{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:16:38Z","timestamp":1778786198998,"version":"3.51.4"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammation is a critical component in the process of resolved hepatitis B virus (HBV) infection. The neutrophil-to-lymphocyte ratio (NLR) serves as a sensitive indicator of systemic inflammation and immune activation. Our study aimed to investigate the correlation between elevated NLR levels and the risk of all-cause mortality in patients with resolved HBV infection. Additionally, we evaluated the potential mediating effect of diabetes mellitus (DM) on this correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Our study enrolled 1,146 adult patients with resolved HBV infection from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. We utilized the Restricted Cubic Splines (RCS) and Maximum Selection Rank Statistical Method (MSRSM) to analyze the relationship between the NLR and the risk of all-cause mortality. The impact of NLR was evaluated using a weighted multivariate Cox regression model, and the model\u2019s predictive accuracy was assessed using time-dependent Receiver Operating Characteristic (ROC) curves. An intermediary analysis was conducted to explore the potential influence of DM on the observed relationship.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During follow-up period of 103.54\u202f\u00b1\u202f4.90\u202fmonths, we recorded 207 deaths among the study participants. The analysis using the RCS method revealed a significant positive correlation between the NLR and the risk of all-cause mortality. Those with elevated NLR levels faced a substantially higher mortality risk compared to those with lower levels, as indicated by a Hazard Ratio (HR) of 1.84, with a 95% Confidence Interval (CI) of 1.17 to 2.89 (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.05). The predictive accuracy of the model was substantial, as evidenced by the Area Under the Curve (AUC) for ROC curves at 3, 5, and 10\u202fyears, which were 0.873, 0.870, and 0.862, respectively. Furthermore, mediation analysis indicated that DM significantly influenced the relationship between the NLR and mortality, with a mediation effect of 6.57% (95% Confidence Interval [CI]: 0.64 to 15%; <jats:italic>p<\/jats:italic>\u202f=\u202f0.02).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elevated NLR is significantly associated with an increased risk of all-cause mortality in patients with resolved HBV infection. Concurrently, DM acts as a partial mediator of this association.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpubh.2024.1493439","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T06:16:06Z","timestamp":1736921766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The neutrophil\u2013lymphocyte ratio as a risk factor for all-cause mortality among individuals with resolved HBV infection: evidence from the NHANES 1999\u20132018"],"prefix":"10.3389","volume":"12","author":[{"given":"Chen","family":"Qiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaojie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanlan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengnan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenrui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenjing","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2354","DOI":"10.1136\/gutjnl-2023-330691","article-title":"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","volume":"72","author":"Liu","year":"2023","journal-title":"Gut"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/S2468-1253(22)00386-7","article-title":"Global reporting of progress towards elimination of hepatitis B and hepatitis C","volume":"8","author":"Cui","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.7326\/0003-4819-154-5-201103010-00006","article-title":"Virus in the United States: infection, exposure, and immunity rates in a nationally representative survey","volume":"154","author":"Ioannou","year":"2011","journal-title":"Ann Intern Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/S2468-1253(18)30002-5","article-title":"Hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C: a systematic review and meta-analysis","volume":"3","author":"M\u00fccke","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1182\/blood-2018-04-848044","article-title":"Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy","volume":"133","author":"Kusumoto","year":"2019","journal-title":"Blood"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1007\/s40121-022-00680-2","article-title":"Prevalence of cirrhosis\/advanced fibrosis among HBsAg-negative and HBcAb-positive US adults: a Nationwide population-based study","volume":"11","author":"Huang","year":"2022","journal-title":"Infect Dis Ther"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/s40121-023-00766-5","article-title":"Effect of anti-HBs on mortality among resolved HBV infection: a population-based prospective cohort study","volume":"12","author":"Huang","year":"2023","journal-title":"Infect Dis Ther"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/s41598-020-79431-7","article-title":"Neutrophil-to-lymphocyte ratio and mortality in the United States general population","volume":"11","author":"Song","year":"2021","journal-title":"Sci Rep"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"110489","DOI":"10.1016\/j.intimp.2023.110489","article-title":"The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure","volume":"121","author":"Wang","year":"2023","journal-title":"Int Immunopharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3636","DOI":"10.3390\/ijms23073636","article-title":"Neutrophil to lymphocyte ratio: an emerging marker of the relationships between the immune system and diseases","volume":"23","author":"Buonacera","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"108235","DOI":"10.1016\/j.intimp.2021.108235","article-title":"Peripheral blood neutrophil-to-lymphocyte ratio in inflammatory bowel disease and disease activity: a meta-analysis","volume":"101","author":"Fu","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ckj\/sfac248","article-title":"Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: associations with mortality in a haemodialysis cohort","volume":"16","author":"Mayne","year":"2023","journal-title":"Clin Kidney J"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"911779","DOI":"10.3389\/fimmu.2022.911779","article-title":"The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with the severity of autoimmune encephalitis","volume":"13","author":"Liu","year":"2022","journal-title":"Front Immunol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"693","DOI":"10.3892\/etm.2015.2537","article-title":"Association between hepatitis B virus infection and diabetes mellitus: a meta-analysis","volume":"10","author":"Cai","year":"2015","journal-title":"Exp