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CRP/albumin ratio in acute pancreatitis

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 Original Article  
CRP/albumin /  Pacute
ratio in pancreatitis
ancreas
Predictive value of C-reactive protein/albumin
ratio in acute pancreatitis
Mustafa Kaplan, Ihsan Ates, Muhammed Yener Akpinar, Mahmut Yuksel, Ufuk Baris Kuzu,
Sabite Kacar, Orhan Coskun and Ertugrul Kayacetin
Ankara, Turkey
BACKGROUND: Serum C-reactive protein (CRP) increases
and albumin decreases in patients with inflammation and in-
fection. However, their role in patients with acute pancreatitis
is not clear. The present study was to investigate the predictive
significance of the CRP/albumin ratio for the prognosis and
mortality in acute pancreatitis patients.
METHODS: This study was performed retrospectively with
192 acute pancreatitis patients between January 2002 and June
2015. Ranson scores, Atlanta classification and CRP/albumin
ratios of the patients were calculated.
RESULTS: The CRP/albumin ratio was higher in deceased pa-
tients compared to survivors. The CRP/albumin ratio was pos-
itively correlated with Ranson score and Atlanta classification
in particular and with important prognostic markers such as
hospitalization time, CRP and erythrocyte sedimentation rate.
In addition to the CRP/albumin ratio, necrotizing pancreatitis
type, moderately severe and severe Atlanta classification, and
total Ranson score were independent risk factors of mortal-
ity. It was found that an increase of 1 unit in the CRP/albumin
ratio resulted in an increase of 1.52 times in mortality risk. A
prediction value about CRP/albumin ratio >16.28 was found
to be a significant marker in predicting mortality with 92.1%
sensitivity and 58.0% specificity. It was seen that Ranson and
Atlanta classification were higher in patients with CRP/albu-
min ratio >16.28 compared with those with CRP/albumin ra-
tio ≤16.28. Patients with CRP/albumin ratio >16.28 had a 19.3
times higher chance of death.
Author Affiliations: Department of Gastroenterology, Turkey Yuksek
Ihtisas Training and Research Hospital, Ankara 06100, Turkey (Kaplan
M, Akpinar MY, Yuksel M, Kuzu UB, Kacar S, Coskun O and Kayacetin
E); Department of Internal Medicine, Ankara Numune Training and Re-
search Hospital, Ankara 06100, Turkey (Ates I)
Corresponding Author: Ihsan Ates, MD, PhD, Department of Internal
Medicine, Ankara Numune Training and Research Hospital, Ankara
06100, Turkey (Tel: +0903125084666; Fax: +0903123113958; Email:
dr.ihsanates@hotmail.com)
© 2017, Hepatobiliary Pancreat Dis Int. All rights reserved.
doi: 10.1016/S1499-3872(17)60007-9
Published online April 24, 2017.
Hepatobiliary Pancreat Dis Int，Vol 00，No 0 • Month，2017 • www.hbpdint.com • 
CONCLUSION: The CRP/albumin ratio is a novel but promis-
ing, easy-to-measure, repeatable, non-invasive inflammation-
based prognostic score in acute pancreatitis.
(Hepatobiliary Pancreat Dis Int 2017;00:000-000)
KEY WORDS: Atlanta classification;
C-reactive protein;
Glasgow prognostic score;
Ranson score;
acute pancreatitis
Introduction
A
cute pancreatitis (AP) is a severe inflammation
of the pancreas presented with sudden onset and
severe abdominal pain and has high morbidity
and mortality rate. Although its etiology is not known
for certain, it is mostly associated with gallstones and
alcohol.[1] It is associated with intra-acinar activation of
proteolytic enzymes, leukocyte chemoattraction, release
of cytokines, oxidative stress and microcirculatory in-
jury.[2-4] The common factor in all these mechanisms is
an excessive inflammatory response.
The prognosis of the disease varies depending on the
severity of the disease. Approximately 75%-80% of cases
progress mildly and can be cured solely with intravenous
fluid treatment and supportive care. The remaining cases
progress with mortality and severe complications up to
30%-50%.[5] For this reason, early diagnosis of the dis-
ease and determination of a therapeutic strategy accord-
ing to disease severity are of great importance. Several
scoring systems are used in order to determine the dis-
ease severity. However, none of these scoring systems can
determine the severity within the first hour of admission.
For this reason, there is a need for easy-to-use and inex-
pensive indices that can determine the disease severity
and give an idea about the prognosis within minutes in
clinical practice.
Serum C-reactive protein (CRP) is a positive acute

