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Original Article
1 2 3Nandhini. N.E , Ponnudhali. D , Evangeline Jones
INTRODUCTION:he most common cause of acute abdomen
in young adults in acute appendicitis.
Delay in diagnosis and surgery for this Tcondition may lead to various complications like
perforation, abdominal abscess, urinary retention,
small bowel obstruction and peritonitis causing an
increase in morbidity and even mortality of the
patients. Incidence of perforated appendicitis in 1
adults is about 13-37% . Every investigation that
can contribute towards a diagnosis of appendicitis 2is valuable to emergency surgeon .
Address for correspondence:
Dr.D.Ponnudhali, Associate Professor, Department of Biochemistry, Vinayaka Missions Kirupananda Variyar Medical College, Salem. Email id: [email protected] Ph. No: 9443171055.
1Final year Postgraduate Student, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College, VMRF(DU) Salem, TN. 2Associate Professor, Dept. of Biochemistry, Vinayaka Missions's Kirupananda Medical College,VMRF(DU) Salem, Tamilnadu. 3Professor and HOD, Vinayaka Missions's Kirupananda Medical College, Department of Biochemistry, Salem, VMRF(DU) Tamilnadu .
Bilirubin - A Predictor Of Appendiceal Perforation
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
http://dx.doi.org/10.31975/NJBMS.2018.8402
ABSTRACT
Introduction: Acute appendicitis is the most common abdominal emergency. Any delay in the diagnosis and treatment, could result in life threatening complications like perforated appendicitis. Though non-specific tests like WBC count, C reactive protein are routinely done, they are not of much diagnostic value. Recent studies have shown that increase in pre-operative serum bilirubin levels could predict the occurrence of perforated appendicitis.
Aims and objectives:
1) To assess the serum bilirubin (Total, Direct, Indirect) levels in acute and perforated appendicitis.
2) To look for any associated changes in liver enzymes.
3) To analyze the sensitivity and specificity of serum bilirubin and its utility as a diagnostic/ predictive marker of perforated appendicitis.
Materials and methods: A Retrospective study - Medical records of sixty patients who had underwent open appendicectomy during the last one year were scrutinized and all the relevant information noted . 30 patients who underwent surgery for simple appendicitis formed group 1. 30 patients who underwent surgery for perforated appendicitis formed group 2. Their pre-operative laboratory serum bilirubin values and other liver parameter values were collected and analyzed. All the above parameters were compared between two groups using independent student 't' test and ROC curve obtained for Bilirubin ,with SPSS 23 software.
Results: Total bilirubin levels were significantly increased in patients with perforated appendicitis (p=.000) compared to patients with simple appendicitis. Similar increase in serum direct and indirect bilirubin levels (p=.000) were noticed in perforated appendicitis patients. Total Bilirubin (cut-off: 0.80mg/dl) has sensitivity 80% and specificity 75%.
Conclusion: Assessing serum bilirubin levels pre-operatively could have significant value in predicting appendicular perforation. Serum bilirubin being an inexpensive and routinely done test in all labs, with its high sensitivity and specificity, better qualifies as a diagnostic marker for perforated appendicitis even in a rural care centre.
Key words: Serum total bilirubin, acute appendicitis, Alvarado's score, perforated appendicitis
179
surgery for simple appendicitis. Group 2: 30
patients who underwent surgery for perforated
appendicitis.
We collected LFT reports from records of 60
patients who were admitted with acute abdomen
out of which 30 patients were found to have
perforated appendicitis and 30 patients were found
to have simple appendicitis without any perforation
or gangrenous changes during surgery. Patients
were excluded from the study if they did not have
LFTs performed on admission, if they had a history
of confirmed hepatitis or liver disease or if they
were known to have persistently deranged LFTs.
Patients undergoing interval appendectomies,
appendectomies for other indications and patient
with negative appendectomies confirmed on
histological report were excluded from the study.
Other exclusion criteria were patient with risk
factors for hepatic disease such as alcoholism, a
history of viral hepatitis, Gilbert's disease, Dubin-
Johnson syndrome, benign recurrent intra-hepatic
cholestasis, and other documented biliary,
hemolytic or liver diseases associated with
hyperbilirubinemia.
STATISTICAL ANALYSIS:
Statistical analysis was done using the software
SPSS version 23 and data expressed as mean ± SD.
Differences in mean between the 2 groups were
analyzed using independent t test. Comparisons
were made between two groups of patients: those
with simple acute appendicitis and those with
appendiceal perforation. Mean levels of bilirubin,
and other LFTs were compared between groups.
The sensitivities, specificities, positive predictive
values and negative predictive values of serum
Various markers such as WBC count are identified
for diagnosing acute appendicitis. WBC count is
not specific for acute appendicitis and CRP may be
only significantly raised once perforation takes 3place . So these markers are used along with
various diagnostic scores such as Alvarado score,
Modified Alvarado score, Pediatric Appendicitis
score(PAS) for diagnosing acute appendicitis. But
none of them evaluates the risk of perforation in 4acute appendicitis . Though various imaging
modalities like computed tomography (CT) scan,
magnetic resonance imaging (MRI) and
ultrasonography may help in early diagnosis of
perforated appendix, they may not be readily
available in many health centers and also time 5, 6,7,8consuming .
