红细胞分布宽度/血小板比值、血小板/淋巴细胞比值、中性粒细胞/淋巴细胞比值对慢性丙型肝炎肝硬化代偿期的预测价值

杨娜; 何华; 赵天业; 陶雪蓉; 吴燕华; 姜晶

doi:10.3969/j.issn.1001-5256.2021.06.021

红细胞分布宽度/血小板比值、血小板/淋巴细胞比值、中性粒细胞/淋巴细胞比值对慢性丙型肝炎肝硬化代偿期的预测价值

DOI: 10.3969/j.issn.1001-5256.2021.06.021

吉林大学第一医院临床研究部，长春 130021

基金项目:

国家重点研发项目 (2017YFC0907405);

吉林省科技发展计划项目 (20200403098SF);

吉林省省级财政2019年重点疾病防治项目

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：杨娜负责撰写论文，赵天业、陶雪蓉负责整理数据，何华、吴燕华负责修改论文，姜晶负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

作者简介:
杨娜(1995—)，女，主要从事肝癌筛查研究

通信作者:
吴燕华，wuyanhua@jlu.edu.cn

姜晶，jiangjing19702000@jlu.edu.cn

中图分类号: R512.63; R575.2
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出版历程
- 收稿日期: 2021-02-24
- 录用日期: 2021-04-23
- 出版日期: 2021-06-20

Value of red blood cell distribution width-to-platelet ratio, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio in predicting compensated liver cirrhosis in patients with chronic hepatitis C

Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, China

Research funding:

(2017YFC0907405);

(20200403098SF);

