Hidalgo et al. BMC Gastroenterology (2023) 23:51 BMC Gastroenterology https://doi.org/10.1186/s12876-023-02684-9 RESEARCH ARTICLE Open Access The role of high serum triglyceride levels on pancreatic necrosis development and related complications Nils Jimmy Hidalgo1,2, Elizabeth Pando1,2* , Piero Alberti2, Rodrigo Mata2, Nair Fernandes2, Montse Adell2, Sara Villasante2, Laia Blanco2, Joaquim Balsells2 and Ramon Charco2 Abstract Background The relevance of elevated serum triglyceride (TG) levels in the early stages of acute pancreatitis (AP) not induced by hypertriglyceridemia (HTG) remains unclear. Our study aims to determine the role of elevated serum TG levels at admission in developing pancreatic necrosis. Methods We analyzed the clinical data collected prospectively from patients with AP. According to TG levels meas- ured in the first 24 h after admission, we stratified patients into four groups: Normal TG (< 150 mg/dL), Borderline-high TG (150–199 mg/dL), High TG (200–499 mg/dL) and Very high TG (≥ 500 mg/dL). We analyzed the association of TG levels and other risk factors with the development of pancreatic necrosis. Results A total of 211 patients were included. In the Normal TG group: 122, in Borderline-high TG group: 38, in High TG group: 44, and in Very high TG group: 7. Pancreatic necrosis developed in 29.5% of the patients in the Normal TG group, 26.3% in the Borderline-high TG group, 52.3% in the High TG group, and 85.7% in the Very high TG group. The trend analysis observed a significant association between higher TG levels and pancreatic necrosis (p = 0.001). A multivariable analysis using logistic regression showed that elevated TG levels ≥ 200 mg/dL (High TG and Very high TG groups) were independently associated with pancreatic necrosis (OR: 3.27, 95% CI − 6.27, p < 0.001). Conclusions An elevated TG level at admission ≥ 200 mg/dl is independently associated with the development of pancreatic necrosis. The incidence of pancreatic necrosis increases proportionally with the severity of HTG. Keywords Acute pancreatitis, Triglyceride, Pancreatic necrosis, Hypertriglyceridemia Introduction multisystemic organ failure [1–3]. It is widely described Acute pancreatitis (AP) is a highly prevalent disease asso- that pancreatic necrosis is one of the worst complications ciated with local (necrosis, abscesses, and pseudocysts) during severe acute pancreatitis, with mortality rates up and systemic complications such as persistent single or to 35% [4–6]. In that line, early identification of patients at increased risk of pancreatic necrosis is crucial to ini- tiate interventions such as aggressive fluid resuscitation, *Correspondence: organ failure prevention, infection prevention, or earlier Elizabeth Pando admission to an intensive care unit [7–9]. elizabeth.pando@vallhebron.cat 1 Hypertriglyceridemia (HTG) is a known etiology of Universitat Autonoma de Barcelona, Bellaterra, Spain 2 Department of Hepato‑Pancreato‑Biliary and Transplant Surgery, acute pancreatitis. However, the exact mechanism of Hospital Universitari Vall d’Hebron, 119 Passeig de la Vall d’Hebron, pathophysiology is not clearly defined. The most accepted 08035 Barcelona, Spain theory is that the excess triglycerides are hydrolyzed by © The Author(s) 2023. 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The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 2 of 10 pancreatic lipase, forming high concentrations of free and (3) performing contrast computed tomography (CT) fatty acids [10]. Free fatty acid and micelle complexes during hospitalization. damage the pancreas’s vascular endothelium and acinar AP was defined according to the revised Atlanta Clas- cells. The resulting ischemia creates an acidic environ- sification 2012 [26]. The diagnosis of AP requires two of ment leading to the release and activation of pancreatic the following three features: (a) typical radiating abdomi- lipase and proteases, leading to increased autodigestion nal pain, (b) serum amylase or lipase more than three [11]. Excessed free fatty acids also cause β-cell dysfunc- times normal values, and (c) radiological findings sug- tion due to impaired mitochondrial function [12]. Col- gestive of pancreatitis on