自身抗体和D-二聚体检测评估慢性乙型肝炎及乙型肝炎肝硬化患者预后的价值

doi:10.16150/j.1671-2870.2024.02.011

摘要/Abstract

摘要：

目的：分析自身抗体和D-二聚体在慢性乙型病毒性肝炎(慢乙肝)和乙型病毒性肝炎肝硬化（肝硬化）中的水平，探讨其在评估疾病进展、患者预后中的价值。方法：回顾性分析2020年1月至2023年1月就诊于我院的乙肝患者，筛选符合入组标准的连续病例共147例，包括慢乙肝82例（慢乙肝组）、肝硬化65例（肝硬化组）。以同期60例健康体检者为对照组，分析各组自身抗体及D-二聚体的水平。随访1年，以出现消化道出血、肝性脑病甚至死亡为预后不良，将肝硬化患者分为预后良好组和不良组，将自身抗体和D-二聚体等指标纳入二元logistic回归分析，分析肝硬化患者的预后不良的危险因素。结果：慢乙肝组及肝硬化组的自身抗体阳性率分别为25.61%、27.69% (P>0.05)，均高于对照组（8.33%）（P<0.05）。抗核抗体阳性率分别为14.63%、4.62%（P<0.05），余抗体阳性率差异无统计学意义。慢乙肝组、肝硬化组D-二聚体水平分别为0.28(0.19,0.51) mg/L、1.19(0.53,2.49) mg/L（P<0.05），其中肝硬化组高于对照组[0.27（0.20,0.32）]（P<0.05）。肝硬化预后不良组和预防良好组，自身抗体阳性率分别为47.06%、20.83%（P<0.05），D-二聚体水平分别为1.78(0.90,6.28) mg/L、1.06(0.32,2.07) mg/L(P<0.05)。回归分析表明，自身抗体阳性[OR=7.447(2.016~27.507)，P=0.003]、D-二聚体水平升高[OR=1.336(1.028~1.736)，P=0.030]均为肝硬化患者预后不良的危险因素。受试者操作特征曲线显示，自身抗体阳性预测肝硬化预后不良的灵敏度为53.6%，特异度为83.0%；当D-二聚体最佳临界值为≥0.84 mg/L时，预测肝硬化预后不良的灵敏度为88.9%，特异度为44.7%。二者联合预测的灵敏度为72.2%，特异度为85.1%。结论: 相对于健康体检者，慢乙肝和肝硬化患者的自身抗体阳性率和D-二聚体水平升高，但自身抗体阳性率与疾病进程无关，而D-二聚体水平升高与疾病进程相关。抗核抗体阳性率随疾病进展有所下降。自身抗体与D-二聚体联合检测，可用于预测肝硬化患者的预后。

关键词: 乙肝病毒, 慢性乙型肝炎, 肝硬化, 自身抗体, D-二聚体

Abstract:

