How We Predict the Etiology of Acute Pancreatitis

Miguel Pérez-Mateo
Department of Internal Medicine, Gastroenterology Unit, Hospital General Universitario de
Alicante, Miguel Hernández University. Elche, Alicante, Spain
Summary
Although acute pancreatitis (AP) may be the
consequence of numerous etiologic factors,
more than 80% of the episodes are of biliary
or alcoholic origin. Although the clinical
picture is similar irrespective of the etiology,
patients with severe episodes of acute
pancreatitis require specific therapeutic
maneuvers when biliary-induced while, in the
case of alcoholic origin, they only need
general support. As a consequence, the early
estimation of the etiology is of particular
interest, and older age and female sex are
frequent characteristics of AP of biliary
origin. Together with these factors, abnormal
liver function tests have been classically used
to identify biliary etiology. Their intrinsic
value has grown in the era of new imaging
techniques. From another perspective, the
plasmatic level of carbohydrate-deficient
transferrin seems to be the most accurate
technique in differentiating cases of alcohol-
induced acute pancreatitis from other
etiologies.
Acute pancreatitis (AP) is a frequent disease
which represents 0.15-1.5% of all diagnoses
in the emergency room. Although its
prevalence varies in different countries and
even in different areas of a given country, it is
likely that its real prevalence ranges from
200-300 cases per million inhabitants a year
[1, 2, 3]. The list of etiologic factors related to
its development is shown in Table 1.
However, a biliary origin is by far the most
frequent cause, followed by an alcoholic
origin. Together these etiologies are
responsible for 80% of all episodes of AP [4].
In a published series, each one of the
remaining possible etiologic causes affected a
reduced number of patients with AP.
From a clinical perspective, the characteristics
of the episodes of AP having different
etiologies are similar and indistinguishable
from one another. Modern diagnostic tools
permit the identification of the etiology in
most cases, and the acronym “idiopathic” has
become rare [5]. However, many of these new
techniques may not be available in all
hospitals, and some of them are restricted to
academic hospitals. Furthermore, although the
basic clinical characteristics of all episodes
are similar, the suspicion of a biliary origin in
Table 1. Causes of acute pancreatitis.
Mechanical
Toxic and
metabolic
Others
Gallstones
Alcohol
Ischemia
Pancreatic
obstruction
Hyperlipidemia Iatrogenic injury
Pancreas divisum Hypercalcemia
Infection
Sphincter of Oddi
dysfunction
Drugs
Hereditary
Ampullary
obstruction
Scorpion venom Autoimmune
Trauma
Cystic fibrosis
Congenital
malformations

Page 2
JOP. J Pancreas (Online) 2006; 7(3):257-261.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]
258
a patient with severe AP or associated
cholangitis may require an ERCP to confirm
choledocolithiasis and the removal of the
stone. This maneuver improves the clinical
evaluation of the patient [6]. Similarly, the
identification of the alcoholic origin of an
episode of AP, this being the second cause of
AP, is relevant in order to decrease expenses,
and avoid the use of non-necessary diagnostic
tools. In this regard, it is well-known that
information obtained by asking the patient or
his/her relatives is rarely accurate [7] and
questionnaires developed to estimate the
intake of alcohol have a low sensitivity and
specificity (60-95% and 40-95% respectively)
[8].
The association of certain abnormalities in
liver function tests in the first days of an
episode of AP and biliary etiology were
described more than 30 years ago [9]. Since
then, different studies intended to design an
easy-to-use, reliable and cheap method of
identifying the biliary origin of episodes of
AP confirmed that these episodes showed
levels of AST, ALT, alkaline phosphatase and
total bilirubin statistically significantly higher
than episodes of AP of a non-biliary origin
[10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20].
