Acute pancreatitis caused by hypertriglyceridemia

DOI: https://doi.org/10.21203/rs.3.rs-2170082/v1

Abstract

Background and Aim: Although hypertriglyceridemia is a recognized cause of acute pancreatitis, the clinical course remains unknown. Furthermore, lipemic serum can interfere with precise pancreatic enzyme measurements, making it difficult to diagnose acute pancreatitis. The goal was to examine the clinical performance of hypertriglyceridemia acute pancreatitis and the diagnostic utility of pancreatic enzyme serum measurements.

Methods: The demographic, clinical, analytical, and radiological data of 30 patients with hypertriglyceridemia acute pancreatitis were reviewed retrospectively. Acute pancreatitis was diagnosed based on clinical, radiological, and/or laparotomical evidence. When all other reasons were ruled out, serum triglyceride levels of more than 500 mg/dl were deemed the cause of acute pancreatitis.

Results: 40% of the patients were between the ages of 50 and 59. In 22 patients (73.3%), the most frequent symptoms were vomiting, 8 diarrhea or constipation (26.6%), 8 nausea (26.6%), 5 loss of appetite (16.6%), 5 fever (16.6%), and 4 chills (13.3%). The patients' mean white blood cell count was 13020.54, their mean amylase was 1184.50, their mean inflammatory marker (CRP) was 91.43, and their mean creatinine was 1.08. By investigating the link between BISAP and age, gender, and behaviors Due to the limited sample size and wide dispersion, there was no statistical association despite the hints offered by the research samples.

Conclusion: Elevated blood triglyceride levels are linked to a more severe course of pancreatitis. It is important to emphasize the increased incidence of local problems in HTG patients, which increases proportionately and considerably with HTG severity grade.

Introduction

Acute pancreatitis (AP) is an acute inflammatory condition that causes localized pancreatic inflammation and, as a result, a reaction of systemic inflammation. The pancreas, peripancreatic tissues, and even distant organs are all affected by the imaging of AP, which appears as pancreatic edema or necrosis [1, 2]. Gallstones are the most frequent cause of AP in western nations, followed by alcohol addiction and hypertriglyceridemia [3, 4]. Recent investigations have shown that the incidence of hypertriglyceridemia acute pancreatitis (HTG-AP) is significantly greater and has been rising annually in China [510].

Previous research focused more on the clinical characteristics of AP with various etiologies than the specific distinctions between HTG-AP and BAP. The clinical characteristics, complications, and outcomes of pancreatitis brought on by hypertriglyceridemia—one of the most common causes of acute pancreatitis in Syria—are evaluated in this retrospective analysis from July 2021 to October 2022.

Methods

Two hundred and fifty patients’ files were collected and eventually 30 patients (13.5%) were enrolled. Patients who had deficiency in their data, younger than 18 years old, Traumatic acute pancreatitis patients, patients who had who had laboratory value of triglyceride less than 500mg/dl and patients with radiographic or laboratory evidence of other causes were excluded. However, all patients were admitted within 72 hours after symptom onset.

For statistical analyses, we utilized the SPSS 18.0 statistical software program (IBM Analytics, Armonk, NY). Data was reported as median plus interquartile range (IQR) for continuous variables and absolute numbers and percentages for categorical variables, as shown in the tables below. For categorical variables, the x2 test was employed, and for continuous variables, the Student-test or Mann-Whitney test was utilized. A P value of 0.05 was judged statistically significant (2-tailed).

Results

Patients aged 50 to 59 years old accounted for 40% of all patients, followed by patients aged 40 to 49 years old (20%), and patients aged 20 to 29 years old (16.7%). According to marital status, 93.3% of patients were married. By dividing the patients according to the medical history, we had four cases that had joint hyperlipidemia, recurrent pancreatitis, arterial hypertension, and type 2 diabetes (13.3%), while we had two unassociated cases with a history of (6.7%). With regard to surgical history, we had 5 cases with a no previous surgery rate of 16.7%, while 4 cases had cholecystectomy with a rate of (13.3%), and two cases with appendectomy in addition to cardiac catheterization (6.7%). 15 patients (50%) were smokers. The most common symptoms in 22 patients (73.3%) were vomiting, 8 diarrhea or constipation (26.6%), 8 nausea (26.6%), 5 lack of appetite (16.6%), 5 fever (16.6%) and 4 chills (13.3%) [Table 1]

 
Table 1

Patients’ symptoms.

