Serum bilirubin as a predictor of complications of acute appendicitis in adults

K P C Muhammed Irfan; C Rajeev; A Mohamad Safwan; Shafy Ali Khan; KN Vijayan; Liju Varghese

doi:10.4103/ksj.ksj_39_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 28 | Issue : 2 | Page : 182-185

Serum bilirubin as a predictor of complications of acute appendicitis in adults

K P C Muhammed Irfan¹, C Rajeev², A Mohamad Safwan³, Shafy Ali Khan³, KN Vijayan³, Liju Varghese⁴
¹ Department of General Surgery, Government Medical College Hospital Manjeri, Vellarangal, Manjeri, Kerala, India
² Department of General Surgery, General Hospital Thalassery, Palissery, Thalassery, Kerala, India
³ Department of General Surgery, KIMSHEALTH Hospital, Trivandrum, Kerala, India
⁴ Department of General Surgery, Kaduvayil Thangal Charitable Trust Hospital, Chathampara, Thottakkadu, Kallambalam, Thiruvananthapuram, Kerala, India

Date of Submission	17-Nov-2022
Date of Decision	22-Nov-2022
Date of Acceptance	02-Dec-2022
Date of Web Publication	30-Jan-2023

Correspondence Address:
Dr. K P C Muhammed Irfan
Department of General Surgery, KIMSHEALTH Hospital, Thiruvananthapuram - 695 029, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ksj.ksj_39_22

Abstract

Introduction: Acute appendicitis is a very common cause of acute abdomen and the diagnosis is essentially clinical. A decision to operate based on clinical suspicion alone can result in removal of a normal appendix; whereas, if left untreated, appendicitis can result in necrosis and perforation. Therefore, improving the diagnostic accuracy of appendicitis is a need of the hour. This study was conducted to evaluate hyperbilirubinaemia in acute appendicitis to find out its predictive value in complications like perforation. Materials and Methods: This prospective study for diagnostic test evaluation was conducted amongst the inpatients in the Department of General Surgery, KIMSHEALTH Trivandrum, during the period from August 2019 to August 2020. A total number of 100 patients who were admitted with the clinical diagnosis of acute appendicitis were studied, and serum bilirubin and liver function tests were carried out in all of them. Results: Total bilirubin levels when compared with histopathological diagnosis by unpaired samples t-test, the t-value = 0.763, P = 0.447 > 0.05 which shows no statistically significant difference between total bilirubin levels in uncomplicated and complicated acute appendicitis based on histopathological diagnosis. Sensitivity is 81.8%; specificity is 29.2%; positive predictive value (PPV) is 12.5%; negative predictive value (NPV) is 92.9%. Conclusion: Elevated total serum bilirubin levels have a fairly high sensitivity and NPV in predicting complications of acute appendicitis, but the specificity and PPV are quite low, and hence, hyperbilirubinaemia could be used as an aid in diagnosing complicated acute appendicitis along with the clinical findings and ultrasonography findings, but it is not reliable as a standalone diagnostic test. If the total serum bilirubin levels are low, an alternate diagnosis could be suspected, and the chances of complicated appendicitis are quite low, but elevated serum bilirubin values alone cannot confirm the presence of complications. Therefore, our study could not find any correlation between the absolute levels of elevation of total bilirubin values and the presence or absence of complications in acute appendicitis.

Keywords: Acute appendicitis, liver function test, serum bilirubin

How to cite this article:
Muhammed Irfan K P, Rajeev C, Safwan A M, Khan SA, Vijayan K N, Varghese L. Serum bilirubin as a predictor of complications of acute appendicitis in adults. Kerala Surg J 2022;28:182-5

How to cite this URL:
Muhammed Irfan K P, Rajeev C, Safwan A M, Khan SA, Vijayan K N, Varghese L. Serum bilirubin as a predictor of complications of acute appendicitis in adults. Kerala Surg J [serial online] 2022 [cited 2023 Mar 25];28:182-5. Available from: http://www.keralasurgj.com/text.asp?2022/28/2/182/368596

Introduction

Acute appendicitis is the most common surgical emergency in young adults, and amongst the common emergency surgical procedures, appendectomy is the most frequent one.^[1] The diagnosis of acute appendicitis is usually clinical, aided by various laboratory investigations such as C-reactive protein, white blood cell count, ultrasonography (USG) and computed tomography (CT) scan.