Objective To detect autoantibodies and D-dimer in patients with chronic hepatitis B (CHB) or with hepatitis B cirrhosis (cirrhosis), and explore the value of detection in evaluating disease progression and prognosis of the patients. Methods A total of 147 consecutive cases meeting the enrollment criteria were collected in out hospital during January 2020 to January 2023, including 82 cases of CHB(CHB group) and 65 cases of cirrhosis(Cirrhosis group). Sixty healthy subjects were selected as the control, and autoantibody detection and D-dimer level were analyzed. In Cirrhosis group,patients died or suffered from digestive bleeding or hepatic encephalopathy were classified into poor prognosis group, and the other into good prognosis group. The autoantibody positivity and D-dimer level were included in binary logistic regression analysis to idetntify the risk factors for poor prognosis in patients with cirrhosis. Results The positive rate of autoantibody in CHB Group （25.61%）and Cirrhosis group （27.69%）were higher than that in control group（8.33%） (P<0.05).The positive rates of antinuclear antibody in CHB and Cirhosis group were 14.63% and 4.62% (P<0.05), and there was no significant difference in positive rates of other antibodies between CHB and Cirrhosis group. The D-dimer levels in CHB and Cirrhosis groups were 0.28 (0.19,0.51) mg/L and 1.19 (0.53,2.49) mg/L(P<0.05), and D-dimer level in Cirrhosis group was higher than that in control group[0.27(0.20,0.32)] (P<0.05). The positive rates of autoantibody in the poor and good prognosis groups of cirrhosis were 47.06% and 20.83%(P<0.05), and D-dimer levels were 1.78 (0.90,6.28) mg/L and 1.06 (0.32,2.07) mg/L(P<0.05). Regression analysis showed that the positive autoantibody [OR=7.447(2.016-27.507), P=0.003] and D-dimer level increase [OR=1.336(1.028-1.736), P=0.030] were risk factors for poor prognosis in patients with cirrhosis. The receiver operating characteristic curve showed that the sensitivity and specificity of positive autoantibody for predicting poor prognosis of cirrhosis were 53.6% and 83.0%, respectively. When the optimal cut-off value of D-dimer was ≥ 0.84 mg/L, the prediction sensitivity for poor prognosis in cirrhosis patients was 88.9%, and specificity was 44.7%. When combination of D-dimer level and autoantibody positivity was performed, the sensitivity and the specificity for predicting poor prognosis was 72.2%, 85.1%, respectively. Conclusions Autoantibody positive rate and D-dimer level are higher in patients with CHB or cirrhosis compared to the healthy subjects. The positive rate of autoantibody is not related to the disease course, while the increase of D-dimer is related to the disease course. The positive rate of antinuclear antibody decreased with the progression of the disease. Combined detection of autoantibody and D-dimer may be used to predict the prognosis of patients with cirrhosis.

Key words: Hepatitis B virus, Chronic hepatitis B, Cirrhosis, Autoantibody, D-dimer

中图分类号:

刘悦, 吴翰林, 佟武强, 许静. 自身抗体和D-二聚体检测评估慢性乙型肝炎及乙型肝炎肝硬化患者预后的价值[J]. 诊断学理论与实践, 2024, 23(02): 173-179.

LIU Yue, WU Hanlin, TONG Wuqing, XU Jing. The value of autoantibody and D-dimer detection in evaluating the prognosis of patients with chronic hepatitis B and hepatitis B cirrhosis[J]. Journal of Diagnostics Concepts & Practice, 2024, 23(02): 173-179.

