慢性乙型肝炎肝纤维化抗病毒治疗后生活质量与AST/PLT比率、肝硬度值、病理组织学的相关性分析

卢晶; 朴红心; 金雪梅; 崔京淑; 金仁顺

doi:10.3969/j.issn.1001-5256.2021.04.018

慢性乙型肝炎肝纤维化抗病毒治疗后生活质量与AST/PLT比率、肝硬度值、病理组织学的相关性分析

DOI: 10.3969/j.issn.1001-5256.2021.04.018

a.
延边大学附属医院病理科，吉林延吉 133000
b.
延边大学附属医院感染性疾病科，吉林延吉 133000

基金项目:

“十三五”国家科技重大专项课题 (2017ZX10203202-003)

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：朴红心、金仁顺对研究的思路有关键贡献；卢晶、金雪梅、崔京淑参与了研究数据的分析解释过程；金仁顺、卢晶参与了起草和修改了论文的关键内容。

详细信息

作者简介:
卢晶(1979—)，女，主治医师，主要从事肝脏病学研究

朴红心(1969—)，女，主任医师，博士生导师，主要从事肝纤维化机制及治疗的研究

通信作者:
金仁顺，rsjin@163.com

二者对本文贡献相同，同为第一作者

中图分类号: R512.62; R575.2
计量
- 文章访问数: 610
- HTML全文浏览量: 239
- PDF下载量: 72
- 被引次数: 0
出版历程
- 收稿日期: 2020-10-16
- 录用日期: 2020-12-26
- 出版日期: 2021-04-20

Correlation of quality of life with aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement, and histopathology after antiviral therapy for chronic hepatitis B liver fibrosis

a.
Department of Pathology, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China
b.
Department of Infectious Diseases, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China

摘要

摘要: 目的探讨慢性乙型肝炎肝纤维化患者恩替卡韦抗病毒治疗后生活质量与AST和PLT比率(APRI)、肝硬度(LSM)值、病理组织学的相关性。方法选择2013年10月—2015年3月在延边大学附属医院诊断为慢性乙型肝炎伴有肝纤维化的患者95例，全部患者进行恩替卡韦抗病毒治疗，在治疗前、治疗26周、52周和78周时采用SF-36量表进行生活质量测评，瞬时弹性成像技术测定LSM值，并检测血清APRI，其中31例患者在治疗前和治疗78周时进行肝穿刺活检病理组织学检查，观察炎症及纤维化程度，分析抗病毒治疗前后生活质量与APRI、LSM值和病理组织学的关系。计量资料同一指标不同时间点之间的比较采用Kruskal-Wallis H检验，相关性采用Spearman相关分析。结果抗病毒治疗后全部患者生活质量总体上呈上升趋势，健康状况、生理职能、情感职能、躯体疼痛、社会功能、精力状况不同时间点上差异均有统计学意义(H值分别为25.084、8.699、12.293、22.874、12.079、10.403，P值均＜0.05)。全部患者的APRI呈下降趋势，治疗前后比较，差异有统计学意义(H=60.030，P＜0.01)，全部患者的LSM值呈下降趋势，治疗前后比较，差异有统计学意义(H=35.744，P＜0.01)，APRI和LSM与生活质量评分呈负相关(P值均＜0.05)。肝穿刺活检患者抗病毒治疗后组织学炎症好转共22例，纤维化好转共15例，其中炎症好转的同时生活质量也提高有14例，纤维化好转的同时生活质量也提高有8例。结论恩替卡韦抗病毒治疗可提高慢性乙型肝炎肝纤维化患者的生活质量，APRI和LSM值下降可预测慢性乙型肝炎肝纤维化患者的生活质量好转，组织学炎症和纤维化好转对慢性乙型肝炎肝纤维化患者的生活质量好转有一定的影响。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 生活质量 /
- 组织学
Abstract: Objective To investigate the correlation of quality of life (QOL) with aspartate aminotransferase-to-platelet ratio index (APRI), liver stiffness measurement (LSM), and histopathology after entecavir antiviral therapy for patients with chronic hepatitis B liver fibrosis. Methods A total of 95 patients who were diagnosed with chronic hepatitis B and liver fibrosis in The Affiliated Hospital of Yanbian University from October 2013 to March 2015 were enrolled, and all patients underwent entecavir antiviral therapy. Before treatment and at weeks 26, 52, and 78 of treatment, SF-36 scale was used to assess QOL, transient elastography was used to measure LSM, and serum APRI was measured. Among these patients, 31 underwent liver biopsy before treatment and at week 78 of treatment to observe the degree of inflammation and fibrosis, and QOL, APRI, LSM, and histopathology were analyzed before and after antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data at different time points, and a Spearman correlation analysis was performed. Results There was a tendency of increase in QOL after antiviral treatment, and there were significant differences in general health, role-physical, role-motional, bodily pain, social functioning, and vitality at different time points (H=25.084, 8.699, 12.293, 22.874, 12.079, and 10.403, all P < 0.05). There was a tendency of reduction in APRI, with a significant change after treatment (H=60.030, P < 0.01), and there was also a significant reduction in LSM after treatment (H=35.744, P < 0.01). APRI and LSM were negatively correlated with QOL (all P < 0.05). Among the patients who underwent liver biopsy, 22 achieved the improvement in histological inflammation after antiviral therapy, 15 achieved the improvement in fibrosis, 14 achieved the improvement in both inflammation and QOL, and 8 achieved the improvement in both fibrosis and QOL. Conclusion Entecavir antiviral therapy can improve the QOL of patients with chronic hepatitis B liver fibrosis, and reductions in APRI and LSM can predict the improvement in QOL in patients with chronic hepatitis B liver fibrosis. Improvement in histological inflammation and fibrosis have a certain effect on the improvement in QOL in patients with chronic hepatitis B liver fibrosis.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Quality of Life /
- Histology

