Objective: To investigate the association between peripheral blood neutrophil-to-lymphocyte ratio (NLR) and the levels of viral replication and hepatocyte injury in patients with hepatitis B, and to preliminarily explore the potential application of NLR as an auxiliary indicator for assessing hepatic inflammatory activity. Methods: A retrospective study was conducted on 383 patients with hepatitis B who attended Nanning Third People’s Hospital from January 2023 to December 2024 and completed simultaneous testing of hepatitis B virus (HBV) DNA quantification, liver function (ALT, AST), hepatitis B surface antigen, and complete blood count. NLR was calculated, and its correlation with HBV-DNA load and transaminase (ALT, AST) levels was analyzed. Patients were divided into low, medium, and high viral load groups according to HBV-DNA load. Differences in NLR, ALT, and AST levels among groups were compared. Spearman correlation analysis, ROC curve analysis, and multivariate logistic regression analysis were used to evaluate the predictive efficacy of NLR for high HBV-DNA load and the associations among various indicators. Results: NLR levels showed a gradual increasing trend with increasing HBV-DNA load (low → medium → high), and NLR in the high viral load group was significantly higher than that in the non-high viral load group (P < 0.0001). NLR was significantly positively correlated with ALT and AST levels (both P < 0.001). ROC curve analysis showed that the area under the curve (AUC) of NLR for predicting high HBV-DNA load was 0.737, with an optimal cut-off value of 4.088, a sensitivity of 70.19%, and a specificity of 70.97%. Multivariate logistic regression analysis showed that with high viral load as the outcome variable, after adjusting for confounding factors such as sex, age, ALT, and AST, NLR remained an independent predictor of high viral load in patients with hepatitis B (OR = 1.08, 95% CI: 1.01 - 1.15, P = 0.017). Conclusion: NLR is significantly correlated with HBV-DNA load and liver injury indicators in patients with hepatitis B, and it maintains independent predictive value after adjusting for relevant confounding factors. As a convenient and readily available inflammatory marker, NLR can be used in combination with traditional virological and biochemical indicators to facilitate a more comprehensive assessment of hepatic inflammatory status and viral replication activity in patients with hepatitis B. It has certain application potential in clinical settings with limited medical resources or
References
[1]
Xiao, R., Xiao, L.P., Wang, M.H., et al. (2025) Progress in the Application of Serum Inflammatory Factors and Immune Function Indicators in Chronic Hepatitis B Virus Infection. ActaVirologicaSinica, 41, 1600-1608.
[2]
Burki, T. (2024) Who’s 2024 Global Hepatitis Report. TheLancetInfectiousDiseases, 24, e362-e363. https://doi.org/10.1016/s1473-3099(24)00307-4
[3]
Liu, Z., Lin, C., Mao, X., Guo, C., Suo, C., Zhu, D., et al. (2023) Changing Prevalence of Chronic Hepatitis B Virus Infection in China between 1973 and 2021: A Systematic Literature Review and Meta-Analysis of 3740 Studies and 231 Million People. Gut, 72, 2354-2363. https://doi.org/10.1136/gutjnl-2023-330691
[4]
Tian, Q.Y., Yu, J. and Huang, G. (2024) Pathogenesis of Hepatitis B Virus-Associated Intrahepatic Cholangiocarcinoma. JournalofClinicalHepatology, 40, 797-803.
[5]
Xiang, J.Y., Xu, M. and Feng, Y. (2021) Research Progress on the Mechanism of Action of Natural Compounds against HBV. Chinese Pharmacological Bulletin, 37, 1346-1351.
[6]
You, H., Wang, F.S., Li, T.S., et al. (2023) Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition). JournalofPracticalHepatology, 26, 457-478.
[7]
Yuan, L.Y. (2023) Clinical Significance of HBV Serological Markers Combined with HBV-DNA Quantification in the Diagnosis of HBV Infection. ChineseCommunityPhysicians, 39, 104-106.
[8]
Chisari, F.V. and Ferrari, C. (1995) Hepatitis B Virus Immunopathogenesis. AnnualReviewofImmunology, 13, 29-60. https://doi.org/10.1146/annurev.iy.13.040195.000333
[9]
Xie, X.Y. and Wang, H.J. (2020) Analysis of the Relationship between Red Blood Cell Distribution Width, Serum ALT, AST, ALB Levels and Hepatocyte Inflammation in Chronic Hepatitis B. LaboratoryMedicineandClinicalPractice, 17, 1684-1687.
[10]
Niu, Y.S. and Zeng, Q. (2022) Predictive Role of Inflammatory Biomarkers for Prognosis of Liver Transplantation for Hepatocellular Carcinoma. OrganTransplantation, 13, 49-54.
[11]
Liu, Q.Y., Yang, Y.X., Xu, L., et al. (2025) Predictive Value of NLR, PLR, LMR, and PNI for Clinical Efficacy and Prognosis of Targeted Therapy Combined with Immunotherapy for Advanced Hepatocellular Carcinoma. ChineseJournalofCancerBiotherapy, 32, 309-315.