图/表 6

表1

表2

表3

表4

表5

图1

参考文献 29

[1]	毛孝周, 杨涓, 郑盛. 慢性乙型病毒性肝炎患者外周血Th1/Th2相关细胞因子表达的临床意义[J]. 医学信息, 2024, 37(7):102-105.
	MAO X Z, YANG J, ZHENG S. Clinical Significance of Th1/Th2 Related Cytokines Expression in Peripheral Blood of Patients with Chronic Hepatitis B[J]. Med Inform, 2024, 37(7):102-105.
[2]	金梦琳, 韩雨晴, 王玉娴, 等. HBV慢性感染患者血清 ANGPTL 3 4 6水平临床价值研究[J]. 安徽医学, 2023, 44(1):22-26.
	JIN M L, HAN Y Q, WANG Y X, et al. The clinical value study of serum ANGPTL 346 levels in patients with chronic infection with HBV[J]. Anhui Med J, 2023, 44(1):22-26.
[3]	马家秀, 卢卉双, 张津, 等. 乙肝病毒核心相关抗原检测试剂盒的研发及临床检测[J]. 重庆医科大学学报, 2023, 48(7):798-804.
	MA J X, LU H S, ZHANG J, et al. Development and clinical detection of hepatitis B core-related antigen test kit[J]. J Chongqing Med Univ, 2023, 48(7):798-804.
[4]	关婷, 张月, 张东梅, 等. 成年男性葡萄糖-6-磷酸脱氢酶活性低下与乙型肝炎病毒感染的关联性研究[J]. 中华全科医学, 2022, 20(12):2045-2049.
	GUAN T, ZHANG Y, ZHANG D M, et al. Association of low glucose-6-phosphate dehydrogenase enzyme activity with hepatitis B virus infection in adult males[J]. Chin J Gen Pract, 2022, 20(12):2045-2049.
[5]	World Health Organization WHO. Hepatitis B[EB/OL]. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.
[6]	萧焕明, 施梅姐, 谢玉宝, 等. 慢性乙型肝炎相关肝纤维化中医诊疗进展与思考[J]. 临床肝胆病杂志, 2023, 39(2):260-266.
	XIAO H M, SHI M J, XIE Y B, et al. Advances and thoughts in traditional Chinese medicine diagnosis and treatment of chronic hepatitis B-related liver fibrosis[J]. J Clin Hepatol, 2023, 39(2):260-266.
[7]	缪宁, 王富珍, 郑徽, 等. 中国2013-2020年乙型肝炎发病情况估算和病例特征分析[J]. 中华流行病学杂志, 2021, 42(9):1527-1531.
	MIAO N, WANG F Z, ZHENG H. Estimation of incidence of viral hepatitis B and analysis on case characteris-tics in China,2013-2020[J]. Chin J Epidemiol, 2021, 42(9):1527-1531.
[8]	中华医学会消化病学分会. 中国肝硬化临床诊治共识意见[J]. 中华消化杂志, 2023, 43(4):227-247.
	Chinese Society of Gastroenterology, Chinese Medical Association. Chinese consensus on clinical diagnosis and therapy of liver cirrhosis[J]. Chin J Dig, 2023, 43(4):227-247.
[9]	薛瑞霞, 文隆, 雷红鸽, 等. 自身抗体在慢性乙型肝炎和慢性丙型肝炎患者中的特点分析[J]. 临床医药文献杂志, 2019, 6(24):87-88.
	XUE R X, WEN L, LEI H G, et al. Characteristics of autoantibodies in patients with chronic hepatitis B and chronic hepatitis C[J]. Electron J Clin Med Lit, 2019, 6(24):87-88.
[10]	马跃飞, 贺勤, 刘灿, 等. HBV感染与抗平滑肌抗体相关性分析[J]. 中国免疫学杂志, 2022, 38(7):864-867.
	MA Y F, HE Q, LIU C, et al. Correlation analysis of hepatitis B virus infection and anti-smooth muscle antibody[J]. Chin J Immunol, 2022, 38(7):864-867,877.
[11]	冼观秀, 张家明, 陈聪, 等. 乙型肝炎肝硬化患者自身抗体检测及与生化指标和肝纤维化指数的关系[J]. 中国医药科学, 2020, 10(21):173-175,183.
	XIAN G X, ZHANG J M, CHEN C, et al. Autoantibodies detection in patients with hepatitis B cirrhosis and its relationship with biochemical indexes and hepatic fibrosis index[J]. Chin J Med Sci, 2020, 10(21):173-175,183
[12]	曾丽梅, 冯阳修, 谢银光, 等. 免疫指标及肝病相关抗体与自身免疫性肝病相关性[J]. 吉林医学, 2024, 45(2):371-373.
	ZENG L M, FENG Y X, XIE Y G, et al. The correlation between immune indexes and liver disease-related antibodies and autoimmune liver disease[J]. Jilin Med, 2024, 45(2):371-373.
[13]	来小红, 郭卉. 自身抗体谱检测在自身免疫性肝病中的临床意义[J]. 中西医结合肝病杂志, 2023, 33(3):284-288. doi: 10.3969/j.issn.1005-0264.2023.003.025
	LAI X H, GUO H. Clinical significance of autoantibody spectrum detection in autoimmune liver disease[J]. Chin J Integr Tradit West Med Liver Dis, 2023, 33(3):284-288.
[14]	张安敏. 肝功能异常患者中自身抗体及自身免疫性肝病检验的临床意义[J]. 基层医学论坛, 2023, 27(13):92-94.
	ZHANG A M. Clinical significance of autoantibody and autoimmune liver disease test in patients with abnormal liver function[J]. Med Forum, 2023, 27(13):92-94.
[15]	单华静, 黄能为. 血清D-二聚体sRAGE水平对老年冠心病患者介入治疗后短期不良预后的预测价值[J]. 中国动脉硬化杂志, 2024, 32(1):57-64.
