Relation between triglycerides and the severity of acute pancreatitis combined with nonalcoholic fatty liver disease: a retrospective study

Acute pancreatitis (AP) is a common clinical emergency of the abdomen, and its incidence has been gradually increasing in recent years. The etiology of AP is multifactorial, mainly including biliary, alcoholic, hypertriglyceridemia (HTG), and idiopathic. Biliary disease (45%) and alcoholism (20%) are the most common causes of AP in most high-income countries [1]. Recently, with the improvement of living quality and dietary modifications, the proportion of HTG-AP has gradually increased. There is considerable evidence that the proportion of HTG has surpassed alcoholism in China, becoming the second leading cause of AP [2, 3]. Studies have shown that abnormal lipid metabolism has an important impact on the severity and prognosis of AP [4]. A significant proportion of patients with AP have been clinically found to have nonalcoholic fatty liver disease (NAFLD), a liver disease associated with obesity, insulin resistance, type 2 diabetes (T2DM), hypertension, hyperlipidemia, and metabolic syndrome [5]. NAFLD is a specific manifestation of lipid metabolism abnormalities in the liver, and the incidence is increasing annually [6]. A retrospective study found that NAFLD can exacerbate the severity of AP, which is worsened with the increased severity of NAFLD [4]. As TG is a common risk factor for both, there are few studies on the correlation between the three; thus, this study investigated the relation between TG and the severity of disease in patients with AP combined with NAFLD.

AP is a common clinical gastrointestinal emergency with a progressively increasing incidence worldwide [11]. Therefore, a rapid and accurate assessment of the severity of AP is important for appropriate treatment and supportive management [12]. As all we know, HTG is one of the most important etiologic in AP. Elevated TG levels are associated with severity and prognosis of AP, including pancreatic necrosis, organ failure, and so on. As the increasing of TG severity grades, the incidence of localized complications in patients increases significantly and AP becomes more severe [13‐15]. With the improvement of living standards and the adjustment of dietary structure, NAFLD has become the most common liver disease in clinical practice [16]. It has been shown that NAFLD is a risk factor for AP [17], which can aggravate the severity of AP disease.

However, the risk factors for NAFLD aggravating AP severity have not yet been definitely identified by previous studies; therefore, this study aimed to explore the relation between TG and the severity of AP combined with NAFLD. Our study demonstrated that HTG aggravates the severity of AP patients with NAFLD, and TG was an independent risk factor for local complications. Moreover, higher serum TG levels were associated with a higher risk of local complications, suggesting that TG may play an important role in the severity of AP with NAFLD.

Young men were predominant in the HTG group, which is consistent with the clinical characteristics of NAFLD and HTG-AP [16, 18]. The WC and BMI of the HTG group were significantly higher than those of the NHTG group, which may be related to the poor lifestyle habits of young males, and such populations are often accompanied by a high-oil and high-fat diet, staying up late, lack of exercise, and alcohol abuse. Thus, they are more likely to have abnormal lipid metabolism, eventually leading to abdominal obesity. Previous studies have found that obesity is an important risk factor for NAFLD [19], and abdominal obesity is also an independent risk factor for AP [20].

In terms of primary outcomes, the results of this study revealed that the severity of AP was higher in the HTG group than in the NHTG group, as shown by a significantly higher proportion of moderately severe and severe AP in the HTG group than in the NHTG group, as well as a higher incidence of OF and local complications, especially POF and APFC. Meanwhile, in the TG subgroup analysis, the incidence of APFC gradually increased with higher TG levels, indicating that higher TG levels in AP patients with NAFLD may be associated with more severe disease and a relatively worse prognosis. A global epidemiological study on dyslipidemia by Pirillo et al. suggested that HTG is associated with the severity of NAFLD and AP [21]. The study also found that the incidence of moderate and severe NAFLD was also higher when TG was elevated. A clinical study by Mikolasevic et al. found that the presence of NAFLD indicates a higher risk of developing more severe AP and may serve as an additional prognostic tool [12]. TG has an exacerbating effect on both NAFLD and AP severity, and logistic regression analysis also showed that TG is an independent risk factor for APFC in AP patients with NAFLD.

In this study, AP recurrence ≥ 2 times was also identified as a risk factor for APFC. HTG and hypercalcemia are metabolic causes of AP recurrence [22]. Familial chylomicronemia syndrome (FCS) has previously been shown to be associated with an increased risk of AP recurrence, and NAFLD was commonly observed in patients with FCS [23]. The manifestation of FCS is a large accumulation of serum TG, and it can therefore be speculated that elevated serum TG levels increase the risk of developing NAFLD, further increasing the risk of AP recurrence and thus aggravating the condition of AP.

The mechanism by which TG in NAFLD exacerbates the severity of AP has not yet been clarified and needs to be further explored. At present, the possible mechanisms mainly include the following. First, obesity leads to organ steatosis and altered serum adipokines, and an abnormal adipokine environment leads to increased tissue infiltration of monocytes and macrophages, thereby producing proinflammatory cytokines that alter organ function [24]. In addition, as an endocrine organ, adipose tissue can release a variety of adipokines such as adiponectin, resistin, and leptin, which are involved in the occurrence and development of AP. Studies have found that resistin can increase TG levels, which can increase free fatty acid (FFA) levels and also induce hepatic steatosis, thus aggravating abnormal lipid metabolism. The reduced level of adiponectin in the blood of obese patients can reduce FFA metabolism, while its ability to inhibit TNFα decreases, thereby enhancing the body's inflammatory response and aggravating local damage to the pancreas [25, 26]. Last, fatty liver is often associated with HTG, which leads to free radical accumulation, microcirculation disturbances, oxidative stress, and acinar necrosis in AP [27].

This study has several limitations nevertheless. Firstly, as a single-center retrospective study, further validation by multicenter studies is needed. Additionally, as liver biopsy is still the gold standard for describing liver histological changes in patients with NAFLD [28], there are certain errors in the diagnosis of NAFLD by using CT values for the liver and spleen. Furthermore, most of the TG data were collected at admission, which may not reflect the patient's real TG level at the onset of AP, possibly introducing bias.

In conclusion, this study showed that TG is closely related to the severity and local complications in patients with AP complicated with NAFLD and is an independent risk factor for the development of local complications.