December 24, 2013Open Access
Severe Hypertriglyceridemia With Pancreatitis
Key Result
Lomitapide lowered fasting triglyceride levels from >3000 mg/dL to 524 mg/dL at 40 mg/d and prevented pancreatitis over 13 years, but caused progressive steatohepatitis and fibrosis.
Study Design
Type
Case Report (n=1)
Multicenter
No
Structured PICO
Does lomitapide prevent pancreatitis and lower triglycerides in severe intractable hypertriglyceridemia?
P
Population
1 female patient, 44 years old, with severe intractable hypertriglyceridemia (homozygous for P234L mutation in lipoprotein lipase) and near-fatal recurrent pancreatitis.
I
Intervention
Lomitapide 30 mg/d and 40 mg/d
O
Outcome
Fasting triglyceride levels and prevention of pancreatitishard clinical
Lomitapide successfully prevented recurrent pancreatitis and lowered triglycerides in a patient with severe lipoprotein lipase deficiency, though it caused long-term hepatotoxicity.
Main Result
Absolute Event Rate: 524% vs 3109%
Limitations
- Single patient case report limits generalizability
- Long-term treatment resulted in progressive hepatotoxicity, including steatohepatitis and fibrosis
- High dietary fat intake reduces drug efficacy and increases gastrointestinal adverse effects like diarrhea
Abstract
IMPORTANCE: Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. OBSERVATIONS: We report this first case of long-term management of intractable near-fatal recurrent pancreatitis secondary to severe hypertriglyceridemia by a novel use of lomitapide, an inhibitor of microsomal triglyceride transfer protein, recently approved for treatment of familial homozygous hypercholesterolemia. The patient had been hospitalized many times for pancreatitis since age 15 years. Her serum triglyceride level averaged 3900 mg/dL while she received therapy with approved lipid drugs. She is homozygous for a coding mutation (P234L) in lipoprotein lipase, leaving her unable to metabolize triglycerides in chylomicrons and very low density lipoproteins (VLDL). Lomitapide reduces the secretion of chylomicrons and VLDL. Lomitapide, which was started when she was 44 years old after near-fatal pancreatitis, lowered her fasting triglyceride level from greater than 3000 mg/dL to a mean (SD) of 903 (870) mg/dL while she received 30 mg/d and to 524 (265) mg/dL while she received 40 mg/d; eliminated chronic abdominal pain; and prevented pancreatitis. However, fatty liver, present before treatment, progressed to steatohepatitis and fibrosis after 12 to 13 years. CONCLUSIONS AND RELEVANCE: Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.