Cancer Epidemiology and Prevention Program, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Cancer Med. 2023 Feb;12(3):3589-3600. doi: 10.1002/cam4.5185. Epub 2022 Sep 2.
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-related hepatocellular carcinoma (HCC). However, studies in non-alcoholic fatty liver disease (NAFLD) patients are lacking.
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 years of follow-up, 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.
Compared with the lowest tertile of NLR (<1.97), the highest tertile of NLR (≥3.09) was statistically significantly associated with a 43% higher risk of HCC incidence (HR = 1.43, 95% CI: 1.01-2.03, p = 0.031) after adjustment for age, sex, race, body mass index, smoking status, history of type 2 diabetes, hyperlipidemia, hypertension, and fibrosis-4 score category. Conversely the highest tertile of lymphocyte count (≥2.15 K/ul) was significantly associated with a 36% lower risk of HCC (HR = 0.64, 95% CI: 0.43-0.94, p = 0.028) compared to the lowest tertile (<1.55 K/ul). There was no association between neutrophil count and HCC risk.
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.
中性粒细胞与淋巴细胞比值（NLR）或淋巴细胞计数可能是免疫功能的重要标志物。先前的研究表明，较高的 NLR 与乙型肝炎相关肝细胞癌（HCC）的风险增加相关。然而，在非酒精性脂肪性肝病（NAFLD）患者中缺乏相关研究。
利用匹兹堡大学医学中心（UPMC）的电子健康记录，我们创建了一个回顾性队列，其中包括 2004 年至 2018 年间被诊断为 NAFLD 的 27834 例患者，这些患者均具有完整的 NLR 数据。在平均 5.5 年的随访后，有 203 例患者发生 HCC。使用 Cox 比例风险回归计算不同 NLR 和淋巴细胞计数水平与 HCC 发生率相关的风险比（HR）和 95%置信区间（CI）。
与 NLR 的最低三分位（<1.97）相比，NLR 的最高三分位（≥3.09）与 HCC 发生率增加 43%具有统计学显著相关性（HR=1.43，95%CI：1.01-2.03，p=0.031），校正年龄、性别、种族、体重指数、吸烟状况、2 型糖尿病史、高脂血症、高血压和纤维化-4 评分类别后。相反，淋巴细胞计数的最高三分位（≥2.15 K/ul）与 HCC 风险降低 36%具有显著相关性（HR=0.64，95%CI：0.43-0.94，p=0.028），与最低三分位（<1.55 K/ul）相比。中性粒细胞计数与 HCC 风险之间无关联。
较高的 NLR 和较低的淋巴细胞计数与 NAFLD 患者 HCC 风险显著增加相关。这些发现提示需要进一步研究免疫反应和 NAFLD 患者 HCC 发展的监测。
