Predictive Biomarker Signatures in Non-Alcoholic Fatty Liver Disease: Hs-CRP, Monocyte to High-Density Lipoprotein Cholesterol Ratio and Neutrophil Percentage to Albumin Ratio

Predictive Biomarker Signatures in Non-Alcoholic Fatty Liver Disease: Hs-CRP, Monocyte to High-Density Lipoprotein Cholesterol Ratio and Neutrophil Percentage to Albumin Ratio | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Predictive Biomarker Signatures in Non-Alcoholic Fatty Liver Disease: Hs-CRP, Monocyte to High-Density Lipoprotein Cholesterol Ratio and Neutrophil Percentage to Albumin Ratio Shanmukha Sai Bolisetty, Kadiri Venkata Prashanti, Vismai Juluri, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7662492/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: NAFLD (Non-Alcoholic Fatty Liver Disease) is liver fat buildup unrelated to alcohol, linked to obesity, diabetes, and metabolic syndrome. It ranges from simple steatosis to NASH (inflammation/fibrosis). Often asymptomatic, detected via blood tests or imaging. Managed with weight loss, diet, exercise, and controlling metabolic risks to prevent cirrhosis or liver cancer. The present study aims to investigate the association between human serum C-Reactive protein (hs-CRP), monocyte to high-density lipoprotein cholesterol ratio (MHR) and neutrophil percentage to albumin ratio (NPR) with non-alcoholic fatty liver disease (NAFLD) in the South-Indian population. Methods: A cross-sectional study included 102 patients (51 case and 51 control) aged above 18 years who visited the outpatient ward of a tertiary care hospital in Tamil Nadu, India. The diagnosis for NAFLD was done using ultrasonographic findings. Results: NAFLD patients exhibited slightly higher NPAR levels compared to non-NAFLD individuals, though the difference was not statistically significant (p = 0.2064). However, both MHR and HsCRP were significantly elevated in NAFLD (p < 0.001). ROC analysis revealed that HsCRP had near-perfect discriminatory power for NAFLD (AUC = 0.9942), with a cutoff of ≥1.0 mg/L correctly classifying 95.2% of cases. MHR showed moderate predictive ability (AUC = 0.6935), while NPAR performed poorly (AUC = 0.5592). Conclusion: Our findings highlight HsCRP as a highly sensitive marker for NAFLD, though further validation is needed to confirm its diagnostic utility in broader populations. -Reactive protein monocyte to high-density lipoprotein cholesterol ratio neutrophil percentage to albumin ratio non-alcoholic fatty liver disease Figures Figure 1 Figure 2 Figure 3 1. Introduction Nonalcoholic fatty liver disease (NAFLD) has recently been identified as one of the most prevalent global health issues, impacting over 32.4% of individuals globally 1 . The prevalence rate of NAFLD in India is 38.6% 1 . An increasing volume of research suggests that NAFLD patients are at much higher risk of developing hepatocellular carcinoma as well 2 . NAFLD has also been linked to type 2 diabetes, obesity, hypertension, and other aspects of metabolic syndrome 3 . NAFLD refers to a spectrum of illnesses linked with metabolic problems, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can further proceed to liver cirrhosis and consequences 4 , 5 . Over the last several years, the worldwide burden of obesity and related metabolic diseases has increased significantly 6 . NASH is characterized by a variety of pathophysiological changes in the liver, beginning with hepatocyte stress, damage, apoptosis, and inflammation and progressing to fibrosis 7 . In the absence of early diagnosis and effective care, NASH can develop to cirrhosis, with the incidence of severe F3 and F4 fibrosis associated with NASH quickly increasing 8 . Therefore, identification of NAFLD patients is essential in order to optimally manage these cases, and various non-invasive tools have been developed in this regard, although no unique biomarker is solely acknowledged to meet the requirements sufficiently. Early diagnosis and risk stratification of NAFLD are critical for avoiding disease progression and consequences. However, liver biopsy, the gold standard for diagnosing and staging NAFLD, is intrusive, costly, and unsuitable for large-scale screenings 9 . Ultrasonography and elastography are popular imaging modalities, but their usage is limited due to cost, accessibility, and operator dependence 10 . As a result, there is an urgent need for simple, cost-effective, and non-invasive biomarkers that can help identify people at risk for NAFLD, especially those in primary care and resource-limited settings 11 . Several hematological and biochemical ratios have recently been found to be potential inflammatory biomarkers for metabolic and hepatic ailments 12 . Among them, the neutrophil percentage to albumin ratio (NPAR) has been proposed as a new measure for systemic inflammation 13 . Elevated neutrophil counts suggest immunological activation, but low albumin levels might indicate both hepatic impairment and chronic inflammation 14 . Although NPAR has been examined in sepsis and cancer, its involvement in NAFLD is not understood. Another intriguing metric is the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), which links innate immune activity to lipid metabolism 14 , 15 . Monocytes cause hepatic inflammation and fibrosis, whereas HDL cholesterol has anti-inflammatory and antioxidant effects 16 . Elevated MHR has been linked to atherosclerosis, metabolic syndrome, and, more recently, NAFLD 17 , indicating its potential as a substitute for metabolic inflammation. High-sensitivity C-reactive protein (HsCRP) persists as one of the most commonly investigated indicators of systemic inflammation 18 . Elevated HsCRP levels have repeatedly been linked to obesity 19 , insulin resistance 20 , and liver steatosis 21 . However, the extent of its predictive utility for NAFLD diagnosis in various groups is currently being investigated. Given this context, the present study aims to evaluate and compare the clinical utility of NPAR, MHR, and HsCRP in distinguishing individuals with and without NAFLD. By assessing their discriminatory capacity and correlation with clinical and biochemical parameters, this study seeks to identify inflammation-based indices that may serve as practical and non-invasive tools for early identification of NAFLD in clinical practice. 2. Methodology 2.1. Data Collection Procedure This cross-sectional study included 102 patients aged above 18 years who visited the outpatient ward of a tertiary care hospital in Tamil Nadu, India, between March 2023 and March 2025. Patients with a history of alcohol consumption (males > 140g/week, females > 70g/week), drug induced steatohepatitis, acute inflammatory condition, known case of acute and chronic liver disease or malignancy, and coronary artery disease were excluded from the study. Patients on statin therapy, both oral contraceptive pills and hepatotoxic drugs were also excluded from the study. Age, sex and BMI matched individuals without fatty liver on ultrasound abdomen will be included in control group. The patients were diagnosed for NAFLD using ultrasonography. The blood investigations will be done for all the participants in both case (n = 51) and control (n = 51) groups. 