contrast computed tomography lateral injury to pancreatic β-cell can lead to type 3c (CT), magnetic resonance imaging, or abdominal ultra- diabetes and loss of insulin secretion [13, 14]. Some stud- sound studies. ies also suggest that diabetes increases the severity of AP [15], and insulin protects acinar cells from cellular injury Exclusion criteria [16, 17]. (1) Patients with AP of HTG etiology: AP of HTG etiol- The HTG is commonly present in the early stage ogy was defined as when serum TG levels on admission of non-HTG-induced AP, and its clinical significance were ≥ 1000 mg/dL or 500–1000 mg/dL accompanied remains unclear. Some studies have found that triglycer- by lactescent serum in the absence of another etiology ide (TG) elevation upon admission of patients with AP of pancreatitis [27–29], (2) patients with coexistence of predicts poor prognosis and local and systemic complica- another major complication whose origin is not AP (gas- tions [18–22]. trointestinal bleeding, duodenal perforation, bile duct However, no studies specifically analyze the association perforation), (3) other etiology not related to AP (periam- between HTG and the occurrence of pancreatic necro- pullary neoplasia or of the biliary tract of the proximal or sis in patients with non-HTG-induced AP. Considering middle third, severe infectious pathology), (4) transferred that pancreatic necrosis does not necessarily imply organ patients, and (5) patients who arrived at the emergency failure and that non-necrotic pancreatitis can be accom- department with more than 72 h after the onset of symp- panied by organ failure [23], a specific analysis of the toms to reduce the bias of including patients with pro- role of TG in patients with pancreatic necrosis becomes longed disease. necessary. The HTG in the early phases of acute pancreatitis has been explained due to systemic lipolysis secondary to Management of AP acute inflammation and the release of pancreatic lipases Management of AP patients was done according to inter- [24]. The mechanism proposed for pancreatic necrosis national guidelines: initial fluid therapy was installed development in HTG are the impairment in microvas- according to patient characteristics (ringer lactate, cular circulation due to increased viscosity and direct physiological sodium solution) for a urinary output damage to pancreatic cells mediated by TG degradation of ≥ 0.5 ml/kg/hr. No empirical use of ATB. The patient products (free fatty acids) [11, 25]. Therefore, the release was referred to an intensive care unit for management of TG could have an important role in developing or when severe AP was suspected [30]. worsening pancreatic necrosis and be helpful as an early marker. Triglycerides determination and classification Our study aimed to ascertain the role of high stratified We measured the serum TG levels in the first 24 h of serum TG levels at admission in developing pancreatic admission to avoid alterations in TG values that can necrosis and its related complications. occur due to factors such as prolonged fasting or admin- istration of parenteral nutrition. TG levels were measured Methods by enzymatic techniques based on spectrophotomet- Study design ric methods (Beckman Coulter Method). In our labora- A prospective single-cohort observational study of adult tory, the normal reference intervals are 43–200 mg/dL, patients diagnosed with acute pancreatitis in a third-level regardless of the sex and age of the patient. referral center was designed to evaluate the role of high We classified patients according to the triglyceridemia stratified serum TG in developing pancreatic necrosis. stratification proposed by the National Cholesterol Edu- cation Program-Adult Treatment Panel III (NCEP-ATP Study population III) [31] and were divided into four groups: Normal TG Inclusion criteria (< 150 mg/dL), Borderline-high TG (150–199 mg/dL), (1) Patients aged over 18 years with the diagnosis of AP, High TG (200–499 mg/dL) y Very high TG (≥ 500 mg/ (2) determination of TG levels at admission (first 24 h), dL). Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 3 of 10 Data collection Mortality was defined as a death that occurred during The clinical-demographic data collected included age, admission or up to 90 days after discharge. sex, and body mass index (BMI). We recorded previous diabetes mellitus, arterial hypertension, cardiovascular Other biochemical markers at admission disease, chronic lung disease, pre-existing chronic kid- Laboratory markers analyzed were creatinine, hema- ney disease, and dyslipidemia. The etiology of AP was tocrit, blood urea nitrogen (BUN), and C-reactive classified as biliary, alcoholic, idiopathic, post-ERCP, protein. Based on thresholds established in previous and others (drugs, pancreas divisum, autoimmune, studies, the following values were considered elevated: intraductal papillary mucinous neoplasm, post-surgical creatinine ≥ 1.8 mg/dL [37], hematocrit ≥ 44% [38], procedure). BUN ≥ 20 mg/dL [39], C-reactive protein ≥ 15 mg/dL [40]. Computed tomography and pancreatic necrosis The evaluation of AP with computed tomography was Statistical analysis performed. All procedures have a portal venous phase Chi-square test or Fisher’s exact test were used to analyze 35 s after administering intravenous contrast. CT was qualitative variables. Quantitative variables were ana- performed at least 24 h after the onset of abdominal pain lyzed using the Kruskal–Wallis test, and the qualitative and preferably between 72 and 96 h. The indications for variables using linear-by-linear association. For normal performing CT in our hospital were: suspicion of moder- distributions, the quantitative variables were compared ate/severe or severe AP, presence of persistent SIRS, dif- by Student’s t-test for two groups, and the nonparametric ferential diagnosis with other causes of acute abdomen, test used was the Mann–Whitney U test. The Cochran- and etiological study of non-biliary AP. Armitage trend test was used to evaluate the presence of Pancreatic necrosis was defined as the absence of a statistically significant trend association between TG enhancement in pancreatic tissue after contrast- levels and pancreatic necrosis categories. Multivariable enhanced CT. Infected pancreatic necrosis (IPN) was logistic regression analysis was performed to analyze risk defined as a positive culture for microorganisms after factors associated with pancreatic necrosis. Receiver- necrosectomy or interventional drainage (radiological or operating characteristic (ROC) curves for pancreatic endoscopic) [32]. necrosis and the area under the curve (AUC) were calcu- lated using TG levels, biochemical markers, and scoring systems. A value of p < 0.05 was considered statistically Local complications significant. We performed the statistical analyzes using The local complications evaluated were fluid collections, IBM SPSS software, version 20.0 (IBM Corp. in Armonk, pancreatic necrosis, pancreatic necrosis infection, and NY) and Stata version 16 (Stata, College Station, Texas, the need for invasive procedures against necrosis (radio- USA). logical, endoscopic, or surgical). We also evaluated the radiological severity of AP using Ethics the classical CT severity index classification [33] and the This study was performed in line with the principles of modified CT severity index [34, 35]. the Declaration of Helsinki. Approval was granted by the Ethics Committee of Hospital Universitari Vall d’Hebron (PR-AG 328/2017). All participants signed informed con- Systemic complications and outcomes sent to participate in our prospective register. We assessed the severity of AP based on the 2012 revi- sion of the Atlanta Classification [26]. Mild AP is charac- Results terized by the absence of local or systemic complications, Between January 2016 and August 2021, after inclu- while the presence of persistent organ failure defines sion and exclusion criteria, 211 patients were included. severe AP. The moderately severe category includes (Fig. 1). After applying the exclusion criteria of having transient organ failure, patients with deterioration of a CT scan, we did not find differences in baseline char- pre-existing comorbidities, and patients with local com- acteristics when performing an intermediate analysis plications on imaging. Organ failure was defined using between the entire initial cohort and the final popula- the Modify Marshall scoring system [36] as a score of 2 tion. No statistically significant differences were observed or more for one of three organs (renal, cardiovascular, or between patients with CT and without CT in mean respiratory). Persistent organ failure was defined as any TG levels (167.5 ± 127 mg/dL vs. 129.9 ± 54.7 mg/dL, organ failure for more than 48 h. p = 0.137). Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 4 of 10 Fig. 1 Patient enrollment according to inclusion and exclusion criteria. AP: acute pancreatitis, TG: triglyceride, HTG: hypertriglyceridemia Table 1 Demographic and clinical characteristics of acute pancreatitis according to TG levels group Normal TG Borderline-high TG High TG Very high TG p value (< 150 mg/dL) (150–199 mg/dL) (200–499 mg/dL) (≥ 500 mg/dL) N = 122 N = 38 N = 44 N=7 Age, mean ± SD 66.28 ± 19.33 64.87 ± 16.1 59.86 ± 15.82 50.29 ± 10.86 0.01 Sex male, N (%) 71 (58.2) 27 (71.1) 27 (61.4) 6 (85.7) 0.229 BMI Kg/m2, mean ± SD 27.31 ± 5.01 28.52 ± 4.72 27.65 ± 6.47 28.17 ± 8.91 0.506 Previous diseases, N (%) Diabetes 29 (23.8) 10 (26.3) 10 (22.7) 3 (42.9) 0.627 Higher blood pressure 68 (55.7) 27 (71.1) 20 (45.5) 5 (71.4) 0.807 Cardiovascular disease 31 (25.4) 15 (39.5) 7 (15.9) 0 0.168 Lung disease 19 (15.6) 5 (13.2) 5 (11.4) 3 (42.9) 0.719 Chronic kidney disease 12 (9.8) 7 (18.4) 2 (4.5) 0 0.36 Dyslipidemia 38 (31.1) 15 (39.5) 17 (38.6) 3 (42.9) 0.257 Pancreatitis etiology, N (%) Biliary 62 (50.8) 26 (68.4) 17 (38.6) 2 (28.6) 0.197 Alcoholic 20 (16.4) 4 (10.5) 14 (31.8) 4 (57.1) 0.005 Idiopathic 25 (20.5) 5 (13.2) 10 (22.7) 0 0.581 Post-ERCP 3 (2.5) 1 (2.6) 1 (2.3) 1 (14.3) 0.408 Other 12 (9.8) 2 (5.3) 2 (4.5) 0 0.142 TG triglyceride, BMI body mass index, ERCP endoscopic retrograde cholangiopancreatography, Other drugs, pancreas divisum, autoimmune, intraductal papillary mucinous neoplasm, post-surgical procedure, SD standard deviation Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 5 of 10 Patients were divided into four groups according Risk factors for pancreatic necrosis (univariable to the TG level at admission: 122 patients in the Nor- and multivariable analysis) mal TG group (< 150 mg/dL), 38 in the Borderline-high Demographic characteristics, comorbidities, etiology of TG group (150–199 mg/dL), 44 in the High TG group AP, TG levels, and other biochemical markers according (200–499 mg/dL) and 7 in the Very high TG group to pancreatic necrosis were summarized in Table 3. (≥ 500 mg/dL). No differences were found among groups Multivariable analysis showed that elevated TG lev- except in age and pancreatitis etiology (Table 1). The els ≥ 200 mg/dL were associated with the develop- mean TG (mg/dL) was 96.95 ± 27.18 in the Normal TG ment of pancreatic necrosis (OR: 3.27, 95% CI 1.7–6.27, group, 166.21 ± 11.82 in the Borderline-high group, p < 0.001). Hematocrit at admission was also associated 278.75 ± 69.06 in the High TG group, and 705 ± 160.48 in with the development of pancreatic necrosis in the multi- the Very high group. variable analysis (Table 4). ROC analysis for TG levels and other biochemical markers Pancreatic necrosis predicting pancreatic necrosis Pancreatic necrosis occurred in 35.5% of our popula- Area under the curve (AUC) analysis of TG and bio- tion, distributing 29.5% of the patients in the Normal TG chemical markers predicting pancreatic necrosis were as group, 26.3% in the Borderline-high TG group, 52.3% in follows: TG levels: AUC: 0.601 (CI 95% 0.519–0.684), cre- the High TG group, and 85.7% in the Very high TG group atinine: AUC: 0.611 (CI 95% 0.53–0.692), and hematocrit (p = 0.001) (Table 2). The trend analysis of the propor- at admission AUC ROC: 0.644 (CI 95%, 0.562–0.727). We tions between the groups stratified by TG level using the did not find significant statistical differences when com- Cochran-Armitage trend test observed a significant asso- paring the ROC curves using the Delong test (p = 0.709). ciation between higher TG levels and the incidence of The ROC curves of the biochemical markers were plotted pancreatic necrosis (p = 0.001). (Fig. 2). in the Additional file 1. When we analyze the incidence of systemic compli- cations according to the extent of pancreatic necrosis Systemic complications (< 30%, 