The definitive management is surgical, and early surgical intervention can prevent complications like perforation. The risk of perforation increases up to 78.8% by the 8^th day of hospital admission as compared to 28.8% on day 1.^[2] On the other hand, since there are a number of medical causes of right iliac fossa pain, it is important to diagnose acute appendicitis as accurately as possible to avoid unnecessary surgical intervention. Various scoring systems combining the clinical features and laboratory findings such as the Alvarado score,^[3] the AIR score and RIPASA,^[3],[4] have been in clinical use. However, none of these laboratory markers are specific for acute appendicitis, and therefore, any new test or marker that can increase the specificity of diagnosis is very valuable.

In recent years, an association between elevated serum bilirubin and acute appendicitis has been noted. The proposed mechanism is the progressive invasion of bacteria from the inflamed appendix into the portal venous system via the superior mesenteric vein and to the liver. This interferes with the excretion of bilirubin into the biliary canaliculi, aided by the release of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-6.^[5],[6] Considering these facts, this study was conducted to assess the diagnostic value of serum bilirubin as a marker for acute appendicitis and as a predictive tool for the risk of complications of acute appendicitis like perforation.

Materials and Methods

The aim of this work was to study the predictive potential of alteration in serum bilirubin level in the diagnosis of complications of acute appendicitis. We evaluated total serum bilirubin in predicting complications of acute appendicitis in adults. It was a prospective, observational, comparative study from August 2019 to August 2020 on all the patients above 12 years admitted to the Emergency and General Surgery Departments with a clinical diagnosis of acute appendicitis and only those patients whose histopathological reports were suggestive of acute appendicitis and/or its complications were included in the study. Patients with cholelithiasis, hepatobiliary cancer, congenital or acquired biliary disease, hepatitis B surface antigen positive, past history of jaundice or hepatic dysfunction, history of chronic alcohol consumption more than 40 g/day in men and 20 g/day in women for a duration of 10 or more years and patients who were not operated were excluded from the study.

Sample size estimation was done from the reference study, expecting the number of study subjects with hyperbilirubinaemia in acute appendicitis to be 87%,^[7] to determine this with 95% confidence interval and an allowable error of 10% sample size of 50 patients will be recruited to the study. This was calculated by the following equation

Required sample size (n),

Accordingly, the minimum sample size required for this study was 50.

Thorough history taking and clinical examination were done for the patients and the findings were recorded. Blood sample was collected before surgery for complete blood count, liver function test, infectious virology and urine analysis. Ultrasound abdomen and pelvis and CT abdomen if indicated were also done. Based on the clinical diagnosis and investigations, the patients diagnosed to have acute appendicitis were taken up for surgery. The appendectomy specimens were sent for histopathological evaluation and the reports were considered the reference against which the diagnosis based on bilirubin values was compared.

Data were tabulated using MS Excel spreadsheet and analysed with IBM SPSS statistics software 23.0 version (IBM, Delhi). Descriptive statistics frequency analysis and percentage analysis were used for categorical variables and the mean and standard deviation were used for continuous variables. To find the significant difference between the bivariate samples in independent groups, the unpaired t-test was used. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were used to assess the efficacy of total bilirubin in diagnosing acute appendicitis. P < 0.05 was considered statistically significant. The percentage of histopathologically diagnosed acute appendicitis cases with increased serum bilirubin levels was calculated.

Results

In our study, we found that 22% of study subjects were in 18–20 years group (22), 44% in 21–30 years (44), 25% in 31–40 years (25) and 9% in 41–50 years (9). The gender distribution showed 36% of females (36) and 64% of males (64). USG abdomen findings showed that 81% (81) of the study subjects had uncomplicated acute appendicitis and 19% (19) had acute appendicitis with complication. Of 37 patients who underwent CT scanning, 83.8% were found to have uncomplicated acute appendicitis and 16.2% had complicated acute appendicitis. Based on intraoperative diagnosis, 94% (94) of the subjects operated had uncomplicated acute appendicitis and 6% (6) had acute appendicitis with complication. Based on histopathological diagnosis, 89% were found to have uncomplicated acute appendicitis and 11% had complicated acute appendicitis.

There was no statistically significant difference between total bilirubin values in uncomplicated and complicated acute appendicitis based on histopathological diagnosis [Table 1].

