{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:16:03Z","timestamp":1781176563933,"version":"3.54.1"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA255809"],"award-info":[{"award-number":["R01CA255809"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32CA186873"],"award-info":[{"award-number":["T32CA186873"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Blood neutrophil to lymphocyte ratio (NLR) or lymphocyte count may be important markers for immune function. Previous work has shown higher NLR was associated with higher risk of hepatitis B\u2010related hepatocellular carcinoma (HCC). However, studies in non\u2010alcoholic fatty liver disease (NAFLD) patients are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Utilizing the University of Pittsburgh Medical Center (UPMC) electronic health records, we created a retrospective cohort of 27,834 patients diagnosed with NAFLD from 2004 to 2018 with complete NLR data. After an average 5.5\u2009years of follow\u2010up, 203 patients developed HCC. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of HCC incidence associated with different levels of NLR and lymphocyte count.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the lowest tertile of NLR (&lt;1.97), the highest tertile of NLR (\u22653.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR\u00a0=\u00a01.43, 95% CI: 1.01\u20132.03, <jats:italic>p<\/jats:italic><jats:sub>trend<\/jats:sub>\u00a0=\u00a00.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis\u20104 score category. Conversely the highest tertile of lymphocyte count (\u22652.15\u2009K\/ul) was significantly associated with a 36% lower risk of HCC (HR\u00a0=\u00a00.64, 95% CI: 0.43\u20130.94, <jats:italic>p<\/jats:italic><jats:sub>trend<\/jats:sub>\u00a0=\u00a00.028) compared to the lowest tertile (&lt;1.55\u2009K\/ul). There was no association between neutrophil count and HCC risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Higher NLR and lower lymphocyte count are associated with significantly higher risk of HCC among NAFLD patients. These findings warrant further investigation of immune response and surveillance in association with HCC development in NAFLD patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5185","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T07:22:56Z","timestamp":1662103376000},"page":"3589-3600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Neutrophil\u2010lymphocyte ratio in relation to risk of hepatocellular carcinoma in patients with non\u2010alcoholic fatty liver disease"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-3277","authenticated-orcid":false,"given":"Claire E.","family":"Thomas","sequence":"first","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Epidemiology, Graduate School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chuan","family":"Yu","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-1849","authenticated-orcid":false,"given":"Hung N.","family":"Luu","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Epidemiology, Graduate School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedram","family":"Paragomi","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Behari","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4620-3108","authenticated-orcid":false,"given":"Jian\u2010Min","family":"Yuan","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology and Prevention Program University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Epidemiology, Graduate School of Public Health University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0145-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3055"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S61146"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-019-00188-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.061"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.11.020"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0007-z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i10.1508"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0186-y"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(92)91528-G"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.10.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2784537"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.10.008"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1562942"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520903171284"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0204412"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18575"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i9.2807"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000639"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-021-07001-6"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02639.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.52"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-020-1094-5"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31726"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21178"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181a77e59"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000485396"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2020.08.067"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.08.041"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4843"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002217"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195336"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01445-3"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3245"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000490360"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27694"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/08830185.2014.893301"},{"issue":"1","key":"e_1_2_11_42_1","first-page":"31","article-title":"Total lymphocyte counts in adult HIV\/AIDS patients in Port Moresby general hospital","volume":"47","author":"Lavu EK","year":"2004","journal-title":"P N G Med J"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-010-1052-0"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0328-y"},{"key":"e_1_2_11_45_1","first-page":"441","article-title":"Adaptive immunity in cancer immunology and therapeutics","volume":"8","author":"Spurrell EL","year":"2014","journal-title":"ecancermedicalscience"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10966"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.6879"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00197"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00381-6"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.5185","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.5185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T08:24:32Z","timestamp":1732523072000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.5185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1002\/cam4.5185"],"URL":"https:\/\/doi.org\/10.1002\/cam4.5185","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"assertion":[{"value":"2022-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}