EJINME-03398; No of Pages 6

European Journal of Internal Medicine xxx (2016) xxx–xxx

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European Journal of Internal Medicine

journal homepage: www.elsevier.com/locate/ejim

Original Article

Nonalcoholic fatty liver and the severity of acute pancreatitis

I. Mikolasevic a,⁎, L. Orlic b, G. Poropat a, I. Jakopcic c, D. Stimac a, A. Klanac c, F. Carovic c, S. Milic a
a
Department of Gastroenterology, UHC Rijeka, Croatia
b
Department of Nephrology, Dialysis and Kidney Transplantation, UHC Rijeka, Croatia
c
School of Medicine, Rijeka, Croatia

a r t i c l e i n f o a b s t r a c t

Article history: Aim: To explore the effect of nonalcoholic fatty liver as a hepatic manifestation of metabolic syndrome on the
Received 15 July 2016 severity of acute pancreatitis. We hypothesized that patients with nonalcoholic fatty liver would have a more
Received in revised form 24 October 2016 severe form of acute pancreatitis.
Accepted 25 October 2016 Patients and methods: We retrospectively analyzed 822 patients hospitalized with acute pancreatitis. We
Available online xxxx
diagnosed acute pancreatitis and determined its severity according the revised Atlanta classification criteria
from 2012. We assessed nonalcoholic fatty liver with computed tomography.
Keywords:
Nonalcoholic fatty liver
Results: There were 198 (24.1%) patients out of 822 analyzed who had nonalcoholic fatty liver. Patients with
Acute pancreatitis nonalcoholic fatty liver had statistically higher incidence of moderately severe (35.4% vs. 14.6%; p = 0.02) and
Severity severe acute pancreatitis (20.7% vs. 9.6%; p b 0.001) compared to patients without nonalcoholic fatty liver. At
Prognosis the admission patients with nonalcoholic fatty liver had higher values of C-reactive protein as well as at
day three, higher APACHE II score at admission and significantly higher incidence of organ failure and local
complications as well as higher values of computed tomography severity index compared to patients without
nonalcoholic fatty liver. We found independent association between the occurrence of moderately severe and
severe acute pancreatitis and nonalcoholic fatty liver (OR 2.13, 95%CI 1.236–3.689). Compared to patients
without nonalcoholic fatty liver, patients with nonalcoholic fatty liver had a higher death rate, however not
statistically significant (5.6% vs. 4.3%; p = NS).
Conclusion: Presence of nonalcoholic fatty liver at admission can indicate a higher risk for developing more severe
forms of acute pancreatitis and could be used as an additional prognostic tool.
© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

1. Introduction
Around 15 to 25% of all patients with acute pancreatitis progresses to
severe form of acute pancreatitis. Consequently, the death rate is much
higher in this subgroup of patients. The possibility to predict the severity
of this disease could help identify patients with increased risk of mor-
bidity and mortality and assist in appropriate early triage to intensive
care units and selection of patients for specific interventions. Therefore,
research with intention to detect and develop not only a more accurate
diagnostic, but prognostic tool as well, is increasing worldwide [1]. Use
of a clinical scoring systems and specific laboratory tests are the two
most common approaches in determining prognosis in acute pancreati-
tis. The majority of research to evaluate methods for prediction of acute
pancreatitis severity is focused on death as the outcome of interest as a
well-defined relevant outcome. Patients with severe acute pancreatitis
often need intensive care treatment, therefore early evaluation and
risk stratification for patients with acute pancreatitis is important to
differentiate patients with mild versus severe disease. Also, predictions
of outcome should be applied accurately and reliably, preferably within
⁎ Corresponding author.
E-mail address: ivana.mikolasevic@gmail.com (I. Mikolasevic).
the first 24 h of admission to hospital. The Acute Physiology and Chronic
Health Evaluation scale (APACHE II) scale, Bedside Index of Severity in
Acute Pancreatitis (BISAP), Ranson's criteria, the Imrie scoring system
and the Computed Tomography (CT) Severity Index are systems for
classifying severity of acute pancreatitis. Even though serum lipase
and amylase levels remain the most common used laboratory test for
diagnosing acute pancreatitis, other biomarkers and inflammatory
mediators have been investigated as potential biomarkers to help pre-
dict the outcome of acute pancreatitis. The most studied, and widely
available as well, is the C-reactive protein. Other markers of systemic
inflammation that were studied were interleukins 6 and 8 and some
others [1,2,3,4,5,6,7]. In the revised Atlanta classification system
measures of severity of acute pancreatitis were revised [8].
Incidence of nonalcoholic fatty liver disease is increasing together
with higher incidence of obesity and metabolic syndrome. Nonalcoholic
fatty liver disease as the most common chronic liver disease today is
closely related to metabolic syndrome and its individual components:
diabetes mellitus type 2, arterial hypertension, obesity and dyslipidemia
[9]. Recently, we have conducted a study in which we have explored the
influence of metabolic syndrome on acute pancreatitis course. We
discovered that the existence of metabolic syndrome at admission indi-
cates on higher risk for moderately severe and severe acute pancreatitis,

