Hypertriglyceridaemia, LPL deficiency and pancreatitis -pathogenesis and therapeutic options

Abstract

Severe hypertriglyceridaemia (HTG) is recognised as the third most common cause of acute pancreatitis. While secondary causes of HTG such as excess alcohol, obesity and diabetes are well recognised, identification and treatment of primary genetic disorders such as lipoprotein lipase (LPL) deficiency remain a challenge. HTG secondary to such genetic disorders does not respond to established medical therapy, resulting in recurrent episodes of acute pancreatitis. A very low fat diet remains first-line therapy in the treatment of severe HTG secondary to LPL deficiency, and in resistant cases insulin, heparin and plasma apheresis are used with some success. Viral vector-delivered gene therapy is a novel treatment option that is currently being tested in patients with LPL deficiency with promising results.

Alipogene Tiparvovec: A Review of Its Use in Adults with Familial Lipoprotein Lipase Deficiency

“…The disease is characterized by hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, including diabetes mellitus [1][2][3][4]. However, the most debilitating clinical manifestation of the disease is recurrent, severe and potentially life-threatening acute pancreatitis, with severe hypertriglyceridaemia being one of the primary risk factors for pancreatitis and the third leading cause of acute pancreatitis [2][3][4]. Pancreatitis is associated with an increased risk of pancreatic cancer [5] and results in significant morbidity and mortality in 20-30 % of patients, impacting on health-related qualityof-life and placing a significant economic burden on healthcare systems [3,4].…”

“…The disease is characterized by hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, including diabetes mellitus [1][2][3][4]. However, the most debilitating clinical manifestation of the disease is recurrent, severe and potentially life-threatening acute pancreatitis, with severe hypertriglyceridaemia being one of the primary risk factors for pancreatitis and the third leading cause of acute pancreatitis [2][3][4].…”

Management of severe hypertriglyceridaemia

“…The precise mechanism of pancreatitis due to SHTG is not known. It has been suggested that high local levels of FFA released by pancreatic lipase during hydrolysis of TG present in chylomicrons exceed the binding capacity of albumin and induce inflammation [11,12]. According to another hypothesis, increased chylomicron levels lead to excessive plasma viscosity, resulting in hypoxia and local acidosis in pancreatic capillaries, which increases toxicity of FFA [13].…”