phase reactant synthesized by the liver and its level in the
blood increases within hours in response to inflamma-
tion and infection.[6, 7] It is frequently used in infection
and inflammation follow-up due to its short half-life,
easy measurement and close relationship with prognosis
of the disease.[8-10] It can be used for diagnosis, treatment
follow-up and mortality prediction especially in inflam-
matory cases.[11, 12]
Albumin is a negative acute phase reactant synthesized
by the liver and its level in the blood decreases during in-
flammation. In previous studies, albumin was shown to be
associated with inflammation severity, disease prognosis
and mortality.[13-15] The reason for this is the close relation-
ship between inflammation and malnutrition.
The CRP/albumin ratio is a new inflammation-based
prognostic score and it is correlated to the inflammation
severity[16] and mortality.[17] However, there is no study
available in the literature which investigates the relation-
ship of this marker with disease prognosis and mortality.
The present study investigated the predictive significance
of the CRP/albumin ratio for prognosis and mortality in
AP patients.
Methods
Patients
We reviewed the files of AP patients in the Gastroen-
terology Clinic of Turkey Yuksek Ihtisas Training and
Research Hospital between January 2002 and June 2015.
A total of 300 patients were retrieved initially, 108 were
excluded from the study due to lack of follow-up and
insufficient laboratory values. Patients with documented
cardiovascular and cerebrovascular diseases, known re-
nal and liver failure or malignancy diagnosis and those
who had infectious disease within the last month were
excluded from the study. Our patients were over the age
of 18, hospitalized with AP diagnosis according to At-
lanta criteria. Laboratory parameters had been recorded
and computed tomographies were performed to evaluate
pancreatitis severity at least at the date of admission. Fi-
nally 192 patients were included in the analysis.
A diagnosis of AP was made using the Atlanta criteria
which requires the presence at least 2 of the followings: 1)
abdominal pain highly suggestive of acute pancreatitis; 2)
elevations in serum amylase and/or lipase to more than
3 times the upper limit of normal; 3) the presence of
characteristic radiological findings (ultrasonography or
computerized tomography) of AP.[18, 19]
Relevant information such as age, gender, laboratory
findings, complications, radiologic findings, duration of
hospital stay, Ranson score, Atlanta classification, mor-
tality status were retrieved from patient files. According
 • Hepatobiliary Pancreat Dis Int，Vol 00，No 0 • Month，2017 • www.hbpdint.com
Hepatobiliary & Pancreatic Diseases International
to the Atlanta classification, patients without local or sys-
temic complications and organ failure were classified as
mild AP; those with transient organ failure - organ fail-
ure that resolves within 48 hours and/or local or systemic
complications - were classified as moderately severe AP;
and those with persistent organ failure were classified as
severe AP. For patients with pancreatitis associated with
gallstones and other reasons, Ranson criteria were calcu-
lated at 0 h and 48 h separately and a total Ranson score
was achieved. All laboratory findings of the patients were
obtained at the time of admission.
Statistical analysis
Statistical Package for Social Sciences (SPSS) for
Windows 20 (IBM SPSS Inc., Chicago, USA) and Med-
Calc 11.4.2 (MedCalc Software, Mariakerke, Belgium)
softwares were used for statistical assessments. The
normal distribution of the data was evaluated with
the Shapiro-Wilk test. Values with normal distribution
were presented as mean±standard deviation and values
without normal distribution were presented as median
(range). Categorical variables were presented as num-
bers and percentages. Numerical values in the deceased
patient group and the survival patient group were com-
pared using the Student’s t test and the Mann-Whitney U
test. Chi-square test and Fisher’s exact test were used in
comparison of categorical data. Univariable Cox regres-
sion analysis was utilized in order to determine the ef-
fects of potential prognostic factors on mortality. Signifi-
cant factors were included in the stepwise multivariate
Cox regression model and independent predictors were
identified. The diagnostic discrimination of independent
predictors in mortality was examined with ROC curve
analysis, area under the curve (AUC).[20] The Youden
index method was used in order to determine the predic-
tion point of the CRP/albumin ratio for mortality. The
Kaplan-Meier analysis was used to show the effect of the
determined prediction value on survival. In statistical
analysis, a P<0.05 with 95% confidence interval and 5%
margin of error was considered statistically significant.
Results
Entire population findings
The study population consisted of 192 patients, 120 fe-
males (62.5%) and 72 males (37.5%). The mean age of
the patients was 61.9±18.0 years. One hundred eighty-
five (96.4%) of the patients had abdominal pain, 15
(7.8%) had jaundice, 32 (16.7%) had fever, 39 (20.3%)
had nausea, and 1 (0.5%) was asymptomatic. The dis-
tribution of the patients in terms of etiology was as fol-
lows: 154 (80.2%) gallstone, 5 (2.6%) alcohol, 3 (1.6%)
CRP/albumin ratio in acute pancreatitis