http://dx.doi.org/10.1016/j.ejim.2016.10.019
0953-6205/© 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019
2 I. Mikolasevic et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
as well as for the higher death rate [10]. According to the literature,
there are very few studies about the relationship between fatty liver
(FL) and severity and clinical outcomes in AP [11].
Thus, we aimed to explore the effect of nonalcoholic fatty liver
(NAFL) as a hepatic manifestation of metabolic syndrome on the
severity of acute pancreatitis. Our hypothesis was that patients with
nonalcoholic fatty liver would have a more severe form of disease.
2. Patients and methods
We analyzed 1070 patients with acute pancreatitis admitted to our
hospital between January 1st, 2008 and June 30th, 2015. We defined
acute pancreatitis as an occurrence of typical upper abdominal pain
(nausea or vomiting) within the first 48 h prior to admission and eleva-
tion of serum lipase or amylase levels at least 3 times the upper limit of
normal. We excluded patients with a relapse of acute pancreatitis or
with an exacerbation of chronic pancreatitis, patients with incomplete
medical data, patients with active malignancy, those who were younger
than 18 years and those who were receiving medications that can cause
liver steatosis (corticosteroids, amiodarone, etc.). Patients with other
causes of chronic liver disease were not a part of this analysis. All
patients had a CT scan performed on the fifth day of hospitalization in
order to confirm diagnosis and evaluate local complications. CT severity
index (CTSI) was calculated for all patients. Out of 1070 initially
analyzed patients we excluded 215 patients' cause of alcoholic etiology
of acute pancreatitis and 8 due to missing data. From the rest of 847
patients, 6 were excluded because of uncertain etiology of acute pancre-
atitis and 19 because of other exclusion criteria (taking the medications
that can lead to liver steatosis). In the end, we had 822 patients that we
included in final analysis, Fig. 1.
We extracted history, demographic and laboratory data from medical
record. Details such as gender, age, weight, height, waist circumference,
and previous alcohol consumption were acquired. Respectively, consum-
mation of more than 14 alcohol drinks/week in women and more than
21 alcohol drinks/week in men was considered as excessive alcohol con-
sumption. Relevant conditions assessed from medical records included
arterial hypertension (AH), obesity, type 2 diabetes mellitus, dyslipid-
emia, coronary artery disease, and chronic kidney disease. Obesity was
defined according to the World Health Organization (WHO) Western
Pacific Region as a BMI N 25 kg/m2 [12]. Use of all medications was
noted at admission as well. Initial laboratory tests taken at admission
included full and differential blood count, arterial blood gasses and
biochemistry.
Fig. 1. Flow-chart of included and excluded patients.
Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019
According to its severity, defined by the revised Atlanta classification
from 2012, acute pancreatitis was divided into three groups. Mild acute
pancreatitis defined by absence of organ failure, local or systemic
complications; moderate acute pancreatitis characterized by the
existence of transient organ failure (lasting continuously less than
48 h), exacerbation of concomitant diseases and/or development of
local complications; and severe acute pancreatitis (SAP) defined by
presence of persistent organ failure (lasting continuously for more
than 48 h) affecting respiration, renal function or the cardiovascular sys-
tem. Local complications included peripancreatic fluid collections,
pseudocysts, pancreatic and peripancreatic necrosis (sterile or infected),
and walled-off necrosis (sterile or infected). Walled-off necrosis was not
separately analyzed due to small number of patients with this complica-
tion [8,13,14]. We initially assessed acute pancreatitis severity by
calculating the APACHE II score. We calculated the correlation of nonal-
coholic fatty liver presence with severity of acute pancreatitis using a
score of 8 or more as a cut-off value for severe acute pancreatitis.
Nonalcoholic fatty liver was diagnosed according to the presence of all
following criteria: (A) steatosis detected by imaging (CT scan or abdomi-
nal ultrasound). Fatty liver was diagnosed if liver density showed attenu-
ation of 10 HU compared to the spleen, or if liver density was less than
40 HU; (B) absence of alcoholic liver disease; (C) absence of medications
and diseases that can cause liver steatosis; and (D) absence of other
causes of chronic liver disease [15,16].
The primary endpoint is to evaluate the association between
nonalcoholic fatty liver and severity of acute pancreatitis.
Secondary endpoints:
- association between the presence of nonalcoholic fatty liver and
acute pancreatitis severity according to the APACHE II and CTSI
scores.
- association between the presence of nonalcoholic fatty liver and
acute pancreatitis severity according to the levels of C-reactive pro-
tein measured at admission and on the third day of hospital stay.
- number of local (peripancreatic fluid collections, pseudocysts,
pancreatic and peripancreatic necrosis) complications of acute
pancreatitis in accordance with presence of nonalcoholic fatty liver.
- incidence of organ failure in acute pancreatitis patients in accor-
dance with presence of nonalcoholic fatty liver.
- length of hospital stay in high dependency unit, intensive care unit
(ICU) and total length of hospital stay in acute pancreatitis patients
with nonalcoholic fatty liver compared to patients without nonalco-
holic fatty liver.
- association of nonalcoholic fatty liver presence and acute pancreati-
tis severity independently from other components of metabolic
syndrome (obesity, arterial hypertension, type 2 diabetes mellitus
and dyslipidemia).
- compare the survival rate between acute pancreatitis patients with
and without nonalcoholic fatty liver.
We used descriptive statistics (mean and SD) to analyze statistical
data and χ2 test or Fisher's exact test to test the differences between
categorical variables. The importance of the difference between two in-
dependent groups was tested by using Student's t-test or ANOVA,
where appropriate. We used the logistic regression analysis to analyze
multivariable regression (the results were presented as odds ratio
[OR] and 95% confidence intervals [CI]). As statistically significant we
considered P value b0.05. For statistical analysis we used MedCalc sta-
tistical software package, version 10 (MedCalc,Mariakerke, Belgium)
and IBM SPSS v22.
3. Results
Out of 822 analyzed patients with acute pancreatitis 198 of them
(24.1%) had nonalcoholic fatty liver. Demographic and clinical character-
istics of analyzed patients are shown in Table 1. The mean age of our
 I. Mikolasevic et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx 3