HTML全文

表 1 全部患者SF-36量表生活质量评分

指标	0周(n=95)	26周(n=88)	52周(n=83)	78周(n=54)	H值	P值
GH	45.0(30.0~55.0)	55.0(40.0~70.0)¹⁾	60.0(45.0~70.0)¹⁾	57.5(45.0~75.0)¹⁾	25.084	＜0.001
PF	95.0(80.0~95.0)	95.0(85.0~100.0)	95.0(80.0~100.0)	90.0(80.0~100.0)	3.333	0.541
RP	50.0(0~100.0)	100.0(25.0~100.0)²⁾	100.0(25.0~100.0)²⁾	100.0(18.8~100.0)²⁾	8.699	0.034
RE	67.0(0~100.0)	100.0(33.0~100.0)¹⁾	100.0(0~100.0)	100.0(33.0~100.0)¹⁾	12.293	0.006
SF	75.0(62.5~87.5)	87.5(65.6~100.0)¹⁾	87.5(62.5~100.0)¹⁾	75.0(62.5~100.0)²⁾	12.079	0.007
BP	74.0(62.0~84.0)	82.0(74.0~100.0)¹⁾	84.0(74.0~100.0)¹⁾	84.0(74.0~100.0)¹⁾	22.874	＜0.001
VT	60.0(50.0~75.0)	65.0(55.0~78.8)²⁾	70.0(55.0~80.0)²⁾	70.0(55.0~80.0)¹⁾	10.403	0.015
MH	64.0(48.0~76.0)	68.0(52.0~80.0)	64.0(52.0~80.0)	68.0(56.0~77.0)	4.911	0.178
注：与0周比较，1)P＜0.01；2)P＜0.05。

下载: 导出CSV

表 2 全部患者0~78周APRI和LSM

周数	例数	APRI	LSM(kPa)
0	95	1.05(0.84~2.16)	16.20(9.40~21.90)
26	88	0.51(0.34~0.90)¹⁾	10.35(7.60~16.40)¹⁾
52	83	0.61(0.38~0.98)¹⁾	8.40(6.70~13.30)¹⁾²⁾
78	54	0.46(0.27~0.83)¹⁾⁴⁾	8.25(6.45~11.48)¹⁾³⁾
H值		60.030	35.744
P值		＜0.001	＜0.001
P趋势		＜0.001	＜0.001
注：与0周比较，1)P＜0.01；与26周比较，2)P＜0.05，3)P＜0.01；与52周比较，4)P＜0.05。