[12]
Zeng, F.J. and Zhuang, P. (2022) Research Progress on the Immune-Tolerant Phase of Chronic Hepatitis B Virus Infection. ModernDigestion&Intervention, 27, 1602-1605.
[13]
Ion, C.I., Andrei, R.E., HoriaTeodor, C., et al. (2023) Systemic Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Colon Cancer. Chirurgia (Bucharest, Romania: 1990), 118, 260-271.
[14]
Peng, Y.R., Zeng, Y., Zhang, Y.Z., et al. (2025) Predictive and Prognostic Value of Peripheral Blood Inflammatory Markers in Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer. JournalofCentralSouthUniversity (MedicalEdition), 50, 1-19.
[15]
Haugdahl, T.N., Karine, A., Ilona, U., et al. (2021) Systemic Inflammation Markers and Cancer Incidence in the UK Biobank. EuropeanJournalofEpidemiology, 36, 841-848.
[16]
Yang, X.F., Yang, X.Q., Ma, H.W., et al. (2025) Application of Peripheral Blood Inflammatory Markers in Prognostic Evaluation of Patients with Acute-on-Chronic Liver Failure. JournalofClinicalHepatology, 41, 2418-2423.
[17]
Chen, X., Li, Q. and Zhang, M. (2024) Clinical Research Progress of Neutrophil-to-Lymphocyte Ratio in Chronic Hepatitis B. ChineseJournalofHepatology, 32, 721-726.
[18]
Xian, M.J., Chen, J., Xu, H.Q., et al. (2025) Predictive Value of Neutrophil-to-Lymphocyte and Platelet Ratio (NLPR) for Recompensation in Patients with Hepatitis B Cirrhosis and Ascites and Construction of a Nomogram Model. JournalofClinicalHepatology, 41, 2329-2335.
[19]
Lin, Z., et al. (2025) Elevated Serum DcR3, Fas, and NLR Ratio Are Correlated with the Progression of Liver Cirrhosis. AmericanJournalofTranslationalResearch, 17, 1057-1064. https://doi.org/10.62347/hwym7712
[20]
Tan, X.S., Du, D.M., Zeng, Z.P., et al. (2025) Changes in Neutrophil-to-Lymphocyte Ratio before and after Initial Interventional Therapy for Hepatocellular Carcinoma Predict Patient Overall Survival. ChineseJournalofInterventionalImagingandTherapy, 22, 86-90.
[21]
Lyu, Z.J., Zhang, Q., Ning, J.X., et al. (2026) Predictive Value of PLR, NLR, and LMR for the Occurrence of Cirrhosis in Patients with Viral Hepatitis B. JournalofImmunology, 42, 949-954.
[22]
Zoulim, F., Chen, P., Dandri, M., Kennedy, P.T. and Seeger, C. (2024) Hepatitis B Virus DNA Integration: Implications for Diagnostics, Therapy, and Outcome. JournalofHepatology, 81, 1087-1099. https://doi.org/10.1016/j.jhep.2024.06.037
[23]
Zhu, L.F., Zhou, P., Cai, H.Y., et al. (2025) Past, Present, and Future of Biomarkers for Functional Cure of Chronic Hepatitis B. ActaVirologicaSinica, 41, 279-290.
[24]
Buonacera, A., Stancanelli, B., Colaci, M. and Malatino, L. (2022) Neutrophil to Lymphocyte Ratio: An Emerging Marker of the Relationships between the Immune System and Diseases. InternationalJournalofMolecularSciences, 23, Article No. 3636. https://doi.org/10.3390/ijms23073636
[25]
Zhang, Y., Shi, K., Zhu, B., Feng, Y., Liu, Y. and Wang, X. (2024) Neutrophil Extracellular Trap Scores Predict 90-Day Mortality in Hepatitis B-Related Acute-On-Chronic Liver Failure. Biomedicines, 12, Article No. 2048. https://doi.org/10.3390/biomedicines12092048
[26]
Carranza Lira, S. and García Espinosa, M. (2021) Differences in the Neutrophil/Lymphocyte Ratio and the Platelet/Lymphocyte Ratio in Pregnant Women with and without Covid‐19. InternationalJournalofGynecology&Obstetrics, 157, 296-302. https://doi.org/10.1002/ijgo.13840
[27]
Zhu, L., Wang, B.Y., Hu, R.Q., et al. (2025) Evaluation of the Predictive Value of Neutrophil-to-Lymphocyte Ratio Combined with International Normalized Ratio for Short-Term Prognosis in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. ElectronicJournalofEmergingInfectiousDiseases, 10, 27-33.
[28]
Wang, J., Zhao, Y., Liu, X., et al. (2024) Systematic Review and Meta-Analysis of Neutrophil-to-Lymphocyte Ratio as a Biomarker in Chronic Hepatitis B. Journal of Gastroenterology and Hepatology, 39, 892-901.