hypertriglyceridemia, 18 (9.4%) hereditary, 3 (1.6%) en- Correlation

doscopic retrograde cholangiopancreatography (ERCP), The CRP/albumin ratio had a positive correlation
and 9 (4.7%) other etiologies. With regard to AP compli- with age (r=0.394, P<0.001), hospitalization (r=0.420,
cations, 17 (8.9%) of the patients had acute renal failure, P<0.001), urea (r=0.518, P<0.001), INR (r=0.327; P<0.001),
8 (4.2%) had abscess, 10 (5.2%) had sepsis, 9 (4.7%) had leukocyte (r=0.461; P<0.001), creatinine (r=0.294; P<0.001),
pseudocyst, 3 (1.6%) had ascites, 5 (2.6%) had hematoma, ESR (r=0.651; P<0.001), CRP (r=0.978; P<0.001), Atlanta
and 6 (3.1%) had cholangitis. 153 (79.7%) of the patients classification (r=0.437; P<0.001), total Ranson score
had edematous and 39 (20.3%) had necrotizing pancreati- (r=0.518; P<0.001) and a negative correlation with
tis. 38 (19.8%) patients died. The median hospitalization follow-up (r=-0.272; P<0.001), AST (r=-0.253, P=0.005),
length of the patients was 9 days (2-100) and the median ALT (r=-0.292; P<0.001), GGT (r=-0.229; P<0.001),
follow-up length was 63 months (1-126). calcium (r=-0.504; P<0.001), total protein (r=-0.429;
Twenty-nine (15.1%) of the patients had Ranson P<0.001) and albumin (r=-0.536, P<0.001) levels (Table 1).
score of “0”, 36 (18.8%) had Ranson score of “1”, 44
(22.9%) had Ranson score of “2”, 31 (16.1%) had Ran- Independent risk factors
son score of “3”, 17 (8.9%) had Ranson score of “4”, 25
Significant prognostic factors were included in the
(13.0%) had Ranson score of “5”, and 10 (5.2%) had
backward stepwise regression analysis (Tables 2-4). In the
Ranson score of “6”. One hundred twenty-seven (66.1%)
Cox regression model and multivariable regression anal-
patients had a “mild” Atlanta classification, 36 (18.8%)
had a “moderately severe” Atlanta classification, and 29
(15.1%) had a “severe” Atlanta classification. Table 2. Demographic charecteristics and clinical findings of
study population
Variables HR 95% CI P value
Table 1. The relationships between CRP/albumin ratio and other Age 1.021 1.003-1.040 0.023
clinical characteristics Gender
CRP/albumin ratio Female ref ref ref
Variables
r P value Male 0.967 0.486-1.925 0.967
Age 0.394 <0.001 Symptom
Hospitalization 0.420 <0.001 Abdominal pain 2.245 0.034-14.841 0.035
Follow-up -0.272 <0.001 Jaundice 1.531 0.527-4.445 0.434
Urea 0.518 <0.001 Fever 3.474 1.822-6.626 <0.001
AST -0.253 0.005 Nausea 4.684 2.450-8.955 <0.001
ALT -0.292 <0.001 Asymptomatic 0.049 0.001-1.996 0.901
GGT -0.229 0.001 Etiology
Alkaline phosphatase -0.172 0.117 Gallstone 0.204 0.106-0.391 <0.001
Amylase 0.091 0.210 Alcohol ref ref ref
Lipase 0.017 0.810 Hipertriglyceridemia ref ref ref
Lactate dehydrogenase 0.074 0.308 Hereditary ref ref ref
Total bilirubin -0.083 0.252 Post-ERCP ref ref ref
Direct bilirubin -0.109 0.131 Others ref ref ref
Calcium -0.504 <0.001 ERCP 0.568 0.292-1.103 0.095
INR 0.327 <0.001 Complications
Hemoglobulin -0.068 0.348 ARF 7.074 3.633-13.773 <0.001
White blood cell 0.461 <0.001 Abscess 4.096 1.678-9.997 0.002
Creatinine 0.294 <0.001 Sepsis 9.048 4.324-18.934 <0.001
Total protein -0.429 <0.001 Pseudocyst 1.078 0.257-4.519 0.918
Platelet -0.093 0.201 Ascites 1.859 0.438-7.891 0.400
ESR 0.651 <0.001 Hematoma 8.584 2.908-25.333 <0.001
CRP 0.978 <0.001 Cholangitis 10.486 4.177-26.322 <0.001
Albumin -0.536 <0.001 Pancreatitis type
Total Ranson score 0.518 <0.001 Necrotizing 10.564 5.097-21.894 0.001
Atlanta score 0.437 <0.001 Edematous ref ref ref
AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: Hospitalization 1.032 1.018-1.046 0.001
gama-glutamyltransferase; CRP: c-reactive protein; INR: international ERCP: endoscopic retrograde cholangiopancreatography; ARF: acute
normalized ratio; ESR: erythrocyte sedimentation rate. renal failure; HR: hazard ratio; 95% CI: 95% confidence interval.

