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Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children

Report From INSPPIRE

Liu, Quin Y.*; Abu-El-Haija, Maisam; Husain, Sohail Z.; Barth, Bradley§; Bellin, Melena||; Fishman, Douglas S.; Freedman, Steven D.#; Gariepy, Cheryl E.**; Giefer, Matthew J.††; Gonska, Tanja‡‡; Heyman, Melvin B.§§; Himes, Ryan; Lin, Tom K.; Maqbool, Asim||||; Mascarenhas, Maria||||; McFerron, Brian A.¶¶; Morinville, Veronique D.##; Nathan, Jaimie D.; Ooi, Chee Y.***; Perito, Emily R.§§; Pohl, John F.†††; Rhee, Sue§§; Schwarzenberg, Sarah J.; Shah, Uzma‡‡‡; Troendle, David§; Werlin, Steven L.§§§; Wilschanski, Michael||||||; Zimmerman, M. Bridget¶¶¶; Lowe, Mark E.###; Uc, Aliye****

Journal of Pediatric Gastroenterology and Nutrition: August 2019 - Volume 69 - Issue 2 - p 206–211
doi: 10.1097/MPG.0000000000002405
Original Article: Pancreatology

Objective: The aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors.

Study Design: Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable.

Results: Of 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%).

Conclusions: Children with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

*Cedars-Sinai Medical Center, Los Angeles, CA

Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH

Department of Pediatrics, Stanford University, Palo Alto, CA

§University of Texas Southwestern Medical School, Dallas, TX

||University of Minnesota Masonic Children's Hospital, Minneapolis, MN

Baylor College of Medicine, Houston, TX

#Harvard Medical School, Boston, MA

**Nationwide Children's Hospital, Columbus, OH

††Seattle Children's Hospital, Seattle, WA

‡‡Hospital for Sick Children, Toronto, ON, Canada

§§University of California San Francisco, San Francisco, CA

||||Children's Hospital of Philadelphia, Philadelphia, PA

¶¶Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN

##Montreal Children's Hospital, McGill University, Montreal, QC, Canada

***School of Women's and Children's Health, Medicine, University of New South Wales and Sydney Children's Hospital Randwick Sydney, Australia

†††University of Utah, Salt Lake City, UT

‡‡‡Massachusetts General Hospital for Children, Harvard Medical School, Boston, MA

§§§Medical College of Wisconsin, Milwaukee, WI

||||||Hadassah Hebrew University Hospital, Jerusalem, Israel

¶¶¶Department of Biostatistics, University of Iowa, Iowa City, IA

###Washington University School of Medicine, St Louis, MO

****University of Iowa Stead Family Children's Hospital, Iowa City, IA.

Address correspondence and reprint requests to Aliye Uc, MD, Stead Family Department of Pediatrics, University of Iowa Health Care, 200 Hawkins Drive, BT 1120-C, Iowa City, IA 52242 (e-mail:

Received 2 November, 2018

Accepted 1 May, 2019

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,