2.2. Data Entry and Analysis The statistical analysis was done using STATA version 17. The p-value of less than 0.05 was seen to be statistically significant. 2.3. Ethical Considerations The authors have received the institutional ethical committee clearance certificate from SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India for conducting this research on humans. Informed consent was provided to the patients in both English and native language prior to data collection. Special care was taken about there are no violation of human rights during conducting this research. 3. Results The NPAR with NAFLD is shown in Table 1 . A two-sample t-test was used to compare participants with and without NAFLD. NAFLD patients had a slightly higher average NPAR (14.55 ± 2.11) than non-NAFLD patients (13.97 ± 2.81), but this difference was not statistically significant (t = -1.27, p = 0.2064). Table 1 Two-sample t-tests for Neutrophil Percentage to Albumin Ratio Variable NAFLD = No Mean ± SD NAFLD = YES Mean ± SD t-value p-value Neutrophil Percentage to Albumin Ratio 13.97 ± 2.81 14.55 ± 2.11 -1.27 0.2064 The non-parametric comparison of the MHR and HsCRP using the Mann-Whitney U test is displayed in Table 2 . The findings indicate that the HsCRP levels of those with and without NAFLD varied statistically significantly. With a z-score of -9.34 (p < 0.001), those with NAFLD had considerably higher rankings (Rank Sum = 5409) than those without the condition (Rank Sum = 1851). Similarly, those with NAFLD had a considerably higher MHR (Rank Sum = 4327 vs. 2934; z = -3.66, p < 0.001). Thus, it is clear from the data that NAFLD is associated with considerably higher levels of both the MHR and HsCRP. Table 2 Mann-Whitney U Test for High Sensitivity C Reactive Protein and Monocyte to HDL Ratio by NAFLD Status Group N Rank Sum Expected z p-value NAFLD = No 60 1851 3630 -9.34 < 0.001 NAFLD = Yes 60 5409 3630 NAFLD = No 60 2934 3630 -3.66 < 0.001 NAFLD = Yes 60 4327 3630 The summary data for the mean and standard deviation of the laboratory and clinical parameters are displayed in Table 3 . Hemoglobin, white blood cell count, platelet count, absolute leukocyte count, and neutrophil percentage were all somewhat higher in persons with NAFLD. The findings indicate that lipid indicators, including triglycerides, VLDL, and total cholesterol, as well as liver function tests like AST, ALT, and alkaline phosphatase, were higher in the NAFLD subjects. Furthermore, individuals with NAFLD had significantly higher HsCRP levels (1.91 ± 0.68 vs. 0.57 ± 0.25), which is associated with systemic inflammation. Those with NAFLD also had higher MHR and NPAR values. Table 3 Summary Statistics by NAFLD Status Variable NAFLD = No (Mean ± SD) NAFLD = Yes (Mean ± SD) Age 46.58 ± 17.32 50.88 ± 11.37 Hemoglobin 12.97 ± 1.77 13.19 ± 1.98 White blood cells 6929.08 ± 1996.49 7184.17 ± 1884.18 Platelets 280.18 ± 67.27 297.43 ± 74.66 Absolute leucocyte count 2142.33 ± 689.31 2253.67 ± 590.53 Neutrophil percentage 60.48 ± 8.57 60.78 ± 6.79 Total bilirubin 0.83 ± 0.35 0.75 ± 0.31 Direct bilirubin 0.15 ± 0.07 0.15 ± 0.08 Alkaline phosphatase 68.62 ± 21.09 81.95 ± 24.50 Aspartate aminotransferase 23.92 ± 13.89 25.60 ± 10.23 Alanine aminotransferase 20.25 ± 10.68 24.77 ± 11.44 Total cholesterol 190.35 ± 44.04 189.60 ± 40.32 Triglycerides 104.60 ± 51.02 122.67 ± 48.38 High density lipoprotein 48.78 ± 10.82 46.45 ± 10.86 Low density lipoprotein 134.80 ± 38.67 136.00 ± 34.98 Very low-density lipoprotein 21.00 ± 10.17 25.33 ± 11.66 High sensitivity C reactive protein 0.57 ± 0.25 1.91 ± 0.68 Ultrasound 3.00 ± 0.00 1.18 ± 0.39 Albumin 4.40 ± 0.50 4.21 ± 0.38 Neutrophil Percentage to Albumin Ratio 13.97 ± 2.81 14.55 ± 2.11 Monocyte to HDL Ratio 9.42 ± 4.95 13.47 ± 6.54 The ROC curve for the NPAR as NAFLD predictor is shown in Fig. 1 . The low discriminating ability is indicated by the Area Under the Curve (AUC), which was just 0.5592. This finding implies that in this group, the NPAR cannot be utilized as a stand-alone marker to identify people with NAFLD. The receiver operating characteristic (ROC) curve for the MHR that predicts NAFLD is shown in Fig. 2 . An AUC of 0.6935 indicates a moderate capacity for discrimination. This finding suggests that the MHR has a mild ability to distinguish between those with and without NAFLD. The ROC curve, assessing HsCRP's ability to predict the presence of NAFLD, is shown in Fig. 3 . With an AUC of 0.9942, the diagnostic accuracy is high. HsCRP can nearly fully distinguish between those with and without NAFLD in this group, according to an AUC of 0.9942. This finding indicates a substantial correlation between NAFLD in this group and systemic inflammation, as measured by HsCRP levels. Nonetheless, it is worth noting that the HsCRP distribution across NAFLD status showed almost complete separation. All individuals with HsCRP values below 1.0 mg/L (n = 57) didn’t have NAFLD, while 95.2% of individuals with HsCRP ≥ 1.0 mg/L (60 of 63) were classified as having NAFLD. This threshold-based separation could explain the exceptionally high area under the curve (AUC = 0.9942) observed in the ROC analysis, indicating the near-perfect discriminatory ability of HsCRP for identifying NAFLD in this cohort, although external validation is warranted. 4. Discussion This study aimed to evaluate the utility of inflammatory biomarkers NPAR, MHR, and HsCRP in identifying NAFLD. Our findings suggest that among these, HsCRP demonstrated the strongest discriminatory capacity, followed by MHR, while NPAR showed no significant association with NAFLD status. In the present study, NPAR levels were marginally elevated in individuals with NAFLD compared to those without (14.55 ± 2.11 vs. 13.97 ± 2.81), but the difference was not statistically significant. This is in contrast with studies that have identified NPAR as a significant marker of systemic inflammation in liver conditions. Wang et al., 2024 reported that elevated NPAR was associated with hepatic steatosis severity in a Chinese adult population 22 . Similarly, in their study by Waili et al., 2025 found that NPAR was independently associated with liver fibrosis in patients with acute-on-chronic liver failure 23 . The discrepancy may stem from differences in patient populations, NAFLD diagnostic methods, or disease stages. It is plausible that in our cohort, consisting predominantly of individuals with early or subclinical NAFLD, the inflammatory burden was not sufficient to influence albumin levels or neutrophil percentages significantly. Furthermore, NPAR may be more sensitive to acute or severe inflammation, as shown in advanced liver fibrosis by Liu et al., 2023 24 . Our findings support previous literature that identifies MHR as a promising marker of metabolic and cardiovascular inflammation. Individuals with NAFLD had significantly higher MHR values, and the ROC analysis yielded an AUC of 0.6935, suggesting moderate discriminatory capacity. This aligns with the results of Kohsari et al., 2022 , on Kurdish cohort study in Iran showing the correlation of the MHR levels in NAFLD patients 25 . Likewise, Wang et al., 