A Systematic Review on Clinicopathological Evaluation of Neutrophil-Percentage-To-Albumin-Ratio (NPAR): An Emerging Biomarker for Hepato-Pathology and Hepato-Oncology
DOI:
https://doi.org/10.36283/ziun-pjmd14-2/067Keywords:
Neutrophil, Albumin, Hepatopathology, Hepatocellular Carcinoma, BiomarkersAbstract
Background: The Neutrophil Percentage to Albumin Ratio (NPAR) proved to be an advanced combined pathological marker for assessing hepatopathology and hepatocellular carcinoma (HCC). The diagnostic value of NPAR remained unclear because research on its clinical applications and performance in contrast to typical biomarkers remains scarce. The goal of this evaluation was to methodically analyze and assess NPAR’s role as a biomarker in the examination of hepatopathology and hepatocellular carcinoma.
Methods: A systematic review in line with PRISMA guidelines used MEDLINE, Scopus, and Web of Science databases to access research articles published from January 2010 to January 2025. The research included original peer-reviewed studies and systematic reviews in the English language that examined the link between NPAR and liver diseases alongside HCC cases. Researchers excluded articles that were not peer-reviewed, along with abstracts and studies lacking complete or sufficient data etc. The researchers evaluated studies based on their research methods, NPAR threshold requirements, and diagnostic capabilities in actual clinical practice. Study bias risk was evaluated through analysis of the Evidence Project Risk of Bias Tool. The authors performed a qualitative data synthesis to provide a comparative understanding of NPAR’s therapeutic relevance.
Results: The initial search yielded 89 articles, which were screened based on inclusion criteria. After reviewing titles and abstracts, 30 articles met the inclusion criteria. Following full-text review, 12 studies were selected for final analysis. Participant samples ranged from 100 to 3000 individuals. Numerous studies in the review examined NPAR's performance as both a diagnostic and prognostic indicator. NPAR proved to be a superior marker to standard biomarkers ALT, AST, and bilirubin for chronic liver disease and HCC diagnosis in most published studies. Clinical implementation of NPAR showed effective results in high-risk patient screening, disease progression tracking, and survival outcome estimation. Research combined NPAR measurements with other biomarkers to demonstrate how it could work with multiple diagnostic markers.
Discussion: The Neutrophil Percentage to Albumin Ratio (NPAR) has proven itself as a vital biomarker for managing liver diseases and hepatocellular carcinoma. The medical field needed sustained, large-scale assessments to establish NPAR's worth as a diagnostic tool, prognostic indicator, and therapeutic target in hepatopathology and hepatocellular carcinoma.
References
Mak LY, Liu K, Chirapongsathorn S, Yew KC, Tamaki N, Rajaram RB et al. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol. 2024 Dec;21(12):834-851. doi: 10.1038/s41575-024-00967-4.
Labenz C, Arslanow A, Nguyen-Tat M, Nagel M, Wörns MA, Reichert MC et al. Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL. J Hepatol. 2022 Sep;77(3):695-701. doi: 10.1016/j.jhep.2022.04.009.
Sharma KK, Mohsin M, Mittal P, Ali Z, Fatma N, Upadhyay P et al. Diagnosis of the Initial Stage of Hepatocellular Carcinoma: A Review. Curr Pharm Des. 2024;30(22):1708-1724. doi: 10.2174/0113816128298875240321073907.
Anstee QM, Castera L, Loomba R. Impact of non-invasive biomarkers on hepatology practice: Past, present and future. J Hepatol. 2022 Jun;76(6):1362-1378. doi: 10.1016/j.jhep.2022.03.026.
Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? J Hepatol. 2023 Jan;78(1):207-216. doi: 10.1016/j.jhep.2022.08.036.
Liu CF, Chien LW. Predictive Role of Neutrophil-Percentage-to-Albumin Ratio (NPAR) in Nonalcoholic Fatty Liver Disease and Advanced Liver Fibrosis in Nondiabetic US Adults: Evidence from NHANES 2017-2018. Nutrients. 2023 Apr;15(8):1892. doi: 10.3390/nu15081892.
Cucoranu DC, Pop M, Niculescu R, Kosovski IB, Toganel RO, Licu RA et al. The Association of Nonalcoholic Fatty Liver Disease With Neutrophil-to-Lymphocyte Ratio and Neutrophil-Percentage-to-Albumin Ratio. Cureus. 2023 Jun;15(6):e41197. doi: 10.7759/cureus.41197.
Chen G, Fan L, Yang T, Xu T, Wang Z, Wang Y et al. Prognostic nutritional index (PNI) and risk of non-alcoholic fatty liver disease and advanced liver fibrosis in US adults: Evidence from NHANES 2017-2020. Heliyon. 2024 Feb;10(4):e25660. doi: 10.1016/j.heliyon.2024.e25660.
Nørgaard BL, Gaur S, Fairbairn TA, Douglas PS, Jensen JM, Patel MR et al. Prognostic value of coronary computed tomography angiographic derived fractional flow reserve: a systematic review and meta-analysis. Heart. 2022 Feb;108(3):194-202. doi: 10.1136/heartjnl-2021-319773.