73.3

22

vomiting

26.6

8

Diarrhea/ constipation

26.6

8

nausea

16.6

5

lack of appetite

16.6

5

fever

13.3

4

chills

As for the vital signs, the average heart rate of the patients was 85.72 beats per minute with a deviation of 13.087, while the mean temperature of the patients was 37.54 Celsius with a deviation of 0.387, and the average number of breaths was 20.13 times per minute with a deviation of 4.167 [Table 2]

 
Table 2

Patients’ vital signs.

breaths

temperature

Heart rate

 

20.13

37.54

85.72

SMA

4.167

.387

13.087

standard deviation

14

37

60

Less value

32

38

120

Highest value

The mean white blood cell count in the patients was 13020.54, deviation 5001,944, mean hemoglobin 13.26, deviation 2.189, mean platelet count 235.62, deviation 89.172, mean sed rate 45.39, deviation 26.631, mean PT 77.25, deviation 43.337, mean INR 14.622, deviation 4.48 [Table 3].

 
Table 3

Patients’ hematologic profile.

INR

PT

ESR

Platelets

HB

WBCs

 

4.48

77.25

45.39

235.62

13.26

13020.54

SMA

14.622

43.337

26.631

89.172

2.189

5001.944

standard deviation

1

16

17

135

9

16

Less value

67

209

101

465

18

27500

Highest value

The average total bilirubin was 0.98, with a deviation of 1.115, where the mean direct bilirubin was 0.60, with a deviation of 0.974, while the mean of the liver enzymes were as follows: 54.90 for AST, with a deviation of 103.421, and 57.19 for ALT, with a deviation of 130,851, and 122.04 for ALP, with a deviation of 81.347, and 61. GGT, with a deviation of 71.592 [Table 4] 

 
Table 4

Liver function test.

GGT

ALP

ALT

AST

Bilirubin direct

Bilirubin total

 

61.38

122.04

57.19

54.90

.60

.98

SMA

71.592

81.347

130.851

103.421

.974

1.115

Standard deviation

7

40

9

11

0

0

Less value

380

325

722

532

4

4

Highest value

As for the mean amylase, it was 1184.50 with a deviation of 1122.668, and the mean glutamate was 245.23 with a deviation of 114.206, and the mean inflammatory marker (CRP) was 91.43, with a deviation of 82.558, and the mean creatinine was 1.08, with a deviation of 1.129, and the mean of sodium was 137.74, with a deviation of 2.917, and the mean of potassium was 4.09024, with a deviation of 2.2. with deviation of 3.435. [Table 5].

 
Table 5

Patients’ laboratory values.

Ca

K

NA

Cr

CRP

GLU

Amylase

 

2.90

4.02

137.74

1.08

91.43

245.23

1184.50

SMA

3.435

.724

2.917

1.129

82.558

114.206

1122.668

Standard deviation

1

3

131

1

2

56

9

Less value

10

5

143

7

300

468

5450

Highest value

The mean urea nitrogen in the blood was 29.05, with a deviation of 17.645, and the mean of urea nitrogen was 34.79, with a deviation of 29.391 [Table 6]

 
Table 6

Patients’ Urea and BUN

urea

BUN

 

34.79

29.05

SMA

29.391

17.645

Standard deviation

10

5

Less value

170

85

Highest value

Moving on to the percentage of triglycerides, 56.6% of patients had a mild to moderate elevation (150-999 mg/dl) (2-10 mmol/L), and 43.3% had a severe to very severe elevation (>1000 mg/dl) (>10 mmol/L). According to the BISAP indicator, the mean was 1.40 with a deviation of 0.814. According to the BISAP warning indicator, the least likely to die from 0-2 points was 93.3%, and the group most likely to die from 3-5 points was 6.7% [Table 7] whereby 40% of the patients were classified as each of (1) and (2), and 13.3% were classified as (0).

 
Table 7

BISAP score.

ratio

number

 

40

12

1

40

12

2

13.3

4

0

6.7

2

3

100

30

 

By studying the relationship between BISAP and age, gender, and habits  There was no statistical relationship despite the indications provided by the study samples due to the small sample size in addition to the large distribution, where the P-value of the relationship between BISAP index and sex equals 0.676 [Table 8 ], and between BISEP index and age group equals 0.752 [Table 9], and between BISEP index and pathological antecedents It equals 0.550, the BISEP index and family history equals 0.097, the BISEP index and habits equals 0.570 [Table 10], the BISEP index and symptoms equals 0.643, and the BISEP index and triglycerides equals 0.569 [Table 11], all of which are greater than 0.005 and thus have no statistical relationship. 