Table 1
Demographic and clinical data of analyzed patients.

Characteristic All patients (n = 822) No-FL (n = 624) FL p

(n = 198)

Age (y) 63.9 ± 17 63.9 ± 17.4 63.9 ± 15.4 NS

Male, n(%) 402 (48.9%) 289 (46.3%) 113 (57.1%) NS
T2DM, n(%) 105 (13.1%) 60 (9.6%) 45 (22.7%) 0.002
Arterial hypertension, n(%) 378 (46%) 270 (43.3%) 108 (54.5%) 0.007
Dyslipidemia, n(%) 95 (11.6%) 51 (8.2%) 44 (22.2%) 0.005
BMI (kg/m2) 27.8 ± 4.6 27.3 ± 4.6 29.1 ± 4.6 b0.0001
Waist circumference (cm) 101.7 ± 13.5 100.1 ± 13.1 105.4 ± 13.6 0.0003
Coronary heart disease, n(%) 88 (10.7%) 73 (11.7%) 15 (7.6%) NS
Chronic kidney disease, n(%) 26 (3.2%) 21 (3.4%) 5 (2.5%) NS
Etiology of AP
Biliary, n(%) 688 (83.7%) 531 (85.1%) 157 (79.3%) NS
Hyperlipidemia cause, n(%) 9 (1.1%) 4 (0.6%) 5 (2.5%) NS
Other, n(%) 125 (15.2%) 89 (14.3%) 36 (18.2%) NS

