降低肝脏弹性临界值对慢性丙型肝炎患者获得持续病毒学应答后肝纤维化的评估价值

仇丽霞; 宋静静; 梁珊; 柳雅立; 张晶

doi:10.3969/j.issn.1001-5256.2021.12.016

降低肝脏弹性临界值对慢性丙型肝炎患者获得持续病毒学应答后肝纤维化的评估价值

DOI: 10.3969/j.issn.1001-5256.2021.12.016

首都医科大学附属北京佑安医院肝病三科，北京 100069

基金项目:

首都医学大学附属北京佑安医院院内中青年人才孵育项目 (YNKTTS20180105);

北京市丙型病毒性肝炎“发现-转诊-治疗”一体化综合管理模式研究 (2020-1-3011)

详细信息

通信作者:
张晶，drzhangjing@163.com

仇丽霞、宋静静对本文贡献相同，为共同第一作者

中图分类号: R512.63
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出版历程
- 收稿日期: 2021-05-19
- 录用日期: 2021-07-15
- 出版日期: 2021-12-20

The cut off value of liver stiffness measurement needs to be lowered to predict liver fibrosis after sustained virologic response in chronic hepatitis C patients

Third Department of Liver Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China

Research funding:

Incubation Program for Young and Middle-aged Talents in Beijing YouAn Hospital Affiliated to Capital Medical University (YNKTTS20180105);

Study on Integrated Management Model of 'Screening-Referral-Treatment' for Viral Hepatits C in Beijing (2020-1-3011)

摘要

摘要: 目的拟在获得SVR后随访的慢性丙型肝炎患者中，通过肝穿刺病理进一步验证无创肝纤维化诊断方法对于肝纤维化的预测能力。方法本研究为前瞻性队列研究，所有患者为2015年10月—2017年12月首都医科大学附属北京佑安医院就诊的慢性丙型肝炎患者，在获得持续病毒学应答(SVR)后进行规律随访并完成肝穿刺病理检查，用病理验证无创肝纤维化方法的诊断效能。根据受试者工作特征曲线(ROC曲线)评价LSM、APRI和FIB-4对肝纤维化的诊断能力。应用STATA及R语言，采用Delong法比较ROC曲线下面积(AUC)。结果共96例患者成功入组。获得SVR后LSM较基线显著降低，LSM诊断SVR后肝硬化的AUC为0.89，显著高于APRI (AUC=0.67)及FIB-4(AUC=0.69)(P值均＜0.05)。其中LSM最佳cut off值为7.95 kPa，根据最佳特异度，LSM＞9.15 kPa，可考虑诊断肝硬化，阳性似然比为5.91；LSM＜6.85 kPa排除进展期肝纤维化，阴性预测值为0.98。随访时间和抗病毒方案对LSM的诊断能力没有影响。结论慢性丙型肝炎患者获得SVR后需降低肝脏弹性临界值来评估肝纤维化。
- 丙型肝炎, 慢性 /
- 肝硬化 /
- 弹性成像技术 /
- 持续病毒学应答
Abstract: Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.
- Hepatitis C, Chronic /
- Liver Cirrhosis /
- Elasticity Imaging Techniques /
- Sustained Virologic Response

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图 1 患者筛选流程图

下载: 全尺寸图片幻灯片

图 2 CHC患者获得SVR后无创性肝纤维化指标诊断肝硬化的效能比较

下载: 全尺寸图片幻灯片

图 3 CHC患者获得SVR后无创性肝纤维化指标诊断进展期肝纤维化的效能比较

下载: 全尺寸图片幻灯片

表 1 抗病毒治疗前患者一般情况

项目	数值
年龄(岁)	57.44(55.00~62.95)
男[例(%)]	33(34.40)
BMI(kg/m²)	25.70±5.82
治疗方法[例(%)]
PR方案	33(34.4)
DAA	42(43.8)
PR方案+DAA	21(21.9)
随访时间(月)	26.81±10.18
WBC(10⁹/L)	5.46±1.99
HGB(g/L)	138.27±17.74
PLT(×10⁹/L)	160.38±59.95
ALT(U/L)	50.60(32.53~81.73)
AST(U/L)	45.60(34.30~63.68)
Alb(g/L)	44.00(42.50~46.70)
TBil(μmol/L)	16.40(13.00~21.00)
PT(s)	11.30(10.80~11.93)
INR	1.00(0.97~1.05)
HCV RNA(log₁₀IU/ml)	3.02(0.67~7.00)
HCV基因型[例(%)]
1b	70(72.9)
2a	16(16.7)
分型失败	10(10.4)
LSM(kPa)	10.60(7.80~14.00)
APRI	1.20(0.76~1.91)
FIB-4	2.24(0.97~3.57)