 
Table 8

Relationship between BISAP and gender.

number

BISAP Score

 

3

2

1

0

18

2

7

7

2

number

female

sex

60.0%

6.7%

23.3%

23.3%

6.7%

ratio

12

0

5

5

2

number

male

40.0%

0.0%

16.7%

16.7%

6.7%

ratio

30

2

12

12

4

number

The Total

100.0%

6.7%

40.0%

40.0%

13.3%

ratio

p-value = 0.676



 
Table 9

Relationship between BISAP and age.

The Total

BISAP Score

 

3

2

1

0

3

1

1

1

0

number

≥ 60

Age

10.0%

3.3%

3.3%

3.3%

0.0%

ratio

5

0

2

2

1

number

20–29

16.7%

0.0%

6.7%

6.7%

3.3%

ratio

4

0

2

1

1

number

30–39

13.3%

0.0%

6.7%

3.3%

3.3%

ratio

6

1

1

3

1

number

40–49

20.0%

3.3%

3.3%

10.0%

3.3%

ratio

12

0

6

5

1

number

50–59

40.0%

0.0%

20.0%

16.7%

3.3%

ratio

30

2

12

12

4

number

The Total

100.0%

6.7%

40.0%

40.0%

13.3%

ratio

p-value = 0.752


 
Table 10

Relationship between BISAP and habits.

The Total

BISAP Score

 

3

2

1

0

15

1

8

5

1

number

smoke

Habits

50.0%

3.3%

26.7%

16.7%

3.3%

ratio

2

0

0

1

1

number

Smoke&alcohol

6.7%

0.0%

0.0%

3.3%

3.3%

ratio

13

1

4

6

2

number

none

43.3%

3.3%

13.3%

20.0%

6.7%

ratio

30

2

12

12

4

number

The Total

100.0%

6.7%

40.0%

40.0%

13.3%

ratio

P-value = 0.570


 
Table 11

Relationship between BISAP and triglycerides.

The Total

BISAP Score

 

3

2

1

0

16

0

6

8

2

number

mild to moderate (150–999 mg/dl) (2–10 mmol/L)

Triglycerides

53.3%

0.0%

20.0%

26.7%

6.7%

ratio

1

0

1

0

0

number

Nothing

3.3%

0.0%

3.3%

0.0%

0.0%

ratio

13

2

5

4

2

number

severe to very severe (> 1000 mg/dl) (> 10 mmol/L)

43.3%

6.7%

16.7%

13.3%

6.7%

ratio

30

2

12

12

4

number

The Total

100.0%

6.7%

40.0%

40.0%

13.3%

ratio

p-value = 0.569

Discussion

Data recently revealed that pancreatitis caused by HTG-AP has become the second common cause of acute pancreatitis AP in China, with a reported incidence rate of 12.3% in 2003 [9], 18.1% in 2007 [10], and 25.6% in 2013 [11], much higher than that in Western countries. Pancreatitis caused by high blood triglycerides is rare in Western countries (1.5-5%), but it is well documented [7, 8]. Due to the rarity of this condition, our study's sample was limited to 30 individuals with acute pancreatitis brought on by high lipid levels.

In our study, there were 40% fewer male patients with pancreatitis brought on by high triglycerides than female patients, who made up 60% of the entire sample. This contrasts with a study done in China in 2018 where the ratio of male to female patients was higher. The age range with the highest patient prevalence was 30 to 49 years old, which is relatively young when compared to other age ranges. These findings corroborated findings from a 2020 study conducted in Hungary that found that pancreatitis brought on by high triglycerides was associated with younger age and with masculine sex [12], as well as findings from Zheng et al. [13] and Zhu et al. [14] that high triglycerides in the blood are significantly related to younger age and male sex. This is not surprising given that alcohol-related HTG affects males more than other types of HTG and contributes to its development at a younger age [4, 15, 16]. On the other hand, biliary causes are more common in women and the elderly [3, 15]. The disparity between our study and other global studies in terms of gender is probably the result of the limited sample size and the rise in the societal ratio of females to males.

According to Scherer et al. [4], who advise suspicion of HTG-AP in cases of heavy alcohol consumption, poorly controlled diabetes, and metabolic syndrome, including obesity, type 2 diabetes was the most prevalent companion disease among patients, with 16 patients having it. Our findings were also consistent with a study conducted in 2020 that linked high triglyceride levels in the blood to diabetes and obesity in patients [12].