2022 demonstrated that MHR was significantly higher in NAFLD patients compared to controls and correlated with fibrosis severity and liver stifness 17 . MHR integrates innate immune activity (monocyte count) and lipid anti-inflammatory properties (HDL levels), both of which are altered in NAFLD due to chronic low-grade inflammation and dyslipidemia 26 . Our study further supports this pathophysiological association and emphasizes the potential of MHR as a simple, cost-effective marker that may assist in screening or risk stratification. High-sensitivity CRP showed the most robust association with NAFLD in our study. Not only were HsCRP levels significantly elevated in individuals with NAFLD (1.91 ± 0.68 mg/L vs. 0.57 ± 0.25 mg/L), but the ROC curve demonstrated an AUC of 0.9942, indicating near-perfect discriminatory ability. This finding mirrors several previous studies. Soppert et al., 2023 conducted a meta-analysis and concluded that elevated CRP levels were consistently associated with NAFLD and NASH across multiple studies 27 . Interestingly, Kumar et al., 2020 observed that HsCRP was a strong predictor of NAFLD in a large population-based cohort, even after adjusting for obesity and metabolic syndrome in a cohort of north Indian population 28 . 29 Yoneda et al ., 2007 reported AUCs of 0.82–0.89 for HsCRP in metabolic-associated fatty liver disease (MAFLD), while Park et al noted HsCRP ≥ 1.5 mg/L predicted advanced fibrosis (AUC = 0.76) 29 . Our higher AUC may reflect stricter cohort selection (e.g., exclusion of confounding comorbidities) or earlier disease detection. Furthermore, the sharp separation at the 1.0 mg/L threshold in our dataset—where nearly all individuals above this cut-off had NAFLD—suggests a potential diagnostic utility. While HsCRP is not specific to NAFLD and may be influenced by other inflammatory conditions, the near-complete separation observed supports its role in NAFLD screening. However, as Lee et al., 2019 cautioned, the specificity of HsCRP may drop in populations with higher comorbidity burdens or concurrent infections. Thus, while our findings are highly promising, validation in larger and more diverse populations is necessary. The observed associations between NAFLD and elevated inflammatory markers support the growing consensus that NAFLD is not merely a hepatic manifestation of obesity, but a chronic inflammatory condition with systemic implications. The elevated levels of liver enzymes (ALT, AST), lipid parameters (VLDL, triglycerides, total cholesterol), and inflammatory blood counts (WBC, neutrophils) in NAFLD participants in our study further reinforce the interplay between hepatic steatosis and systemic inflammation. Our findings are consistent with the broader literature suggesting that NAFLD is a hepatic component of metabolic syndrome, driven by insulin resistance, dyslipidemia, and chronic inflammation. According to a study by Khura et al., 2019 , CRP, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels are elevated in NAFLD and may contribute to disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis 30 . 5. Conclusion While our findings are consistent with numerous previous research, there are certain limitations. To begin, the diagnosis of NAFLD was most frequently made using clinical or imaging criteria rather than a liver biopsy, which might lead to misclassification, especially in the early stages of the illness. Secondly, the cross-sectional design may prohibit causal inference. Lastly, we did not account for confounding variables such as BMI, diabetes, or medication usage, which can all alter inflammatory markers independently. Furthermore, the high AUC obtained for HsCRP may indicate overfitting, particularly if the NAFLD and non-NAFLD groups were very homogenous. As a result, our findings should be verified in external cohorts with diverse demographic and clinical characteristics. This niche-specific and race-specific study conducted on South Indian population adds to the existing body of evidence suggesting that inflammation plays a critical role in NAFLD. While NPAR did not show significant association, both MHR and HsCRP were elevated in NAFLD, with HsCRP showing exceptional diagnostic performance. These findings are consistent with prior research and highlight the potential of inflammation-based markers, particularly HsCRP, as accessible tools for identifying NAFLD. However, further longitudinal and multicentric studies are needed to validate these markers and determine their utility in clinical risk prediction models. Abbreviations NAFLD: Nonalcoholic Fatty Liver Disease NASH: Nonalcoholic Steatohepatitis NPAR: Neutrophil Percentage to Albumin Ratio MHR: Monocyte-to-high-density lipoprotein cholesterol ratio HsCRP: High-sensitivity C-reactive protein ROC: Receiver Operating Characteristic MAFLD: Metabolic-Associated Fatty Liver Disease Declarations Ethics Approval and Consent to Participate Ethical clearance was obtained from the SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology Institutional Ethics Committee in compliance with the Helsinki Declaration prior to conducting the research. Informed consent was obtained from all participants before the study. Individuals who were unwilling to participate were excluded from the study. Consent for publication All authors have given their consent to participate in the study. Availability of data and materials All data has been provided, which has been generated from this research. Individual data of participants of this research cannot be provided to protect study participant privacy. Competing interests The authors declare no competing interests. Funding The authors gratefully acknowledge the financial support by SRM Medical College & Research Centre for bearing the defrayed costs of publishing this article. Authors' contributions S.S.B. and S.N.M.S conceptualized the study and all authors were involved in the design of the methodology. S.S.B., K.V.P., V.J., J.S., S.G. and S.N.M.S contributed to the collection of relevant literature and data. S.S.B., A.H.S.A.K and T.M. wrote the first draft of the manuscript and made the figures. S.N.M.S. contributed in the review and editing of the manuscript. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version. Acknowledgements Not applicable. References Riazi K, Azhari H, Charette JH, et al. 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Mediators Inflamm . 2021;2021(1):6642246. doi:10.1155/2021/6642246 Soppert J, Brandt EF, Heussen NM, et al. Blood Endotoxin Levels as Biomarker of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol . 2023;21(11):2746-2758. doi:10.1016/j.cgh.2022.11.030 Kumar R, Porwal YC, Dev N, Kumar P, Chakravarthy S, Kumawat A. Association of high-sensitivity C-reactive protein (hs-CRP) with non-alcoholic fatty liver disease (NAFLD) in Asian Indians: A cross-sectional study. J Fam Med Prim Care . 2020;9(1):390. doi:10.4103/jfmpc.jfmpc_887_19 Yoneda M, Mawatari H, Fujita K, et al. High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol . 2007;42(7):573-582. doi:10.1007/s00535-007-2060-x Department of Medicine, PGIMER and Dr. RML Hospital, New Delhi, India, Singh P. Evaluation of Pro-Inflammatory Markers IL-6 and TNF-a and their Correlation with Non-Alcoholic Fatty Liver Disease. J Adv Res Med . 