Advanced chronic liver disease (aCLD) is a significant public health concern. Further, it is more prevalent and severe in the elderly, Thus displaying a higher risk of decompensation. A study investigated the impact of ageing on the pathophysiology of aCLD in aged rats and humans along with evaluating simvastatin as a therapeutic option in aged animals. 

Young (1 month) and old (16 months) rats were utilized to induce aCLD. aCLD-old animals were randomized to receive simvastatin (5 mg/kg) or vehicle (PBS) for 15 days. Assessment of the Hepatic and systemic hemodynamic, liver cells phenotype and hepatic fibrosis were done. 

Additionally, young and aged cirrhotic patients underwent evaluation for the gene expression signature of cirrhosis. 

The following observations were made-

• A more severe form of aCLD was described in aged animals. 
• They demonstrated increased portal hypertension and liver fibrosis due to profound deregulations in the phenotype of the main hepatic cells: hepatocytes 
• Aged animals also demonstrated more extensive cell death and poorer function in the hepatocytes, LSEC being further capillarized, HSC over-activated and a significant increase in macrophage infiltration. 
• The gene expression signature of cirrhosis was significantly different among young and aged patients, showing modifications in sinusoidal-protective pathways and confirming the pre-clinical observations. 
• Improvements in the hepatic sinusoidal milieu, causing significant amelioration in portal hypertension was observed after simvastatin administration for 15-day to aged cirrhotic rats.

This study explains the presence of a distinctive aCLD pathobiology in aged individuals. 

 A real-life pre-clinical model is warranted to develop more reliable therapeutic strategies and ageing may activate different or additional molecular mechanisms contrasting the youngs. Simvastatin can be studied further for its potential for improvements in this condition.

Source: Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease. Aging and disease. 2019, 10(4): 684-698 https://doi.org/10.14336/AD.2019.0127