Hepatobiliary Pancreat Dis Int，Vol 00，No 0 • Month，2017 • www.hbpdint.com • 

 Hepatobiliary & Pancreatic Diseases International

ysis, the CRP/albumin ratio (HR=1.52, 95% CI: 1.23-1.89, HR=11.47, 95% CI: 6.58-20.0, P<0.001, respectively),
P<0.001), necrotizing pancreatitis type (HR=4.44, 95% CI: and total Ranson score (HR=1.50, 95% CI: 1.27-1.78,
3.56-5.32, P<0.001), moderately severe and severe Atlanta P<0.001) were independent risk factors of mortality. An
classification (HR=6.66, 95% CI: 4.96-8.96, P<0.001; increase of 1 unit in the CRP/albumin ratio resulted in
an increase of 1.52 times in mortality risk.
Fig. 1 shows the diagnostic assessment of indepen-
Table 3. Distribution of laboratory findings by risk groups
dent predictors of mortality. Accordingly, independent
Variables HR 95% CI P value
predictors with high AUC values did not show a diagnos-
Urea 1.090 1.050-1.130 <0.001
tic difference in terms of predicting mortality. A predic-
AST 0.999 0.997-1.002 0.084
ALT 0.996 0.994-0.998 0.008
tion value of CRP/albumin ratio >16.28 was found to be
GGT 0.999 0.997-1.001 0.070 a significant marker in predicting mortality (sensitivity:
Alkaline phosphatase 0.993 0.990-0.996 0.009 92.1%; specificity: 58.0%; AUC: 0.835; P<0.001). The
Amylase 1.000 0.999-1.001 0.467 mortality risk of the patients whose CRP/albumin ratio
Lipase 1.001 0.998-1.004 0.125 were higher than 16.28 (35/99) was 19.271 times higher
Lactate dehydrogenase 1.001 0.995-1.007 0.073 when compared to the patients with a CRP/albumin
Total bilirubin 0.739 0.572-0.954 0.020 ratio ≤16.28 (3/93) (HR=19.271, 95% CI: 5.849-63.491,
Direct bilirubin 0.706 0.518-0.962 0.028
P<0.001). The median survival length of the patients
Calcium 0.097 0.043-0.215 <0.001
INR 1.355 1.013-1.812 0.041
with a CRP/albumin ratio>16.28 was 55 months (95%
Hemoglobin 0.903 0.788-1.036 0.146 CI: 45.6-64.4). The 1-, 3-, and 5-year survival rates were
White blood cell 1.000 0.995-1.005 0.759 90.4%±0.03%, 67.5%±0.06%, and 23.5%±0.11% (Fig. 2).
Creatinine 1.575 1.310-1.894 <0.001
Total protein 0.557 0.414-0.750 <0.001
Table 4. Distribution of prognostic scores by risk groups
Platelet 0.999 0.992-1.006 0.091
Erythrocyte sedimentation rate 1.031 1.020-1.042 <0.001 Variables HR 95% CI P value
Albumin 0.391 0.279-0.549 <0.001 Total Ranson score 2.195 1.728-2.788 0.001
CRP 1.110 1.080-1.150 <0.001 Atlanta score
CRP/albumin 1.346 1.250-1.450 <0.001 Mild ref ref ref
AST: aspartate aminotransferase; ALT: alanine aminotransferase; GGT: Moderately severe 7.842 2.455-25.052 0.001
gama-glutamyltransferase; HR: hazard ratio; 95% CI : 95% confidence Severe 27.726 9.608-80.011 0.001
interval; INR: international normalized ratio. HR: hazard ratio; 95% CI: 95% confidence interval.

