Acute Pancreatitis due to Hypertriglyceridemia

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The relationship between triglycerides and pancreatic damage has been studied over the years. It is now known that Hypertriglyceridemia (HTG) is the 3rd leading cause of acute pancreatitis (less prevalent only than biliary and alcoholic causes). However, the presence of HTG is common in all etiologies of acute pancreatitis.

How do you know if triglycerides (TG) are the cause or just an epiphenomenon present in an acute pancreatitis of another etiology?

Concept

Hypertriglyceridemia is defined as an increase in serum triglyceride levels above 150 mg/dL. This increase can be categorized into:

• Mild HTG: 150-199 mg/dL
• Moderate HTG: 200-999 mg/dL
• Severe HTG: 1000-1999 mg/dL
• Very severe HTG: > 2000 mg/dL

HTGs are classified into:

• Primary – patients with genetic alterations that do not allow the correct metabolism of triglycerides. These causes were cataloged by Friderickson into types I to V. The types most associated with acute pancreatitis are: types I, IV and V.
• Secondary: some patients raise TG due to: obesity, poorly controlled diabetes, hypercaloric and hyperlipidic diet, pregnancy and alcohol use. In addition, some medications are known to cause HTG and should be researched in this context (eg: retinoids, protease inhibitors, anti-psychotics, calcineurin inhibitors, diuretics and estrogens)

The risk of acute pancreatitis (PA) occurring in individuals with HTG is considered when TG rises > 1000 mg/dL (around 5%) and increases greatly when TG > 2000 mg/dL (risk becomes 10-20%). When analyzing the population with severe hypertriglyceridemia, about 20% reported a previous history of acute pancreatitis, a value much higher than the prevalence found in the population.

Pathophysiology

The pathophysiology of pancreatitis by HTG is complex, and to this day not completely understood. It is known that TG in the microcirculation induces the release of pancreatic lipase, which cleave the molecules into free fatty acids (which are lipotoxic to pancreatic cells). These, in turn, lead to endothelial injury with capillary extravasation. TG also activate substances such as tramboxane, phospholipase A and prostaglandins that lead to vasoconstriction and pancreatic ischemia.

Triglycerides and free fatty acids also tend to group together in the form of micelles, which increases plasma viscosity and leads to gland ischemia.

Added to this we also have the imbalance in intracellular calcium, oxidative stress in organelles, which also precipitate the early activation of trypsin, still within the pancreas.

Diagnosis

The diagnosis of PA by HTG is given in the same way as other etiologies, with the Atlanta criteria, when 2 of the 3 criteria are present (upper abdominal pain, elevation of pancreatic enzymes > 3 the limit of the method and compatible imaging exam) associated with elevation of TG > 1,000 mg/dL.

Here it is important to remember that PAs originating from other causes (biliary, alcoholic and drug) can raise TG in the acute phase, but rarely at levels > 1000 mg/dL. This elevation is seen as an epiphenomenon.

As for severity, in studies conducted, it was observed that PA by HTG tends to be more severe compared to other etiologies. In meta-analyses and systematic reviews, it was observed that these patients evolved with higher severity scores, higher recurrence rates, more ICU admissions, and higher mortality.

Treatment

The initial treatment is based on support, as in any pancreatitis: hydration, analgesia and nutritional support (especially for severe PAs).

Among the specific approaches, the following stand out:

• Heparin pump: heparin can be used in monotherapy or associated with other modalities (such as the insulin pump). The anticoagulant initially increases the degradation of TG into free fatty acids. This effect, however, is temporary and hepatic consumption of plasma lipoprotein lipase causes a rebound increase in TG after discontinuation of the infusion. In addition, heparin infusion increases hemorrhagic events, especially in severe PAs with local complications.
• Insulin pump: continuous insulin infusion also increases the activation of lipoprotein lipase and decreases the release of free fatty acids by adipocytes and promotes the metabolism of these fatty acids by hormone-sensitive cells. It can be used in conjunction with heparin therapy, but the studies that evaluated the results are small. This modality has the potential to reduce TG levels by 50-75% in 3 days.
• Plasmapheresis: this therapy mechanically removes excess chylomicrons from the bloodstream. Similarly, it appears to reduce the levels of pro-inflammatory cytokines, which are determinants for severity in the initial phase of PA. However, the results regarding relevant outcomes (multiple organ dysfunction, mortality) did not favor plasmapheresis over supportive therapy. In addition, these patients had higher ICU admission rates (since it is a procedure performed in an intensive care unit), always need central catheter placement and may present an infusion reaction to plasma. It is a safe therapy to be performed in pregnant women.
• Hemofiltration: this is another controversial therapy, which tends to remove lipids and cytokines from plasma. Although it removes TG quickly and effectively, there was no difference in relevant clinical outcomes, in addition to having a high cost.

Follow-up

Patients who have already had PA by HTG need follow-up after discharge to reduce the risks of recurrence. The use of hypolipidemic agents (such as fibrates) is recommended as soon as the patient is already able to resume the diet orally, still in the hospital. The goal in outpatient treatment is to keep TG levels < 500 mg/dL.

Patients with primary HTGs should be followed by specialists in the lipid area.

In summary, HTG is a relevant cause of PA, especially in patients with primary hypertriglyceridemias. Triglyceride dosage should be done in the first few hours, as levels tend to drop significantly with fasting. The therapeutic approach is similar to that of other pancreatitis, and specific therapies can be associated for short-term TG reduction. Patients should always be referred for follow-up post discharge, to reduce the risk of a new event.

References

1. Yang, AL & McNabb-Blatar, J. Hypertriglyceridemia and acute pancreatitis. Pancreatology 20 (2020) 795-800
2. Qiu, M et al. Comprehensive review on the pathogenesis of hypertriglyceridaemia associated acute pancreatitis. Annals of Medicine 2023, VOL. 55, No. 2, 2265939
3. de Pretis, N et al. Hypertriglyceridemic pancreatitis: Epidemiology, pathophysiology and clinical management. United European Gastroenterology Journal 2018, Vol. 6(5) 649–655
4. Bálint, ER et al. Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta?analysis. Sci Rep 2020 Oct 21;10(1):17936.

How to cite this article

Marzinotto M. Acute Pancreatitis by Hypertriglyceridemia Gastropedia 2024, vol 1. Available at: gastropedia.com.br/gastroenterology/pancreas/acute-pancreatitis-by-hypertriglyceridemia/