the mono-infected, immune mediated, and that in co-infection the mechanism may be cytokine induced. The proposed model for liver damage would be by direct effect of HIV in increasing TNFa, and then the cascade of cytokines, and also direct effect in the liver cells.
This study needs to be done using a larger number of participants and should include more patients with severe liver disease in order to be more representative of the general population. The lack of a hepatitis C in vitro model precludes the measuring of all these mediators, and the interaction with HIV.
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