2019;06(02):1-6. doi:10.24321/2349.7181.201906 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7662492","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":527045369,"identity":"2aedffde-a8d4-4e20-ad25-518cb5d2ac70","order_by":0,"name":"Shanmukha Sai Bolisetty","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Shanmukha","middleName":"Sai","lastName":"Bolisetty","suffix":""},{"id":527045372,"identity":"245e9567-8494-46d6-acdc-57e581ef11e9","order_by":1,"name":"Kadiri Venkata Prashanti","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Kadiri","middleName":"Venkata","lastName":"Prashanti","suffix":""},{"id":527045374,"identity":"934b314b-1dd0-4194-8a93-74f3310406c5","order_by":2,"name":"Vismai Juluri","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Vismai","middleName":"","lastName":"Juluri","suffix":""},{"id":527045375,"identity":"7ffd7b12-42d9-4cbd-80f9-e63225e37c27","order_by":3,"name":"Jennie Santhanam","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Jennie","middleName":"","lastName":"Santhanam","suffix":""},{"id":527045378,"identity":"61ee070f-c7a1-4890-bca1-db5255884972","order_by":4,"name":"Siva Govindan","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Siva","middleName":"","lastName":"Govindan","suffix":""},{"id":527045379,"identity":"0b7fe008-e26e-41d9-9758-68d59bbd6dbe","order_by":5,"name":"Tridip Mitra","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Tridip","middleName":"","lastName":"Mitra","suffix":""},{"id":527045381,"identity":"19a5b34e-e2e7-46b2-b4ec-8f8416c4c564","order_by":6,"name":"A. H. Sruthi Anil Kumar","email":"","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"H. Sruthi Anil","lastName":"Kumar","suffix":""},{"id":527045383,"identity":"799244af-f83b-4a27-b621-912e852dad2c","order_by":7,"name":"S. N. Meenakshi Sundari","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIie3PMQrCMBSA4SeFdAm6vlLREwgRobh5lbrokkEQHIMg1MUbeAoX50KgLj1ABkFBqItgcRCHDqYFJ6nVzSH/UF5KPpIAmEx/WwhA7LkeWLFkr+EzqdOw2Izfkxb6xYhQtb+zXETHRywGxDknNzURAuzFFmGyLyVeHI27KyWHgct7a84kAo1mCCwpJ4p7SNPQJy63LM5CBNR/gMlycrjenSzNL7Y7aSIQ2pcKoihxqbJqAUJPE0ufQitIPPLcZqzfQnlOpBPQ0bTvfyI7mTiXSAzay/ximWg0bLlRaVZO3iP5x/8BmEwmk+m9J2VCTa9A68LKAAAAAElFTkSuQmCC","orcid":"","institution":"SRM Institute of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"S.","middleName":"N. Meenakshi","lastName":"Sundari","suffix":""}],"badges":[],"createdAt":"2025-09-20 05:23:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7662492/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7662492/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":93805866,"identity":"887eefca-b849-4b2e-ad90-a3a60e7446ec","added_by":"auto","created_at":"2025-10-17 18:03:38","extension":"tif","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":266810,"visible":true,"origin":"","legend":"","description":"","filename":"Figure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/df96313db50cac90e2d6af99.tif"},{"id":93805861,"identity":"42d816a7-87f4-4e5b-ba47-80a4827c82a0","added_by":"auto","created_at":"2025-10-17 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18:03:38","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":87417,"visible":true,"origin":"","legend":"","description":"","filename":"6261ab78b8ef4058a160e0fe24f187fa1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/4eca6a915b6f0c0af53d7a88.xml"},{"id":93805879,"identity":"7a99f785-c214-4cbe-94a0-c5c3ae040460","added_by":"auto","created_at":"2025-10-17 18:03:38","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94593,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/89bc5be8248de8f575605f21.html"},{"id":93805860,"identity":"62602e4a-cc08-4748-aee1-ae6fbb78465b","added_by":"auto","created_at":"2025-10-17 18:03:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":309376,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC Curve for Neutrophil Percentage-to-Albumin Ratio in Predicting NAFLD\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/6867cbf70ec628121a13b305.png"},{"id":93806443,"identity":"b91ecd5c-86f3-4570-91db-945a781541f5","added_by":"auto","created_at":"2025-10-17 18:11:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":290991,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC Curve for Monocyte-to-HDL Ratio in Predicting NAFLD\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/0df4fb250b294531e540f072.png"},{"id":93805864,"identity":"8a415e11-c653-45d5-8872-e9fcd45a37de","added_by":"auto","created_at":"2025-10-17 18:03:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":293526,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eROC Curve for High-Sensitivity C-Reactive Protein in Predicting NAFLD\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/5313647aca95dad32d593732.png"},{"id":96710482,"identity":"c9892546-81aa-4bb2-92a1-057eb78d0c4d","added_by":"auto","created_at":"2025-11-25 10:10:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1517444,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7662492/v1/e1efa765-24b9-4578-b315-7e752b64ca26.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Biomarker Signatures in Non-Alcoholic Fatty Liver Disease: Hs-CRP, Monocyte to High-Density Lipoprotein Cholesterol Ratio and Neutrophil Percentage to Albumin Ratio","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eNonalcoholic fatty liver disease (NAFLD) has recently been identified as one of the most prevalent global health issues, impacting over 32.4% of individuals globally\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. The prevalence rate of NAFLD in India is 38.6%\u003csup\u003e1\u003c/sup\u003e. An increasing volume of research suggests that NAFLD patients are at much higher risk of developing hepatocellular carcinoma as well\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. NAFLD has also been linked to type 2 diabetes, obesity, hypertension, and other aspects of metabolic syndrome\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNAFLD refers to a spectrum of illnesses linked with metabolic problems, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which can further proceed to liver cirrhosis and consequences\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Over the last several years, the worldwide burden of obesity and related metabolic diseases has increased significantly\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. NASH is characterized by a variety of pathophysiological changes in the liver, beginning with hepatocyte stress, damage, apoptosis, and inflammation and progressing to fibrosis\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. In the absence of early diagnosis and effective care, NASH can develop to cirrhosis, with the incidence of severe F3 and F4 fibrosis associated with NASH quickly increasing\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Therefore, identification of NAFLD patients is essential in order to optimally manage these cases, and various non-invasive tools have been developed in this regard, although no unique biomarker is solely acknowledged to meet the requirements sufficiently.