Table 1: Comparison of total bilirubin with histopathological diagnosis by unpaired t-test

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The comparison of total bilirubin with histopathological diagnosis by unpaired samples t-test showed t = 0.763, P = 0.447 > 0.05, which shows no statistically significant difference between total bilirubin values in uncomplicated and complicated acute appendicitis based on histopathological diagnosis [Table 2].

Table 2: Comparison of direct bilirubin with histopathological diagnosis by unpaired t-test

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The comparison of indirect bilirubin with histopathological diagnosis by unpaired samples t-test showed t = 0.849, P = 0.415 > 0.05, which shows no statistically significant difference between indirect bilirubin in uncomplicated and complicated acute appendicitis based on histopathological diagnosis [Table 3].

Table 3: Comparison of indirect bilirubin with histopathological diagnosis by unpaired t-test

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We found that the sensitivity, specificity, PPV and NPV of total bilirubin with histopathological diagnosis were 81.8%, 29.2%, 12.5% and 92.9%, respectively [Figure 1].

Figure 1: Sensitivity, specificity, PPV and NPV of total bilirubin with histopathological diagnosis. PPV: Positive predictive value, NPV: Negative predictive value

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Discussion

Our study showed that hyperbilirubinaemia is present in most of the cases of acute appendicitis, and there is a comparatively higher incidence of hyperbilirubinaemia in complicated cases of acute appendicitis than in uncomplicated cases. However, the study did not find a positive association between the absolute value of elevated total serum bilirubin level and the presence of complications in acute appendicitis.

It suggests that while total serum bilirubin levels are fairly sensitive and have good PPV in diagnosing acute appendicitis, the specificity and NPV are low. Furthermore, no statistically significant differences could be found in the serum bilirubin levels between uncomplicated and complicated acute appendicitis.

The sensitivity and NPVs of total serum bilirubin are fairly high, which suggests that an alternate diagnosis could be suspected if the serum bilirubin levels are low, and low serum bilirubin levels could mean less chance of complicated appendicitis. The specificity and PPVs are quite low, which suggests that total serum bilirubin as a test is not useful in predicting complicated acute appendicitis, and can only be used as an adjunct to clinical findings and other laboratory and imaging tests.

When we reviewed the literature, few studies with the diagnostic value of serum bilirubin in acute appendicitis and its complications were found. While most of them acknowledge the predictive value of serum bilirubin in acute appendicitis, especially in perforated cases, some studies did not find any significant association.

A meta-analysis by Giordano et al.^[8] concluded that the presence of hyperbilirubinaemia does not alone distinguish a perforation in acute appendicitis. Serum bilirubin level is of some value as a predictor of appendiceal perforation. Patients with hyperbilirubinaemia with symptoms and signs consistent with severe acute appendicitis should be considered for early appendectomy.^[8] A retrospective cohort study by Chambers et al.^[9] concluded that there were differences in mean bilirubin between histological groups. However, this did not relate to clinical significance as bilirubin levels were still within normal clinical limits. Diagnosis of complicated appendicitis should be made on clinical grounds, combined with biochemical/haematological investigations, but there should not be independent reliance on investigations such as bilirubin.

Bhangu et al.^[10] found that acute appendicitis is frequently seen in patients in their second and third decades of life, and that there is a male predominance. Giordano^[8] reported 87% prevalence of hyperbilirubinaemia amongst cases with acute appendicitis.

The main strength of our study was prospective study with applicability in an emergency setting in a developing country, where availability of CT and other costly biomarkers is beyond the reach of poor patients. The limitations of our study were study participants less in number, duration of the study was short and patients of paediatric age group were not part of this study.

Conclusion

Elevated total serum bilirubin level has a fairly high sensitivity and NPV in predicting complications of acute appendicitis, but the specificity and PPV are quite low, and hence, hyperbilirubinaemia could be used as an aid in diagnosing complicated acute appendicitis along with the clinical findings and USG findings, but it is not reliable as a standalone diagnostic test. If the total serum bilirubin levels are low, an alternate diagnosis could be suspected, and the chances of complicated appendicitis are quite low, but elevated serum bilirubin values alone cannot confirm the presence of complications. Therefore, our study could not find any correlation between the absolute levels of elevation of total bilirubin values and the presence or absence of complications in acute appendicitis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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