Significantly different clinical features between hypertriglyceridemia and biliary acute pancreatitis: a retrospective study of 730 patients from a tertiary center

Acute pancreatitis (AP) is an acute inflammatory disease which is characterized by local pancreatic inflammation and consequently systemic inflammatory response. The imaging of AP manifests as pancreatic edema or necrosis involving the pancreas as well as peripancreatic tissues and even distant organs [1, 2]. In the western countries, the most common etiology of AP was gallstones, followed by alcohol abuse and hypertriglyceridemia [3, 4]. While the incidence of hypertriglyceridemia acute pancreatitis (HTG-AP) was much higher in China and has been increasing year by year according to the recent studies [5‐10].

Previous studies well reported the clinical features of AP with different etiologies, rather than the detailed differences between HTG-AP and BAP. In this retrospective study from July 2013 to October 2016, we compared the clinical features, complications and outcomes between hypertriglyceridemia and biliary acute pancreatitis patients, as the two leading etiologies of acute pancreatitis in China.

This retrospective study demonstrated significantly different clinical features between HTG-AP and BAP patients. The results indicated that HTG-AP patients were younger, more male, more ratio of high fat diet, higher BMI and higher prevalence of AKI/ARDS/DVT/MODS, but, the BAP patients had higher incidence of IPN and chylous fistula. Moreover, the multivariate analysis showed that HTG-AP was independently associated with more AKI as adjusting by age, gender, body mass index, diabetic mellitus, fatty liver and high-fat diet, but not with ARDS and DVT. However, BMI was found to be independently associated with AKI, ARDS and DVT. The results suggested that higher incidence of AKI in HTG-AP was significantly and independently associated with the etiology, but more ARDS and DVT were more due to higher BMI.

HTG-AP is a rare but well-documented type of AP in Western countries (1.3–5%) [7, 8]. Recently, accumulating data have shown that HTG-AP has become the second common cause of AP in China, with a reported incidence up to12.3% in 2003 [9], 18.1% in 2007 [10], and 25.6% in 2013 [11], much higher than that in Western countries. In our center, which is the largest AP referral center in China, HTG-AP accounted for about 30% from 2013 to 2016, being also the second leading cause of AP. Previous studies had compared HTG-AP with other common etiologies, but the results vary. Linares et al. [12] reported that patients with HTG-AP suffered a more severe clinical course than those with alcohol or gallstone-induced based on the index such as ICU admission, CRP, and Balthazar scores and similar findings were repeatedly reported in the literature [13]. Tai et al. [14] reported no significant difference in specific complications like ARDS, AKI, gastrointestinal bleeding and sepsis. Besides, clinical studies assessing the impact of the TG level on the severity of AP also showed conflicting results. Zhang et al. [15], S. Balachandra et al. [16] and Fortson MR et al. [7] showed no difference detected in severity, based on APACHE II scores or complications in patients with the level of TG. While some reports demonstrated that patients with high level of triglyceride may suffer worse clinical outcome. A previous study showed that the level of TG in AP patients are independently and proportionally correlated with persistent organ failure regardless of etiology [17], in another study, AP patients with HTG (> 500 mg/dL) had higher 24 h APACHE II scores, more systemic complications and higher mortality [18].

The underlying pathogenesis of HTG-AP is not fully understood and the most widely accepted explanation hitherto is the “free fatty acids (FFA)” theory. It is assumed that at the onset of pancreatitis, a large amount of pancreatic lipase releases into the systemic circulation hydrolyzing serum TGs and adipose tissue, which would consequently generate high concentrations of free fatty acids with detergent properties. Free fatty acid micelle complexes injure the vascular endothelium and acinar cells of the pancreas, making internal environment increasingly acidic and ischemic, which triggers further free fatty acid toxicity and accelerate systemic inflammatory response [19]. Furthermore, direct tissue injury and lipotoxicity via mitochondrial stress [20‐22] may cause the up-regulation of cytokines and the inflammatory cascade, predisposing to systemic inflammatory response [22].

In the complications of AP, the incidence of AKI was also found to be higher in HTG-AP in other reports [23]. Wu et al. indicated that TG may do a direct damage to renal parenchyma as reacting with pancreatic lipase around kidney tubules. The pancreatic enzymes assembled in glomerulus aggravates the damage of renal function [23]. Also Scheuer et al. reported that, the infiltrated TG in glomerular and tubulointerstitial could make the glomerulosclerosis grow worse in mouse model [24].

Moreover, the results in this study also showed that higher BMI was independently associated with AKI, ARDS and DVT in multivariate analysis. Up to date, quite a few articles had showed that BMI may increase the severity of AP from clinical findings and animal models [25]. A possible explanation is that adipose tissue appears as chronic inflammation releasing pro-inflammatory cytokines and obese individuals are more likely to have lifestyle-related chronic diseases/ respiratory problems [25, 26]. Obesity has also been inferred associated with an increased risk of extrapancreatic complications such as shock, renal failure, respiratory insufficiency, and fatal outcome [27, 28].

Furthermore, the results found the BAP patients suffered more infected local complications than HTG-AP. In BAP patients, when the gallstones pass through the Vater ampulla, spasm, fibrosis and obstruction of the hepatopancreatic ampulla happens, resulting in biliopancreatic reflux and the exclusion of bile and pancreatic juices. Then the elevated levels of bile and pancreatic juices and activation of pancreatic enzymes are responsible for pancreatitis attacking ultimately in this abnormal physiological status [3]. The refluxing of infected bile transfer into the pancreatic duct may generate Escherichia coli and other bacteria leading to the infection [29].

In conclusion, this study showed significantly different clinical features between HTG-AP and BAP patients. HTG-AP patients suffered higher occurrence rates of AKI/ARDS/DVT/MODS, while IPN was more common in BAP patients. After the multivariate analysis adjusted by age, gender, BMI, diabetes, fatty liver and high fat diet, HTG-AP was found to be significantly and independently related with more incidence of AKI. However, higher BMI was found to be related with AKI, ARDS and DVT. Further, larger prospective studies should be performed to study the features between the different etiologies of AP and the effect of BMI on disease severity.