Journal of Health and Nutrition Research Vol.
No.
2, 2025, pg.
815-821, https://doi.
org/10.
56303/jhnresearch.
Journal homepage: https://journalmpci.
com/index.
php/jhnr/index e-ISSN: 2829-9760 Evaluation of C-Reactive Protein.
Neutrophil-To-Lymphocyte Ratio, and Absolute Neutrophil Count as Simple Diagnostic Markers for Spontaneous Bacterial Peritonitis Ayu Sekarani Damana Putri1*.
Supriono2.
Vera Diana Tonowidjojo1.
Junjun Fitriani1.
Gede Nanda Utama1.
Andi Alfia Muthmainah1.
Andi Nur Asrinawati1 1 Faculty of Medicine.
Tadulako University.
Palu.
Indonesia 2 Faculty of Medicine.
Brawijaya University.
Malang.
Indonesia Corresponding Author Email: ayusekaranidp@gmail.
Copyright: A2025 The author.
This article is published by Media Publikasi Cendekia Indonesia.
ORIGINAL ARTICLES
ABSTRACT
Submitted: 7 June 2025 Spontaneous bacterial peritonitis (SBP) is a serious complication of liver cirrhosis with high morbidity and mortality.
Early diagnosis is crucial.
however, ascitic fluid analysis is invasive and often yields a low culture positivity rate.
This study aimed to evaluate the diagnostic performance of C-reactive protein (CRP), absolute neutrophil count (ANC), and neutrophilto-lymphocyte ratio (NLR) as non-invasive markers for the early detection of SBP.
A prospective observational study was conducted on 90 liver cirrhosis patients with ascites undergoing diagnostic paracentesis at Saiful Anwar Hospital.
Indonesia.
CRP.
ANC, and NLR levels were compared between the SBP and non-SBP groups.
Receiver operating characteristic (ROC) curves were used to assess diagnostic accuracy, and logistic regression identified independent predictors.
NLR and ANC levels were significantly higher in SBP patients .
= 0.
004 and p = 0.
033, respectivel.
, while the difference in CRP levels was not statistically significant .
= NLR showed the best performance .
8%, specificity 2%) at a cut-off of 6.
8 and was independently associated with SBP (OR = 09, p = 0.
ANC had similar sensitivity but lower specificity, while CRP demonstrated the weakest predictive value.
In conclusion.
NLR and ANC are emerging as promising, simple, and cost-effective non-invasive biomarkers for the early screening of SBP in cirrhotic patients, particularly in settings where paracentesis is not readily available.
NLR, in particular, holds significant diagnostic value.
Conversely.
CRP may be less reliable in this patient population.
Larger multicenter studies are needed to validate these findings Accepted: 4 July 2025 Keywords:
Spontaneous Bacterial Peritonitis.
Neutrophil-To-Lymphocyte-Ratio.
Diagnostic Tools.
Liver Cirrhosis This work is licensed under a Creative Commons Attribution-NonCommercialShareAlike 4.
0 International License Access this article online Key Messages:
Quick Response Code The neutrophil-to-lymphocyte ratio (NLR) demonstrates superior diagnostic accuracy over absolute neutrophil count (ANC) and Creactive protein (CRP), emerging as a promising, simple, and costeffective non-invasive biomarker for the early screening of spontaneous bacterial peritonitis in patients with liver cirrhosis.
Ayu Sekarani Damana Putri.
Supriono.
Vera Diana Tonowidjojo.
Junjun Fitriani.
Gede Nanda Utama.
Andi Alfia Muthmainah.
Andi Nur Asrinawati, .
GRAPHICAL ABSTRACT
INTRODUCTION
Cirrhotic individuals have impaired defensive mechanisms against microorganisms, resulting in diminished bacterial clearance.
Bacterial infections are a significant complication of cirrhosis, accounting for 25%-46% of hospitalizations due to acute decompensation events in patients with cirrhosis.
Spontaneous bacterial peritonitis (SBP) is a severe bacterial infection occurring in the ascitic fluid of liver cirrhotic patients without a discernible source of infection.
The prevalence of SBP in cirrhotic patients varies, ranging from 3.
5% in outpatients to 36% in hospitalized patients.
Early screening is essential because delayed diagnosis can lead to high mortality rates, with reported mortality rates as high as 40% .
The current gold standard for SBP diagnosis is diagnostic paracentesis followed by ascitic fluid SBP is confirmed by a polymorphonuclear leukocyte (PMN) count of Ou250 cells/mmA, regardless of positive culture results.