\u003c/p\u003e\u003cp\u003eEarly diagnosis and risk stratification of NAFLD are critical for avoiding disease progression and consequences. However, liver biopsy, the gold standard for diagnosing and staging NAFLD, is intrusive, costly, and unsuitable for large-scale screenings\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Ultrasonography and elastography are popular imaging modalities, but their usage is limited due to cost, accessibility, and operator dependence\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. As a result, there is an urgent need for simple, cost-effective, and non-invasive biomarkers that can help identify people at risk for NAFLD, especially those in primary care and resource-limited settings\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSeveral hematological and biochemical ratios have recently been found to be potential inflammatory biomarkers for metabolic and hepatic ailments\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Among them, the neutrophil percentage to albumin ratio (NPAR) has been proposed as a new measure for systemic inflammation\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Elevated neutrophil counts suggest immunological activation, but low albumin levels might indicate both hepatic impairment and chronic inflammation\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Although NPAR has been examined in sepsis and cancer, its involvement in NAFLD is not understood.\u003c/p\u003e\u003cp\u003eAnother intriguing metric is the monocyte-to-high-density lipoprotein cholesterol ratio (MHR), which links innate immune activity to lipid metabolism\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Monocytes cause hepatic inflammation and fibrosis, whereas HDL cholesterol has anti-inflammatory and antioxidant effects\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Elevated MHR has been linked to atherosclerosis, metabolic syndrome, and, more recently, NAFLD\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, indicating its potential as a substitute for metabolic inflammation.\u003c/p\u003e\u003cp\u003eHigh-sensitivity C-reactive protein (HsCRP) persists as one of the most commonly investigated indicators of systemic inflammation\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Elevated HsCRP levels have repeatedly been linked to obesity\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e, insulin resistance\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, and liver steatosis\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, the extent of its predictive utility for NAFLD diagnosis in various groups is currently being investigated.\u003c/p\u003e\u003cp\u003eGiven this context, the present study aims to evaluate and compare the clinical utility of NPAR, MHR, and HsCRP in distinguishing individuals with and without NAFLD. By assessing their discriminatory capacity and correlation with clinical and biochemical parameters, this study seeks to identify inflammation-based indices that may serve as practical and non-invasive tools for early identification of NAFLD in clinical practice.\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Data Collection Procedure\u003c/h2\u003e\u003cp\u003eThis cross-sectional study included 102 patients aged above 18 years who visited the outpatient ward of a tertiary care hospital in Tamil Nadu, India, between March 2023 and March 2025. Patients with a history of alcohol consumption (males\u0026thinsp;\u0026gt;\u0026thinsp;140g/week, females\u0026thinsp;\u0026gt;\u0026thinsp;70g/week), drug induced steatohepatitis, acute inflammatory condition, known case of acute and chronic liver disease or malignancy, and coronary artery disease were excluded from the study. Patients on statin therapy, both oral contraceptive pills and hepatotoxic drugs were also excluded from the study. Age, sex and BMI matched individuals without fatty liver on ultrasound abdomen will be included in control group.\u003c/p\u003e\u003cp\u003eThe patients were diagnosed for NAFLD using ultrasonography. The blood investigations will be done for all the participants in both case (n\u0026thinsp;=\u0026thinsp;51) and control (n\u0026thinsp;=\u0026thinsp;51) groups.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Data Entry and Analysis\u003c/h2\u003e\u003cp\u003eThe statistical analysis was done using STATA version 17. The p-value of less than 0.05 was seen to be statistically significant.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Ethical Considerations\u003c/h2\u003e\u003cp\u003e The authors have received the institutional ethical committee clearance certificate from SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India for conducting this research on humans. Informed consent was provided to the patients in both English and native language prior to data collection.\u003c/p\u003e\u003cp\u003eSpecial care was taken about there are no violation of human rights during conducting this research.\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eThe NPAR with NAFLD is shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A two-sample t-test was used to compare participants with and without NAFLD. NAFLD patients had a slightly higher average NPAR (14.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11) than non-NAFLD patients (13.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81), but this difference was not statistically significant (t = -1.27, p\u0026thinsp;=\u0026thinsp;0.2064).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTwo-sample t-tests for Neutrophil Percentage to Albumin Ratio\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;No\u003c/p\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;YES\u003c/p\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003et-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil Percentage to Albumin Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.2064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe non-parametric comparison of the MHR and HsCRP using the Mann-Whitney U test is displayed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The findings indicate that the HsCRP levels of those with and without NAFLD varied statistically significantly. With a z-score of -9.34 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), those with NAFLD had considerably higher rankings (Rank Sum\u0026thinsp;=\u0026thinsp;5409) than those without the condition (Rank Sum\u0026thinsp;=\u0026thinsp;1851). Similarly, those with NAFLD had a considerably higher MHR (Rank Sum\u0026thinsp;=\u0026thinsp;4327 vs. 2934; z = -3.66, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Thus, it is clear from the data that NAFLD is associated with considerably higher levels of both the MHR and HsCRP.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMann-Whitney U Test for High Sensitivity C Reactive Protein and Monocyte to HDL Ratio by NAFLD Status\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRank Sum\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eExpected\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ez\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1851\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-9.