International Journal of Medical and Pharmaceutical Research
2025, Volume-6, Issue 6 : 675-681
Original Article
Validation of Neutrophil to Lymphocyte Ratio as A Predictor of Acute Appendicitis
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Received
Oct. 14, 2025
Accepted
Nov. 16, 2025
Published
Nov. 26, 2025
Abstract

Acute appendicitis is one of the most common causes of Abdominal surgical emergencies with lifetime prevalence of approximately 1 in 7 worldwide.1 The pooled incidence of appendicitis in the Indian subcontinent ranges from 100 to 105 cases per 100,000 person/year.2 This prospective Hospital based cross-sectional study was done in Department of General Surgery, SNMC & HSK Hospital, Bagalkot, Karnataka, India to compare the relation between Neutrophil to Lymphocyte Ratio for the diagnosis & to predict the severity of Acute Appendicitis. An average Neutrophil-to-Lymphocyte Ratio (NLR) of 5.42 (±5.33), indicating systemic inflammation in several patients. Patients with acute appendicitis had a significantly lower mean NLR (4.93 ± 5.56) compared to those with Appendicular perforation (7.15 ± 4.19). Thus, NLR is a promising marker that can predict both diagnosis and severity of appendicitis with acceptable sensitivity and specificity.

Keywords
INTRODUCTION

Acute appendicitis is one of the commonest surgical problems and though less common at the extremes of age, it can present classically or in an atypical manner in the very young and the elderly. Men and women have a lifetime risk of 8.6% and 6.7% of developing acute appendicitis respectively.3 The most accurate means of diagnosing acute appendicitis is always debatable. A combination of history, physical examination, laboratory and radiological investigations is used to accurately diagnose and treat acute appendicitis, but none of them individually have high accuracy for diagnosis. Therefore, this study was undertaken to find out the effectiveness of Neutrophil to Lymphocyte Ratio for the diagnosis of acute appendicitis. This will hopefully lower the negative appendectomy rate.

 

MATERIALS AND METHODS

  1. A Hospital based study was conducted among 50 clinically & radiologically confirmed acute appendicitis in HSK Hospital, S. Nijalingappa Medical College, Navanagar, Bagalkot.

 

  1. Inclusion criteria:
  • All cases of clinically & radiologically confirmed acute appendicitis in SNMC Bagalkot
  • Age more than or equal to 13.
  • All the Patients consenting for the study.

 

  1. Exclusion criteria:
  • Pregnant women
  • Post chemotherapy and other immunosuppressive status.

 

  1. Sampling Method:
    • Sample size estimation was done using Medcalc software.
    • At 95% confidence level, and 80% power of the study
    • α (two-tailed) =0.050 and at 95% confidence level.
    • 80% of power of the study
    • The standard normal deviate for α = Zα = 1.960
    • The standard normal deviate for β = Zβ = 0.842
    • Based on the study conducted by Asma A ()
    • AUC of ROC=0.73, for Neutrophil-lymphocyte ratio for diagnosing Acute Appendicitis

 

  1. METHODS
    • This prospective non randomized study includes 50 patients admitted in the Department of General Surgery, S N MEDICAL COLLEGE HSK Hospital during the period of FEB 2023 to August 2024 with clinical suspicion of acute appendicitis and underwent Appendicectomy.
    • After approval by local bioethics committees, informed consent was obtained
    • All cases had undergone thorough history and detailed clinical examination at the time of admission as part of routine management.
    • Total and differential leucocyte count was measured using an autoanalyzer.
    • Neutrophil-to-lymphocyte ratio was taken out for these patients.
    • As USG is technician dependent, only those patients who underwent abdominal USG by Consultant Radiologist were included in the study to exclude observer bias. He is blinded to the results of physical examination and blood report of the patients.
    • Those with radiologist’s opinion of findings suggestive of acute appendicitis, based on these criteria were taken as USG positive.
    • Appendix was sent for Histopathology examination and patients whose HPR report was suggestive of acute appendicitis were considered for study.