Ther Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1378311","DOI":"10.3389\/fmicb.2024.1378311","article-title":"Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study","volume":"15","author":"Yu","year":"2024","journal-title":"Front Microbiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0140-6736(94)90934-2","article-title":"\u201cOccult\u201d hepatitis B virus as source of infection in liver transplant recipients","volume":"343","author":"Chazouill\u00e8res","year":"1994","journal-title":"Lancet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/lt.500050301","article-title":"Severe clinical course of de novo hepatitis B infection after liver transplantation","volume":"5","author":"Crespo","year":"1999","journal-title":"Liver Transpl Surg"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"30","DOI":"10.7326\/M15-1121","article-title":"Hepatitis B virus reactivation and prophylaxis during solid tumor chemotherapy: a systematic review and Meta-analysis","volume":"164","author":"Paul","year":"2016","journal-title":"Ann Intern Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.ekir.2024.01.009","article-title":"Hepatitis B virus status and clinical outcomes in IgA nephropathy","volume":"9","author":"Gao","year":"2024","journal-title":"Kidney Int Rep"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/hep.29082","article-title":"Role of surface antibody in Hepatitis B reactivation in patients with resolved infection and hematologic malignancy: a meta-analysis","volume":"66","author":"Paul","year":"2019","journal-title":"Hepatology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.3390\/jpm12121957","article-title":"Direct-acting antivirals and the risk of Hepatitis B reactivation in Hepatitis B and C co-infected patients: a systematic review and Meta-analysis","volume":"12","author":"Oh","year":"2022","journal-title":"J Pers Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1111\/imm.13423","article-title":"Neutrophil and remnant clearance in immunity and inflammation","volume":"165","author":"Singhal","year":"2022","journal-title":"Immunology"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s00018-015-2055-3","article-title":"Innate lymphoid cells in intestinal immunity and inflammation","volume":"73","author":"Bostick","year":"2016","journal-title":"Cell Mol Life Sci"},{"key":"ref24","first-page":"444","article-title":"Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative\/laser-treated retinopathy in type 2 diabetic patients","volume-title":"Diabetologia","author":"Targher","year":"2008"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1080\/17474124.2018.1463158","article-title":"The role of neutrophil to lymphocyte ratio for the assessment of liver fibrosis and cirrhosis: a systematic review","volume":"12","author":"Peng","year":"2018","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s12902-024-01689-z","article-title":"Predictive role of neutrophil-to-lymphocyte ratio in metabolic syndrome: meta-analysis of 70,937 individuals","volume":"24","author":"Qiu","year":"2024","journal-title":"BMC Endocr Disord"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nm.4275","article-title":"Targeting mitochondrial dysfunction can restore antiviral activity of exhausted HBV-specific CD8 T cells in chronic hepatitis B","volume":"23","author":"Fisicaro","year":"2017","journal-title":"Nat Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"528","DOI":"10.3390\/biom11040528","article-title":"Neutrophil-to-lymphocyte ratio as a cardiovascular risk marker may be less efficient in women than in men","volume":"11","author":"Trtica Majnari\u0107","year":"2021","journal-title":"Biomol Ther"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.jhep.2018.02.032","article-title":"Development of a scoring system to predict hepatocellular carcinoma in Asians on antivirals for chronic hepatitis B","volume":"69","author":"Hsu","year":"2018","journal-title":"J Hepatol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/jvh.13077","article-title":"Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: a population-based cohort study","volume":"26","author":"Shyu","year":"2019","journal-title":"J Viral Hepat"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.cgh.2005.12.007","article-title":"The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence","volume":"4","author":"El-Serag","year":"2006","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1007\/s44197-024-00237-1","article-title":"Global burden and trends of primary liver Cancer attributable to comorbid type 2 diabetes mellitus among people living with Hepatitis B: an observational trend study from 1990 to 2019","volume":"14","author":"Xie","year":"2024","journal-title":"J Epidemiol Glob Health"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/kjm2.12762","article-title":"The interplay between chronic hepatitis B and diabetes mellitus: a narrative and concise review","volume":"40","author":"Huang","year":"2024","journal-title":"Kaohsiung J Med Sci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e112257","DOI":"10.1371\/journal.pone.0112257","article-title":"Concordance between patient self-reports and claims data on clinical diagnoses, medication use, and health system utilization in Taiwan","volume":"9","author":"Wu","year":"2014","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1111\/jgh.13670","article-title":"Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: a population-based cohort study","volume":"32","author":"Huang","year":"2017","journal-title":"J Gastroenterol Hepatol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1007\/s00415-023-11973-y","article-title":"Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study","volume":"271","author":"Marzo","year":"2024","journal-title":"J Neurol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1237618","DOI":"10.3389\/fendo.2023.1237618","article-title":"Association between resolved hepatitis B virus infection and femoral and spinal bone mineral density in American adults: a cross-sectional study","volume":"14","author":"Yang","year":"2023","journal-title":"Front Endocrinol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1186\/s12933-023-01998-y","article-title":"The neutrophil\u2013lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003\u20132016","volume":"22","author":"Dong","year":"2023","journal-title":"Cardiovasc Diabetol"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2024.1493439\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T06:16:09Z","timestamp":1736921769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2024.1493439\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":38,"alternative-id":["10.3389\/fpubh.2024.1493439"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2024.1493439","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"article-number":"1493439"}}