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Chronic Pancreatitis Is Characterized by Distinct Complication Clusters That Associate With Etiological Risk Factors

Olesen, Søren S., MD, PhD1,2; Nøjgaard, Camilla, MD, PhD3; Poulsen, Jakob L., MD, PhD1; Haas, Stephan L., MD, PhD4; Vujasinovic, Miroslav, MD, PhD4; Löhr, Matthias, MD, PhD4; Lindkvist, Björn, MD, PhD4; Bexander, Louise, MD4; Gulbinas, Antanas, MD, PhD5; Kalaitzakis, Evangelos, MD, PhD, MSc6; Ebrahim, Mohamed, MD6; Erchinger, Friedemann, MD, PhD7,8; Engjom, Trond, MD, PhD8,9; Roug, Stine, MD10; Novovic, Srdan, MD, PhD3; Hauge, Truls, MD, PhD11,12; Waage, Anne, MD, PhD13; Laukkarinen, Johanna, MD, PhD14; Parhiala, Mikael, MD14; Pukitis, Aldis, MD15; Ozola-Zālīte, Imanta, MD15; Drewes, Asbjørn M., MD, PhD, DMSc1,2 for the Scandinavian Baltic Pancreatic Club

American Journal of Gastroenterology: April 2019 - Volume 114 - Issue 4 - p 656–664
doi: 10.14309/ajg.0000000000000147

OBJECTIVES: Chronic pancreatitis (CP) is characterized by several disease-related complications and multiple etiological risk factors. Past studies of associations between complications and risk factors have mostly been limited to single complications or highly focused on single etiologies. Using an objective data-driven approach (cluster analysis), we characterized complication clusters and their associations with etiological risk factors in a large cohort of patients with CP.

METHODS: This was a multicenter, cross-sectional study including 1,071 patients with CP from the Scandinavian and Baltic countries. Complications to CP were classified according to the M-ANNHEIM system, and treelet transform was used to derive complication clusters. Cluster complication frequencies were analyzed for their association with main etiological risk factors (smoking and alcohol).

RESULTS: The mean age of participants was 57 years and 66% were men. Alcohol (55%) and smoking (53%) were the most common etiological risk factors and seen in combination in 36% of patients. Cluster analysis identified 3 distinct complication clusters characterized by inflammation, fibrosis, and pancreatic insufficiencies. An independent association between inflammatory complications and alcoholic etiology was seen (odds ratio [OR] 2.00 [95% CI [confidence interval], 1.38–2.90], P < 0.001), whereas smoking was associated with fibrosis-related complications (OR 2.23 [95% CI, 1.56–2.3.20], P < 0.001) and pancreatic insufficiencies (OR 1.42 [95% CI, 1.00–2.01], P = 0.046).

DISCUSSION: Three distinctive clusters of complications to CP were identified. Their differing associations with alcoholic and smoking etiology indicate distinct underlying disease mechanisms.

1Centre for Pancreatic Diseases, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark;

2Department of Clinical Medicine, Aalborg University, Aalborg, Denmark;

3Department of Gastroenterology, Hvidovre University Hospital, Copenhagen, Denmark;

4Centre for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden;

5Institute for Digestive Research and Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania;

6Copenhagen University Hospital/Herlev, University of Copenhagen, Copenhagen, Denmark;

7Voss Hospital, Department of Medicine, Voss, Norway;

8Department of Clinical Medicine, University of Bergen, Bergen, Norway;

9Haukeland University Hospital, Department of Medicine, Bergen, Norway;

10Abdominalcenter K, Bispebjerg Hospital, Copenhagen, Denmark;

11Department of Gastroenterology, Oslo University Hospital, Oslo, Norway;

12Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;

13Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway;

14Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, and Tampere University, Tampere, Finland;

15Centre of Gastroenterology, Hepatology and Nutrition, Pauls Stradins Clinical University Hospital, Riga, Latvia.

Correspondence: Søren S. Olesen, MD, PhD. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received September 20, 2018

Accepted January 02, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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