Correlation Analysis of Peripheral Blood SAA/CRP and NLR Levels with HBV-DNA Lload and Degree of Disease in CHB Patients
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摘要:
目的 探究慢性乙型肝炎（chronic hepatitis B，CHB）患者外周血淀粉样蛋白A（serum amyloid A，SAA）与C反应蛋白（C-reactive protein，CRP）比值（SAA/CRP）、中性粒细胞与淋巴细胞比值（neutrophils lymphocytes ratio，NLR）水平与乙型肝炎病毒-脱氧核糖核酸（HBV-DNA）载量及病情程度的相关性。 方法 选取2020年6月至2022年6月达州市中西医结合医院100例CHB患者作为研究组，根据病情程度分为轻度（单纯CHB，n = 36）、中度（乙肝代偿期肝硬化，n = 33）和重度（乙肝失代偿期肝硬化，n = 31）。另选同期、同年龄段50例健康志愿者作为对照组，比较研究组不同病情程度、对照组一般资料、血清SAA/CRP、NLR水平，并比较研究组不同HBV-DNA载量患者血清SAA/CRP、NLR水平，分析CHB患者血清SAA/CRP、NLR水平与HBV-DNA载量、病情程度的相关性；所有患者均行抗病毒治疗，治疗24周，比较不同抗病毒疗效患者治疗前、治疗后12周、24周血清SAA/CRP、NLR水平及变化值，分析治疗前后血清SAA/CRP、NLR水平变化值预测疗效的价值。 结果 重度CHB患者血清SAA/CRP、NLR水平>中度CHB患者>轻度CHB患者>健康人群（P < 0.05）；高载量患者血清SAA/CRP、NLR水平>中载量患者>轻载量患者（P < 0.05）；CHB患者血清SAA/CRP、NLR水平与HBV-DNA载量（r = 0.756、0.709）、病情程度（r = 0.776、0.745）呈正相关（P < 0.05）；无应答患者治疗后12周、24周外周血SAA/CRP、NLR水平均高于应答患者，变化值均低于应答患者（P < 0.05）；SAA/CRP△1、NLR△1单独预测的AUC分别为0.752、0.773，联合预测△1的AUC为0.861；SAA/CRP△2、NLR△2单独预测的AUC分别为0.796、0.819，联合预测△2的AUC为0.967，大于联合预测△1的AUC（P < 0.05）。 结论 CHB患者的SAA/CRP、NLR与CHB HBV-DNA载量及病情程度具有相关性，临床可通过其水平变化评估病情及预测预后。 Abstract:Objective To investigate the correlation and clinical significance of peripheral blood serum amyloid A （SAA） to C-reactive protein （CRP） ratio （SAA/CRP）, neutrophils lymphocytes ratio （NLR） and HBV-DNA levels and disease severity in patients with chronic hepatitis B （CHB）, so as to find out the correlation between SAA and CRP （SAA/CRP）, neutrophils lymphocytes ratio （NLR） and hepatitis B virus-deoxyribonucleic acid （HBV-DNA）. Methods From June 2020 to June 2022, 100 patients with CHB in our hospital were selected as the study subject and were divided into the mild group （simple CHB, 36 cases）, the moderate group （cirrhosis in the compensated stage of hepatitis B, 33 cases） and the severe group （cirrhosis in the decompensated stage of hepatitis B, 31 cases） according to the degree of disease. And at the same time, another 50 healthy volunteers with the same age were selected as the control group. Different disease degrees, general information, serum SAA/CRP and NLR levels in the control group, and serum SAA/CRP and NLR levels in patients with different HBV-DNA loads in the study group were compared respectivly and the correlation between the serum SAA/CRP and NLR levels in patients with CHB and HBV-DNA loads and disease degrees were analyzed. The correlation between the serum SAA/CRP, NLR levels and HBV-DNA load and the degree of disease in CHB patients was analyzed. All patients were treated with the antiviral therapy for 24 weeks, and serum SAA/CRP, NLR levels and the change values of patients with different antiviral efficacies were compared before the treatment and 12 weeks and 24 weeks after the treatment and the value of the change values of serum SAA/CRP, NLR levels before and after the treatment was analyzed so as to predict the efficacy of the therapy. Results Serum SAA/CRP and NLR levels in severe patients > moderate patients > mild patients > control group （P < 0.05）; serum SAA/CRP and NLR levels in high carrier patients > moderate carrier patients > mild carrier patients （P < 0.05）; serum SAA/CRP and NLR levels in CHB patients were positively correlated with HBV-DNA load （r = 0.756, 0.709） , and disease extent （r = 0.776, 0.745） were positively correlated （P < 0.05）;The levels of peripheral blood SAA/CRP and NLR at 12 and 24 weeks after the treatment were higher in non-responders than in responders, and the change values were lower than in responders （P < 0.05）; the AUCs predicted by SAA/CRP∆1 and NLR∆1 alone were 0.752, 0.773 for SAA/CRP△1 and NLR△1 alone, and 0.861 for combined prediction of △1; the AUCs for SAA/CRP△2 and NLR△2 alone were 0.796 and 0.819, respectively, and 0.967 for combined prediction of △2, which were greater than those for combined prediction of △1 （P < 0.05）. Conclusion SAA/CRP and NLR are significantly correlated with HBV-DNA load and disease extent in CHB, and the changes in their levels can be used clinically to assess the disease and predict the prognosis, so as to target the follow-up treatment and improve the prognosis. -