Fig. 1. Diagnostic assessment of independent predictors of mortality with ROC curve analysis. AUC:��������������������������������
area under curve; SE: standard
error; 95% CI: 95% confidence interval; CRP: C-reacitive protein.

 • Hepatobiliary Pancreat Dis Int，Vol 00，No 0 • Month，2017 • www.hbpdint.com

CRP/albumin ratio in acute pancreatitis
Fig. 2. Survival analysis of acute pancreatitis patients according to
CRP/albumin ratio.
Eleven (11.1%) of the patients with a CRP/albumin
ratio >16.28 had Ranson score of 4, 22 (22.2%) had Ran-
son score of 5, 10 (10.1%) had Ranson score of 6. These
values were 6.5%, 3.2% and 0 respectively for the patients
with a CRP/albumin ratio ≤16.28 (P<0.001). 50 (50.5%)
of the patients with a CRP/albumin ratio >16.28 had a
mild Atlanta classification, 23 (23.2%) had a moderately
severe Atlanta classification, 26 (26.3%) had a severe At-
lanta classification. These values were 82.8%, 14.0% and
3.2% respectively for the patients with a CRP/albumin
ratio ≤ 16.28 (P<0.001).
Discussion
The present study demonstrated that the CRP/albumin
ratio was higher in deceased AP patients compared to
those survived and it was a prognostic factor. The CRP/
albumin ratio was positively correlated with Ranson
score, and Atlanta classification in particular and with
important prognostic markers such as hospitalization
time, CRP and ESR. As well known, necrotizing pancre-
atitis type, moderately severe and severe Atlanta clas-
sification, and total Ranson score were independent risk
factors of mortality; the present study showed that CRP/
albumin ratio was another predictor of mortality in AP
patients.
AP is a common gastrointestinal emergency and its
mortality can reach up to 40%. For this reason, it is of
great importance to identify patients to be treated ag-
gressively at the time of admission. There is a need for a
simple, repeatable and non-invasive laboratory procedure
that does not require additional time and is easy to mea-
sure at the time of admission. Thus, we investigated the
usability of the CRP/albumin ratio for the determination
of prognosis and mortality in patients who are admit-
ted to our clinic with an AP diagnosis. Several studies
showed that both markers are used in the diagnosis,
Hepatobiliary Pancreat Dis Int，Vol 00，No 0 • Month，2017 • www.hbpdint.com • 
treatment follow-up and prognosis determination.[11, 13]
CRP especially was very valuable in acute response due
to its short half-life.[11] CRP levels are frequently used at
the time of admission and later during the treatment in
AP patients.[21] Wang et al[22] showed that low albumin
and high CRP were markers of poor outcome and this
support the idea that CRP and albumin could be used
for predicting the mortality risk in AP patients.
The CRP/albumin ratio is widely used to predict the
patient outcomes in many diseases such as colorectal
cancer[23] and sepsis[24] etc. However, the role of CRP/al-
bumin ratio in AP prognosis is not clear. The present
study showed that CRP/albumin ratio was higher in de-
ceased patients compared to those who survived which
demonstrated the prognostic value in AP patients.
Median age, acute renal failure, abscess, sepsis, cholan-
gitis rate, hospitalization length and necrotizing pancreati-
tis type were higher in the deceased group compared with
survivors, which were consistent with the literature.[25-27�]
We also found that the CRP/albumin ratio, Atlanta and
Ranson scores, presence of necrosis were independent
risk factors of mortality, which were mostly consistent
with Ferreira’s study.[25] Our data implied that the CRP/
albumin ratio may be useful for prognostic purposes
in AP. Although the Ranson score has been used in AP
prognosis for more than three decades, its biggest dis-
advantage is that it requires 48 hours for assessment.
Atlanta classification, another global standard tool for
assessment of AP severity, maintains its complexity due
to confusing terms related to disease severity.[28] Because
of this complexity, we investigated the prognostic sig-
nificance of the CRP/albumin ratio in AP and found
that the CRP/albumin ratio was directly related with AP
prognosis.
Kim et al showed that the CRP/albumin ratio was
superior to the CRP level in predicting mortality in pa-
tients with septic shock; if the cut-off value is 5.09, the
sensitivity and specificity of this ratio were 61% and the
Kaplan-Meier curve analysis showed a significantly high-
er 180-day mortality rate in patients with a CRP/albumin
ratio>5.09, compared to patients with a lower CRP/albu-
min ratio.[24] In our study, compared with patients who
had a CRP/albumin ratio <16.28, those with a CRP/al-
bumin ratio ≥16.28 had a 19.3 times higher risk of death.
Also, the fact that 1-, 3- and 5-year survival rates were
found to be lower in the patients with a CRP/albumin
ratio >16.28 supports the findings of the above men-
tioned study. Similarly, Kawashima et al[29] found that the
5-year survival rate decreased in patients diagnosed with
lung carcinoma as CRP/albumin ratio increased.
Presence of gallstones in etiology was a marker of
lower mortality. This might be due to low prevalence of

