What is the cause of familial hypertriglyceridemia (FHTG) and liver cirrhosis?

From the Guidelines

Familial hypertriglyceridemia is a genetic disorder that can contribute to the development of liver cirrhosis, and management involves triglyceride-lowering medications and dietary modifications to prevent progression of both conditions and reduce the risk of life-threatening complications. Familial hypertriglyceridemia is a genetic disorder that causes elevated triglyceride levels in the blood, which can lead to pancreatitis, cardiovascular disease, and fatty liver disease 1. When left untreated, the fatty infiltration of the liver can progress to nonalcoholic steatohepatitis (NASH) and eventually cirrhosis. Liver cirrhosis itself is characterized by irreversible scarring of liver tissue, resulting in impaired liver function. This condition disrupts normal lipid metabolism, potentially worsening hypertriglyceridemia in affected individuals. The combination of these conditions creates a dangerous cycle where each exacerbates the other.

Key Considerations

• Familial hypertriglyceridemia can increase the risk of pancreatitis, cardiovascular disease, and fatty liver disease 1
• Liver cirrhosis can disrupt normal lipid metabolism, potentially worsening hypertriglyceridemia in affected individuals 1
• Management typically involves triglyceride-lowering medications like fibrates (gemfibrozil 600mg twice daily or fenofibrate 145mg daily), omega-3 fatty acids (2-4g daily), and statins when appropriate 1
• Dietary modifications are crucial, including restricting fat intake to less than 15% of total calories, limiting simple carbohydrates, avoiding alcohol, and maintaining a low-sodium diet 1
• Regular monitoring of liver function and lipid profiles is essential, as is screening for complications like hepatocellular carcinoma in cirrhotic patients 1

Treatment Approach

The treatment goal for patients with moderate hypertriglyceridemia is a non–high-density lipoprotein cholesterol level of 30 mg per dL (0.78 mmol per L) higher than the low-density lipoprotein goal, as recommended by the NCEP ATP III 1. Fibrates are the first-line treatment in patients with hypertriglyceridemia who are at risk of pancreatitis. Fibrates, niacin, and n-3 fatty acids, alone or in combination, should be considered in patients with moderate to severe hypertriglyceridemia. Statins have a modest triglyceride-lowering effect (typically 10% to 15%) and may be useful to modify cardiovascular risk in patients with moderately elevated triglyceride levels. However, they should not be used alone in patients with severe or very severe hypertriglyceridemia.

From the FDA Drug Label

Estrogen therapy, thiazide diuretics and beta-blockers, are sometimes associated with massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia patients with active liver disease, including those with primary biliary cirrhosis and unexplained persistent liver function abnormalities

The cause of familial hypertriglyceridemia and liver cirrhosis is not directly stated in the label. However, it is mentioned that certain factors such as estrogen therapy, thiazide diuretics, and beta-blockers can contribute to massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia. Additionally, liver cirrhosis is listed as a contraindication for fenofibrate, indicating a potential relationship between liver disease and the medication, but the label does not provide a direct cause-and-effect relationship between the two conditions 2.

From the Research

Familial Hypertriglyceridemia and Liver Cirrhosis

• Familial hypertriglyceridemia is a condition characterized by elevated levels of triglycerides in the blood, which can increase the risk of liver disease, including liver cirrhosis 3, 4.
• Studies have shown that hypertriglyceridemia is a risk factor for liver cirrhosis, particularly in middle-aged men 4.
• Non-alcoholic fatty liver disease (NAFLD) is a spectrum of fatty infiltration, inflammation, and fibrosis of the liver caused by metabolic factors, and it is projected to become the leading cause of cirrhosis and need for liver transplantation in the United States 3.
• NAFLD can progress to non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma, and it is often associated with cardiovascular disease and hyperlipidemia 5, 6.

Risk Factors for Liver Cirrhosis

• Overweight and hypertriglyceridemia are independent risk factors for liver cirrhosis in middle-aged men 4.
• Elevated BMI and triglyceride levels are significant independent risk factors for the development of liver cirrhosis 4.
• Insulin resistance, hypertension, and dyslipidemia are also associated with NAFLD and can increase the risk of liver cirrhosis 3, 6.

Treatment and Management

• The mainstays of treatment for NAFLD, NASH, and fibrosis are weight loss and a healthy diet 3.
• Omega-3 fatty acids may be beneficial in managing hypertriglyceridemia in patients with NAFLD, and statins may be useful in managing hyperlipidemia in patients with NAFLD and NASH 3, 7.
• Lipid-lowering drugs may also be effective in treating dyslipidemia associated with NAFLD 6.