FL — fatty liver; T2DM — diabetes mellitus type 2; BMI — body mass index; AP — acute pancreatitis.

patients was 63.9 ± 17 years while 48.9% of them were male. Arterial
hypertension, type 2 diabetes mellitus and dyslipidemia were significant-
ly more common in patients with nonalcoholic fatty liver. Moreover,
patients with acute pancreatitis and fatty liver had significantly higher
body mass index and waist circumference values compared to patients
without fatty liver. There was no significant difference regarding age,
gender, chronic kidney disease, coronary heart disease and etiology of
acute pancreatitis (hypertriglyceridemia, biliary and other etiologies of
acute pancreatitis).
3.1. Primary endpoint
Acute pancreatitis was present in 65.6% of patients, while 19.6% had
moderately severe, and 12.3% had severe acute pancreatitis. A statisti-
cally significant higher incidence of mild acute pancreatitis was found
in patients without fatty liver compared to patients with fatty liver
(75.6% vs. 43.4%; p b 0.001;), while a statistically higher incidence of
moderately severe (35.4% vs. 14.6%; p = 0.02) and severe acute pancre-
atitis (20.7% vs. 9.6%; p b 0.001) was found in patients with fatty liver
compared to those without it (Fig. 2).
3.2. Secondary endpoints
Statistically higher values of APACHE II and CTSI prognostic scores
were found in acute pancreatitis patients with fatty liver compared to
those without, with 8.4 ± 4.1 vs. 7.2 ± 4 (p = 0.0002) and 2.9 ± 2.9
vs. 1.1 ± 2 (p b 0.0001), respectively. C-reactive protein levels measured
on admission and on the third day were significantly higher in patients
with acute pancreatitis and nonalcoholic fatty liver, with mean values of
63.2 ± 74.6 vs. 81.2 ± 98.1 (p = 0.02), and 101.6 ± 150.6 vs. 145.2 ±
110.6 (p = 0.009), respectively. Furthermore, there was significantly
higher incidence of local complications in acute pancreatitis patients
with fatty liver compared to those without fatty liver. Analyzing the in-
cidence of organ failure, we have found that patients with nonalcoholic
fatty liver had statistically higher incidence of organ failure in compari-
son to the patients without fatty liver. Although patients with fatty liver
had higher incidence of one-organ failure in comparison to the patients
without nonalcoholic fatty liver, that difference was not statistically
significant. On the other hand, nonalcoholic fatty liver patients had
higher incidence of multiple-organ failure in comparison to the patients
without nonalcoholic fatty liver, Table 2A.
Compared to patients without fatty liver, patients with fatty liver
had a statistically longer total hospital stay (15.4 ± 10.6 vs. 12.9 ±
8.2; p = 0.0006), higher dependency unit stay (4.5 ± 3.6 vs. 3 ± 3.2;
p b 0.0001) and a statistically longer stay in intensive care unit (1.0 ±
5.1 vs. 0.3 ± 1.9; p = 0.004), Table 2B.
A part from that, we wanted to examine if presence of nonalcoholic
fatty liver can predict the severity of acute pancreatitis independently of
other metabolic syndrome components: type 2 diabetes mellitus, obesi-
ty, dyslipidemia and arterial hypertension. In Table 3 shows an indepen-
dent correlation between fatty liver and the occurrence of moderately
severe and severe acute pancreatitis (OR 2.13, 95% CI 1.236–3.689).
Although the difference between survival rate did not reach statisti-
cal significance, acute pancreatitis patients with nonalcoholic fatty liver
had a higher mortality rate compared to patients without nonalcoholic
fatty liver (5.6% vs. 4.3%; p = NS).

Fig. 2. Severity of AP according to Atlanta classification with the respect to the presence of fatty liver.

Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019
4 I. Mikolasevic et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx

Table 2A Table 3
Clinical, laboratory and imaging data according to presence of fatty liver. Association of metabolic syndrome components and fatty liver with moderately severe
and severe AP (multivariable logistic regression analysis).
Non-FL FL p
(n = 624) (n = 198) Adjust model OR 95% Cl p-value

CRP (mg/dl) — at admission 63.2 ± 74.6 81.2 ± 98.1 0.02 Fatty liver (yes vs. no) 2.13 1.2386–3.6896 0.006
CRP (mg/dl) — at day three 101.6 ± 150.6 145.2 ± 110.6 0.009 Arterial hypertension (yes vs. no) 1.17 0.7058–1.9603 NS
Severity of AP according to APACE II score 7.2 ± 4 8.4 ± 4.1 0.0002 T2DM (yes vs. no) 1.60 0.8311–3.0882 NS
Number of local complications, n(%) 0.3 ± 0.7 0.9 ± 0.9 b0.0001 Dyslipidemia (yes vs. no) 1.42 0.7231–2.8278 NS
Peripancreatic fluid collection, n(%) 99 89 NS BMI (kg/m2) 0.99 0.9464–1.0554 NS
Pancreatic pseudocyst, n(%) 12 8 NS
T2DM — diabetes mellitus type 2; BMI — body mass index.
Acute necrotic collection, n(%) 70 70 0.0001
Persistent organ failure (N48 h), n(%) 80 (12.8%) 41 (20.7%) 0.006
Single organ failure, n(%) 54 (8.7%) 24 (12.1%) NS fatty liver disease is changing the lifestyle, diet and treatment of
Multiple organ failure, n(%) 26 (4.2%) 17 (8.6%) 0.02
CTSI score, mean ± SD 1.1 ± 2 2.9 ± 2.9 b0.0001
combined cardio-metabolic risk factors. A short time ago we have
discovered that the presence of metabolic syndrome is related to more
CRP — C-reactive protein; AP — acute pancreatitis; CTSI — CT severity index; FL — fatty
severe form of acute pancreatitis. Considering that nonalcoholic fatty
liver.
liver disease affects one third of population of western countries and
that is closely related to metabolic syndrome we were wondering
4. Discussion what is the effect of nonalcoholic fatty liver disease, as hepatic manifes-
tation of metabolic syndrome, on course of acute pancreatitis. Consis-
Majority of patients with acute pancreatitis will have a mild form of tent with earlier remark, our analyzed patients with acute pancreatitis
disease and a favorable course. However, 15–20% of all acute pancreati- and nonalcoholic fatty liver disease had significantly more often type
tis patients will develop severe acute pancreatitis which is frequently 2 diabetes mellitus, dyslipidemia and arterial hypertension. Moreover,
related with complicated clinical course and higher death rate. Because acute pancreatitis patients suffering from nonalcoholic fatty liver had
of that, the assessment of the disease severity as soon and accurate as significantly higher body mass index values and waist circumference
possible is of great importance for initiating the appropriate therapy compared to the patients without fatty liver [10,17,18]. As far as we
and supportive management, particularly within the first 24 h after know, there is only one study that investigated the effect of fatty liver
the admission. For the long period many authors have tried to find a on the course of acute pancreatitis. Xu C, et al. [11] examined the
prognostic index that could adequately stratify patients with acute influence of alcoholic fatty liver (AFL) and nonalcoholic fatty liver on
pancreatitis. Although most of the so far examined prognostic methods the severity and survival rate of acute pancreatitis. They came to the
have been useful we still need objective, accurate, fast and simple conclusion that fatty liver could have influence on the severity and clin-
method for early detecting of patients who are at high risk for develop- ical outcome, in other words, it could play a prognostic role in patients
ing a severe form of acute pancreatitis. It would be ideal if there was a with acute pancreatitis. Authors of this study also separated patients
laboratory or clinical test at patients' admission which would help us with alcoholic fatty liver from nonalcoholic fatty liver patients and
to recognize those who could develop a severe acute pancreatitis and they did not find any significant difference in the incidence of acute