下载: 导出CSV

表 2 患者肝组织特征及肝穿时检查结果

临床参数	数据
WBC(10⁹/L)	5.63±1.90
HGB(g/L)	143.05±17.04
PLT(×10⁹/L)	182.84±57.96
PT(s)	11.70(11.30~12.20)
INR	1.04(1.01~1.09)
ALT(U/L)	18.00(14.60~24.35)
AST (U/L)	21.90(19.40~27.05)
TBil(μmol/L)	14.30(10.30~19.30)
Alb(g/L)	45.20(43.70~47.40)
LSM(kPa)	7.10(5.58~9.13)
APRI	0.38(0.26~0.50)
FIB-4	1.74(1.29~2.44)
Ishak评分[例(%)]
0~2分	43(44.79)
3分	23(23.96)
4分	10(10.42)
5~6分	20(20.83)
HAI评分[例(%)]
0~4分	73(76.04)
5~7分	21(21.88)
＞10分	2(2.08)

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表 3 3种无创诊断方法预测CHC患者获得SVR后肝硬化的效能比较

无创指标	AUC	cut off值	敏感度	特异度	Youden指数
LSM	0.89	7.95	0.90	0.77	0.67
APRI	0.67	0.30	0.89	0.44	0.30
FIB-4	0.69	2.17	0.67	0.76	0.43

下载: 导出CSV

表 4 3种无创方法预CHC患者获得SVR后进展期肝纤维化的效能

无创指标	AUC	cut off值	敏感度	特异度	Youden指数
LSM	0.88	6.85	0.97	0.61	0.58
APRI	0.62	0.36	0.67	0.59	0.25
FIB-4	0.63	2.17	0.52	0.76	0.27

下载: 导出CSV

表 5 SVR后CHC肝硬化的LSM临界值

cut off值(kPa)	敏感度(95% CI)	特异度(95%CI)	阳性预测值(95%CI)	阴性预测值(95%CI)	阳性似然比(95%CI)	阴性似然比(95%CI)
9.15	0.70(0.46~0.87)	0.90(0.78~0.94)	0.61(0.39~0.80)	0.92(0.82~0.97)	5.91(3.00~11.64)	0.34(0.17~0.67)
7.95	0.90(0.67~0.98)	0.77(0.66~0.86)	0.51(0.34~0.68)	0.97(0.87~0.99)	3.92(2.52~6.10)	0.13(0.03~0.49)
6.95	0.95(0.73~1.00)	0.59(0.47~0.70)	0.38(0.25~0.53)	0.98(0.87~1.00)	2.33(1.74~3.11)	0.08(0.01~0.58)

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表 6 SVR后CHC进展期肝纤维化的LSM临界值

cut off值(kPa)	敏感度(95%CI)	特异度(95%CI)	阳性预测值(95%CI)	阴性预测值(95%CI)	阳性似然比(95%CI)	阴性似然比(95%CI)
9.15	0.57(0.38~0.74)	0.91(0.81~0.96)	0.74(0.51~0.89)	0.82(0.71~0.90)	6.23(2.73~14.22)	0.48(0.32~0.72)
6.85	0.97(0.81~1.00)	0.62(0.49~0.74)	0.54(0.40~0.67)	0.98(0.86~1.00)	2.55(1.86~3.50)	0.05(0.01~0.38)
6.95	0.90(0.72~0.97)	0.65(0.52~0.76)	0.54(0.39~0.68)	0.93(0.81~0.98)	2.58(1.82~3.67)	0.15(0.05~0.46)

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参考文献(12)

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