Teaching Case

Overweight young adult male patient presenting to emergency department with upper abdominal pain, without peritonism at physical examination. History included heavy cigarette smoking, gastritis, chronic hepatitis C infection.
Routine laboratory tests showed mild leukocytosis, elevated liver transaminases (AST 240 - ALT 120 U/l), amylase (330 U/l), gamma-glutamytranspeptidase (367 U/l); normal bilirubin.

Ultrasound (Fig.1) showed liver steatosis, normal-sized pancreas, normal gallbladder and bile ducts. The next day, CT (Fig.2) requested to investigate clinical diagnosis of acute pancreatitis (AP) showed left-sided peripancreatic and fascial effusion, normal pancreas with focal hypoenhancement at the tail consistent with <30% necrosis, and partial splenic vein thrombosis. The patient had stopped drinking alcohol years earlier, and marked increase of serum triglycerides (2515 mg/dl) underlying AP was noted.
Supportive treatment plus low-molecular-weight heparin allowed clinical resolution. Follow-up colour-Doppler ultrasound (Fig.3) after discharge showed disappearance of thrombosis.
Nine months later (after having stopped fibrate therapy) the patient experienced recurrent AP with left-sided abdominal pain, elevated amylase and lipase levels, and severely increased triglycerides (9700 mg/dl). At MRI (Figs.4, 5) a post-necrotic collection had developed at the pancreatic tail, segmental oedematous AP appeared as restricted diffusion at pancreatic head and neck, without peripancreatic fluid, gallbladder and ductal abnormalities at MR-cholangiopancreatography (Fig.4e).

Albeit rare, severe hypertriglyceridaemia (HTG) is well-established aetiology of acute pancreatitis (AP). HTG over 1000 mg/dL is present in 1.7% of the adult population, it may trigger AP development in 5.4-20% of affected patients, and accounts for 2-10% of all AP occurrences thus representing the third leading cause after gallstones and alcohol. The pathophysiology of HTG-induced AP involves hydrolysis of triglycerides by pancreatic enzymes, hyperviscosity and ischaemia, excessive formation of free fatty acids and lysolecithin from the lipoprotein substrates in the pancreatic bed, leading to overload of the albumin capacity, damage of acinar cells and microvascular (capillary) membranes [1-5].
In some patients, HTG is familiar or secondary to inborn errors of metabolism. Most usually, HTG is encountered in patients with multiple comorbidities such as obesity, diabetes, history of alcohol abuse, renal disease and multiple medications. In these patients, HTG is underdiagnosed and undertreated, in part because of poor compliance to lipid-lowering therapy. For each 100 mg/dl unit of increase in the triglycerides level above 1000 mg/dL, there is a 3% increase of AP risk. The majority of patients suffering from HTG-related AP are young adults (median±standard deviation 39-45±8-10 years) with a 57-70% male predominance. Clinical manifestations and supportive treatment are analogous to those of AP from other causes, but there is consensus that HTG-related AP is often a severe form with high rates of intensive care unit admission (32%). In these patients, amylase levels may be falsely low due to milk-consistency serum. Cross-sectional imaging shows a high prevalence of parenchymal (31%) and peripancreatic (14%) necrosis. As a result, development of acute post-necrotic collections and walled-off pancreatic necrosis is very common (44% of patients) compared to the rarity of pseudocysts. Chronic pancreatitis is reported in 16% of patients [1, 3-7].
As in this patient, further complications such as venous thrombosis may develop, probably resulting from the well-known AP-associated hypercoagulability state including higher plasma levels of fibrinogen and factor VIII, which require anticoagulation [8].
In the acute phase, treatment aims at rapidly decreasing serum triglycerides levels, includes intravenous insulin and may benefit from plasmapheresis. Lifestyle modifications and lipid-lowering drugs (fibrates alone or in conjunction with statins) allow reducing the risk of recurrence [1, 2, 7].