Bao B, Xu S, Sun P, Zheng L. Neutrophil to albumin ratio: a biomarker in non-alcoholic fatty liver disease and with liver fibrosis. Front Nutr. 2024 Apr;11(1):1368459. doi: 10.3389/fnut.2024.1368459.
Li X, Wu M, Chen M, Liu R, Tao Q, Hu Y et al. The Association Between Neutrophil-Percentage-to-Albumin Ratio (NPAR) and Mortality Among Individuals With Cancer: Insights From National Health and Nutrition Examination Survey. Cancer Med. 2025 Jan;14(2):e70527. doi: 10.1002/cam4.70527.
Du X, Wei X, Ma L, Liu X, Guo H, Liu Y et al. Higher levels of neutrophil percentage-to-albumin ratio predict increased mortality risk in patients with liver cirrhosis: a retrospective cohort study. Eur J Gastroenterol Hepatol. 2023 Feb;35(2):198-203. doi: 10.1097/MEG.0000000000002470.
Yu Y, Zhong Z, Yang W, Yu J, Li J, Guo X et al. Neutrophil Percentage-to-Albumin Ratio and Risk of Mortality in Patients on Peritoneal Dialysis. J Inflamm Res. 2023 Dec 21;16:6271-6281.
Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol. 2020 Sep;26(33):5022-5049. doi: 10.3748/wjg.v26.i33.5022.
He MY, Du XJ, Liu YM. Association between neutrophil-albumin ratio and ultrasound-defined metabolic dysfunction-associated fatty liver disease in U.S. adults: evidence from NHANES 2017-2018. BMC Gastroenterol. 2025 Jan;25(1):20. doi: 10.1186/s12876-025-03612-9.
Wang Y, Chen S, Tian C, Wang Q, Yang Z, Che W et al. Association of systemic immune biomarkers with metabolic dysfunction-associated steatotic liver disease: a cross-sectional study of NHANES 2007-2018. Front Nutr. 2024 Sep;11(1):1415484. doi: 10.3389/fnut.2024.1415484.
Feng Y, Xu W, Tang S, Ye Z, Fang P, Abdullah G et al. Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes. Diabetes Res Clin Pract. 2024 Jul;213(1):111749. doi: 10.1016/j.diabres.2024.111749.
Lissing M, Vassiliou D, Floderus Y, Harper P, Bottai M, Kotopouli M et al. Risk of primary liver cancer in acute hepatic porphyria patients: A matched cohort study of 1244 individuals. J Intern Med. 2022 Jun;291(6):824-836. doi: 10.1111/joim.13463
Celikbilek M, Dogan S, Gursoy S, Zararsız G, Yurci A, Ozbakır O et al. Noninvasive assessment of liver damage in chronic hepatitis B. World J Hepatol. 2013 Aug;5(8):439-445. doi: 10.4254/wjh.v5.i8.439.
Zhang Y, Luo Q, Lin X, Wang L, Li Z, Chen J et al. Development and Validation of a New Model Including Inflammation Indexes for the Long-Term Prognosis of Hepatitis B-Related Acute-On-Chronic Liver Failure. J Med Virol. 2024 Dec;96(12):e70110. doi: 10.1002/jmv.70110.
Abou-Fadel J, Reid V, Le A, Croft J, Zhang J. Key Members of the CmPn as Biomarkers Distinguish Histological and Immune Subtypes of Hepatic Cancers. Diagnostics (Basel). 2023 Feb;13(6):1012. doi: 10.3390/diagnostics13061012.
Yao J, Sun J, Ebrahimi F, Bergman D, Green PH, Hagström H et al. Long-term risk of chronic liver disease in patients with celiac disease: a nationwide population-based, sibling-controlled cohort study. The Lan Reg Health–Eur. 2024 Dec;1(1);101201. doi: 10.1016/j.lanepe.2024.101201.
Vaz J, Strömberg U, Midlöv P, Eriksson B, Buchebner D, Hagström H. Unrecognized liver cirrhosis is common and associated with worse survival in hepatocellular carcinoma: A nationwide cohort study of 3473 patients. J Intern Med. 2023 Feb;293(2):184-199. doi: 10.1111/joim.13570.
Zhuang PY, Wang JD, Tang ZH, Zhou XP, Yang Y, Quan ZW et al. Peritumoral Neuropilin-1 and VEGF receptor-2 expression increases time to recurrence in hepatocellular carcinoma patients undergoing curative hepatectomy. Oncotarget. 2014 Nov;5(22):11121-11132. doi: 10.18632/oncotarget.2553.
Yang Y, He X, Tan S, Qu X, Huang W, Cai J et al. The association between immunoinflammatory biomarkers NLR, PLR, LMR and nonalcoholic fatty liver disease: a systematic review and meta-analysis. Clin Exp Med. 2025 Jan;25(1):39. doi: 10.1007/s10238-024-01539-1.