摘要

摘要: 目的通过比较慢性丙型肝炎患者和丙型肝炎肝硬化代偿期患者的血清学指标，分析红细胞分布宽度/血小板比值(RPR)、血小板/淋巴细胞比值(PLR)和中性粒细胞/淋巴细胞比值(NLR)对慢性丙型肝炎肝硬化代偿期的预测价值。方法在2019年9月—12月、2020年9月—12月分别在丙型肝炎发病较为集中的扶余县2个乡镇对慢性丙型肝炎患者开展肝硬化和肝癌筛查。收集所有患者的一般资料，检测其HCV RNA定量、肝功能和血常规，同时行肝瞬时弹性成像和腹部超声检查。计算RPR、PLR、NLR、FIB-4和APRI。计量资料2组间比较采用Mann-Whiney U检验；计数资料2组间比较采用χ²检验。采用受试者工作特征(ROC)曲线选取RPR、PLR的最佳截断值。采用多因素非条件logistic回归模型分析慢性丙型肝炎肝硬化的相关危险因素。采用线性回归趋势性检验分析不同纤维化分期的丙型肝炎患者之间RPR、PLR、FIB-4和APRI的变化趋势。结果共纳入慢性丙型肝炎患者968例，其中确诊为肝硬化代偿期(肝硬化组)患者123例(12.7%)。与慢性丙型肝炎组相比，肝硬化组RPR升高，PLR降低，差异均有统计学意义(P值均＜0.001)。多因素分析结果显示，年龄＞60岁、白蛋白＜40 g/L、RPR＞0.081、PLR＜91.11、FIB-4＞3.25、APRI＞2与丙型肝炎性肝硬化代偿期的发生有关(OR值分别为1.79、10.40、3.83、2.25、3.14、3.60，95%CI值分别为1.12~2.86、3.47~31.18、2.19~6.69、1.31~3.89、1.74~5.67、1.10~11.78，P值分别为0.015、＜0.001、＜0.001、0.004、＜0.001、0.035)。随着纤维化严重程度的加重，RPR、FIB-4、APRI呈逐渐升高趋势，PLR呈逐渐降低趋势(P值均＜0.001)。结论 RPR、PLR与慢性丙型肝炎肝硬化代偿期的发生、纤维化进展程度相关。对于慢性丙型肝炎老年患者(年龄＞60岁)，在监测白蛋白和肝纤维化指标变化的同时，也应定期监测RPR和PLR，以早期发现肝硬化，及时干预治疗，降低肝癌发生率。
- 肝炎，丙型 /
- 肝硬化 /
- 红细胞分布宽度 /
- 平均血小板体积 /
- 中性粒细胞-淋巴细胞比值
Abstract: Objective To investigate the value of red blood cell distribution width-to-platelet ratio (RPR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in predicting chronic hepatitis C (CHC)-related compensated liver cirrhosis by comparing serological markers between CHC patients and patients with compensated hepatitis C cirrhosis. Methods The patients with CHC in two townships of Fuyu County were screened for liver cirrhosis and liver cancer from September to December in 2019 and 2020, respectively. General information was collected; HCV RNA quantification, liver function, and routine blood test results were measured; liver transient elastography and abdominal ultrasound were performed at the same time. RPR, PLR, NLR, fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) were calculated. The Mann-Whiney U test was used for comparison between groups. The chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off values of RPR and PLR. A multivariate unconditional logistic regression analysis was used to investigate the risk factors for CHC-related liver cirrhosis. The linear regression trend test was used to investigate the changing trend of RPR, PLR, FIB-4, and APRI in hepatitis C patients with different fibrosis stages. Results A total of 968 CHC patients were enrolled, among whom 123 (12.7%) were diagnosed with compensated liver cirrhosis (liver cirrhosis group). Compared with the CHC group, the liver cirrhosis group had a significant increase in RPR and a significant reduction in PLR (P < 0.001). The multivariate logistic regression analysis showed that age > 60 years (odds ratio [OR]=1.79, 95% confidence interval [CI]: 1.12-2.86, P=0.015), albumin < 40 g/L (OR=10.40, 95% CI: 3.47-31.18, P < 0.001), RPR > 0.081 (OR=3.83, 95% CI: 2.19-6.69, P < 0.001), PLR < 91.11 (OR=2.25, 95% CI: 1.31-3.89, P=0.004), FIB-4 > 3.25 (OR=3.14, 95% CI: 1.74-5.67, P < 0.001), and APRI > 2 (OR=3.60, 95% CI: 1.10-11.78, P=0.035) were associated with the development of CHC-related compensated liver cirrhosis. With the aggravation of liver fibrosis, RPR, FIB-4, and APRI gradually increased and PLR gradually decreased (all P < 0.001). Conclusion RPR and PLR are associated with the development and fibrosis progression of CHC-related compensated liver cirrhosis. Elderly patients with CHC (age > 60 years) should be monitored for the changes in albumin and liver fibrosis indicators, and RPR and PLR should also be monitored regularly to identify liver cirrhosis in the early stage, give timely treatment, and reduce the incidence rate of liver cancer.
- Hepatitis C /
- Liver Cirrhosis /
- Red Blood Cell /
- Mean Platelet Volume /
- Neutrophil-Lymphocyte Ratio

HTML全文

图 1 RPR、PLR对于鉴别丙型肝炎相关肝硬化代偿期的ROC曲线

下载: 全尺寸图片幻灯片

图 2 RPR、PLR、FIB-4、APRI与肝纤维化严重程度的关系

下载: 全尺寸图片幻灯片

表 1 慢性丙型肝炎肝硬化发生的单因素分析

指标	例数	发生肝硬化[例(%)]	χ²值	P值
性别			1.047	0.306
男	506	59(11.7)
女	462	64(13.9)
年龄			11.543	0.001
≤60岁	539	51(9.5)
＞60岁	429	72(16.8)
教育水平			0.056	0.814
初中及以下	892	114(12.8)
高中及以上	76	9(11.8)
BMI			1.786	0.618
低体重	42	4(9.5)
正常	444	63(14.2)
超重	359	42(11.7)
肥胖	123	14(11.4)
吸烟指数			1.288	0.256
＜40包/年	870	107(12.3)
≥40包/年	98	16(16.3)
体育锻炼			0.294	0.588
否	458	61(13.3)
是	510	62(12.2)
一级亲属肝病史			0.970	0.325
无	847	111(13.1)
有	121	12(9.9)
治疗情况			0.032	0.984
未治疗	252	32(12.7)
抗病毒治疗	687	87(12.7)
治疗方案不明	29	4(13.8)
HCV RNA			0.042	0.838
阴性	700	88(12.6)
阳性	268	35(13.1)

