Hepatocellular carcinoma,human immunodeficiency virus and viral hepatitis in the HAART era

The incidence of hepatocellular carcinoma(HCC)in patients with human immunodeficiency virus(HIV) is rising.HCC in HIV almost invariably occurs in the context of hepatitis C virus(HCV)or hepatitis B virus (HBV)co-infection and,on account of shared modes of transmission,this occurs in more than 33% and 10% of patients with HIV worldwide respectively.It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy(HAART)era,wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop.Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy,which in HIV co-infection presents unique challenges.Once HCC develops,there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies,including liver transplantation.

Studies on the allostimulatory function of dendritic cells from HCV-HIV-1 co-infected patients

There is increasing recognition of the potential morbidity and mortality associated with HIV-1 and hepatitis C (HCV)co-infection. HIV appears to adversely affect HCV disease while the reciprocal effect of HCV on HIV remains controversial.We therefore studied the effect of co-infection on dendritic cell function versus HIV infection alone, as previous work has shown that HCV impairs dendritic cell (DC) function. HIV-1 positive individuals with HCV were matched for CD4count, HIV- 1 RNA viral load and therapy, to HIV- 1 positive patients without HCV. Monocyte-derived DC were generated and mixed leukocyte reactions were performed. We assessed allostimulatory capacity with and without administration of exogenous Thl cytokines, using thymidine uptake and cell division analyses with the vital dye CFSE. We found that monocyte-derived DC from co-infected individuals showed no significant differences in allostimulatory capacity to ex vivo generated DC from HIV-1 infected individuals without HCV. Unlike the situation with HCV infection alone, this impairment was not reversed by increasing concentrations of either interleukin-2 or -12. Monocyte-derived DC from HIV-1 and HCV co-infected individuals have a similar allostimulatory capacity to DC from matched patients with HIV-1alone. These findings are compatible with results of prior clinical studies that found no evidence that HCV co-infection altered HIV disease progression and has implications for immunotherapeutic approaches in co-infected individuals.