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;Yes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5409\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;No\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2934\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-3.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;Yes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3630\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe summary data for the mean and standard deviation of the laboratory and clinical parameters are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Hemoglobin, white blood cell count, platelet count, absolute leukocyte count, and neutrophil percentage were all somewhat higher in persons with NAFLD. The findings indicate that lipid indicators, including triglycerides, VLDL, and total cholesterol, as well as liver function tests like AST, ALT, and alkaline phosphatase, were higher in the NAFLD subjects. Furthermore, individuals with NAFLD had significantly higher HsCRP levels (1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68 vs. 0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25), which is associated with systemic inflammation. Those with NAFLD also had higher MHR and NPAR values.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary Statistics by NAFLD Status\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;No\u003c/p\u003e\u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNAFLD\u0026thinsp;=\u0026thinsp;Yes (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e46.58\u0026thinsp;\u0026plusmn;\u0026thinsp;17.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e50.88\u0026thinsp;\u0026plusmn;\u0026thinsp;11.37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e12.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite blood cells\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e6929.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1996.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e7184.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1884.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e280.18\u0026thinsp;\u0026plusmn;\u0026thinsp;67.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e297.43\u0026thinsp;\u0026plusmn;\u0026thinsp;74.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbsolute leucocyte count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e2142.33\u0026thinsp;\u0026plusmn;\u0026thinsp;689.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2253.67\u0026thinsp;\u0026plusmn;\u0026thinsp;590.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil percentage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e60.48\u0026thinsp;\u0026plusmn;\u0026thinsp;8.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e60.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDirect bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e0.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkaline phosphatase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e68.62\u0026thinsp;\u0026plusmn;\u0026thinsp;21.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e81.95\u0026thinsp;\u0026plusmn;\u0026thinsp;24.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspartate aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e23.92\u0026thinsp;\u0026plusmn;\u0026thinsp;13.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e25.60\u0026thinsp;\u0026plusmn;\u0026thinsp;10.23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlanine aminotransferase\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e20.25\u0026thinsp;\u0026plusmn;\u0026thinsp;10.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e24.77\u0026thinsp;\u0026plusmn;\u0026thinsp;11.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal cholesterol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e190.35\u0026thinsp;\u0026plusmn;\u0026thinsp;44.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e189.60\u0026thinsp;\u0026plusmn;\u0026thinsp;40.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTriglycerides\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e104.60\u0026thinsp;\u0026plusmn;\u0026thinsp;51.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e122.67\u0026thinsp;\u0026plusmn;\u0026thinsp;48.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh density lipoprotein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e48.78\u0026thinsp;\u0026plusmn;\u0026thinsp;10.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e46.45\u0026thinsp;\u0026plusmn;\u0026thinsp;10.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow density lipoprotein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e134.80\u0026thinsp;\u0026plusmn;\u0026thinsp;38.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e136.00\u0026thinsp;\u0026plusmn;\u0026thinsp;34.98\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVery low-density lipoprotein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e21.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e25.33\u0026thinsp;\u0026plusmn;\u0026thinsp;11.66\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh sensitivity C reactive protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e1.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.40\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeutrophil Percentage to Albumin Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e13.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e14.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMonocyte to HDL Ratio\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e9.42\u0026thinsp;\u0026plusmn;\u0026thinsp;4.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e13.47\u0026thinsp;\u0026plusmn;\u0026thinsp;6.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe ROC curve for the NPAR as NAFLD predictor is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The low discriminating ability is indicated by the Area Under the Curve (AUC), which was just 0.5592. This finding implies that in this group, the NPAR cannot be utilized as a stand-alone marker to identify people with NAFLD.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe receiver operating characteristic (ROC) curve for the MHR that predicts NAFLD is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. An AUC of 0.6935 indicates a moderate capacity for discrimination. This finding suggests that the MHR has a mild ability to distinguish between those with and without NAFLD.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe ROC curve, assessing HsCRP's ability to predict the presence of NAFLD, is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. With an AUC of 0.9942, the diagnostic accuracy is high. HsCRP can nearly fully distinguish between those with and without NAFLD in this group, according to an AUC of 0.9942. This finding indicates a substantial correlation between NAFLD in this group and systemic inflammation, as measured by HsCRP levels. Nonetheless, it is worth noting that the HsCRP distribution across NAFLD status showed almost complete separation. All individuals with HsCRP values below 1.0 mg/L (n\u0026thinsp;=\u0026thinsp;57) didn\u0026rsquo;t have NAFLD, while 95.2% of individuals with HsCRP\u0026thinsp;\u0026ge;\u0026thinsp;1.0 mg/L (60 of 63) were classified as having NAFLD. This threshold-based separation could explain the exceptionally high area under the curve (AUC\u0026thinsp;=\u0026thinsp;0.9942) observed in the ROC analysis, indicating the near-perfect discriminatory ability of HsCRP for identifying NAFLD in this cohort, although external validation is warranted.