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表 2 慢性丙型肝炎患者与丙型肝炎相关肝硬化患者血清学指标比较

指标	慢性丙型肝炎组(n=845)	丙型肝炎肝硬化组(n=123)	U值	P值
WBC(×10⁹/L)	5.89(4.88~7.10)	5.07(4.22~6.20)	37 138.0	＜0.001
淋巴细胞数量(×10⁹/L)	1.99(1.58~2.44)	1.71(1.27~2.23)	40 228.0	＜0.001
中性粒细胞数量(×10⁹/L)	3.39(2.64~4.26)	2.83(2.25~3.73)	40 107.0	＜0.001
血小板(×10⁹/L)	193(162~225)	123(86~169)	21 421.0	＜0.001
AST(U/L)	22.7(19.0~28.9)	29.5(24.2~47.1)	27 690.0	＜0.001
ALT(U/L)	18.7(13.4~27.4)	22.9(17.1~41.4)	37 433.0	＜0.001
AAR	1.22(0.97~1.51)	1.31(1.02~1.59)	46 912.0	0.092
GGT(U/L)	23.0(15.5~36.0)	33.0(21.0~76.0)	35 655.0	＜0.001
TBil(μmol/L)	10.0(7.5~13.1)	13.7(9.2~18.9)	33 935.0	＜0.001
红细胞分布宽度(%)	12.7(12.3~13.1)	13.0(12.5~13.8)	37 824.0	＜0.001
血红蛋白(g/L)	151(141~161)	145(136~157)	41 863.5	＜0.001
白蛋白(g/L)	47.3(45.4~49.2)	44.6(42.4~46.9)	28 669.5	＜0.001
总蛋白(g/L)	76.7(73.8~80.1)	76.7(73.7~81.3)	50 408.0	0.590
RPR	0.066(0.057~0.078)	0.108(0.078~0.153)	20 130.0	＜0.001
PLR	96.67(74.37~126.25)	73.00(52.25~90.37)	29 626.0	＜0.001
NLR	1.69(1.27~2.35)	1.84(1.29~2.56)	49 498.5	0.394
FIB-4	1.68(1.27~2.16)	3.38(2.16~5.84)	18 416.0	＜0.001
APRI	0.33(0.25~0.45)	0.75(0.42~1.52)	20 084.5	＜0.001

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表 3 慢性丙型肝炎肝硬化发生的多因素分析

因素	OR值	95% CI	P值
年龄(＞60岁vs ≤60岁)	1.79	1.12~2.86	0.015
白蛋白(＜40 g/L vs ≥40 g/L)	10.40	3.47~31.18	＜0.001
RPR(＞0.081 vs ≤0.081)	3.83	2.19~6.69	＜0.001
PLR(＜91.11 vs ≥91.11)	2.25	1.31~3.89	0.004
FIB~4(＞3.25 vs ≤3.25)	3.14	1.74~5.67	＜0.001
APRI(＞2 vs ≤2)	3.60	1.10~11.78	0.035

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表 4 RPR、PLR与肝纤维化严重程度之间的关系

指标	F0~1	F2	F2~3	F3~4	F4	P值
RPR	0.07(0.05~0.08)	0.07(0.06~0.09)	0.08(0.07~0.12)	0.09(0.07~0.12)	0.13(0.09~0.22)	＜0.001
PLR	99.3(77.3~129.8)	90.3(68.0~115.0)	88.7(58.7~119.8)	76.0(60.6~90.5)	62.4(49.4~88.6)	＜0.001
FIB-4	1.62(1.25~2.07)	1.88(1.39~2.68)	2.64(1.87~3.43)	3.26(2.20~4.64)	3.91(2.71~7.06)	＜0.001
APRI	0.31(0.24~0.41)	0.41(0.29~0.58)	0.58(0.37~0.78)	0.81(0.49~1.37)	1.10(0.51~1.78)	＜0.001

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