Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Jan 14;11(1):1367.
doi: 10.1038/s41598-020-80532-6.

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model

Péter J Hegyi  1   2   3 , Alexandra Soós  4 , Emese Tóth  4 , Attila Ébert  5 , Viktória Venglovecz  5 , Katalin Márta  1 , Péter Mátrai  1 , Alexandra Mikó  1   2 , Judit Bajor  2 , Patrícia Sarlós  2 , Áron Vincze  2 , Adrienn Halász  6 , Ferenc Izbéki  6 , Zoltán Szepes  4 , László Czakó  4 , György Kovács  7 , Mária Papp  7 , Zsolt Dubravcsik  8 , Márta Varga  9 , József Hamvas  10 , Balázs C Németh  4 , Melania Macarie  11 , Ali Tüzün Ince  12 , Dmitry S Bordin  13   14   15 , Elena A Dubtsova  13 , Mariya A Kiryukova  13 , Igor E Khatkov  13   15 , Tanya Bideeva  16 , Artautas Mickevicius  17 , Elena Ramírez-Maldonado  18 , Ville Sallinen  19   20 , Bálint Erőss  1   2 , Dániel Pécsi  1 , Andrea Szentesi  1   4 , Andrea Párniczky  1   21 , László Tiszlavicz  22 , Péter Hegyi  23   24   25
Affiliations
Clinical Trial

Evidence for diagnosis of early chronic pancreatitis after three episodes of acute pancreatitis: a cross-sectional multicentre international study with experimental animal model

Péter J Hegyi et al. Sci Rep. .

Abstract

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Epidemiology and etiology of pancreatitis in the study population. (A) Sex and age distribution across groups. (B) Etiology of pancreatitis across study cohorts. (C) Etiology of recurrent acute pancreatitis (RAP).
Figure 2
Figure 2
Representativeness of the study population. (A) Sex distribution. (B) Age distribution. (C) Lengths of hospitalization. (D) Mortality.
Figure 3
Figure 3
Descriptive and comparative statistics characterising fifteen biomarkers. (A) Epidemiology-based parameters: age, sex, smoking, alcoholic etiology and body mass index (BMI). (B) Etiology-based parameters: biliary or alcoholic etiology, bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). (C) Laboratory-based parameter: red blood cell count (RBC). (D) Pancreas-dependent parameters: pseudocysts, amylase and lipase. (E) Differences in acute pancreatitis (AP) vs recurrent acute pancreatitis (RAP) 5 + and chronic pancreatitis (CP) comparisons in amylase and lipase.
Figure 3
Figure 3
Descriptive and comparative statistics characterising fifteen biomarkers. (A) Epidemiology-based parameters: age, sex, smoking, alcoholic etiology and body mass index (BMI). (B) Etiology-based parameters: biliary or alcoholic etiology, bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). (C) Laboratory-based parameter: red blood cell count (RBC). (D) Pancreas-dependent parameters: pseudocysts, amylase and lipase. (E) Differences in acute pancreatitis (AP) vs recurrent acute pancreatitis (RAP) 5 + and chronic pancreatitis (CP) comparisons in amylase and lipase.
Figure 3
Figure 3
Descriptive and comparative statistics characterising fifteen biomarkers. (A) Epidemiology-based parameters: age, sex, smoking, alcoholic etiology and body mass index (BMI). (B) Etiology-based parameters: biliary or alcoholic etiology, bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). (C) Laboratory-based parameter: red blood cell count (RBC). (D) Pancreas-dependent parameters: pseudocysts, amylase and lipase. (E) Differences in acute pancreatitis (AP) vs recurrent acute pancreatitis (RAP) 5 + and chronic pancreatitis (CP) comparisons in amylase and lipase.
Figure 4
Figure 4
Significant differences between thirteen biomarkers.
Figure 5
Figure 5
Progression from the first acute pancreatitis (AP) episode through recurrent episodes (RAP) towards chronic pancreatitis (CP).
Figure 6
Figure 6
A novel experimental mouse model of reciditive acute pancreatitis and chronic pancreatitis. (A) Histological findings in an experimental mouse model of acute pancreatitis. (B) Necrosis, edema and leukocyte infiltration differences in pancreatitis stages in an experimental mouse model. (C) Serum amylase activity and (D) Serum IL-1β level differences in stages of pancreatitis in an experimental mouse model. (E) CD3 (T cell, brown colour) staining. (F) CD68 (macrophage, brown colour) staining. (G) Fibrosis (blue colour filled triangle), each scale bar represents 100 µm. * = p < 0.05. A detailed description can be found in Supplementary Document 1.
See this image and copyright information in PMC

References

    1. Löhr JM, et al. United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU) United Eur. Gastroenterol. J. 2017;5:153–199. doi: 10.1177/2050640616684695. - DOI - PMC - PubMed
    1. Czakó L, et al. Quality of life assessment after pancreatic enzyme replacement therapy in chronic pancreatitis. Can. J. Gastroenterol. 2003;17:597–603. doi: 10.1155/2003/515848. - DOI - PubMed
    1. Szücs Á, et al. Chronic pancreatitis: multicentre prospective data collection and analysis by the Hungarian Pancreatic Study Group. PLoS ONE. 2017;12:e0171420–e0171420. doi: 10.1371/journal.pone.0171420. - DOI - PMC - PubMed
    1. Amann ST, et al. Physical and mental quality of life in chronic pancreatitis: a case-control study from the North American Pancreatitis Study 2 cohort. Pancreas. 2013;42:293–300. doi: 10.1097/MPA.0b013e31826532e7. - DOI - PMC - PubMed
    1. Machicado JD, et al. Quality of life in chronic pancreatitis is determined by constant pain, disability/unemployment, current smoking, and associated co-morbidities. Am. J. Gastroenterol. 2017;112:633–642. doi: 10.1038/ajg.2017.42. - DOI - PMC - PubMed