CHRONIC LIVER DISEASE AND ITS BURDEN

Chronic liver disease (CLD) is a serious condition, and a major cause of global morbidity and mortality.^1,2 Approximately 2 million people die every year worldwide from liver disease, with cirrhosis accounting for a large majority of those deaths. Liver cirrhosis is ranked as the world’s 11th leading cause of death from all etiologies.¹  

PROGRESSION OF LIVER DISEASE

Hepatic injury results from a variety of causes including viral infections, alcoholism, genetic inheritance, metabolic abnormalities, autoimmune responses, biliary and vascular conditions, drugs, toxins, environmental pollutants, or even cryptogenic reasons. When it persists for 6 months or beyond, hepatic injury is classified as CLD, which may eventually progress to steatosis/steatohepatitis, fibrosis, then to end-stage cirrhosis, and even hepatocellular carcinoma (HCC). Alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD) and drug-induced liver injury (DILI) are among the more common pathologies associated with liver disease progression.²

Oxidative stress has been identified as a common pathological pathway involved in the initiation and progression of the various clinical phenotypes of chronic liver disease. The generation of reactive oxygen species (ROS) and the decrease in endogenous antioxidant defenses are the primary mechanisms that makes oxidative stress hepatotoxic². Targeting oxidative stress during early disease stages could be a useful strategy to preserve intact liver cells and those that still have reversible damage.^1,2 

SILYMARIN

Silymarin is an extract from the dried seeds and fruit of the milk thistle that has been used medicinally for centuries, including liver diseases. It is best known for its scientifically proven antioxidant properties by acting as a free radical scavenger, along with modulating the enzymes responsible for the development of cellular damage, fibrosis and cirrhosis. Clinically, silymarin has been shown to reduce liver dysfunction, may reduce liver-related mortality in patients with cirrhosis and is well-tolerated.¹

Crude silymarin however is lipophilic and poorly soluble in water, with only about 20–50% absorption from the gastrointestinal tract after oral ingestion. This had been a significant limiting factor in its therapeutic use. Many studies were directed at improving the pharmacokinetics of silymarin preparations, but to this day, commercial silymarin products still differ significantly in their content, dissolution, and oral bioavailability.¹

 

References:
1. Gillessen A, Schmidt HH. Adv Ther 2020;37:1279–1301. 2. Aghemo A, et al. Ann Med 2022;54:1548–1560.