Abstract
Recurrent pancreatitis is a potentially fatal complication of severe hypertriglyceridemia. Genetic defects and lifestyle risk factors may render this condition unresponsive to current treatments. 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. Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity.
Highlights
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
A fasting triglyceride level of 1000 to 2000 mg/dL is defined as “severe hypertriglyceridemia” and carries a risk of pancreatitis because after eating, triglyceride levels may rise above 2000 mg/dL. (To convert triglycerides to millimoles per liter, multiply by 0.0113.)
Severe and very severe hypertriglyceridemia can be caused by several genetic defects that impair metabolism by lipoprotein lipase of triglycerides in chylomicrons and very low density lipoproteins (VLDL).[5]
Summary
Lomitapide prevented pancreatitis in severe intractable hypertriglyceridemia but at a potential long-term cost of hepatotoxicity. Severe and very severe hypertriglyceridemia can be caused by several genetic defects that impair metabolism by lipoprotein lipase of triglycerides in chylomicrons and very low density lipoproteins (VLDL).[5] This is called familial chylomicronemia (type 1 dyslipidemia). Microsomal triglyceride transfer protein (MTP) transfers triglycerides and other lipids to apolipoprotein B48 in the enterocyte and apolipoprotein B100 in the hepatocyte, a necessary step to start the assembly of the lipid-protein complex in the enterocyte that will become a chylomicron or in the hepatocyte to become a VLDL or low-density lipoprotein (LDL).[6] Genetic deficiency of MTP causes abetalipoproteinemia, characterized by very low plasma levels of triglycerides.[6] MTP inhibitors could substantially lower plasma triglyceride levels by inhibiting the formation and secretion of triglyceride-rich lipoproteins
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