Do high triglycerides worsen liver health?

High Triglycerides and Liver Health

High triglycerides worsen liver health by contributing to hepatic steatosis (fatty liver) and potentially progressing to more severe forms of liver disease. 1, 2

Relationship Between Triglycerides and Liver Disease

• High triglyceride levels serve as a biomarker for non-alcoholic hepatic steatosis (fatty liver), which is a key component of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) 3, 1
• Excess triglyceride storage in the liver is the defining characteristic of MASLD, which has become the most common chronic liver disease worldwide 3
• Hepatic accumulation of triglycerides occurs when the balance between fatty acid acquisition (from plasma and de novo lipogenesis) exceeds fatty acid oxidation and secretion of very low-density lipoprotein-triglycerides 4
• Elevated triglycerides are frequently associated with insulin resistance, which further promotes hepatic fat accumulation through increased free fatty acid delivery to the liver 3, 5

Mechanisms of Liver Damage

• Excess visceral fat in patients with insulin resistance exposes the liver to higher levels of free fatty acids via the portal circulation, contributing to increased secretion of VLDL and hepatic steatosis 3
• When hepatic triglyceride synthesis cannot accommodate increased free fatty acid accumulation, lipotoxicity can result, leading to hepatocellular damage 5
• Hypertriglyceridemia is associated with ectopic fat deposition in the liver, which can progress from simple steatosis to steatohepatitis, fibrosis, and eventually cirrhosis 3, 6
• The TG/HDL-C ratio has been identified as an independent predictor of incident fatty liver disease, with higher ratios associated with increased risk 7

Clinical Implications and Disease Progression

• MASLD encompasses a spectrum from isolated liver steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, and cirrhosis 3
• MASLD is associated with increased risk of cardiovascular events, chronic kidney disease, hepatic and extrahepatic malignancies, and liver-related outcomes including liver failure and hepatocellular carcinoma 3
• The presence of MASLD is tightly linked to type 2 diabetes, obesity, and other cardiometabolic risk factors, which often coexist with hypertriglyceridemia 3, 2
• Triglyceride levels serve as a marker for metabolic health, with elevated levels indicating potential liver dysfunction and increased cardiovascular risk 1, 2

Paradoxical Protective Role of Triglyceride Synthesis

• Interestingly, some research suggests that the ability to synthesize and store triglycerides in the liver may actually be protective in obesity 5
• When hepatic triglyceride synthesis is inhibited, free fatty acids can accumulate in the liver, potentially leading to increased oxidative stress and liver damage 5
• This suggests that simple steatosis might be a protective adaptation to handle excess fatty acids, while progression to more severe forms of liver disease occurs when this compensatory mechanism fails 5

Management Considerations

• The European Association for the Study of the Liver (EASL) recommends lifestyle modification as the cornerstone of MASLD management, including weight loss, dietary changes, physical exercise, and reducing alcohol consumption 3
• Optimal management of comorbidities, including the use of incretin-based therapies for type 2 diabetes or obesity if indicated, is advised 3
• Evaluating for secondary causes of hypertriglyceridemia is important, including uncontrolled diabetes, alcohol consumption, medications, and family history of dyslipidemia 1
• A 5-10% reduction in body weight can potentially lower triglycerides by approximately 20%, which may help improve liver health 1, 8

Monitoring and Risk Assessment

• A stepwise approach using blood-based scores (such as the fibrosis-4 index) and imaging techniques (such as transient elastography) can help identify advanced fibrosis, which predicts liver-related outcomes 3
• The TG/HDL-C ratio may be useful for identifying individuals at risk for developing fatty liver disease, with optimal cut-off points of 0.88 for men and 0.64 for women 7
• Regular monitoring of liver function and metabolic parameters is important in patients with hypertriglyceridemia to detect early signs of liver disease 2

High triglycerides are both a marker and contributor to liver disease, particularly in the context of metabolic dysfunction. Managing triglyceride levels through lifestyle modifications and appropriate medical therapy can help improve liver health and reduce the risk of progression to more severe forms of liver disease.