Deleuran T, Vilstrup H, Becker U, Jepsen P. Epidemiology of alcoholic liver disease in Denmark 2006-2011: a population-based study. Alcohol Alcohol. 2015 Apr;50(3):352-357. doi: 10.1093/alcalc/agv003.
Samad A, Zafar S, Ahmed MA, Ahsan N, Rizwan M, Shaikh SP et al. A Biomarker-Centric Diagnostic Approach based on Neutrophil Percentage to Albumin Ratio (NPAR) for Diabetic UTIs: Biomarker-Centric Diagnostic Approach for Diabetic Urinary Tract Infections. Pak J of Health Sci. 2024 Jan;11(5):288-295. doi:54393/pjhs.v5i11.2534
Mousa N, Salah M, Elbaz S, Elmetwalli A, Elhammady A, Abdelkader E, et al. Neutrophil percentage-to-albumin ratio is a new diagnostic marker for spontaneous bacterial peritonitis: a prospective multicenter study. Gut Pathog. 2024 Apr 1;16(1):18. doi: 10.1186/s13099-024-00610-2.
Jing Y, Tian B, Deng W, Ren Z, Xu X, Zhang D, et al. The Neutrophil Percentage-to-Albumin Ratio as a Biomarker for All-Cause and Diabetes-Cause Mortality Among Diabetes Patients: Evidence From the NHANES 1988-2018. J Clin Lab Anal. 2024 Nov;38(21):e25110. doi: 10.1002/jcla.25110.
Shang Y, Akbari C, Dodd M, Zhang X, Wang T, Jemielita T, et al. Association between longitudinal biomarkers and major adverse liver outcomes in patients with non-cirrhotic metabolic dysfunction-associated steatotic liver disease. Hepatology. 2024 Aug;1(1);1045. doi: 10.1097/HEP.0000000000001045..
Lan CC, Su WL, Yang MC, Chen SY, Wu YK. Predictive role of neutrophil-percentage-to-albumin, neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios for mortality in patients with COPD: Evidence from NHANES 2011-2018. Respirology. 2023 Dec;28(12):1136-1146. doi: 10.1111/resp.14589.
Wang L, Liu L, Liu X, Yang L. The association between neutrophil percentage-to-albumin ratio (NPAR) and depression among US adults: a cross-sectional study. Sci Rep. 2024 Sep;14(1):21880. doi: 10.1038/s41598-024-71488-y.
Ji W, Li H, Qi Y, Zhou W, Chang Y, Xu D, et al. Association between neutrophil-percentage-to-albumin ratio (NPAR) and metabolic syndrome risk: insights from a large US population-based study. Sci Rep. 2024 Nov;14(1):26646. doi: 10.1038/s41598-024-77802-y.
Yu Y, Zhong Z, Yang W, Yu J, Li J, Guo X, et al. Neutrophil Percentage-to-Albumin Ratio and Risk of Mortality in Patients on Peritoneal Dialysis. J Inflamm Res. 2023 Dec;16(1):6271-6281. doi: 10.2147/JIR.S437256.
Zhang J, Li D, Guo H, Yang J, Zhang H, Wu J, et al. Negative association between the neutrophil percentage-to-albumin ratio (NPAR) and psoriasis: a retrospective cross-sectional study. Arch Dermatol Res. 2025 Jan;317(1):190. doi: 10.1007/s00403-024-03695-6.
Fan D, Wang T, Xiang J, Bai Y, Zhang L, Wang X. Neutrophil percentage-to-albumin ratio is associated with cognitive function in adults aged over 60 years: An analysis of data from the NHANES 2011-2014. J Alzheimers Dis. 2024 Nov;102(1):150-161. doi: 10.1177/13872877241283849.
Tang Y, Hou H, Li L, Yong L, Zhang S, Yan L, et al. Neutrophil Percentage-to-Albumin Ratio: A Good Parameter for the Evaluation of the Severity of Anti-NMDAR Encephalitis at Admission and Prediction of Short-Term Prognosis. Front Immunol. 2022 Apr;13(1):847200. doi: 10.3389/fimmu.2022.847200.
Gong Y, Li D, Cheng B, Ying B, Wang B. Increased neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with severe sepsis or septic shock. Epidemiol Infect. 2020 Apr;148:e87. doi: 10.1017/S0950268820000771.
Sun D, Du X, Cao X, Wu B, Li S, Zhao Y, et al. Neutrophil-Based Bionic Delivery System Breaks Through the Capillary Barrier of Liver Sinusoidal Endothelial Cells and Inhibits the Activation of Hepatic Stellate Cells. Mol Pharm. 2024 Apr;21(4):2043-2057. doi: 10.1021/acs.molpharmaceut.4c00173.
Blonder JM, McCalden TA, Hsia CJ, Billings RE. Polynitroxyl albumin plus tempol attenuates liver injury and inflammation after hepatic ischemia and reperfusion. Life Sci. 2000 Nov;67(26):3231-3239. doi: 10.1016/s0024-3205(00)00907-3.
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