However, this approach has limitations: culture-positive rates remain low .
0%), particularly in patients who have received previous antibiotics, and the process is invasive, timeconsuming, and operator-dependent.
Furthermore, logistical challenges in resource-constrained settings may delay paracentesis and microbiological examination, increasing the risk of treatment delays .
To overcome these challenges, researchers have increasingly concentrated on creating simple, quick, and low-cost marker methods for SBP screening and diagnosis.
Systemic inflammatory indicators such as C-reactive protein (CRP), absolute neutrophil count (ANC), and neutrophil-to-lymphocyte ratio (NLR) have emerged as promising early detection tools for SBP.
CRP is an acute-phase reactant produced by the liver in response to infection and inflammation, whereas ANC is a direct marker of circulating neutrophilsAikey effectors in bacterial defense.
Ae.
The NLR, calculated from a standard blood count, reflects the balance between the neutrophil-driven inflammatory response and the lymphocyte-mediated immune regulation.
NLR, in particular, has been established as a robust prognostic and diagnostic marker in various other acute bacterial infections, including sepsis and pneumonia, suggesting its potential applicability in SBP .
Ae.
While a few preliminary studies have explored NLR for diagnosing SBP .
, their results have been inconsistent, and a definitive optimal cutoff value has not been established, highlighting a critical research gap.
This study aims to assess the diagnostic performance of CRP.
ANC, and NLR in detecting SBP and to develop non-invasive ways to improve clinical practice, particularly in locations where quick paracentesis or ascitic fluid analysis is not readily available.
METHODS
This prospective observational study aimed to evaluate the diagnostic value of ANC.
NLR, and CRP as early markers for spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites.
https://doi.
org/10.
56303/jhnresearch.
Ayu Sekarani Damana Putri.
Supriono.
Vera Diana Tonowidjojo.
Junjun Fitriani.
Gede Nanda Utama.
Andi Alfia Muthmainah.
Andi Nur Asrinawati, .
The study was conducted at Hospitals in Palu and Malang.
Indonesia during 2022-2025, enrolling adult patients (Ou18 year.
with clinically, radiologically, or histologically confirmed liver cirrhosis who presented with ascites and underwent diagnostic paracentesis.
Patients were excluded if they had secondary peritonitis, ongoing systemic infections outside the peritoneum, active malignancy, hematological disorders affecting leukocyte profiles, or if they had received antibiotic treatment prior to Upon enrollment, demographic data, clinical characteristics, and laboratory parameters were Blood samples were analyzed for complete blood count (CBC) with differential to determine ANC and calculate NLR, as well as for serum CRP levels.
Diagnostic paracentesis was performed within six hours of hospital admission or clinical indication, with ascitic fluid analyzed for cell count and differential, culture and sensitivity, and biochemical parameters.
SBP was diagnosed based on an ascitic fluid polymorphonuclear neutrophil (PMN) count of Ou250 cells/mmA, with or without positive ascitic fluid .
Descriptive statistics were utilized to summarize the patient features.
ANC.
NLR, and CRP were compared between SBP and non-SBP groups using Mann-Whitney U-test.
Diagnostic accuracy was determined using receiver operating characteristic (ROC) curve analysis, which calculated the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for each biomarker.
Furthermore, multivariate logistic regression was used to find independent predictors of SBP.
A p-value of <0.
05 indicated statistical significance.
RESULTS
Characteristic of Subjects Table 1 show the baseline clinical and laboratory characteristics of the study subjects, stratified into Spontaneous Bacterial Peritonitis (SBP) .
and Non-SBP .
Demographically, the SBP was slightly older and predominantly male .
80%) compared to the Non-SBP group .
60%).
While Hepatitis B was the leading etiology of liver disease in both cohorts, alcoholic liver disease was observed exclusively in patients with SBP.
Clinically, the SBP group presented with markers indicative of more severe systemic inflammation and organ dysfunction.
This is evidenced by a substantially higher mean white blood cell (WBC) count .
,672 vs.
10,054.
71 /AAL) and lower hemoglobin .
68 vs.
76 g/dL).
Furthermore, patients with SBP demonstrated signs of more advanced liver decompensation, including lower mean serum albumin .
41 vs.
62 g/dL) and elevated AST .
96 vs.
57 U/L).
A critical distinction was observed in renal function, with mean urea .