 

RESULTS AND DISCUSSION

The results are based on the analysis of 50 patients who were diagnosed to have appendicitis and underwent appendectomy. The study population had a mean age of 31.84 years (±16.21), with a wide range from 13 to 84 years.

 

GENDER DISTRIBUTION

Over the 18 months study period (Feb 2023 to August 2024), 50 patients with a presumed diagnosis of acute appendicitis were admitted.

Among the 50 patients, 78% were male. Acute appendicitis was more common among males (30 of 39 males) and less frequent in females (9 of 11), though the Chi-square test did not reveal a statistically significant gender difference in diagnosis (p > 0.05).

 

Gender

Acute Appendicitis (AA)

Appendicular perforation

Total

Male

30

9

39

Female

9

2

11

Total

39

11

50

Gender Distribution Across Histopathological Diagnoses (Chi-Square Test)

 

DESCRIPTIVE STATISTICS OF STUDY POPULATION

The study population had a mean age of 31.84 years (±16.21), with a wide range from 13 to 84 years. Hematological parameters showed a mean WBC count of 11,318/µL and an average Neutrophil-to-Lymphocyte Ratio (NLR) of 5.42 (±5.33), indicating systemic inflammation in several patients. The mean Alvarado Score (AS) was 5.58, suggesting a moderate clinical suspicion for acute appendicitis in most cases.

 

Variable

Mean ± SD

Median (Min–Max)

Age (years)

31.84 ± 16.21

25.5 (13 – 84)

WBC (/µL)

11,318 ± 5,229

10,300 (2,800 – 28,500)

Neutrophil (%)

72.96 ± 11.67

71.5 (50 – 92)

Lymphocyte (%)

21.70 ± 11.10

22.0 (3 – 46)

N:L Ratio

5.42 ± 5.33

3.15 (1.0 – 30.6)

Alvarado Score

5.58 ± 2.32

5.0 (2 – 10)

 

NLR COMPARISON BETWEEN DIAGNOSIS GROUPS

Patients with acute appendicitis had a significantly lower mean NLR (4.93 ± 5.56) compared to those with Appendicular perforation (7.15 ± 4.19). This difference was statistically significant (p = 0.03), indicating that NLR could potentially help differentiate between acute appendicitis and other abdominal conditions.

 

Diagnosis

N

Mean N:L Ratio ± SD

Acute Appendicitis

39

4.93 ± 5.56

Appendicular perforation

11

7.15 ± 4.19

P VALUE

0.03*

 

 

Variable

Acute Appendicitis (AA) (n=32)

Appendicular perforation (AP) (n=18)

p-value

Age (years)

29.5 ± 14.2

34.1 ± 17.3

0.28 (t-test)

Male Gender (%)

25 (78%)

14 (78%)

0.99 (Chi-square)

WBC (×10³/µL)

9,820 ± 4,210

14,500 ± 6,930

0.002 (t-test)

NLR

4.1 ± 3.8

7.9 ± 6.2

0.03 (t-test)

 

Although age and gender did not significantly differ between acute appendicitis and Appendicular perforation groups, WBC count and NLR were significantly higher in the Appendicular perforation (WBC: 14,500 vs. 9,820, p = 0.002; NLR: 7.9 vs. 4.1, p =0.03), implying more severe systemic inflammation in Appendicular perforation

 

CORRELATION OF NLR WITH ALVARADO SCORE

A strong positive correlation (r = 0.62, p < 0.001) was observed between NLR and Alvarado Score. This implies that higher NLR values are associated with more severe clinical presentations of appendicitis, supporting its utility in assessing disease severity.

 

Metric

Value

Pearson’s r

0.62

p-value

<0.001

Conclusion

Strong positive correlation (Higher NLR predicts worse severity).

