| |
HBV & HCV & Accelerated Senescence: premature aging
|
| |
| |
Ageing of the chronic HBV patients is strongly linked to liver cells senescence, while HBV infection may also affect hepatocyte and other liver cells senescence. Senescent cells produce several pro‐inflammatory and angiogenic factors, altering hepatic tissue microenvironment, likely favouring carcinogenesis in the neighbouring non‐senescent cells.10 Thus, it is reasonable to assume that cellular senescence may play an important role in HBV‐related hepatocarcinogenesis.10....In particular, current oral antiviral therapy can inhibit HBV replication in almost all treated compliant patients resulting in improvement in liver necroinflammation and fibrosis and even reversion of cirrhosis, but HCC may still develop especially in old patients with advanced liver disease before treatment. 2, 4, 6 Therefore, HCC remains the main challenge in diagnosed chronic HBV patients, as its incidence is decreased but not eliminated even after many years of effective HBV therapy.2, 6 Chronic hepatitis B, with or without cirrhosis, is associated with more pronounced DNA damage of lymphocytes, since such patients were found to have higher levels of peripheral DNA damage compared to chronic HBV carriers and healthy individuals.39, 40 Studies in chronic liver diseases, such as non‐alcoholic fatty liver disease (NAFLD), have shown that hepatocytes undergo senescence and exhibit various key aspects.43 Telomere shortening in the liver has been detected in patients infected with hepatitis C virus, in conjunction with accumulation of senescent cells during fibrosis progression in patients with chronic hepatitis C.44 .....Indeed, senolytic drugs which target the anti‐apoptotic response of senescent cells, such as signalling through BCL‐2 family members (Navitoclax/ABT‐263 or ABT‐737), have been proven effective in inducing cell death in senescent cells; https://onlinelibrary.wiley.com/doi/full/10.1111/liv.14659
Accelerated aging & HBV: Chronic HBV, higher anti-CMVIgG titer and CD8þT-cell count were each associated with increased age advancement, independently of HIV-status/group. In this multivariable analysis, only cumulative exposure to saquinavir (average increase of 1.17 (0.49, 1.85) years per year of exposure,P<0.001) and nadir CD4þT-cell count lessthan 200 cells/ml (average increase of 3.00 (0.22 to 6.22)years,P<0.07), as well as chronic HBV (7.35 (0.42-14.29) years ,P=0.04) and total anti-CMV IgG antibody titer (1.86 (0.22-3.51) years per one log increase,P=0.03), retained their significant associations. Whilst thisdifference in age advancement did not appear to be explained by differences in participant characteristics, chronic viral co-infections such as CMV and HBV, prior immunosuppression and exposure to some antiretroviral drugs may have contributed to this age advancement. CMV and HBV co-infections may causepremature aging of the immune system in PLWH bytheir chronic antigenic stimulation, inducing systemicimmune activation https://www.natap.org/2018/HIV/Do_people_living_with_HIV_experience_greater_age.992.pdf
In multivariable analysis including significant factors after adjusting for HIV-status/group (P<0.1), the average increase in age advancement (95% CI) remained significant for chronic HBV [10.05 (3.45-16.64) years,P¼0.003], total anti-CMV IgG antibody titer [1.83(0.51- 3.15) years per one log (AU) increase,P¼0.007]and CD8þT cell [0.44 (0.02-0.85) years per 100 cells/mlincrease,P¼0.04]. Even after adjusting for chronic HBV,total anti-CMV IgG and CD8þT-cell, HIV-positiveCOBRA participants exhibited a greater age advancment compared with both the HIV-negative participants[mean increase (95% CI) 4.5 (1.6-7.5),P¼0.003] and blood donors [mean increase (95% CI): 19.0 (12.6-25.4),P<0.001], with the HIV-negative COBRA participants also exhibiting greater age advancement than blood donors [mean increase (95% CI) 13.5 (7.1-20.0,P<0.001].
Chronic immune activation likely accelerates senescence that is driven by HIV itself or by co-infections (CMV, hepatitis B virus, hepatitis C virus, etc).
https://www.natap.org/2010/HIV/021510_01.htm
More frequent reactivation of CMV in HIV may contribute to immune aging in HIV patients.
https://www.natap.org/2014/CROI/croi_210.htm
| |
| |
| |
|
|
|