46 vs.
69 mg/dL) and creatinine .
17 vs.
20 mg/dL) levels being markedly higher in the SBP group, suggesting a high prevalence of concurrent acute kidney Table 1 Baseline Characteristic of Subjects Characteristic SBP Group .
Non-SBP Group .
Age, years .
ean A SD) 28 A 9.
1 A 7.
Male, n (%) Female, n (%) Etiology of Liver Disease - Hepatitis B, n (%) 33 .
- Hepatitis C, n (%) 6 .
- Alcoholic Liver Disease, n (%) 3 .
- Others, n (%) 5 .
Hemoglobin, g/dL .
ean A SD) 68 A 2.
76 A 3.
WBC, /AAL .
ean A SD) 15672 A 8364.
71 A 6951.
Platelet, /AAL .
ean A SD) 44 A 109274.
17 A 158408.
AST.
U/L .
ean A SD) 96 A 118.
57 A 49.
ALT.
U/L .
ean A SD) 78 A 54.
15 A 20.
Albumin, g/dL .
ean A SD) 41 A 0.
62 A 1.
Urea, mg/dL .
ean A SD) 46 A 74.
69 A 23.
Creatinine, mg/dL .
ean A SD) 17 A 1.
20 A 0.
https://doi.
org/10.
56303/jhnresearch.
Ayu Sekarani Damana Putri.
Supriono.
Vera Diana Tonowidjojo.
Junjun Fitriani.
Gede Nanda Utama.
Andi Alfia Muthmainah.
Andi Nur Asrinawati, .
The comparison of inflammatory markers between groups demonstrated that patients with ascitic SBP had higher NLR.
ANC, and CRP levels compared to non-SBP patients.
The mean NLR was significantly higher in the SBP group .
compared to the non-SBP .
95 A 07.
42, p = 0.
Similarly, the mean ANC was significantly elevated in SBP patients .
65 A 9.
75 y 10A/AAL) compared to non-SBP patients .
32 A 5.
74 y 10A/AAL, p = 0.
Although CRP levels were higher in the SBP group .
23 mg/L) than in the non-SBP group .
77 mg/L), the difference was not statistically significant .
= 0.
(Table Table 2.
Comparison of Inflammatory Markers Between SBP and Non-SBP Groups Marker SBP Group .
Non-SBP Group .
p-value NLR .
ean A SD) 05 A 05.
95 A 07.
ANC .
10A/AAL, mean A SD) 65 A 9.
32 A 5.
CRP .
g/L, mea.
PMN Count in Ascitic Fluid 20 A 144292.
49 A 975.
ells/mmA, mean A SD) Among the markers assessed.
NLR demonstrated the highest sensitivity .
8%) and a specificity 2% at a cut-off value of 6.
CRP exhibited a sensitivity of 77.
3% and a lower specificity of 50% with a cut-off value of 4.
ANC showed a sensitivity of 81.
8% but similarly limited specificity at 50% using a cut-off of 8.
4 y 10A/AAL (Figure .
Figure 1.
Sensitivity, specificity and Cut-Off points of NLR.
CRP.
ANC
Marker
NLR
CRP
ANC
Table 3.
Correlation between Inflammatory Markers and SBP Status p-value 95% CI 45Ae82.
39Ae14.
12Ae5.
Statistical analysis revealed that NLR was significantly associated with the presence of SBP .
= .
, with an odds ratio (OR) of 11.
% CI: 1.
45Ae82.
and an RA value of 0.
412, indicating a strong predictive relationship.
In contrast.
CRP and ANC did not show statistically significant associations with SBP status .
= 0.
351 and p = 0.
845, respectivel.
(Table .
Comparatively.
NLR demonstrated superior diagnostic performance over CRP and ANC, underscoring its potential as a reliable and readily available screening tool for early SBP detection in cirrhotic patients.
DISCUSSION
SBP is one of the leading causes of mortality among people with end-stage liver disease.
The clinical presentation of SBP ranges greatly, from asymptomatic individuals to those with fever, abdominal https://doi.
org/10.
56303/jhnresearch.
Ayu Sekarani Damana Putri.
Supriono.
Vera Diana Tonowidjojo.
Junjun Fitriani.
Gede Nanda Utama.
Andi Alfia Muthmainah.
Andi Nur Asrinawati, .
discomfort, acute renal damage, abnormal liver function tests, and hepatic encephalopathy.
