Clinical Research On The Relationship Between The Severity Of Hyperlipidemic Acute Pancreatitis And Free Fatty Acid Levels

1.Background:Acute pancreatitis,one of the acute abdomen of gastroenterology,is the most common pancreatic disease.80%of AP patients have mild condition who only need short hospitalization[1].About 20%of patients develop severe acute pancreatitis(SAP),which is characterized by persistent organ failure or infected pancreatic necrosis,with significantly increased mortality[2-4].Clinical observations have found that AP caused by various causes can have mild to moderate elevated serum lipids.Severe hyperlipidemia(triglyceride>1000mg/dl;11.29mmol/L)may directly lead to pancreatitis[5],hyperlipidemic pancreatitis(HLAP).The incidence of HLAP is mainly associated with hypertriglyceridemia(HTG),but not with serum cholesterol levels[6],Many studies have shown that HLAP progression is more severe than AP caused by other causes[5,7,8].However,whether the absolute level of TG is related to the severity of the disease remains controversial[7,9-12].Exact pathogenesis of HLAP is unclear.According to theory proposed by Havel[13],excessive TG is hydrolyzed by high levels of pancreatic lipase to form high concentrations of free fatty acids(FFAs),which exceeds binding capacity of albumin.They self-polymerize into a micellar structure with detergent properties,which damages acinar cells and pancreatic capillaries,causing ischemia to form an acidic environment,which in turn triggers FFAs toxicity[13,14].It can be inferred that pancreatic damage caused by HLAP is associated with FFAs,and we hypothesized that free fatty acids are independent risk factors for the severity of HLAP.2.Objective:Primary objective of this study was to evaluate the role of serum free fatty acids in predicting the severity of hyperlipidemia pancreatitis(HLAP).3.Methods:A retrospective study was performed on 263 patients with diagnosis of AP admitted to Qilu Hospital of Shandong University from November 2015 to November 2018.Collecting basic patient information,laboratory findings,and combined disease.According to "Guidelines for the Diagnosis and Treatment of Acute Pancreatitis in China(2013 Shanghai)"[15],AP diagnosis and severity classification were performed.Hyperlipidemia pancreatitis is defined as the presence of serum hypertriglyceridemia(sHTG>11.29mmol/L)for no other reason or when SHTG is greater than 5.65mmol/L,the serum appears chylomicron[16].According to the definition of HLAP,enrolled patients were divided into HLAP group and NHLAP group,clinical data between groups were compared.This single-center study included a limited number of patients(53 in HLAP patients),and further analysis may result in bias.Furthermore,latest meta-analysis for HLAP[17]shows cutoff values used in previous studies for HLAP are not identical,and when TG?5.65mmol/L±the severity of AP increases significantly.Therefore,we further chose 5.65mmol/L as the cutoff value.All patients were divided into three groups according to TG level,<1.7mmol/L;1.7?TG<5.65mmol/L;>5.65mmol/L,and clinical data of the three groups were compared again.Patients with TG>5.65 mmol/L(HLAP high-risk group)were divided into MAP group and MSAP/SAP group according to the severity of AP.Clinical data of the two groups were compared and the relationship between free fatty acids,CRP,free fatty acid combined with CRP and the severity of AP was explored.4.ResultsA total of 263 patients were enrolled in the study,of whom 53 were diagnosed with HLAP and 210 with NHLAP.Main results of the study showed that FFAs and CRP were independent risk factors for the development of MTA/SAP in patients with TG?5.65mmol/L.OR value of free fatty acids was 1.18,and the 95%confidence interval was(1.03-1.34),P<0.05.OR value of CRP was 1.05,and the 95%confidence interval was(1.01-1.10),P<0.05.Area under the free fatty acid ROC curve was 0.93,the sensitivity was 89.5%,specificity was 83.7%.Area under the CRP ROC curve was 0.92,and the sensitivity for predicting the severity of the disease was 92.1%and the specificity was 81.4%.Area under the ROC curve of CRP combined with free fatty acids was 0.98,the sensitivity was 97.4%,and the specificity was 95.3%.From the secondary results,HLAP and NHLAP patients were mainly middle-aged men,and compared with NHLAP patients,HLAP patients were younger and had higher levels of BMI.In addition,HLAP group had higher levels of leukocyte,cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,free fatty acids(71.21±21.77vs35.34±14.36,p<0.05),fasting serum glucose,lipase,CRP and PCT,lower levels of albumin(33.02±5.43vs36.9±5.38,P<0.05)and amylase.Patients in the high-risk group(TG>5.65mmol/L)were more young(39.91±11.11)and the BMI was significantly higher than the other groups(27.42±3.91).Patients in this group had higher levels of leukocyte,cholesterol,low-density lipoprotein,free fatty acids,fasting serum glucose,and CRP levels,albumin levels were lower than in the other two groups.In terms of comorbidities,the incidence of fatty liver and diabetes in patients with HLAP is higher than in patients with NHLAP.Compared with MAP group,MSAP/SAP group had higher levels of BMI,free fatty acids,fasting serum glucose and CRP,while serum calcium levels were lower.There was no significant difference in albumin levels between the two groups(MSAP/SAP 34.33±5.64 vs MAP 33.81±5.66,P=0.67).§.ConclusionFor patients with TG>5.65mmol/L AP,CRP and free fatty acids are independent risk factors for the development of MSAP/SAP,and are positively correlated with the severity of the disease.Both of them have higher sensitivity and specificity for predicting the severity of the disease,and the combination of the two can better predict the condition,which provides a new basis for clinical prediction of the severity of patients with hyperlipidemia.