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study aimed to evaluate the utility of inflammatory biomarkers NPAR, MHR, and HsCRP in identifying NAFLD. Our findings suggest that among these, HsCRP demonstrated the strongest discriminatory capacity, followed by MHR, while NPAR showed no significant association with NAFLD status.\u003c/p\u003e\u003cp\u003eIn the present study, NPAR levels were marginally elevated in individuals with NAFLD compared to those without (14.55\u0026thinsp;\u0026plusmn;\u0026thinsp;2.11 vs. 13.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.81), but the difference was not statistically significant. This is in contrast with studies that have identified NPAR as a significant marker of systemic inflammation in liver conditions. \u003cem\u003eWang et al., 2024\u003c/em\u003e reported that elevated NPAR was associated with hepatic steatosis severity in a Chinese adult population\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Similarly, in their study by \u003cem\u003eWaili et al., 2025\u003c/em\u003e found that NPAR was independently associated with liver fibrosis in patients with acute-on-chronic liver failure\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe discrepancy may stem from differences in patient populations, NAFLD diagnostic methods, or disease stages. It is plausible that in our cohort, consisting predominantly of individuals with early or subclinical NAFLD, the inflammatory burden was not sufficient to influence albumin levels or neutrophil percentages significantly. Furthermore, NPAR may be more sensitive to acute or severe inflammation, as shown in advanced liver fibrosis by \u003cem\u003eLiu et al., 2023\u003c/em\u003e\u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur findings support previous literature that identifies MHR as a promising marker of metabolic and cardiovascular inflammation. Individuals with NAFLD had significantly higher MHR values, and the ROC analysis yielded an AUC of 0.6935, suggesting moderate discriminatory capacity. This aligns with the results of \u003cem\u003eKohsari et al., 2022\u003c/em\u003e, on Kurdish cohort study in Iran showing the correlation of the MHR levels in NAFLD patients\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Likewise, \u003cem\u003eWang et al., 2022\u003c/em\u003e demonstrated that MHR was significantly higher in NAFLD patients compared to controls and correlated with fibrosis severity and liver stifness\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMHR integrates innate immune activity (monocyte count) and lipid anti-inflammatory properties (HDL levels), both of which are altered in NAFLD due to chronic low-grade inflammation and dyslipidemia\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Our study further supports this pathophysiological association and emphasizes the potential of MHR as a simple, cost-effective marker that may assist in screening or risk stratification.\u003c/p\u003e\u003cp\u003eHigh-sensitivity CRP showed the most robust association with NAFLD in our study. Not only were HsCRP levels significantly elevated in individuals with NAFLD (1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68 mg/L vs. 0.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25 mg/L), but the ROC curve demonstrated an AUC of 0.9942, indicating near-perfect discriminatory ability. This finding mirrors several previous studies. \u003cem\u003eSoppert et al., 2023\u003c/em\u003e conducted a meta-analysis and concluded that elevated CRP levels were consistently associated with NAFLD and NASH across multiple studies\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Interestingly, \u003cem\u003eKumar et al., 2020\u003c/em\u003e observed that HsCRP was a strong predictor of NAFLD in a large population-based cohort, even after adjusting for obesity and metabolic syndrome in a cohort of north Indian population\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. \u003csup\u003e29\u003c/sup\u003e\u003cem\u003eYoneda et al\u003c/em\u003e., 2007 reported AUCs of 0.82\u0026ndash;0.89 for HsCRP in metabolic-associated fatty liver disease (MAFLD), while Park et al noted HsCRP\u0026thinsp;\u0026ge;\u0026thinsp;1.5 mg/L predicted advanced fibrosis (AUC\u0026thinsp;=\u0026thinsp;0.76)\u003csup\u003e29\u003c/sup\u003e. Our higher AUC may reflect stricter cohort selection (e.g., exclusion of confounding comorbidities) or earlier disease detection.\u003c/p\u003e\u003cp\u003eFurthermore, the sharp separation at the 1.0 mg/L threshold in our dataset\u0026mdash;where nearly all individuals above this cut-off had NAFLD\u0026mdash;suggests a potential diagnostic utility. While HsCRP is not specific to NAFLD and may be influenced by other inflammatory conditions, the near-complete separation observed supports its role in NAFLD screening. However, as \u003cem\u003eLee et al., 2019\u003c/em\u003e cautioned, the specificity of HsCRP may drop in populations with higher comorbidity burdens or concurrent infections. Thus, while our findings are highly promising, validation in larger and more diverse populations is necessary.\u003c/p\u003e\u003cp\u003eThe observed associations between NAFLD and elevated inflammatory markers support the growing consensus that NAFLD is not merely a hepatic manifestation of obesity, but a chronic inflammatory condition with systemic implications. The elevated levels of liver enzymes (ALT, AST), lipid parameters (VLDL, triglycerides, total cholesterol), and inflammatory blood counts (WBC, neutrophils) in NAFLD participants in our study further reinforce the interplay between hepatic steatosis and systemic inflammation.\u003c/p\u003e\u003cp\u003eOur findings are consistent with the broader literature suggesting that NAFLD is a hepatic component of metabolic syndrome, driven by insulin resistance, dyslipidemia, and chronic inflammation. According to a study by \u003cem\u003eKhura et al., 2019\u003c/em\u003e, CRP, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels are elevated in NAFLD and may contribute to disease progression from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eWhile our findings are consistent with numerous previous research, there are certain limitations. To begin, the diagnosis of NAFLD was most frequently made using clinical or imaging criteria rather than a liver biopsy, which might lead to misclassification, especially in the early stages of the illness. Secondly, the cross-sectional design may prohibit causal inference. Lastly, we did not account for confounding variables such as BMI, diabetes, or medication usage, which can all alter inflammatory markers independently. Furthermore, the high AUC obtained for HsCRP may indicate overfitting, particularly if the NAFLD and non-NAFLD groups were very homogenous. As a result, our findings should be verified in external cohorts with diverse demographic and clinical characteristics.