Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2 - PubMed (original) (raw)

Multicenter Study

doi: 10.1016/j.jpeds.2024.114298. Epub 2024 Sep 12.

Matthew J Giefer 2, Fuchenchu Wang 3, Gretchen A Cress 4, Maisam A Abu-El-Haija 5, Ankur Chugh 6, Reuven Z Cohen 7, Elissa M Downs 8, Douglas S Fishman 9, A Jay Freeman 10, Cheryl E Gariepy 10, Tanja Y Gonska 11, Amit S Grover 12, Doug Lindblad 13, Quin Y Liu 14, Asim Maqbool 15, Jacob A Mark 16, Brian A McFerron 17, Megha S Mehta 18, Veronique D Morinville 19, Kenneth Ng 20, Robert A Noel 21, Chee Y Ooi 22, Emily R Perito 23, Madhura Y Phadke 13, Wenly Ruan 9, Sarah Jane Schwarzenberg 8, David M Troendle 18, Michael Wilschanski 24, Yuhua Zheng 25, Ying Yuan 3, Mark E Lowe 26, Aliye Uc 4; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer

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Multicenter Study

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2

Zachary M Sellers et al. J Pediatr. 2025 Jan.

Abstract

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.7 mmol/L), any HTG (≥150 mg/dL; ≥1.7 mmol/L), mild-moderate HTG (150-499 mg/dL; 1.7-5.6 mmol/L), moderate HTG (500-999 mg/dL; 5.6-11.3 mmol/L), and severe HTG groups (≥1000 mg/dL; ≥11.3 mmol/L), based on highest serum triglyceride value. Laboratory, imaging, pancreatitis and hospital events, complications, and quality of life data were analyzed.

Results: In children with acute recurrent or CP and HTG, there was no increase in the number of pancreatitis attacks per person-years, nor an increase in CP prevalence. However, HTG severity was associated with increased pancreatic inflammation, pancreatic cysts, pain, hospital days, number of hospitalizations, intensive care, and missed school days.

Conclusions: Mild-moderate HTG in children with acute recurrent or CP was not associated with increased pancreatitis frequency, nor increased development of CP, but was associated with increased pancreatitis complications and disease burden. As a treatable condition, treatment of mild-moderate HTG may be considered to reduce pancreatitis-associated complications and medical burden in children with acute recurrent or CP.

Keywords: lipids; pancreas; pediatric; triglycerides.

Copyright © 2024 Elsevier Inc. All rights reserved.

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Conflict of interest statement

Declaration of Competing Interest Z.M.S. is currently an employee of 4D Molecular Therapeutics Inc and a consultant for BridgeBio Pharma and Renexxion. M.A.H. is the president of CAPER, a board member of CAPER, and a board member of the National Pancreas Foundation. T.G. received a research grant from Vertex Pharmaceuticals, and she is a consultant for Cystic Fibrosis Foundation (CFF). C.Y.O. is a consultant for and has received research grant from Vertex Pharmaceuticals. E.R.P. is a consultant for BridgeBio and Ultragenyx. S.J.S. is a consultant for UpToDate, Nestle, Abbvie, Renexxion, and the CFF. A.J.F. is a consultant for Takeda and AbbVie, CFF, and is a member of the CAPER board. V.D.M. is an Associate Editor for JPGN Reports. D.M.T. is an Associate Editor for JPGN. M.W. is a consultant for and has received research grants from Vertex Pharmaceuticals. M.E.L. receives royalties from Millipore Inc and UpToDate and consults for CFF. A.U. is a consultant for CFF and Abbvie Inc. The other authors declare no conflicts of interest.

Figures

Figure 1.

Figure 1.. Elevated serum TG levels are not associated with increased CP.

A. The proportion of individuals with ARP or CP were compared between those in the normal TG vs. HTG groups and normal TG vs. mild-moderate HTG or moderate HTG or severe HTG were compared by Fisher’s exact test with P values < 0.05 indicated. B. Probability distribution of being free from CP diagnosis for those with normal TG, mild-moderate HTG, moderate HTG, and severe HTG who eventually developed CP. There was no significant difference in pairwise comparisons between groups using Log-Rank test. Each hash mark represents a single subject. C. ARP incidence density for each of the cohorts. P value indicates comparison between normal TG and severe HTG by Pearson’s Chi-squared test.

Figure 2.

Figure 2.. Pancreatitis-associated complications in ARP/CP subjects with HTG.

Percent of cohorts with exocrine pancreatic insufficiency (EPI) (A, B), subjectively atrophic pancreas (A, C), presence of pancreatic cysts (A, D), pancreatic ductal (PD) irregularities (A, E), kidney (A, F) or lung failure (A, G). P values were determined by Fisher’s exact test with only values <0.05 indicated.

Figure 3.

Figure 3.. Burden of disease in ARP/CP subjects with HTG.

A-F. Comparison of total days with pain (A), total days hospitalized (B), number of hospitalizations over the last 12 months (C) or lifetime (D), and number of emergency room (ER) visits over the last 12 months (E) or lifetime (F) and number of missed school days in last 30 days (G) in those with normal TG, HTG, mild-moderate HTG, severe HTG, and very severe HTG. P values were determined by Wilcoxon rank-sum test and only values <0.05 are indicated. Comparisons were made between normal TG vs. HTG groups and normal TG vs. mild-moderate HTG or severe HTG or very severe HTG. Line = median, upper box edge = 75th percentile, lower box edge = 25th percentile, whiskers = 5-95th percentile, open circle = values outside 5-95th percentile. H. Proportion of cohorts requiring intensive care unit (ICU) care were compared between those in the normal TG vs. HTG groups and normal TG vs. mild-moderate HTG or severe HTG or very severe HTG were compared by Fisher’s exact test with P values < 0.05 indicated.

References

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