	SHAN H J, HUANG N W. The predictive value of serum D-dimer and sRAGE levels for short-term adverse prognosis in elderly patients with coronary heart disease after interventional therapy[J]. Chin J Arterioscler, 2024, 32(1):57-64.
[16]	REN H, LIU Y, LU J, et al. Evaluating the clinical value of MRI multi-model diffusion-weighted imaging on liver fibrosis in chronic hepatitis B patients[J]. Abdom Radiol(NY), 2021, 46(4):1552-1561.
[17]	孙璀, 曹琳琳, 刘俊. 不同肝病患者血清自身抗体谱阳性率调查[J]. 实用肝脏病杂志, 2023, 26(3):368-371.
	SUN C, CAO L L, LIU J. Prevalence of serum autoantibody spectrums in patients with different liver diseases[J]. J Pract Hepatol, 2023, 26(3):368-371.
[18]	CAO Q, MEI Z. Predictive value of elevated serum D-dimer for short-term prognosis in patients with HBV-related acute-on-chronic liver failure[J]. Exp Ther Med, 2022, 24(1):472. doi: 10.3892/etm.2022.11399 pmid: 35761810
[19]	LU Y Y, XIN J J, LI P, et al. D-dimer contributes to the diagnosis and prognosis in hepatitis B-related acute-on-chronic liver failure[J]. Zhonghua Gan Zang Bing Za Zhi, 2022, 30(10):1082-1091.
[20]	中华医学会肝病学会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 实用肝脏病杂志, 2023, 26(3):18-39.
	Chinese Association of Hepatology, Chinese Association of Infectious Diseases. Guidelines for the prevention and treatment of chronic hepatitis B(version 2022)[J]. J Pract Hepatol, 2023, 26(3):18-39.
[21]	李晨, 谭钧元, 许祥. 乙型肝炎肝硬化急性恶化患者慢加急性肝衰竭的发生情况及预后分析[J]. 临床肝胆病杂志, 2020, 36(9):1960-1965.
	LI C, TAN J Y, XU X. Development and prognosis of acute-on-chronic liver failure in patients with acute deterioration of hepatitis B virus-related liver cirrhosis[J]. J Clin Hepatol, 2020, 36(9):1960-1965.
[22]	ZAMOR P J, LANE A M. Interpretation of HBV serologies[J]. Clin Liver Dis, 2021, 25(4):689-709. doi: 10.1016/j.cld.2021.06.012 pmid: 34593148
[23]	金宇, 刘晓玲, 黄怡丹. 免疫球蛋白和自身抗体在乙型肝炎肝硬化发病和进展中的表达及与预后的关系[J]. 中国现代医学杂志, 2023, 33(4):56-61.
	JIN Y, LIU X L, HUANG Y D. The role of immunoglobulin and autoantibodies in the pathogenesis and progression of hepatitis B cirrhosis and their correlation with prognosis[J]. Chin J Mod Med, 2023, 33(4):56-61.
[24]	LI BA, LIU J, HOU J, et al. Autoantibodies in Chinese patients with chronic hepatitis B: prevalence and clinical associations[J]. World J Gastroenterol, 2015, 21(1):283-291.
[25]	马继登, 吕艳稞, 李子安, 等. 25(OH)D、D-D和FDP对类风湿关节炎活动度的鉴别诊断价值[J]. 检验医学与临床, 2024, 21(2):161-165.
	MA J D, LV Y K, LI Z A, et al. The value of 25(OH)D,D-D and FDP in the differentiation of rheumatoid arthritis activity[J]. Lab Med Clin, 2024, 21(2):161-165.
[26]	BAYRAM A A, AL-DAHMOSHI H O M, AL-KHAFAJI N S K, et al. Study of the D-dimer, C-reactive protein, and autoantibodies markers among HBV infected patients in Babylon province, Iraq[J]. Biomedicine (Taipei), 2021, 11(4):67-72.
[27]	孙孟甜. 凝血四项联合D-二聚体水平检测在乙型肝炎肝硬化患者出血风险预测中的作用[J]. 中国民康医学, 2020, 32(3):118-120.
	SUN M T. The role of four coagulation items combined with D-dimer level detection in the prediction of blee-ding risk in patients with hepatitis B cirrhosis[J]. Med J Chin People's Health, 2020, 32(3):118-120.
[28]	曹蕾, 桂建雄. 乙肝肝硬化患者D-D、MPV、PDW、AFP-L3、GP-73的变化与HBV-DNA的关系[J]. 湖南师范大学学报(医学版), 2021, 18(3):167-170.
	CAO L, GUI J X. Relationship between changes of D-D, MPV, PDW, AFP-L3 and GP-73 and HBV-DNA in patients with hepatitis B cirrhosis[J]. J Hunan Norm Univ(Med Sci), 2021, 18(3):167-170.
[29]	徐静, 纪冬, 王春艳, 等. 乙型肝炎肝硬化患者血浆D-二聚体水平变化的临床意义[J]. 临床肝胆病杂志, 2020, 36(3):551-555.
	XU J, JI D, WANG C Y, et al. Clinical significance of the change in plasma D-dimer in patients with hepatitis B cirrhosis[J]. J Clin Hepatol, 2020, 36(3):551-555.

