Severe hypertriglyceridemia (sHTG), defined as a triglyceride (TG) concentration ≥ 500 mg/dL (≥ 5.7 mmol/L) is an important risk factor for acute pancreatitis. Although lifestyle, some medications, and certain conditions such as diabetes may lead to HTG, sHTG results from a combination of major and minor genetic defects in proteins that regulate TG lipolysis. Familial chylomicronemia syndrome (FCS) is a rare disorder caused by complete loss of function in lipoprotein lipase (LPL) or LPL activating proteins due to two homozygous recessive traits or compound heterozygous traits. Multifactorial chylomicronemia syndrome (MCS) and sHTG are due to the accumulation of rare heterozygous variants and polygenic defects that predispose individuals to sHTG phenotypes. Until recently, treatment of sHTG focused on lifestyle interventions, control of secondary factors, and nonselective pharmacotherapies that had modest TG-lowering efficacy and no corresponding reductions in atherosclerotic cardiovascular disease events. Genetic discoveries have allowed for the development of novel pathway-specific therapeutics targeting LPL modulating proteins. New targets directed towards inhibition of apolipoprotein C-III (apoC-III), angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like protein 4 (ANGPTL4), and fibroblast growth factor-21 (FGF21) offer far more efficacy in treating the various phenotypes of sHTG and opportunities to reduce the risk of acute pancreatitis and atherosclerotic cardiovascular disease events.

重度高甘油三酯血症 （sHTG），定义为甘油三酯 （TG） 浓度≥ 500 mg/dL （≥ 5.7 mmol/L），是急性胰腺炎的重要危险因素。尽管生活方式、某些药物和某些疾病（如糖尿病）可能导致 HTG，但 sHTG 是由调节 TG 脂肪分解的蛋白质的主要和次要遗传缺陷共同引起的。家族性乳糜微粒血症综合征 （FCS） 是一种罕见的疾病，由两个纯合隐性状或复合杂合性状引起的脂蛋白脂肪酶 （LPL） 或 LPL 激活蛋白功能完全丧失。多因素乳糜微粒血症综合征 （MCS） 和 sHTG 是由于罕见的杂合变异和多基因缺陷的积累，使个体易患 sHTG 表型。直到最近，sHTG 的治疗主要集中在生活方式干预、次要因素的控制和非选择性药物治疗，这些药物具有适度的 TG 降低疗效，并且没有相应地减少动脉粥样硬化性心血管疾病事件。遗传学发现允许开发靶向 LPL 调节蛋白的新型通路特异性疗法。针对抑制载脂蛋白 C-III （apoC-III）、血管生成素样蛋白 3 （ANGPTL3）、血管生成素样蛋白 4 （ANGPTL4） 和成纤维细胞生长因子-21 （FGF21） 的新靶点在治疗 sHTG 的各种表型方面提供了更多的疗效，并有机会降低急性胰腺炎和动脉粥样硬化性心血管疾病事件的风险。