These studies were included in a meta-
analysis [21] which showed that
transaminsases are more useful in detecting
the biliary origin of AP than the other
parameters reported. According to this
research, values of transaminases 3 times the
upper normal limit show a positive predictive
value of 95% for the diagnosis of biliary-
induced AP. Similarly, in order to design a
multifactorial predictive system, we have
investigated the behavior of different
biochemical parameters in a series of 45 cases
of AP (33 of biliary origin and 12 of alcoholic
origin) [22]. The logistic regression analysis
performed based on 4 variables (age, sex, C-
reactive protein on day 1 and ALT on day 2)
accurately predicted the etiology in 97.7% of
all cases (44 out of 45 cases), and estimated
the likelihood of biliary origin by the
application of a mathematical formula.
Thereafter, the introduction of new diagnostic
tools raised doubt as to the usefulness of liver
function tests in predicting the biliary origin
of AP. A seminal study from Ros et al. [23] in
a series of 51 patients with “idiopathic” AP
reported that age, previous repetitive episodes
of AP and abnormal liver function tests were
significantly related to the presence of biliary
microlithiasis. Grau et al. [24] obtained
similar results by examining the bile from 91
patients with “idiopathic” AP. ALT analyzed
in the first 24 hours after admission (cut-off
equal to 1.2 times the upper normal limit)
showed a sensitivity of 73%, a specificity of
86% and a PPV of 92% in predicting the
presence of microlithiasis.
Recently, endoscopic ultrasound (EUS) has
become the most accurate technique for
detecting chole- and choledocolithiasis [25].
Hence, several authors have re-evaluated the
role of biochemical abnormalities for
predicting a biliary etiology in episodes of
AP. Ammori et al. [26] reported a sensitivity,
specificity, PPV and NPV for liver function
tests of 91, 100, 100 and 85%, respectively.
When combining this evaluation with EUS,
these values reached 98, 100, 100 and 96%
respectively. Two similar studies published
recently reached similar conclusions. Liu et
al. [27] (Hong Kong) performed EUS in a
series of 139 patients with AP in the first 24
hours after admission and identified the
etiology in all cases. Therefore, the sensitivity
of EUS for identifying the biliary origin of
AP was 100%. Multivariate analysis disclosed
that female sex, age over 58 years, and ALT
greater than 150 U/L became independent
predictors of biliary origin. With these three
factors, the sensitivity was 93% and overall
accuracy was 80%. Similar results were
obtained by Levy et al. [28] in a multicenter
study performed in France and Switzerland.
Patients who had a normal abdominal
ultrasound underwent EUS. Using this
diagnostic approach only 14 patients (7%)
remained in the group of “idiopathic” AP.
Again, female sex, increased age and
increased ALT levels at admission were
considered independent predictive variables
of biliary origin in the multivariate analysis.
The likelihood of biliary origin might be
estimated with the formula 1 / (1+exp(4.6967

Page 3
JOP. J Pancreas (Online) 2006; 7(3):257-261.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]
259
- 0.0656 x age [years] - 0.6909 x ALT [times
of the upper limit of the reference range] +
1.1208 x sex [1 for men, 0 for women]).
Information obtained from recent studies
reinforces the idea that early determination of
liver function tests still constitutes a valid
method for predicting the biliary origin of AP.
Traditionally, certain biochemical parameters
such as GGT and MCV have been considered
in identifying alcoholic etiology of AP
episodes. However, it has been shown that
these parameters are not useful in
distinguishing AP episodes of alcoholic origin
from those of other origins [29]. Other studies
reported that an increased lipase/amylase ratio
is characteristic of AP episodes of alcoholic
origin. Gumaste et al. [30] reported that the
lipase/amylase ratio has a sensitivity of 91%
for detecting the alcoholic origin of AP. In the
study by Tenner and Steinberg [31], only
alcohol-induced AP showed a lipase/amylase
ratio higher than 5 (specificity of 100%,
although with a low sensitivity of 31%).
