Advanced chronic liver disease has become a major public health concern. It is more prevalent and severe in the elderly with carrying a higher risk of decompensation. The authors of the present study aimed at elucidating the effects of aging on the pathophysiology of advanced chronic liver diseases in aged experimental animals and humans. Moreover, they also assessed simvastatin therapy as a therapeutic option in experimental animals.

These advanced chronic liver diseases was induced in young at 1 month and old at 16 months, experimental animals. A subgroup of advanced chronic liver diseases, old experimental animals were randomized to administer simvastatin (5 mg/kg) or vehicle (placebo) for a period of 15 days. These were analysed for hepatic and systemic hemodynamic, liver cells phenotype and hepatic fibrosis. 

Moreover, the gene expression of cirrhosis was measured in a both groups of young and aged patients with cirrhosis. The results showed that a more severe form of advanced liver disease was developed in aged  experimental animals. Portal hypertension and liver fibrosis got worsened as a result of deregulations in the phenotype of the main hepatic cells. Hepatocytes exhibited more extensive cell-death and poorer function, liver sinusoidal endothelial cells were further capillarized, hepatic stellate cell over-activated with remarkably elevated macrophage infiltration. The gene expression of cirrhosis was found to be significantly different between young and aged patients, suggestive of modifications in sinusoidal-protective pathways, establishing the pre-clinical observations. Moreover, simvastatin administered for 15-day to aged cirrhotic experimental animals showed improvement in hepatic sinusoidal milieu, causing relief in portal hypertension.

This study supports the fact that advanced chronic liver disease pathobiology varies in aged individuals. Owing to the fact that the median age of patients with advanced chronic liver disease is increasing, a real-life pre-clinical model should be implemented to provide more appropriate therapeutic approaches.

Source: Raquel Maeso-Díaz,Martí Ortega-Ribera,Erica Lafoz, et al. Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease[J]. Aging and disease, 2019, 10(4): 684-698.