Why would a patient with Primary Sclerosing Cholangitis (PSC) have elevated triglycerides but normal cholesterol levels?

Why PSC Patients May Have Isolated Hypertriglyceridemia

In PSC, elevated triglycerides with normal cholesterol most commonly reflects secondary metabolic causes rather than the cholestatic disease itself, since PSC typically causes hypercholesterolemia, not isolated hypertriglyceridemia. 1, 2

The Expected Lipid Pattern in PSC

PSC characteristically produces hypercholesterolemia, not isolated hypertriglyceridemia:

• Total cholesterol is typically elevated in PSC patients, with baseline values averaging 207 mg/dL (range 127-433 mg/dL), and 41% of patients have total cholesterol above the 95th percentile 2, 3
• Triglycerides are usually normal or only mildly elevated in PSC, with baseline values averaging 102 mg/dL (range 41-698 mg/dL), and only 2% of early-stage patients and 17% of advanced patients have elevated triglyceride levels 2, 3
• Cholesterol levels correlate with disease severity, with total and LDL cholesterol correlating significantly with liver biochemistries (alkaline phosphatase and bilirubin), indicating that cholestasis drives cholesterol elevation 2
• The mechanism differs from typical dyslipidemia because cholestatic liver disease produces abnormal lipoproteins, including lipoprotein X, which is a protective response to bile acid accumulation in the systemic circulation 4, 5

Secondary Causes to Investigate

When a PSC patient has isolated hypertriglyceridemia, look for metabolic and lifestyle factors that are independent of the cholestatic disease:

Metabolic Syndrome Components

• Obesity, insulin resistance, and diabetes independently elevate triglycerides regardless of PSC status 1
• These conditions are common comorbidities that can coexist with PSC

Lifestyle and Dietary Factors

• High simple carbohydrate intake is a major contributor to triglyceride elevation 1
• Excessive alcohol consumption commonly causes hypertriglyceridemia 1
• Weight gain directly raises triglyceride levels 1

Medication-Induced Hypertriglyceridemia

• Thiazide diuretics, beta-blockers, corticosteroids, and immunosuppressants can all elevate triglycerides 1
• This is particularly relevant in PSC patients who may be on immunosuppressive therapy or have received liver transplantation 6

Clinical Management Approach

Address secondary causes systematically rather than attributing the lipid abnormality to PSC itself:

• For triglycerides 150-199 mg/dL (mildly elevated): Focus on lifestyle modification including weight loss if overweight, reducing simple carbohydrates, increasing physical activity, and eliminating excessive alcohol 1
• For triglycerides 200-999 mg/dL (moderately elevated): Consider pharmacotherapy if cardiovascular risk factors are present, in addition to lifestyle changes 1
• For triglycerides ≥1000 mg/dL (severely elevated): Immediate treatment is required to prevent pancreatitis 1
• Review all medications to identify and modify drugs contributing to hypertriglyceridemia 1

Important Caveats

Do not overlook fat-soluble vitamin deficiencies, which are the actual nutritional complication of PSC:

• Vitamin A deficiency occurs in 40% of early PSC patients and 82% of advanced patients 3
• Vitamin D deficiency occurs in 14% of early PSC patients and 57% of advanced patients 3
• Vitamin E deficiency occurs in 2% of early PSC patients and 43% of advanced patients 3
• Screen and supplement fat-soluble vitamins (A, D, E) in all PSC patients, especially those with advanced disease 6, 3

The cardiovascular risk paradox: Despite elevated cholesterol levels in PSC, the incidence of coronary artery disease is only 4%, suggesting that cholestatic hypercholesterolemia may not carry the same cardiovascular risk as typical dyslipidemia 2