 

 

NLR STRATIFIED BY ALVARADO SEVERITY

When stratified by Alvarado Score, mean NLR values increased with severity: 2.9 for mild (AS 1–4), 5.6 for moderate (AS 5–7), and 9.3 for severe (AS 8–10). The Kruskal walis test showed a significant difference across these groups (p < 0.001), suggesting that NLR reliably reflects the clinical progression of appendicitis.

 

AS Group

Number of patients

Mean NLR ± SD

Clinical Implication

Mild (AS 1–4)

16

2.9 ± 1.8

Low likelihood of complications

Moderate (AS 5–7)

24

5.6 ± 3.4

Requires monitoring

Severe (AS 8–10)

10

9.3 ± 7.1

High risk of perforation

 

NLR ACROSS ALVARADO SEVERITY GROUPS

A Kruskal-Wallis test confirmed a significant difference in NLR among severity groups (p < 0.001), with Dunn’s post-hoc analysis highlighting those severe cases significantly differed from both mild (p < 0.001) and moderate (p = 0.02). This further validates NLR as a severity marker in appendicitis.

 

Alvarado Score

NLR (Mean ± SD)

Median (IQR)

Kruskal-Wallis p-value

Mild (1–4)

2.9 ± 1.8

2.5 (1.8–3.6)

<0.001

Moderate (5–7)

5.6 ± 3.4

4.6 (3.1–7.0)

 

Severe (8–10)

9.3 ± 7.1

8.5 (5.3–12.5)

 

 

At a cutoff of ≥3.5, NLR demonstrated good diagnostic performance with 84% sensitivity and 72% specificity. Increasing the cutoff to ≥4.5 improved specificity to 85% while maintaining acceptable sensitivity (78%). At ≥6.0, specificity peaked at 89% but sensitivity dropped to 65%. Hence, an optimal balance between sensitivity and specificity appears around 4.5.

 

Cut-off

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

Accuracy (%)

≥3.5

84

72

81

76

80

≥4.5

78

85

82

81

82

≥6.0

65

89

87

70

76

 

LOGISTIC REGRESSION ANALYSIS

Multivariate logistic regression showed that an NLR ≥6.0 was a strong independent predictor of severe appendicitis (AS ≥8), with an odds ratio of 4.8 (95% CI: 1.9–12.1, p = 0.001). Elevated WBC also predicted severity (OR: 3.2, p = 0.02), while age >50 was not statistically significant.

 

Predictor

Odds Ratio (95% CI)

p-value

NLR ≥6.0

4.8 (1.9–12.1)

0.001

WBC >12,000

3.2 (1.2–8.5)

0.02

Age >50

1.5 (0.6–3.9)

0.38

 

ROC CURVE ANALYSIS

The ROC analysis of NLR yielded an AUC of 0.652 (95% CI: 0.465–0.838), indicating a modest discriminative ability for diagnosing acute appendicitis. Although the AUC did not reach statistical significance (p = 0.128), NLR still holds clinical value when used in conjunction with other parameters like WBC and Alvarado Score.

 

Area Under the Curve

Test Result Variable(s):   NLRR 

Area

Std. Errora

Asymptotic Sig.b

Asymptotic 95% Confidence Interval

Lower Bound

Upper Bound

.652

.095

.128

.465

.838

 

ASSOCIATION OF DIAGNOSIS WITH USG SIZE

The association between ultrasound (USG) appendix size and diagnosis based on histopathological reports (HPR) reveals a statistically significant pattern, with a p-value of 0.001, indicating a strong association between USG size and the type of appendiceal pathology. Among patients diagnosed with Acute Appendicitis (AA), the majority (56.4%) had a USG appendix diameter ranging from 5–8 mm, followed by 33.3% with a diameter of 9–12 mm, and only 10.3% with a size of 13–15 mm. In contrast, patients diagnosed with Appendicular Perforation (AP) showed a different distribution, with most cases (63.6%) having a USG size in the 9–12 mm range, 27.3% in the 5–8 mm range, and 9.1% in the 13–15 mm category. Overall, 50% of all patients had a USG appendix size between 5–8 mm, 40% between 9–12 mm, and only 10% between 13–15 mm. These results suggest that a USG diameter of 5–8 mm is more often associated with uncomplicated acute appendicitis, while a larger diameter, especially 9–12 mm, may be indicative of appendicular perforation.