图 1 SAA/CRP、NLR水平与HBV-DNA载量的相关性
A：SAA/CRP与HBV-DNA载量相关性；B：NLR与HBV-DNA载量相关性；赋值：低载量=1，中载量=2，高载量=3。
Figure 1. Correlation between SAA/CRP，NLR levels and HBV-DNA loads
图 2 SAA/CRP、NLR水平与病情程度的相关性
A：SAA/CRP与病情程度相关性；B：NLR与病情程度相关性；赋值：轻度=1，中度=2，重度=3。
Figure 2. Correlation between SAA/CRP and NLR levels and the extent of the disease
表 1 一般资料及SAA/CRP、NLR水平[（$ \bar x \pm s$）/n（%）]
Table 1. General information and SAA/CRP and NLR levels[（$ \bar x \pm s $）/n（%）]
项目 研究组 对照组（n=50） F/χ2 P 轻度（n=36） 中度（n=33） 重度（n=31） 性别 0.772 0.856 男 22（61.11） 19（57.58） 21（67.74） 30（60.00） 女 14（38.89） 14（42.42） 10（32.26） 20（40.00） 年龄（岁） 41.63±9.31 43.07±10.24 45.60±10.53 42.81±9.76 0.931 0.427 体重指数（kg/m2） 23.16±1.95 23.41±2.04 22.89±1.91 23.04±2.11 0.393 0.758 吸烟史 2.205 0.531 有 4（11.11） 5（15.15） 7（22.58） 6（12.00） 无 32（88.89） 28（84.85） 24（77.42） 44（88.00） 饮酒史 7.142 0.068 有 3（8.33） 6（18.18） 9（29.03） 5（10.00） 无 33（91.67） 27（81.82） 22（70.97） 45（90.00） 合并症 高血压 5（13.89） 5（15.15） 6（19.35） − 0.397 0.820 高脂血症 3（8.33） 4（12.12） 4（12.90） − 0.419 0.811 糖尿病 2（5.56） 5（15.15） 3（9.68） − 1.767 0.413 ALB（g/L） 32.18±3.51 27.63±3.29 23.17±3.04 41.05±4.29 177.400 <0.001* AST（IU/L） 46.32±9.17 60.58±10.24 72.13±11.59 27.69±7.38 164.500 <0.001* ALT（IU/L） 49.45±9.02 62.17±11.36 71.84±12.73 28.76±8.14 136.274 <0.001* PT（s） 17.69±3.28 19.54±3.92 21.16±4.27 12.51±1.93 54.015 <0.001* SAA/CRP 2.51±0.73 3.83±0.86 5.12±0.90 1.24±0.26 225.853 <0.001* NLR 2.28±0.35 2.76±0.34 3.15±0.32 1.68±0.30 150.930 <0.001* *P < 0.05。 
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表 2 不同HBV-DNA载量SAA/CRP、NLR水平（$ \bar x \pm s$）
Table 2. Levels of SAA/CRP and NLR for different HBV-DNA loads（$ \bar x \pm s $）
HBV-DNA载量 n SAA/CRP NLR 低载量 30 2.60±0.63 2.33±0.31 中载量 33 3.75±0.65 2.71±0.35 高载量 37 4.68±0.71 3.02±0.33 F 80.511 35.997 P <0.001* <0.001* *P < 0.05。
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表 3 不同疗效患者治疗前后SAA/CRP、NLR水平（$ \bar x \pm s$）
Table 3. Levels of SAA/CRP and NLR before and after treatment in patients with different therapeutic effects（$ \bar x \pm s$）
疗效 n SAA/CRP NLR 治疗前 治疗后12周 治疗后24周 治疗前 治疗后12周 治疗后24周 无应答 38 3.91±0.85 3.69±0.80 3.52±0.82 2.78±0.36 2.53±0.31 2.35±0.32 应答 62 3.65±0.76 3.18±0.61 3.00±0.58 2.67±0.34 2.16±0.29 2.04±0.28 t 1.545 3.597 3.708 1.536 6.033 5.088 P 0.116 0.001* <0.001* 0.128 <0.001* <0.001* *P<0.05。
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表 4 不同疗效患者治疗前后SAA/CRP、NLR水平变化值（$ \bar x \pm s $）
Table 4. Values of changes in SAA/CRP and NLR levels before and after treatment in patients with different efficacies（$ \bar x \pm s $）
疗效 n SAA/CRP NLR △1 △2 △1 △2 无应答 38 0.22±0.04 0.39±0.08 0.25±0.06 0.43±0.08 应答 62 0.47±0.12 0.65±0.15 0.51±0.14 0.63±0.12 t 15.093 11.279 12.827 9.991 P <0.001* <0.001* <0.001* <0.001* △1为治疗12周后与治疗前差值的绝对值；△2为治疗24周后与治疗前差值的绝对值；*P<0.05。
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表 5 血清SAA/CRP水平、外周血NLR水平变化值预测疗效的价值
Table 5. Value of changes in serum SAA/CRP levels and peripheral blood NLR levels in predicting efficacy of treatment
指标 截断值 AUC 95%CI 敏感度（%） 特异度（%） P 下限 上限 SAA/CRP△1 0.30 0.796 0.704 0.870 86.84 64.52 <0.001* NLR△1 0.34 0.819 0.729 0.889 86.84 66.13 <0.001* 联合预测 − 0.967 0.911 0.993 94.74 88.71 <0.001* *P<0.05。
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