下载: 导出CSV

表 3 25例治疗前后炎症、纤维化与生活质量评分

生活质量	炎症[例(%)]			纤维化[例(%)]
生活质量	好转	不变	进展	好转	不变	进展
提高	14(56)	1(4)	1(4)	8(32)	6(24)	1(4)
下降	8(32)	1(4)	0(0)	7(28)	1(4)	2(8)

下载: 导出CSV

表 4 APRI和LSM与生活质量的相关分析

指标	GH	PF	RP	RE	SF	BP	VT	MH
APRI
r值	-0.201	-0.110	-0.243	-0.021	-0.125	-0.291	-0.139	-0.109
P值	＜0.001	0.049	＜0.001	＜0.001	0.025	＜0.001	0.013	0.052
LSM
r值	-0.191	-0.117	-0.016	-0.218	-0.077	-0.188	-0.090	-0.191
P值	0.001	0.036	0.005	＜0.001	0.169	0.001	0.108	0.001

下载: 导出CSV

参考文献(17)

[1]	ZHANG L, ZHANG J, ZHOU G, et al. SF-36 scale to evaluate the improvement of quality of life in HBeAg positive patients with chronic hepatitis B treated with antiviral therapy[J]. Chongqing Med, 2017, 46(32): 4582-4584. DOI: 10.3969/j.issn.1671-8348.2017.32.037. 张林, 张婧, 周钢, 等. SF-36量表评价HBeAg阳性慢性乙型肝炎患者抗病毒治疗对生活质量的改善[J]. 重庆医学, 2017, 46(32): 4582-4584. DOI: 10.3969/j.issn.1671-8348.2017.32.037.
[2]	Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
[3]	ZHANG LX, ZHANG H, ZHANG W. Effect of comprehensive intervention program on quality of life of patients with chronic hepatitis B[J]. Guangdong Med J, 2014, 35(19): 3122-3124. 张利霞, 张会, 张苇. 综合干预方案对慢性乙型肝炎患者生活质量的影响[J]. 广东医学, 2014, 35(19): 3122-3124.
[4]	LI HJ, HE JS, HU SL, et al. Clinical effficacy of acoustic radiation force pulse imaging、transient elastography、aspartate aminotransferase to platelet ratio index in the detection of liver fibrosis degree of hepatitis B[J]. Clin J Med Offic, 2020, 48(9): 1090-1091, 1094. DOI: 10.16680/j.1671-3826.2020.09.35. 栗红江, 何久胜, 胡素玲, 等. 声辐射力脉冲成像技术、瞬时弹性成像技术及天冬氨酸氨基转移酶与血小板比率指数联合检测乙型肝炎肝纤维化程度临床效能[J]. 临床军医杂志, 2020, 48(9): 1090-1091, 1094. DOI: 10.16680/j.1671-3826.2020.09.35.
[5]	ZHENG SQ, WANG QZ. Current status and prospects of research on noninvasive diagnosis of liver fibrosis[J]. J Clin Hepatol, 2019, 35(1): 197-200. DOI: 10.3969/j.issn.1001-5256.2019.01.043. 郑少秋, 王启之. 无创肝纤维化诊断研究现状与前景[J]. 临床肝胆病杂志, 2019, 35(1): 197-200. DOI: 10.3969/j.issn.1001-5256.2019.01.043.
[6]	WU FX, GAO BH, NIU CY, et al. Value of aspartate aminotransferase -to-platelet ratio index in diagnosis and prediction of liver fibrosis degree in patients with chronic hepatitis B[J]. J Clin Hepatol, 2017, 33(8): 1483 -1486. DOI: 10.3969/j.issn.1001-5256.2017.08.014 吴方雄, 高保华, 牛春燕, 等. APRI评分对慢性乙型肝炎肝纤维化程度的诊断及预测价值[J]. 临床肝胆病杂志, 2017, 33(8): 1483-1486. DOI: 10.3969/j.issn.1001-5256.2017.08.014
[7]	AFIFY SM, TABLL A, NAWARA HM, et al. Five fibrosis biomarkers together with serum ferritin level to diagnose liver fibrosis and cirrhosis[J]. Clin Lab, 2018, 64(10): 1685-1693. DOI: 10.7754/Clin.Lab.2018.180502.
