Concentrations of ssDNA in liver tissue and its correlation with sFas and sFasL in serum of patients infected with HBV, HCV, HCV and HIV

Abstract

Purpose: The concentration of nucleic acids that undergo apoptosis (ssDNA) determines the actual activity of programmed cell death. ssDNA concentrations in liver tissue of patients with chronic HBV, HCV and HCV and HIV infections were assessed. The concentration of this nucleic acid was analyzed in relation to the concentrations of serous apoptosis indicators, sFas and sFasL receptor proteins, the activity of inflammatory processes and fibrosis in liver tissue as well as HBV, HCV and HIV viraemia.

Patients: The study included 153 patients: 48 chronic HBV infected, 86 chronic HCV infected and 19 HCV and HIV infected.

Patients and methods: The concentrations of HBV-DNA, HCV-RNA and HIV-RNA were determined by use of RT-PCR method. CD3+, CD4+ and CD8+ lymphocytes count were detected in HIV infected patients' blood by use of a flow cytometer. The concentration of ssDNA was determined by use of monoclonal antibodies and ELISA tests. The concentrations of sFas and sFasL in serum were determined by use of an immunoenzymatic method (ELISA).

Results: The concentration of ssDNA in liver tissue of both HCV and HBV infected patients was higher in comparison to those co-infected with HCV and HIV (1332 x 10(-6) g/mg, +/-664 x 10(-6); vs 1508 x 10(-6) microg/mg, +/-810 x 10(-6); vs 886 x 10(-6) microg/mg, +/- 388 x 10(-6); p < 0.004). No correlation between ssDNA concentration and HBV and HCV viraemia was observed. In patients infected with HCV genotype 3, the concentration of ssDNA was 1343 x 10(-6) microg/mg, +/-700 x 10(-6), comparable from patients infected with genotype 1, 296 x 10(-6) microg/mg, +/- 615 x 10(-6). The highest concentration of ssDNA in liver tissue was detected in HBV infected patients with low inflammatory activity (1645 x 10(-6) microg/mg, +/-987) and low fibrosis (1606 x 10(-6) microg/mg, +/- 876 x 10(-6). Mild inflammatory changes and low fibrosis were observed in all HCV and HIV infected patients. No correlation between ssDNA concentration in liver tissue and HIV viraemia (r = 0.03; p = 0.90), HCV, CD8+ and CD4+ count (r = -11; p = 0.66) was observed. The concentration of ssDNA among HCV and HIV infected patients correlated with the concentration of sFas in serum (r = 0.52; p < 0.02).

Conclusions: HCV, HBV and HIV viraemias do not correlate with ssDNA concentration in liver tissue. In patients with HCV and HIV infections, CD4+ and CD3+ counts do not correlate with the concentration of ssDNA in liver tissue. HIV infection seems to inhibit apoptosis processes in liver tissue of HCV and HIV co-infected patients. In the case of HCV and HIV infections, the concentration of sFas in serum correlates with the concentration of ssDNA in liver tissue.