30–50% and > 50%), we observe that a greater Incidence of organ failure, multi-organ failure, and per- extent of necrosis presented a higher incidence of organ sistent organ failure increased significantly and accord- failure (24.4% vs. 50% vs. 85.7%, p < 0.001), severe pancre- ingly to the increase in TG levels groups (p = 0.009, atitis (15.6% vs. 37.5% vs. 71.4%, p < 0.001) and mortality p < 0.001, p < 0.001, respectively), but not for mortality (2.2% vs. 31.2% vs. 35.7%, p < 0.001). (p = 0.062). Table 2 Pancreatic necrosis and complications of acute pancreatitis according to TG levels group Normal TG Borderline-high TG High TG Very high TG p value (< 150 mg/dL) (150–199 mg/dL) (200–499 mg/dL) (≥ 500 mg/dL) N = 122 N = 38 N = 44 N=7 Local complications, N (%) Fluid collections 50 (41) 14 (36.8) 27 (61.4) 6 (85.7) 0.005 Pancreatic necrosis 36 (29.5) 10 (26.3) 23 (52.3) 6 (85.7) 0.001 Percentage of necrosis < 30% 26 (21.3) 4 (10.5) 12 (27.3) 3 (42.9) 0.298 Percentage of necrosis 30–50% 6 (4.9) 4 (10.5) 4 (9.1) 2 (28.6) 0.051 Percentage of necrosis > 50% 4 (3.3) 2 (5.3) 7 (15.9) 1 (14.3) 0.005 Pancreatic necrosis infection 13 (10.7) 2 (5.3) 6 (13.6) 3 (42.9) 0.135 Invasive procedure against necrosis, N (%) All types of procedures 14 (11.5) 2 (5.3) 12 (27.3) 3 (42.9) 0.004 Radiological 7 (5.7) 1 (2.6) 7 (15.9) 0 0.181 Endoscopic 7 (5.7) 1 (2.6) 6 (13.6) 1 (14.3) 0.103 Surgical 6 (4.9) 1 (2.6) 1 (2.3) 1 (14.3) 0.92 Radiological score CTSI, mean ± SD 2.97 ± 2.22 3.03 ± 2.71 4.56 ± 2.79 6.14 ± 2.61 < 0.001 MCTSI, mean ± SD 4.69 ± 2.77 4.41 ± 3.19 5.93 ± 3.08 7.71 ± 2.69 0.007 TG triglyceride, SD standard deviation, CTSI computed tomography severity index, MCTSI Modified computed tomography severity index Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 6 of 10 Fig. 2 The proportion of pancreatic necrosis for the categories of TG levels in patients with acute pancreatitis. Cochran-Armitage test for trend was significant (p = 0.001). TG: triglyceride Discussion When exploring the role of other potential factors Our study found that TG levels ≥ 200 mg/dL (High TG related to necrosis, such as age, sex, and previous comor- and Very high TG) were a risk factor for developing bidities were not associated with the development of pan- pancreatic necrosis. Elevated TG levels were associated creatic necrosis. These results agree with previous studies with a higher incidence of pancreatic necrosis, and this [37, 38, 47]. In that line, we tested serum creatinine, BUN, association was more significant at higher TG levels. hemoconcentration at admission, and C-reactive protein, This study is one of the few studies published in the all previously described as predictors of severity in AP literature that demonstrated the relation between ele- [40, 48]. We found that hemoconcentration at admission vated TG levels and pancreatic necrosis development. was associated with pancreatic necrosis, consistent with In this line, Tariq et al. [41] found that local compli- previous studies’ results [38, 49]. cations such as pancreatic necrosis are associated One of the hypotheses explaining the increase of TG in with higher TG levels (3.11% vs. 12% in the group of AP is the lipolysis of the visceral fat occurring in the early TG > 200 mg/dl, p = 0.001). phases of the disease, considering TGs compose 80% to We also found that higher levels of TG are associated 90% of the volume of adipocytes [50, 51]. The release of with the extent of parenchymal necrosis. Those findings activated pancreatic enzymes (pancreatic lipases), cat- support our hypothesis that TG has a role in necro- echolamines, and glucagon into the systemic circulation sis development and are similar to those reported by leads to an accelerated breakdown of adipose tissue, TG Cheng et al. [24]. Another relevant finding was a higher releasing, and an increased serum lipid concentration proportion of the need for invasive procedures against [24, 52, 53]. The increase in TG levels leads to an increase necrosis in the elevated triglycerides groups, which in blood viscosity that further favors microcirculation agrees with the fact that the extent of pancreatic necro- disorders of the pancreatic parenchyma. In addition, TG sis is associated