Group	N(case)	Autoantibody positive [case (%)]	D-dimer (mg/L)
Control	60	5(8.33%)	0.27(0.20,0.32)
Chronic hepatitis B^a	82	21(25.61%)^a	0.28(0.19,0.51)
Cirrhosis^a	65	18(27.69%)^a	1.19(0.53,2.49)^a

Group	N(case)	ANA	RO-52	GP210	ASMA	AMA	LC-1	SLA	LKM-1
Chronic hepatitis B	82	12(14.63)	6(7.32)	2(2.44)	1(1.22)	1(1.22)	5(6.10)	0	0
Cirrhosis	65	3(4.62)	7(10.77)	2(3.08)	0	3(4.62)	4(6.15)	2(3.08)	1(1.54)
P		0.046	0.464	0.813	0.372	0.229	0.989	0.115	0.260

Item	Good prognosis（n=48）	Poor prognosis（n=48）	P
Gender (Male/female)	32/16	12/5	0.766
Age (years)	52.06±12.64	55.50±12.66	0.331
HBV infection years (years)	10(1,20)	10(0.048,22.50)	0.559
D-dimer (mg/L)	1.06(0.32,2.07)	1.78(0.90,6.28)	0.026
Autoantibody positive [case(%)]	10(20.83)	8(47.06)	0.038

Independent variable	B	SE	Wald	P	OR	95%CI
Autoantibody	2.008	0.667	9.071	0.003	7.447	2.016-27.507
D-dimer (mg/L)	0.290	0.134	4.708	0.030	1.336	1.028-1.736

Independent variable	Cutoff	AUC(95%CI)	Sensitivity (%)	Specificity (%)
Autoantibody	0.50	0.693(0.539-0.846)	53.60	83.00
D-dimer (mg/L)	0.84	0.680(0.541-0.818)	88.90	44.70
Combination	0.43	0.824(0.719-0.930)	72.20	85.10