In such condition clinical and laboratory
investigations may be the only, cheaper and readily
available options for diagnosis. Recent studies
have shown that elevated serum bilirubin is a useful
predictor of appendiceal perforation. The present
study was conducted to assess relationship between
appendicular perforation and serum bilirubin
levels, which could aid in preoperative diagnosis of
perforated appendicitis.
MATERIALS AND METHODS :
Study Design: Our study had been conducted in
Government Hospital, Bhavani and Vinayaka
Missions's Kirupananda Variyar Medical College
Hospital, Salem. It was a retrospective study
conducted in 60 patients admitted for
appendicectomy surgery during the period of
August 2016- July 2017. They were divided into 2
groups. Group 1:30 patients who underwent
Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
Table 2 : Mean and standard deviation for other
liver parameters in patients with acute
appendicitis without perforation (group 1) and
acute appendicitis with perforation (group 2)
The ROC curve analysis for serum total bilirubin
levels was done, with the Area Under the Curve
(AUC) being 0.825. The sensitivities, specificities,
PPVs and NPVs for different cut-off levels of
serum bilirubin were tabulated. At the optimum
cut-off level -0.8 mg/dl of serum total bilirubin,
sensitivity and specificity were 80% and 75%
respectively. Figure 1 depicts the ROC Curve of
total bilirubin.
Table 3 depicts the cut off values of serum total
bilirubin with their sensitivity, specificity, positive
predictive value (PPV) and negative predictive
value (NPV)
Table 3: Sensitivity and Specificity of serum
total bilirubin
180
bilirubin for both simple acute appendicitis and
perforated appendicitis was calculated. The
receiver operating characteristic (ROC) curve for
bilirubin was obtained
RESULTS :
The Bilirubin levels (total, direct, indirect) and
other liver parameters were analyzed in 30 patients
with simple appendicitis and 30 patients with
perforated appendicitis. The mean and standard
deviations of bilirubin (total, direct, indirect)
levels are depicted in Table 1.
There is a significant increase in the total bilirubin
levels (1.0 ± 0.28 mg/dl) in group 2 patients,
compared to the patients (0.61 ± 0.18 mg/dl) in
group 1 (p=0.001). There is a significant increase in
the serum direct and indirect bilirubin levels (0.30
± 0.13 mg/dl, 0.73 ± 0.19mg/dl,p=0.001) in group 2
patients, compared to the patients in group 1 (0.16 ±
0.08 mg/dl ,0.44 ± 0.16mg/dl,p=0.000).
Table 1: Mean and standard deviation for
Bilirubin in patients with acute appendicitis
without perforation (group 1) and acute
appendicitis with perforation (group 2).
*P value <0.05 is considered significant.
We compared the other liver function tests in both
the groups. There was not any significant
difference and they were with in normal limits in
both the groups. Table 2 depicts the other liver
functions tests in group 1 and group 2.
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis
181
Lipopolysaccharides associated with E. coli can
affect hepatocyte uptake and bile acid secretion15.
The patients with perforated appendicitis, show a
proinflammatory cytokine and nitric oxide –
triggered cholestasis by impairing hepatocellular 16
and bile duct function.
In our study we have found that patients with
perforated appendicitis had hyperbilirubinemia
with no changes in enzyme levels.There are few 17,18
other studies, having reported similar findings.
A retrospective analysis conducted by Atahan et al.,
found that symptom duration (p=0.002), total
bilirubin (p=0.000) and elevated leucocyte counts
(p=0.011) were significant independent variables
for identifying acute perforated appendicitis 19
against the suppurative ones .
A retrospective cohort study performed by Kaser
etal., in two centers compared the efficacies of
hyperbilirubinemia, CRP, leucocyte count and age 20as markers of perforated appendicitis . They came
to the conclusion that hyperbilirubinemia is a
statistically significant marker of perforated
appendicitis.
We have also assessed the AUC in ROC curve
analysis to determine the appropriate levels of
serum bilirubin at which it identifies perforated
appendicitis. As the AUC for total bilirubin is >0.8 ,
it can be considered as a marker to predict the
occurence of perforation among patients with acute
appendicitis. At the cut-off level of 0.8mg/dl, serum
total Bilirubin has a sensitivity of 80% and
specificity of 75%. Its utility as a predictive
biomarker has to be confirmed by further
prospective studies conducted in larger
populations.
Fig 1. ROC Curve for total bilirubin
DISCUSSION:
Acute appendicitis appears to be the most common
cause for “Acute Surgical abdomen”with
appendicular perforation being the most significant 9 ,10 ,11 ,12complication . The major organisms
commonly seen in normal appendix as well as acute
appendicitis are Eschericia coli, Bacteroids fragilis 13and various facultative anaerobes .
In acute appendicitis and perforated appendicitis
there is a compromised wall integrity resulting in 14following changes .
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis
Acute appendicitis/ appendicular perforation
Translocation of bacterial endotoxins/cytokines(from appendicular lumen to portal system thereby liver)
Alters the physiology of biliary excretion.