According to Fortson et al. [7], DM diabetes mellitus and liver lubrication were discovered to be significant risk factors for HLAP in a 1995 study in which the history of HLAP patients was investigated retrospectively. In a 2015 study [11], the incidence of DM in HLAP patients was 84.62% (as opposed to individuals with non-HHLAP pancreatitis, 9.37%).

It is now generally accepted that serum TG levels > 1000 mg/dL can hasten the development of acute pancreatitis AP, even though some studies have shown higher values [17, 18]. The majority of the patients in our study had lipid content between 150 and 999 mg/dL, and in 53% of patients, 43% of patients had lipid levels above 1000 mg/dL. In particular, for mild to moderate TG increases in the serum, the detection of HTG elevation as the cause of acute pancreatitis AP is frequently postponed or might even be ignored. According to data from one study, over 1,000 mg/dL seems arbitrary because TG levels below 500 mg/dl should raise serious concerns, especially when there are no other obvious reasons for AP [19]. According to other studies, it is uncertain if HTG is a temporary phenomenon, a cause of or a contributing factor to AP [20], because modest to moderate increases in TG can emerge in the early stages of AP for any etiology in up to 47% of patients [21]. Two patients in our study drank alcohol in addition to smoking, although a 2014 study found that HTG's involvement in triggering AP among alcoholics is similarly debatable [22].

In contrast to a Chinese study published in 2015 that found that high levels of HTG lipids were caused by acute pancreatitis AP, our study found no association between high lipid levels and poor prognosis in BISAP score. Data also suggested that high levels of HTG below 500 mg/dl should not be taken into account as a contributing factor in the etiology of AP [19]. The investigation conducted by Fortson et al. [7] and these findings are in agreement.

The average amylase in our study was 1184.50 units/liter, which is significantly higher than the normal value. This is somewhat in contrast to the findings of the Zhang et al. study [19], which found that average amylase levels were twice as high as normal. Only 21.43% of patients in the HTGP group had amylase levels that rose above three times the upper limit of the normal range, which is much lower than the value reached in pancreatitis brought on by bile. This could be because our study only included 30 patients, whereas Zhang's study had 244, which resulted in a smaller sample size. This discrepancy between our study's findings and those of the Chinese study may be attributable to the possibility raised by Cameron et al. [23] that hyperlipidemia may interfere with the precise measurement of amylase in the laboratory or that an amylase inhibitor may be present in the serum of these patients, reducing interference with TG triglycerides through the sequential dilution of the amylase sample in the serum [24].

All of the patients in our study had abdominal pain, which varied in severity between individuals. We also discovered numerous accompanying symptoms, including vomiting and fever. When these findings were compared to those of other clinical studies evaluating the impact of TG levels on AP intensity, they produced contradictory findings, with Zhang et al. [19], S. Balachandra et al. [25], and Fortson MR et al. [7] finding no difference in severity through TG. While some studies have found that patients with high triglyceride levels have poorer clinical outcomes, a previous study found that the level of TG in AP patients is independently and proportionately associated with persistent organ failure regardless of etiology [26], and in another study, AP patients with HTG (> 500 mg/dL) had higher APACHE II scores within 24 hours, more systemic complications, and higher mortality [27].

Conclusion

Triglyceride levels in the blood are associated with a more severe course of pancreatitis. It is critical to stress that the occurrence of local difficulties in HTG patients increases proportionately and significantly with HTG severity grade.

Declarations

Acknowledgments:

We are thankful to the management of the Syrian Private University and for their support in the field of medical training and research. We are thankful to everyone who participated in this study.

Funding:

This research received no specific grant from SPU or any other funding agency in the public, commercial or non-profit sectors.

Availability of data and materials:

All data related to this paper’s conclusion are available and stored by the authors. All data are available from the corresponding author on a reasonable request.

Ethics approval and consent to participate:

This study was approved by the Institutional Review Board (IRB) at the Syrian Private University (SPU). All Participants confirmed their written consent by signing the consent form. Participation in the study was voluntary and participants were assured that anyone who was not inclined to participate or decided to withdraw after giving consent would not be victimized. All information collected from this study was kept strictly confidential.

Consent for Publication:

Not applicable.

Competing interests:

The authors declare that they have no competing interests.

Authors’ contributions:

RN was responsible for study design, literature search, and write-up; RN was responsible for data analysis; RN participated in literature search and write-up; AA participated in the study design and reviewed the final draft. All authors read and approved the final draft.

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