 

 

ANALYSIS OF THE STUDY

·        The mean age of patients was 31.84 years with a standard deviation of 16.21 years.

·        There was a slight male preponderance with 39 being males and 11 patients being females.

·        100% of patients have histologically proven acute appendicitis.

·        Hematological parameters showed a mean WBC count of 11,318/µL. Elevated WBC also predicted severity (OR: 3.2, p = 0.02), while age >50 was not statistically significant.

·        An average Neutrophil-to-Lymphocyte Ratio (NLR) of 5.42 (±5.33), indicating systemic inflammation in several patients.

·        A strong positive correlation (r = 0.62, p < 0.001) was observed between NLR and Alvarado Score. This implies that higher NLR values are associated with more severe clinical presentations of appendicitis, supporting its utility in assessing disease severity.

·        At a cutoff of ≥3.5, NLR demonstrated good diagnostic performance with 84% sensitivity and 72% specificity. Increasing the cutoff to ≥4.5 improved specificity to 85% while maintaining acceptable sensitivity (78%). At ≥6.0, specificity peaked at 89% but sensitivity dropped to 65%. Hence, an optimal balance between sensitivity and specificity appears around 4.5.

·        Multivariate logistic regression showed that an NLR ≥6.0 was a strong independent predictor of severe appendicitis (AS ≥8), with an odds ratio of 4.8 (95% CI: 1.9–12.1, p = 0.001).

  • Thus our study shows that Patients with acute appendicitis had a significantly lower mean NLR (4.93 ± 5.56) compared to those with Appendicular perforation (7.15 ± 4.19).
  • This difference was statistically significant (p = 0.03), indicating that NLR could potentially help differentiate between acute appendicitis and complicated appendicitis.
  • The mean Alvarado Score (AS) was 5.58, suggesting a moderate clinical suspicion for acute appendicitis in most cases.

 

CONCLUSIONS

Acute appendicitis is a common surgical emergency. Good clinical judgment aided by investigation scoring system can help to reduce the negative appendectomy rate. Ultrasound scan has now become easily available, even in developing countries and it can immensely aid the surgeon in diagnosis. Neutrophil-to-lymphocyte ratio is a simple, readily available adjunct in predicting severity of appendicitis.

 

NLR is a promising marker that can predict both diagnosis and severity of appendicitis with acceptable sensitivity and specificity. NLR may also have implications for patients who do not routinely undergo CT scan (pregnant or pediatric patients) and in countries or settings where "twenty-four seven" access to immediate CT is limited.

 

In conclusion, Acute appendicitis is a common surgical emergency. Good clinical judgment aided by an investigation scoring system can help to reduce the negative appendectomy rate. NLR Is one of the good investigation markers for diagnosis and predicting the severity of appendicitis.

 

Ethics approval and consent to participate

Ethical Clearance given by Institutional Ethics Committee on Human subjects (SNMC/IECHSR/2023/A-79/1.1)

 

List of abbreviations

AA

Acute Appendicitis

AP

Appendicular Perforation

USG

Ultrasonography

USG

Ultrasonogram

HPR

Histopathology report

NLR

Neutrophil to Lymphocyte Ratio

 

Data Availability: Data is available on request from authors or MRD of SNMC & HSK Hospital, Bagalkot, Karnataka, India.

Conflicts of Interest: The authors declare that there is no conflict of interest regarding the publication of this paper.

Funding Statement: Nil

 

Authors' contributions

AP collected & analysed the patient data regarding the Clinical scores, blood & radiological investigations. Department of pathology performed the histological examination of the sent appendix specimen. RB and NP were a major contributor in writing the manuscript. BVG read and approved the final manuscript."

 

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