Novel Inflammatory Markers and Their Association with the Severity of Hypertriglyceridemia-Associated Acute Pancreatitis

Lin Zhong,1,2 Jiezhu Ding,3 Manqin Chen,2 Xiaoyu Cai,2 Ling Chen,2 Xianrong Du,2 Yinhua Rao,2 Dingguo Zhang4 1Department of Gastroenterology, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Department of Gastroenterology, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Peking University, Shenzhen, Guangdong, People’s Republic of China; 4Department of Surgical Endoscopy Center, Shenzhen People’s Hospital (The First Affiliated Hospital, Southern University of Science and Technology; The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Dingguo Zhang, Email [email protected]: To investigate associations between novel inflammatory biomarkers and disease severity in Hypertriglyceridemia-associated acute pancreatitis (HTG-AP) and to evaluate their prognostic utility for risk stratification.Methods: This retrospective cohort study included 340 HTG-AP patients. Neutrophil-to-high-density lipoprotein Cholesterol Ratio (NHR), Monocyte-to-High-Density Lipoprotein Cholesterol Ratio (MHR), Lymphocyte-to-HDL cholesterol ratio (LHR), Platelet-to-high-density lipoprotein cholesterol ratio (PHR), Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and aggregate index of systemic inflammation (AISI) indices were calculated. Multivariable logistic regression (unadjusted/age-sex-adjusted/fully-adjusted models) was conducted, and ROC analysis was performed to determine the predictive performance for MSAP+SAP/SAP.Results: Among 340 HTG-AP patients (156 MAP, 130 MSAP, 54 SAP), novel inflammatory markers NHR, SII, SIRI, MHR, PHR, and AISI significantly increased with severity (P < 0.01). Restricted cubic splines revealed nonlinear associations of NHR, SII, AISI, MHR, and SIRI with MSAP+SAP risk (Overall P < 0.05; Nonlinear P < 0.05). In fully adjusted models: For each 1-unit increase in NHR, the OR was 1.06 (95% CI: 1.03– 1.09; P < 0.001). Comparing the highest tertile (Q3) to the lowest (Q1), the OR was 6.03 (95% CI: 2.98– 12.19; P < 0.001). MHR Q3 vs Q1: OR=4.52 (2.26– 9.03; P < 0.001). SIRI Q3 vs Q1: OR = 3.12 (1.61– 6.06; P < 0.001). SII Q3 vs Q1: OR 3.12–(1.61– 6.04; P < 0.001). AISI Q3 vs Q1: OR = 2.74 (95% CI: 1.42– 5.28; P = 0.003). LHR and PHR showed no statistically significant associations (P > 0.05). ROC analysis demonstrated that NHR was the best predictor of MSAP+SAP (AUC = 0.701; optimal cutoff = 14.484), outperforming other indices (SII: AUC = 0.666; LHR: AUC = 0.505).Conclusion: NHR is a novel independent predictor of moderate-severe or severe HTG-AP, with the highest tertile conferring a 6.03-fold increased risk (95% CI: 2.98– 12.19; P < 0.001) and an AUC of 0.701 for MSAP+SAP prediction. SII, MHR, SIRI, and AISI provide complementary prognostic value, supporting early risk stratification using NHR (cutoff = 14.484).Keywords: hypertriglyceridemia-associated acute pancreatitis, novel inflammatory markers, NHR, disease severity, severity prediction