with the need for more invasive pro- can be hydrolyzed by lipases released during pancreatitis cedures [42, 43]. However, we did not find a significant [54], and large amounts of free fatty acids (FFA) produced association with higher TG values regarding infected directly damage pancreatic acinar cells and increase the pancreatic necrosis. This could be explained because extent of parenchymal necrosis [55, 56]. Also, the excess the etiology of infected pancreatic necrosis involves FFA in the circulation induces positive regulation of other mechanisms, such as bacterial translocation from cytokines and activation of inflammatory cascades pre- the intestinal tract, administration of total parenteral disposing to organ failure [57]. nutrition, and extrapancreatic sources of infections Our study included a period in which the COVID-19 [44–46]. pandemic occurred. Patients included after inclusion/ Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 7 of 10 Table 3 Characteristics of acute pancreatitis according to pancreatic necrosis No Pancreatic necrosis Pancreatic necrosis p value N = 136 N = 75 Age, mean ± SD 64.53 ± 19.13 63.48 ± 16.24 0.414 Sex male, N (%) 78 (57.4) 53 (70.7) 0.056 BMI (Kg/m2), mean ± SD 27.62 ± 5.73 27.63 ± 4.77 0.883 Previous diseases, N (%) Diabetes 34 (25) 18 (24) 0.872 Higher blood pressure 73 (53.7) 47 (62.7) 0.207 Cardiovascular disease 39 (28.7) 14 (18.7) 0.109 Lung disease 18 (13.2) 14 (18.7) 0.292 Chronic kidney disease 18 (13.2) 3 (4) 0.032 Dyslipidemia 46 (33.8) 27 (36) 0.75 Pancreatitis etiology, N (%) Biliary 64 (47.1) 43 (57.3) 0.153 Alcoholic 27 (19.9) 15 (20) 0.98 Idiopathic 26 (19.1) 14 (18.7) 0.936 Post-ERCP 3 (2.2) 3 (4) 0.453 Other 16 (11.8) 0 0.003 Serum TG (mg/dL), mean ± SD 144.53 ± 85.81 209.17 ± 181.29 0.015 TG Category, N (%): (a) Normal TG (< 150 mg/dL) 86 (63.2) 36 (48) 0.032 (b) Borderline-high TG (150–199 mg/dL) 28 (20.6) 10 (13.3) 0.189 (c) High TG (200–499 mg/dL) 21 (15.4) 23 (30.7) 0.009 (d) Very high TG (≥ 500 mg/dL) 1 (0.7) 6 (8) 0.005 TG ≥ 150 mg/dL (b + c + d) 50 (36.8) 39 (52) 0.032 TG ≥ 200 mg/dL (c + d) 22 (16.2) 29 (38.7) < 0.001 Biochemical markers at admission Creatinine (mg/dL), mean ± SD 1.05 ± 0.61 1.19 ± 0.58 0.008 Hematocrit (%), mean ± SD 41.28 ± 5.73 44.35 ± 6.37 0.001 BUN (mg/dL), mean ± SD 20.89 ± 11.12 24.55 ± 15.27 0.151 C-reactive protein (mg/dL), mean ± SD 5.99 ± 8.99 9.17 ± 11.08 0.066 TG triglyceride, SD standard deviation, BMI body mass index, ERCP endoscopic retrograde cholangiopancreatography, Other drugs, pancreas divisum, autoimmune, intraductal papillary mucinous neoplasm, post-surgical procedure, BUN Blood urea nitrogen exclusion criteria did not present active SARS-CoV-2 were performed at the discretion of treating physicians, infection and were not vaccinated in the days before not all patients from the initial cohort underwent CT admission for acute pancreatitis. Some authors have scan. Our analysis only included patients with CT to reported acute pancreatitis and HTG after COVID-19 avoid this bias. We analyzed the entire initial cohort and vaccination [58, 59]. the patients who underwent CT scan and found no dif- A recent meta-analysis found that pancreatic necrosis ferences in baseline characteristics. occurs more frequently in alcoholic pancreatitis than in However, our study has strengths, such as the prospec- biliary pancreatitis. However, differences in the propor- tive data collection, the exclusion of HTG-induced AP, tion of pancreatic necrosis by etiology were analyzed in and the exclusion of patients with more than 72 h from few studies, which does not allow comparison with other the onset of symptoms and admission to reduce the bias etiologies [60]. Our study found no association between of including patients with prolonged disease. alcoholic pancreatitis and pancreatic necrosis. We propose considering hypertriglyceridemia as a Our study had limitations, such as not knowing the potential risk factor for pancreatic necrosis development. serum TG levels before the pancreatitis episode. There- In that line, it is necessary identified the pathological fore, it is unclear whether elevated TG levels preceded mechanisms of TG increasing in AP, and the pathways the