\u003c/p\u003e\u003cp\u003eThis niche-specific and race-specific study conducted on South Indian population adds to the existing body of evidence suggesting that inflammation plays a critical role in NAFLD. While NPAR did not show significant association, both MHR and HsCRP were elevated in NAFLD, with HsCRP showing exceptional diagnostic performance. These findings are consistent with prior research and highlight the potential of inflammation-based markers, particularly HsCRP, as accessible tools for identifying NAFLD. However, further longitudinal and multicentric studies are needed to validate these markers and determine their utility in clinical risk prediction models.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNAFLD: Nonalcoholic Fatty Liver Disease\u003c/p\u003e\n\u003cp\u003eNASH: Nonalcoholic Steatohepatitis\u003c/p\u003e\n\u003cp\u003eNPAR: Neutrophil Percentage to Albumin Ratio\u003c/p\u003e\n\u003cp\u003eMHR: Monocyte-to-high-density lipoprotein cholesterol ratio\u003c/p\u003e\n\u003cp\u003eHsCRP: High-sensitivity C-reactive protein\u003c/p\u003e\n\u003cp\u003eROC: Receiver Operating Characteristic\u003c/p\u003e\n\u003cp\u003eMAFLD: Metabolic-Associated Fatty Liver Disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical clearance was obtained from the SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology Institutional Ethics Committee\u0026nbsp;in compliance with the Helsinki Declaration prior to conducting the research. Informed consent was obtained from all participants before the study. Individuals who were unwilling to participate were excluded from the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have given their consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data has been provided, which has been generated from this research. Individual data of participants of this research cannot be provided to protect study participant privacy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the financial support by SRM Medical College \u0026amp; Research Centre for bearing the defrayed costs of publishing this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.S.B. \u0026nbsp;and S.N.M.S conceptualized the study and all authors were involved in the design of the methodology. S.S.B., K.V.P., V.J., J.S., S.G. and S.N.M.S contributed to the collection of relevant literature and data. S.S.B., A.H.S.A.K and T.M. wrote the first draft of the manuscript and made the figures. S.N.M.S. contributed in the review and editing of the manuscript. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRiazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. \u003cem\u003eLancet Gastroenterol Hepatol\u003c/em\u003e. 2022;7(9):851-861. doi:10.1016/S2468-1253(22)00165-0\u003c/li\u003e\n\u003cli\u003eGeh D, Manas DM, Reeves HL. Hepatocellular carcinoma in non-alcoholic fatty liver disease\u0026mdash;a review of an emerging challenge facing clinicians. \u003cem\u003eHepatobiliary Surg Nutr\u003c/em\u003e. 2021;10(1):59-75. doi:10.21037/hbsn.2019.08.08\u003c/li\u003e\n\u003cli\u003eDharmalingam M, Yamasandhi PG. Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus. \u003cem\u003eIndian J Endocrinol Metab\u003c/em\u003e. 2018;22(3):421-428. doi:10.4103/ijem.IJEM_585_17\u003c/li\u003e\n\u003cli\u003eZarghamravanbakhsh P, Frenkel M, Poretsky L. Metabolic causes and consequences of nonalcoholic fatty liver disease (NAFLD). \u003cem\u003eMetab Open\u003c/em\u003e. 2021;12:100149. doi:10.1016/j.metop.2021.100149\u003c/li\u003e\n\u003cli\u003eZhang H, Zhou XD, Shapiro MD, et al. Global burden of metabolic diseases, 1990\u0026ndash;2021. \u003cem\u003eMetabolism\u003c/em\u003e. 2024;160:155999. doi:10.1016/j.metabol.2024.155999\u003c/li\u003e\n\u003cli\u003eObesity and overweight. Accessed August 5, 2025. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight\u003c/li\u003e\n\u003cli\u003ePierantonelli I, Svegliati-Baroni G. 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Evaluation of Pro-Inflammatory Markers IL-6 and TNF-a and their Correlation with Non-Alcoholic Fatty Liver Disease. \u003cem\u003eJ Adv Res Med\u003c/em\u003e. 2019;06(02):1-6. doi:10.24321/2349.7181.201906\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"-Reactive protein, monocyte to high-density lipoprotein cholesterol ratio, neutrophil percentage to albumin ratio, non-alcoholic fatty liver disease","lastPublishedDoi":"10.21203/rs.3.rs-7662492/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7662492/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eNAFLD (Non-Alcoholic Fatty Liver Disease) is liver fat buildup unrelated to alcohol, linked to obesity, diabetes, and metabolic syndrome. It ranges from simple steatosis to NASH (inflammation/fibrosis). Often asymptomatic, detected via blood tests or imaging. Managed with weight loss, diet, exercise, and controlling metabolic risks to prevent cirrhosis or liver cancer. The present study aims to investigate the association between human serum C-Reactive protein (hs-CRP), monocyte to high-density lipoprotein cholesterol ratio (MHR) and neutrophil percentage to albumin ratio (NPR) with non-alcoholic fatty liver disease (NAFLD) in the South-Indian population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA cross-sectional study included 102 patients (51 case and 51 control) aged above 18 years who visited the outpatient ward of a tertiary care hospital in Tamil Nadu, India. The diagnosis for NAFLD was done using ultrasonographic findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e NAFLD patients exhibited slightly higher NPAR levels compared to non-NAFLD individuals, though the difference was not statistically significant (p = 0.2064). However, both MHR and HsCRP were significantly elevated in NAFLD (p \u0026lt; 0.001). ROC analysis revealed that HsCRP had near-perfect discriminatory power for NAFLD (AUC = 0.9942), with a cutoff of ≥1.0 mg/L correctly classifying 95.2% of cases. MHR showed moderate predictive ability (AUC = 0.6935), while NPAR performed poorly (AUC = 0.5592).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Our findings highlight HsCRP as a highly sensitive marker for NAFLD, though further validation is needed to confirm its diagnostic utility in broader populations.\u003c/p\u003e","manuscriptTitle":"Predictive Biomarker Signatures in Non-Alcoholic Fatty Liver Disease: Hs-CRP, Monocyte to High-Density Lipoprotein Cholesterol Ratio and Neutrophil Percentage to Albumin Ratio","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-17 18:03:33","doi":"10.21203/rs.3.rs-7662492/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a01ecf51-aa78-48d3-8625-78803c62b30e","owner":[],"postedDate":"October 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-25T05:23:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-17 18:03:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7662492","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7662492","identity":"rs-7662492","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}