While ascitic fluid analysis is critical for detecting SBP, conducting a paracentesis presents various hurdles.
As an invasive procedure, paracentesis carries inherent risks, such as haemorrhage and intestinal perforation, often necessitating safety measures like ultrasound guidance to minimize complications.
Thrombocytopenia and coagulopathy, which are frequent in cirrhosis, enhance the procedural risk, restricting its usage, especially in resource-limited settings.
As a result, diagnostic paracentesis is routinely underused, potentially leading to misdiagnosis, delayed therapy, or ineffective antibiotic This emphasizes the need for a quick, non-invasive, and simply applied biomarker to help predict SBP in cirrhotic patients with ascites.
This study demonstrated that NLR and ANC were significantly elevated in patients with ascites-SBP compared to those with ascites without SBP.
NLR showed the strongest association with SBP status, with a sensitivity of 81.
8% and specificity of 68.
2% at a cut-off value of 6.
ANC also displayed significant diagnostic potential, although its specificity was lower.
While CRP levels were higher in SBP patients, the difference was not statistically significant.
Our analysis found no significant correlation between these serum inflammatory markers and ascitic fluid PMN counts.
The findings regarding NLR are consistent with previous studies that have highlighted NLR as a reliable marker for infections, including SBP, in cirrhotic patients.
NLR is a simple parameter to easily assess the inflammatory status of a subject.
Infection can cause the medulla to produce more neutrophils and reduce lymphocyte counts by apoptosis if the source of infection is not completely eliminated.
Similarly.
ANC was significantly higher among SBP patients in this study, corroborating findings that demonstrated ANC as a strong diagnostic marker with high sensitivity and specificity.
For instance.
Sheta et al.
showed that an ANC >2.
804 could discriminate SBP from non-SBP with a sensitivity of 84% and a specificity of 78% .
Our NLR cut-off aligns with findings from Mousa et al.
, who reported that an NLR value >2.
89 distinguished SBP from non-SBP cases with 80.
3% sensitivity and 88.
specificity, supporting its role as an accessible diagnostic tool.
Neutrophils play a key defensive role through phagocytosis, degranulation, and reactive oxygen species (ROS) production, following chemokinedirected migration to infection sites.
Cirrhosis is associated with increased bacterial translocation, especially across the intestinal barrier, even without active infection.
Despite this heightened inflammatory activity, cirrhosis impairs overall immune competence due to reduced expression of toll-like receptors and cytopenia, making patients more vulnerable to infections.
Lymphopenia, commonly due to hypersplenism from portal hypertension, also contributes to immune imbalance.
This shift in white blood cell compositionAiparticularly an elevated neutrophil-to-lymphocyte ratioAireflects both immune activation and suppression, as seen in various disease states.
Conversely, the results regarding CRP were less definitive.
While some have suggested that CRP may be a useful adjunct in diagnosing infections in cirrhosis, others reported that its diagnostic accuracy decreases in advanced liver disease, possibly explaining the nonsignificant results observed in this cohort.
Ae.
As reported by Pieri et al.
, baseline CRP in cirrhotic patients is already elevated, and in the setting of infection, the increase in CRP may be blunted in those with more severe liver dysfunction .
This study had several limitations.
A primary limitation was the relatively small sample size, which may have introduced selection bias and reduced the statistical power for subgroup analyses.
The singlecenter design may limit the generalizability of the results.
Potential confounding factors, such as the severity of liver disease .
MELD score.
, concomitant infections, and the timing of paracentesis relative to symptom onset, were not fully controlled for.
Additionally, missing data and unmeasured variables may have influenced the diagnostic accuracy estimates.
CONCLUSION
The significant association between elevated NLR and SBP supports its use as a simple, rapid, and inexpensive screening tool for the early identification of SBP in cirrhotic patients presenting with ascites.
Future multicenter studies with larger sample sizes are needed to validate the diagnostic value of NLR.
ANC, and CRP in diverse patient populations.
Prospective studies that incorporate comprehensive liver disease severity assessments and standardized timing of paracentesis could help refine existing prediction https://doi.
org/10.
56303/jhnresearch.
Ayu Sekarani Damana Putri.
Supriono.
Vera Diana Tonowidjojo.
Junjun Fitriani.
Gede Nanda Utama.
Andi Alfia Muthmainah.
Andi Nur Asrinawati, .
FUNDING
This research received no external funding.
CONFLICTS OF INTEREST
The authors declare no conflict of interest.
REFERENCES