development of acute pancreatitis or whether acute by which TGs and FFA are involved in pancreatic tis- pancreatitis caused elevated TG levels. Because CT scans sue damage and systemic complications, to develop new Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 8 of 10 Table 4 Univariate and multivariable analysis of factors associated with pancreatic necrosis Univariate analysis Multivariable analysis OR (95% CI) p value OR (95% CI) p value Age ≥ 65 years 0.81 (0.46–1.41) 0.454 Sex male 1.79 (0.98–3.27) 0.058 BMI ≥ 30 Kg/m2 0.8 (0.42–1.53) 0.507 Diabetes 0.95 (0.49–1.83) 0.872 Cardiovascular disease 0.57 (0.29–2.69) 0.111 Lung disease 1.51 (0.7–3.23) 0.295 Chronic kidney disease 0.27 (0.08–0.96) 0.043 0.29 (0.07–1.16) 0.08 Dyslipidemia 1.1 (0.61–1.99) 0.75 Biliary etiology 1.51 (0.86–2.67) 0.154 Alcoholic etiology 1.01 (0.49–2.04) 0.98 Triglyceride ≥ 200 mg/dL* 3.27 (1.7–6.27) < 0.001 3.99 (1.86–8.58) < 0.001 Creatinine ≥ 1.8 mg/dL 1.01 (0.33–3.15) 0.98 Hematocrit ≥ 44% 3.29 (1.82–5.98) < 0.001 4.92 (2.45–9.91) < 0.001 BUN ≥ 20 mg/dL 1.39 (0.79–2.46) 0.254 C-reactive protein ≥ 15 mg/dL 2.37 (1.1–5.1) 0.027 1.39 (0.99–1.94) 0.053 OR odds ratio, CI confidence interval, BMI body mass index, BUN Blood urea nitrogen *High TG + Very high TG treatment strategies for diminishing the impact of pan- Author contributions NJH: project development, data collection and analysis, manuscript writing creatic necrosis. Studies in HTG-induced AP suggest and editing. EP: project development, data collection and analysis, manuscript that enzyme blockers, early removal of TG, and toxic free writing and editing. PA: project development, data collection and analysis, fatty acids by plasmapheresis may be advantageous [61– manuscript writing and editing. RM: data collection, manuscript editing. NF: data collection, manuscript editing. MA: data collection, manuscript editing. 63]; however, there is a lack of studies in patients with AP SV: data collection, manuscript editing. LB: data collection, manuscript editing. not induced by HTG. JB: project development, manuscript editing. RC: project development, manu- script writing and editing. All authors read and approved the final manuscript. Funding Conclusions Not applicable. Elevated TG levels in the early stages of AP were a risk Availability of data and materials factor associated with the development of pancreatic The datasets used and analyzed during the current study are available from necrosis. The incidence of pancreatic necrosis increases the corresponding author on reasonable request. proportionally with the severity of HTG. More research is necessary to know the pathophysiological mechanism Declarations that explains this relationship and design novel interven- Ethics approval and consent to participate tions for pancreatic necrosis. This study was performed in line with the principles of the Declaration of Hel- sinki. Approval was granted by the Ethics Committee of Hospital Universitari Supplementary Information Vall d’Hebron (PR-AG 328/2017). All participants signed informed consent to participate in our prospective register. The online version contains supplementary material available at https://​doi.​ org/​10.​1186/​s12876-​023-​02684-9. Consent for publication All authors give permission for publication. Additional file 1: Table S1. Performance of biochemical markers at admission in predicting pancreatic necrosis: Triglyceride ≥ 200 mg/dL, Competing interests Creatinine ≥ 1.8 mg/dL, Hematocrit ≥ 44%, BUN ≥ 20 mg/dL, C-reactive The authors declare that they have no competing interests. protein ≥15 mg/dL. Fig. S1. Receiver operating characteristic (ROC) curve for pancreatic necrosis of triglycerides and biochemical markers at admission. Received: 7 September 2022 Accepted: 17 February 2023 Acknowledgements This publication has been made as part of the Doctoral Program in Surgery and Morphologic Sciences of the Universitat Autònoma de Barcelona, Spain. Departments of Surgery and Morphological Science at the Universitat Autònoma Hidalgo et al. BMC Gastroenterology (2023) 23:51 Page 9 of 10 References 25. Zeng Y, Wang X, Zhang W, Wu K, Ma J. Hypertriglyceridemia aggravates 1. 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