[8]	KEMP W, LEVY M, WELTMAN M, et al. Australian Liver Association (ALA) expert consensus recommendations for the use of transient elastography in chronic viral hepatitis[J]. J Gastroenterol Hepatol, 2015, 30(3): 453-462. DOI: 10.1111/jgh.12865.
[9]	ŞAHIN A, NAM\|DURU M, BALKAN A, et al. Assessment of histopathological alterations in patients with chronic hepatitis B infection following long-term oral antiviral therapy[J]. Saudi Med J, 2018, 39(10): 999-1005. DOI: 10.15537/smj.2018.10.23056.
[10]	SUN Y, ZHOU J, WANG L, et al. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment[J]. Hepatology, 2017, 65(5): 1438-1450. DOI: 10.1002/hep.29009.
[11]	Chinese Society of Infectious Diseases and Parasitology, Chinese Society of Hepatology, Chinese Medical Association. Prevention and treatment of viral hepatitis[J]. Chin J Infect Dis, 2001, 19(1): 56-62. DOI: 10.3760/j.issn:1000-6680.2001.01.027. 中华医学会传染病与寄生虫病学分会、肝病学分会. 病毒性肝炎防治方案[J]. 中华传染病杂志, 2001, 19(1): 56-62. DOI: 10.3760/j.issn:1000-6680.2001.01.027.
[12]	WONG CK, LAM ET, LAM CL. Comparison of direct-measured and derived short form six dimensions (SF-6D) health preference values among chronic hepatitis B patients[J]. Qual Life Res, 2013, 22(10): 2973-2981. DOI: 10.1007/s11136-013-0403-z.
[13]	WARE J, GANDEK B. Overview of SF-36 health survy and the international quality of life assessment (IQOLA) project[J]. J Clin Epidemiol, 1998, 51(11): 903-912. DOI: 10.1016/s0895-4356(98)00081-x.
[14]	XUE X, CAI S, OU H, et al. Health-related quality of life in patients with chronic hepatitis B during antiviral treatment and off-treatment[J]. Patient Prefer Adherence, 2017, 11: 85-93. DOI: 10.2147/PPA.S127139.
[15]	ZHOU H, XU QX, ZHANG ZG, et al. Clinical efficacy and quality of life evaluation of entecavir in patients with chronic hepatitis B[J]. Chin J Integr Tradit West Med Liver Dis, 2013, 23(6): 324-327. 周虹, 徐秋仙, 张振纲, 等. 恩替卡韦治疗慢性乙型肝炎患者的临床疗效及其生存质量评价[J]. 中西医结合肝病杂志, 2013, 23(6): 324-327.
[16]	Consensus expert committee on clinical application of transient elastography (TE). Consensus expert on clinical application of transient elastography (TE) (2015)[J/CD]. Chin J Hepatol(Electronic Edition), 2015, 7(2): 12-18. DOI: 10.3969/j.issn.1674-7380.2015.02.002. 瞬时弹性成像技术(TE)临床应用共识专家委员会. 瞬时弹性成像技术(TE)临床应用专家共识(2015年)[J/CD]. 中国肝脏病杂志(电子版), 2015, 7(2): 12-18. DOI: 10.3969/j.issn.1674-7380.2015.02.002.
[17]	SUN Y, ZHOU J, WANG L, et al. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment[J]. Hepatology, 2017, 65(5): 1438-1450. DOI: 10.1002/hep.29009.