However, other investigations reported that
the ratio quoted was not useful in
differentiating alcoholic from non-alcoholic
AP [13, 29, 32, 33]. It has also been reported
that both an increase in the plasmatic activity
of trypsin [33] or a trypsin-2-alpha1-
antitrypsin/trypsinogen-1 ratio [34] correctly
identified an alcoholic origin. Our group
reported that levels of serum trypsin activity
are significantly higher in patients with
episodes of AP of alcoholic origin when
compared with episodes of other etiologies
[35].
The measurement of carbohydrate-deficient
transferrin (CDT) may detect an excessive
consumption of alcohol [36] and it has been
used to detect the alcoholic origin of AP.
Jaakola et al. [29] showed that levels of CDT
higher than 17 U/L show a 27% sensitivity
and 100% specificity in the detection of an
alcoholic origin. Our group reported similar
results in a group of 70 patients with AP [35].
Furthermore, multivariate analysis of all the
parameters evaluated in this investigation, age
less than 44 years, plasma CDT greater than
22.5 U/L and trypsin activity greater than 152
U/L correctly identified the alcoholic origin in
98% of the episodes; these results are similar
to data published elsewhere [37].
In summary, by means of simple biochemical
studies, it is possible to correctly predict the
biliary or alcoholic origin of AP episodes in
approximately 80% of cases when performed
in the first hours after admission. However, a
biliary origin needs to be confirmed with
imaging techniques before considering any
specific form of therapy. The negativity of
these markers should suggest investigating
other possible etiologic factors with specific
analytical or morphological tests.
Keywords
Alcoholism; carbohydrate-
deficient
transferrin;
Cholelithiasis;
Diagnosis; Liver Function Tests; Pancreatitis,
Acute Necrotizing /etiology
Abbreviations AP: acute pancreatitis; CDT:
carbohydrate-deficient transferrin
Correspondence
Miguel Pérez-Mateo
Department of Internal Medicine
Hospital General Universitario de Alicante
c/ Pintor Baeza 12
03010 Alicante
Spain
 
 
References
1. Appelros S , Borgström A. Incidence, aetiology
and mortality rate of acute pancreatitis over 10 years in
a defined urban population in Sweden. Br J Surg 1999;
86:465-70. [PMID 10215815]
2. Lankisch PG, Assmus C, Maisonneuve P,
Lowenfels AB. Epidemiology of pancreatic diseases in
Luneburg County. A study in a defined german
population. Pancreatology 2002; 2:469-77. [PMID
12378115]
3. Carballo F, Mateos J. Pancreatitis aguda:
Epidemiología y etiología. In: Navarro S, Pérez-Mateo
M, Guarner L, eds. Tratado de Páncreas Exocrino.
Barcelona, Spain: J&C Ediciones Médicas, 2002:118-
32.

Page 4
JOP. J Pancreas (Online) 2006; 7(3):257-261.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]
260
4. Gullo L, Migliori M, Olah A, Farkas G, Levy P,
Arvanitakis C, et al. Acute pancreatitis in five european
countries: etiology and mortality. Pancreas 2002;
24:223-7. [PMID 11893928]
5. van Brummelen SE, Venneman NG, van Erpecum
KJ, VanBerge-Henegouwen GP. Acute idiopathic
pancreatitis: does it really exist or is it a myth? Scand J
Gastroenterol 2003; 38(Suppl 239):117-22. [PMID
14743894]
6. Sharma VK, Howden CW. Metaanalysis of
randomized controlled trials of endoscopic retrograde
cholangiography and endoscopic sphincterotomy for
the treatment of acute biliary pancreatitis. Am J
Gastroenterol 1999; 94:3211-4. [PMID 10566716]
7. Moore RD, Bone LR, Geller G, Mamon JA,
Stokes EJ, Levine DM. Prevalence, detection and
treatment of alcoholism in hospitalized patients. JAMA
1989; 261:403-7. [PMID 2909780]
8. O'Connor PG, Schottenfeld RS. Patients with
alcohol problems. N Engl J Med 1998; 338:592-602.