those in higher risk for it [1,2,11]. pancreatitis and the clinical severity between those two groups. We
Even though nonalcoholic fatty liver disease is mostly benign con- have excluded all patients with previous significant alcohol consumption.
dition, it can be associated with serious conditions, with inflamma- Moreover, we excluded all patients whose laboratory results indicated on
tion and hepatocyte necro-apoptosis, non-alcoholic steatohepatitis possible alcohol consumption and all acute pancreatitis patients with
(NASH). These patients are at risk of developing fibrosis within one uncertain etiology of acute pancreatitis as well. Similar to the results of
fifth of them will progress to liver cirrhosis. Also, patients suffering study by Xu C et al. [11] we have found that patients without fatty liver
from nonalcoholic fatty liver disease and even those without developed had statistically higher incidence of mild acute pancreatitis compared to
cirrhosis have a higher risk for occurrence of hepatocellular carcinoma. the patients without it. On the other hand, we discovered that there is sta-
As a very frequent condition, with occurrence in one third of population tistically higher incidence of moderately severe and severe acute pancre-
in the developed world, nonalcoholic fatty liver disease is the third atitis in patients with fatty liver compared to those without it. In addition,
cause of liver transplantation in the United States. Furthermore, since when two groups compared, acute pancreatitis patients with fatty liver
incidence of obesity and metabolic syndrome is increasing its incidence had significantly higher incidence of local complications as well as statis-
is growing as well so, in the near future, we can expect that it will be- tically significant higher incidence of organ failure. Regarding the total
come the most common indication for liver transplantation. Moreover, hospital stay and duration of hospital stay in intensive care unit and in
the problem of hepatocytes being “fatty” overcomes the liver itself, high dependency unit, we noticed that patients with nonalcoholic fatty
since it is increasing the risk for chronic kidney disease, cardiovascular liver had significantly longer hospitalization, stay in intensive care unit
disease, some malignancy and death. Also, it duplicates the risk for as well as stay in high dependency unit.
T2DM, independent of the severity of liver injury [17,18]. Current According to the literature, the APACHE II score, CT Severity Index
treatments for nonalcoholic fatty liver disease include weight loss, and C-reactive protein are well known predictors of severity of acute
management of type 2 diabetes mellitus, dyslipidemia and arterial pancreatitis [6,7,19]. In this study our analyzed patients with nonalco-
hypertension, or, in general, they are focused on the factors that can holic fatty liver had statistically higher levels of C-reactive protein at
cause the disease. Shortly, the only possible treatment for nonalcoholic the admission and on third day as well, they also had higher values of
CT severity index and APACHE II score compared to the patients without
Table 2B fatty liver. These results show that there is correlation between
Duration of hospital stay with regarding the presence of fatty liver. presence of fatty liver and well known prognostic factors for acute
Non-FL FL p pancreatitis.
(n = 624) (n = 198) Obesity is known as prognostic factor for local and systemic compli-
Duration of hospitalization (days) 12.9 ± 8.2 15.4 ± 10.6 0.0006 cations, severity and death in acute pancreatitis and it is also factor that
Duration of hospital stay in high 3 ± 3.2 4.5 ± 3.6 b0.0001 is amplifying systemic inflammatory response in patients with acute
dependency unit (days) pancreatitis [11,20]. Having in mind that nonalcoholic fatty liver is asso-
Duration of hospital stay in ICU (days) 0.3 ± 1.9 1.0 ± 5.1 0.004 ciated with all the components of metabolic syndrome and that we have
FL — fatty liver; ICU — intensive care unit. recently found a connection between metabolic syndrome and severe

Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019
 I. Mikolasevic et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
form of acute pancreatitis, we were interested if the presence of fatty
liver can predict the severity of acute pancreatitis independently of
other metabolic syndrome components (arterial hypertension, obesity,
type 2 diabetes mellitus and dyslipidemia). There is no doubt that non-
alcoholic fatty liver disease is in fact part of metabolic syndrome. But,
what is interesting, we have found that nonalcoholic fatty liver disease
is independently related with the occurrence of moderately severe
and severe acute pancreatitis. In addition, it is know that the liver is
central organ and source of different biomarkers of inflammation and
endothelial dysfunction. Secretion of these biomarkers is increased in
presence of metabolic syndrome and insulin resistance. Nowadays,
there is more and more evidences suggesting that the production and
release of proinflammatory cytokines is increased in patients with non-
alcoholic fatty liver disease / non-alcoholic steatohepatitis. Therefore,
higher oxidative stress, abnormal lipoprotein metabolism and increased
release of inflammatory cytokines are considered to take part in
proatherogenic effect of nonalcoholic fatty liver disease [21–28]. On
the other side, it is known that Kuppfer cells in liver tissue have
increased capacity in fatty liver. Consequently, it is possible that, with
realizing the inflammatory mediators, they have a significant role in
the course of acute pancreatitis resulting in the exacerbation of systemic
inflammatory response and pulmonary injury [11,29]. In our study we
have found that nonalcoholic fatty liver was independent risk factor
for more severe form of acute pancreatitis, dispensable from obesity
and other metabolic syndrome components. Thereby, the presence of
nonalcoholic fatty liver at hospitalization should be considered in
acute pancreatitis severity scoring system and patients with previous
known nonalcoholic fatty liver at admission should get more attention.
Although it is the most common chronic liver disease today, not
enough attention is given to nonalcoholic fatty liver disease in everyday
clinical practice. Study made by Reddy S et al. [30] supports
abovementioned. They have found that diagnosis of nonalcoholic fatty
liver disease among hospitalized patients is much less common
compared to those noted in out-patient cohort studies. The gap in
prevalence of nonalcoholic fatty liver disease in outpatient studies,
compared with hospitalized ones, indicates that nonalcoholic fatty
liver disease is unrecognized in hospital patients and that impact of
nonalcoholic fatty liver disease on clinical outcomes and health care
resources utilization is not recognized and it is not well studied [30].
Considering that incidence of nonalcoholic fatty liver disease is increas-
ing and results of our study, as well as results of study by Xu C et al. [11],
we have to pay more attention to this liver disease, especially as prog-
nostic factor which could help us in prognosis of some diseases such
as acute pancreatitis. Also, it could help us in stratification of patients,
to recognize those under higher risk for severe acute pancreatitis at
the admission.
Previous studies that used CT and ultrasonography as well as some
other imaging methods (transient elastography with controlled attenu-
ation parameter [CAP], magnetic resonance imaging, etc.) have all
shown acceptable levels of sensitivity for detecting nonalcoholic fatty
liver disease. Although liver biopsy is “golden” standard for diagnosing
nonalcoholic fatty liver disease and other chronic liver diseases we
must not forget that it is invasive method [15,16]. In our study we
have used ultrasonography and CT scans for detection of nonalcoholic
fatty liver disease with excluding patients with excessive alcohol con-
sumption, those who were taking the medications that can lead to
liver steatosis and those with other chronic liver disease. One of the lim-
itations of our study is the absence of liver biopsy in diagnosis of nonal-
coholic fatty liver disease and histological comparison of liver biopsy
samples. Another limitation factor is a retrospective design of this
study. On the other hand, this study has several essential strengths. It
shows that nonalcoholic fatty liver detected at admission is related
with more severe course of acute pancreatitis and so far there is not a
lot of data about this connection in literature. In our analysis patients
with nonalcoholic fatty liver had much higher APACHE II and CT severity
index scores as well as C-reactive protein values, at admission and on
Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019
5
the third day of hospitalization, which are all well-known prognostic
factors for acute pancreatitis course. Therefore, further studies are
necessary in order to determine if presence of fatty liver at admission
can be prognostic factor for patients with acute pancreatitis and
excluded alcohol consumption, medications that can lead to liver
steatosis and other chronic liver disease. Detection of fatty liver with
some of the noninvasive imaging methods, for example with transient
elastography with controlled attenuation parameter, together with
other prognostic scoring systems, could be a valuable prognostic factor
for patients with acute pancreatitis in everyday clinical practice. More-
over, detection of nonalcoholic fatty liver could help us to recognize
those patients who are under higher risk to develop severe form of
acute pancreatitis. Since incidence of nonalcoholic fatty liver disease is
constantly increasing, in future, we can expect and higher incidence of
patients with severe acute pancreatitis too. These findings are important
not only for the gastroenterologists, but also for physicians of other sub-
specialties (nephrologists, cardiologists, endocrinologists, etc.), as well
as for general practitioners.
Conflict of interest statement
All authors have no conflict of interest.
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Please cite this article as: Mikolasevic I, et al, Nonalcoholic fatty liver and the severity of acute pancreatitis, Eur J Intern Med (2016),
http://dx.doi.org/10.1016/j.ejim.2016.10.019