Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts2Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts3Harvard Medical School, Boston, Massachusetts.
Harvard Vanguard Medical Associates, Boston, Massachusetts.
JAMA Intern Med. 2014 Mar;174(3):443-7. doi: 10.1001/jamainternmed.2013.13309.
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.
复发性胰腺炎是严重高甘油三酯血症的一种潜在致命并发症。遗传缺陷和生活方式风险因素可能使这种情况对目前的治疗方法没有反应。
我们报告了首例因严重高甘油三酯血症引起的难治性近致命性复发性胰腺炎的长期治疗病例，该病例使用了一种新的 microsomal triglyceride transfer protein 抑制剂lomitapide，该抑制剂最近被批准用于治疗家族性纯合子高胆固醇血症。自 15 岁以来，该患者因胰腺炎多次住院。她的血清甘油三酯水平平均为 3900mg/dL，同时接受了批准的降脂药物治疗。她是脂蛋白脂肪酶编码突变（P234L）的纯合子，使其无法代谢乳糜微粒和极低密度脂蛋白（VLDL）中的甘油三酯。Lomitapide 可减少乳糜微粒和 VLDL 的分泌。当她在 44 岁时因近致命性胰腺炎而开始服用 lomitapide 时，她的空腹甘油三酯水平从大于 3000mg/dL 降至平均（SD）903（870）mg/dL，同时服用 30mg/d；降至 524（265）mg/dL，同时服用 40mg/d；消除了慢性腹痛；并预防了胰腺炎。然而，在治疗前存在的脂肪肝在 12 至 13 年后进展为脂肪性肝炎和纤维化。
Lomitapide 可预防严重难治性高甘油三酯血症中的胰腺炎，但存在潜在的长期肝毒性风险。