[PMID 9475768]
9. Paloyan D, Simonowitz D. Diagnostic
considerations in acute alcoholic and gallstone
pancreatitis. Am J Surg 1976; 32:329-31. [PMID
962008]
10. Sillero C, Pérez-Mateo M, Vázquez N, López MT.
Comportamiento de los parámetros biológicos
hepáticos en la fase temprana de la pancreatitis aguda.
Gastroenterol Hepatol 1981; 4:504-8.
11. McMahon M, Pickford IR. Biochemical prediction
of gallstones early in an attack of acute pancreatitis.
Lancet 1979; 2:541-3. [PMID 89554]
12. Davidson BR, Neoptolemos JP, Leese T, Carr-
Locke DL. Biochemical prediction of gallstones in
acute pancreatitis: a prospective study of three systems.
Br J Surg 1988; 75:213-5. [PMID 2450614]
13. Sadowski DC, Todd JK, Sutherland LR.
Biochemical models as early predictors of the etiology
of acute pancreatitis. Dig Dis Sci 1993; 38:637-43.
[PMID 7681746]
14. Neoptolemos JP, London N, Bailey I, Shaw D,
Carr-Locke DL, Fossard DP, Moossa AR. The role of
clinical and biochemical criteria and endoscopic
retrograde cholangiopancreatography in the urgent
diagnosis of common bile duct stones in acute
pancreatitis. Surgery 1986; 100:732-42. [PMID
2876528]
15. Goodman AJ, Neoptolemos JP, Carr-Locke DL,
Finlay DB, Fossard DP. Detection of gall stones after
acute pancreatitis. Gut 1985; 26:125-32. [PMID
2578422]
16. Van Gossum A, Seferian V, Rodzynek JJ,
Wettendorff P, Cremer M, Delcourt A. Early detection
of biliary pancreatitis. Dig Dis Sci 1984; 29:97-101.
[PMID 6199168]
17. Wang SS, Lin XZ, Tsai YT, Lee SD, Pan HB,
Chou YH, et al. Clinical significance of
ultrasonography, computed tomography, and
biochemical tests in the rapid diagnosis of gallstone-
related pancreatitis: a prospective study. Pancreas
1988; 3:153-8. [PMID 3287369]
18. Wettendorff P, van Gossum A, Delcourt A.
Gallstones and acute hepatitis. Lancet 1981; 1:675.
[PMID 6110908]
19. Glazer G, Murphy F, Clayden GS, Lawrence RG,
Craig O. Radionuclide biliary scanning in acute
pancreatitis. Br J Surg 1981; 68:766-70. [PMID
7296245]
20. Scholmerich J, Gross V, Johannesson T,
Brobmann G, Ruckauer K, Wimmer B, et al. Detection
of biliary origin of acute pancreatitis. Comparison of
laboratory tests, ultrasound, computed tomography,
and ERCP. Dig Dis Sci 1989; 34:830-3. [PMID
2656135]
21. Tenner S, Dubner H, Steinberg W. Predicting
gallstone pancreatitis with laboratory parameters: a
meta-analysis. Am J Gastroenterol 1994; 89:1863-6.
[PMID 7942684]
22. Tourné I, Viedma JA, Pérez-Mateo M.
Biochemical model of logistic regression for early
prediction of the etiology of acute pancreatitis. Rev Esp
Enferm Dig 1997; 89:885-96. [PMID 9494376]
23. Ros E, Navarro S, Bru C, Garcia-Puges A,
Valderrama R. Occult microlithiasis in 'idiopathic'
acute pancreatitis: prevention of relapses by
cholecystectomy or ursodeoxycholic acid therapy.