complications and patients with pancreatitis associated
with gallstones were treated with ERCP urgently in our
clinic.
The limitations of our study include the retrospective
nature, single-center, low population study, which may
limit the prognostic value of the CRP/albumin ratio. The
other limitation of our study is biliary pancreatitis ratio.
Mortality rate in AP is found 19.8% during the hos-
pitalization in our study. This might be due to most of
AP patients that admitted to our emergency room took
medical treatment in emergency and discharged and
excluded from the study because of non-hospitalization.
Additionally because our hospital is third stage education
hospital, more complicated patients admit to our clinic.
In literature there are studies that mortality rate reached
to 30%.[30-32] Possible bias was likely. However, we think
our patients count is enough for statistical analysis. Addi-
tional prospective studies with larger populations involv-
ing multiple centers are necessary to accurately evaluate
the CRP/albumin ratio as a predictor of mortality.
In summary, this study demonstrated that as a cheap,
repeatable, non-invasive systemic inflammation-based
marker, the CRP/albumin ratio is an independent pre-
dictor of overall survival for patients with AP. The CRP/
albumin ratio could be used to predict prognosis in pa-
tients with AP like other prognostic scores or laboratory
parameters.
Contributors: KM and AI were responsible for the study design,
analysis and interpretation of the data, drafting of the manuscript.
AMY performed the statistical analysis. YM and CO interpreted
the data. KS and KE revised the manuscript for important intel-
lectual content. All authors contributed to the design and inter-
pretation of the study and to further drafts. KM and AI contrib-
uted equally to this study. KM is the guarantor.
Funding: None.
Ethical approval: The study was approved by the Institutional
Review Board of the Turkey Yuksek Ihtisas Training and Research
Hospital (2015-0625). All participants provided written informed
consent.
Competing interest: No benefits in any form have been received
or will be received from a commercial party related directly or in-
directly to the subject of this article.
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Received March 30, 2016
Accepted after revision December 21, 2016