Induces intrahepatic cholestasis
Hyperbilirubinemia
182
CONCLUSION:
It is evident that Serum Bilirubin has a remarkable
role in identifying patients presenting with
perforated appendicitis. Serum Bilirubin with all its
beneficial attributes, is quite cheap, feasible and an
easily available laboratory test even in peripheral
health care centers. Hence it could be a useful
biomarker either alone or in combination with other
radiological methods, in the preoperative diagnosis
of perforated appendicitis.
REFERENCES:
1. Stumvoll M, Goldstein BJ, van Haften TW.
Type 2 diabetes: Principles of pathogenesis and
therapy. Lancet 2005; 365: 1333 – 46.
2. A. Q. Khan, Anirudha Patil, Praful Pawar. Role
of Hyperbilirubinemia as a Diagnostic
Predictor of Appendicular Perforation.
International Journal of Science and Research.
2014; 3(12):358-400.
3. Ghimire P, Thapa , Yogi N, Ghimire P. Role of
serum bilirubin as a marker of acute gangrenous
appendicitis. Nepal Journal of Medical
Sciences.2013;27(4):232-236
4. Salvatore Giordano, Markus Paakkonen
Paulina Salminen, Juha M Gronroos.
International Journal Of Surgery. 2012 ;23(7):
796-800.
5. N.D'Souza, D.Karim, R.Sunthareswaran.
Bilirubin : A new diagnostic marker of
appendicitis. International journal of surgery.
2013; 11(2):1114-1117.
6. Andrew Emmanuel, Peter Murchan, Ian
Wi l son , Pau l Ba l fe . The va lue o f
hyperbilirubinaemia in the diagnosis of acute
appendicitis. Ann R CollSurgEngl 2011; 93:
213–217.
7. Amalesh T, Shankar M, Shankar R: CRP in
acute ap- pendicitis – is it a necessary
investigation? International journal of surgery
2004;2:88-9.
8. Khan MN, Davie E, Irshad K: The role of white
cell count and C-reactive protein in the
diagnosis of acute appendicitis. J Ayub Med
Coll Abbottabad 2004;16:17- 9.
9. deDombal FT, Leaper DJ, Staniland JR, et al:
Com- puter-aided diagnosis of acute abdominal
pain. BMJ 1972;2:9-13.
10. O' Connel PR. “The Vermiform Appendix”. In:
Williams NS, BulstrodeCJK, O'Connell PR
(Ed.). Bailey and Love's - Short practice of
surgery.2008; 25:1204-8.
11. Smink DS, Soybel DI. “Appendix and
Appendectomy”. In: Zinner MJ, Stanely W
( e d s ) M a i n g o t ‟ s a b d o m i n a l
operations.2007;11:589-612.
12. Balthazar EJ, Megibow AJ, Siegel SE.
Appendicitis: prospective evaluation with high
resolution CT. Radiology 1991;180:21-4.
13. Rao PM, Boland GW.Imaging of acute right
lower abdominal quadrant pain. ClinRadiol
1998;53:639-49.
14. Bixby SD, Lucey BC, Soto JA: Perforated
versus nonperforated acute appendicitis:
accuracy of multide- tector CT detection.
Radiology 2006;6:780-786.
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis
183
14. Mohammad Vaziri, Abdolreza Pazouki,
Zeinab Tamannaie, Farshid Maghsoudloo,
Mohadeseh Pishgahroudsar i , Shahla
Chaichian. Comparison of pre-operative
bilirubin level in simple appendicitis and
perforated appendicitis. Medical Journal of the
Islamic Republic of Iran.2013;27(3):109-112.
15. Green RM, Beier D, Gollan JL: Regulation of
hepatocyte bile salt transporters by endotoxin
and inflammatory cytokines in rodents.
Gastroenterology 1996; 111: 193 – 198.
16. Whiting JF, Green RM. TNF-alfa decrease
hepatocyte bile salt uptake and mediated
e n d o t o x i n i n d u c e d c h o l e s t a s i s .
Hepatology.1995;22:1273-78.
17. Estrada JJ, Petrosyan M, Barnhart J:
Hyperbilirubinemia in appendicitis: a new
predictor of perforation. J GastrointestSurg
2007;24(11):714 – 718.
18. Khan S: Elevated serum bilirubin in acute
appendicitis: a new diagnostic tool. Kathmandu
Univ Med J.2008; 6: 161 – 165.
19. Atahan K, Ureyen O, Aslan E.Preoperative
diagnostic role of hyperbilirubinaemia as a
marker of appendix perforation. The Journal of
International Medical Research. 2011;39:609-
618.
20. Käser SA, Fankhauser G, Willi N. Creactive
protein is superior to bilirubin for anticipation
of perforation in acute appendicitis. Scand J
Gastroenterology 2010;45: 885-892.
National Journal of Basic Medical Sciences | Volume 8 | Issue 4 | 2018
Nandhini.N.E., et.al : Serum Bilirubin in Acute Appendicitis
Received on: 18.04.2018 Revised on: 15.05.2018 Accepted on: 18.05.2018