Gastroenterology 1991; 101:1701-9. [PMID 1955135]
24. Grau F, Almela P, Aparisi L, Bautista D, Pascual I,
Pena A, Rodrigo JM. Usefulness of alanine and
aspartate aminotransferases in the diagnosis of
microlithiasis in idiopathic acute pancreatitis. Int J
Pancreatol 1999; 25:107-11. [PMID 10360223]
25. Aube C, Delorme B, Yzet T, Burtin P, Lebigot J,
Pessaux P, et al. MR cholangiopancreatography versus
endoscopic sonography in suspected common bile duct
lithiasis: a prospective, comparative study. AJR Am J
Roentgenol 2005; 184:55-62. [PMID 15615951]
26. Ammori BJ, Boreham B, Lewis P, Roberts SA.
The biochemical detection of biliary etiology of acute
pancreatitis on admission: a revisit in the modern era of
biliary imaging. Pancreas 2003; 26:e32-35. [PMID
12604925]
27. Liu CL, Fan ST, Lo CM, Tso WK, Wong Y, Poon
RT, et al. Clinico-biochemical prediction of biliary
cause of acute pancreatitis in the era of endoscopic
ultrasonography. Aliment Pharmacol Ther 2005;
22:423-31. [PMID 16128680]

Page 5
JOP. J Pancreas (Online) 2006; 7(3):257-261.
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]
261
28. Levy P, Boruchowicz A, Hastier P, Pariente A,
Thevenot T, Frossard JL, et al. Diagnostic criteria in
predicting a biliary origin of acute pancreatitis in the
era of endoscopic ultrasound: multicentre prospective
evaluation of 213 patients. Pancreatology 2005; 5:450-
6. [PMID 15985771]
29. Jaakkola M, Sillanaukee P, Lof K, Koivula T,
Nordback I. Blood tests for detection of alcoholic cause
of acute pancreatitis. Lancet 1994; 343:1328-9. [PMID
7910327]
30. Gumaste V, Dave PB, Weissman D, Messer J.
Lipase/amylase ratio. A new index that distinguishes
acute episodes of alcoholic from nonalcoholic acute
pancreatitis. Gastroenterology 1991; 101:1361-6.
[PMID 1718808]
31. Tenner SM, Steinberg W. The admission serum
lipase: amylase ratio differentiates alcoholic from
nonalcoholic acute pancreatitis. Am J Gastroenterol
1992; 87:1755-8. [PMID 1280405]
32. King LG, Seelig CB, Ranney JE. The lipase to
amylase ratio in acute pancreatitis. Am J Gastroenterol
1995; 90:67-9. [PMID 7528469]
33. Le Moine O, Devaster JM, Deviere J, Thiry P,
Cremer M, Ooms HA. Trypsin activity. A new marker
of acute alcoholic pancreatitis. Dig Dis Sci 1994;
39:2634-8. [PMID 7527752]
34. Andersen JM, Hedstrom J, Kemppainen E, Finne
P, Puolakkainen P, Stenman UH. The ratio of trypsin-
2-alpha(1)-antitrypsin to trypsinogen-1 discriminates
biliary and alcohol-induced acute pancreatitis. Clin
Chem 2001; 47:231-6. [PMID 11159771]
35. Aparicio JR, Viedma JA, Aparisi L, Navarro S,
Martinez J, Perez-Mateo M. Usefulness of
carbohydrate-deficient transferrin and trypsin activity
in the diagnosis of acute alcoholic pancreatitis. Am J
Gastroenterol 2001; 96:1777-81. [PMID 11419828]
36. Stibler H. Carbohydrate-deficient transferrin in
serum: a new marker of potentially harmful alcohol
consumption reviewed. Clin Chem 1991; 37:2029-37.
[PMID 1764777]
37. Basterra G, Casi MA, Alcorta P, Diaz de Otazu R,
Alvarez M, Garcia Campos F. Is carbohydrates-
deficient transferrin the best test of the alcoholic
etiology in acute pancreatitis? Rev Esp Enferm Dig
2001; 93:529-34. [PMID 11692782]

There are no products listed under this category.