肝肌信号强度比及血清标志物对慢性乙型肝炎肝纤维化的诊断价值

温雅; 屈兆宇; 鲁景楠; 阴玮灵; 黄晓旗

doi:10.3969/j.issn.1001-5256.2023.03.014

肝肌信号强度比及血清标志物对慢性乙型肝炎肝纤维化的诊断价值

DOI: 10.3969/j.issn.1001-5256.2023.03.014

延安大学附属医院影像科，陕西延安 716000

基金项目:

延安市科学技术研究发展计划项目 (2018KS-11)

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果有关的利益冲突。

作者贡献声明：温雅、黄晓旗对研究的思路及设计有关键贡献；屈兆宇、鲁景楠参与了研究数据的获取分析解释过程；温雅、阴玮灵、黄晓旗参与起草并修改文章关键内容。

详细信息

通信作者:
黄晓旗，344653354@qq.com (ORCID: 0000-0003-1365-759X)

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出版历程
- 收稿日期: 2022-08-01
- 录用日期: 2022-09-06
- 出版日期: 2023-03-20

Value of liver-muscle signal intensity and serum markers in diagnosis of chronic hepatitis B liver fibrosis

Department of Medical Imaging, Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, China

Research funding:

Science and Technology Research and Development Project of Yan'an (2018KS-11)

More Information

Corresponding author: HUANG Xiaoqi, 344653354@qq.com (ORCID: 0000-0003-1365-759X)

摘要

摘要: 目的结合ALT和肝脏硬度值水平分组，探讨磁敏感加权成像(SWI)的肝肌信号强度比(LMR)及血清标志物诊断慢性乙型肝炎纤维化严重程度的价值。方法回顾性收集2018年10月—2021年9月就诊于延安大学附属医院的慢性乙型肝炎患者255例，将患者分为严重肝纤维化(SLF)组77例与非SLF组178例，SLF组定义为ALT水平在正常范围内且肝脏硬度大于9.0 kPa，或ALT水平高于正常值上限1~5倍且肝脏硬度大于12.0 kPa的患者。在SWI序列下测量肝脏的平均SWI值(SWI_liver)及竖脊肌信号强度并计算LMR。正态分布的计量资料2组间比较采用t检验，非正态分布的计量资料2组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ²检验。利用二元Logistic回归分析SLF的影响因素。采用受试者工作特征(ROC)曲线分析LMR及其联合血清学的诊断效能，使用DeLong检验比较不同AUC的差异。结果 SLF组较非SLF组的ALT(Z=-3.569, P＜0.001)、AST(Z=-5.495, P＜0.001)、透明质酸(HA)(Z=-6.746, P＜0.001)、层粘连蛋白(LN)(Z=-5.459, P＜0.001)、Ⅳ型胶原(Ⅳ-C)(Z=-8.470, P＜0.001)、Ⅲ型前胶原(PCⅢ)(Z=-6.326, P＜0.001)、APRI(Z=-9.004, P＜0.001)、FIB-4(Z=-8.357, P＜0.001) 高，较非SLF组的PTA(t=10.088, P＜0.001)、PLT(t=9.163, P＜0.001)、SWI_liver(t=2.347, P=0.02)、LMR× 10(Z=-4.447, P＜0.001)低。PTA、HA、Ⅳ-C、LMR×10为发生SLF的独立影响因素(P值均＜0.05)。LMR×10诊断SLF的ROC曲线下面积(AUC)为0.675(95%CI: 0.614~0.732), 高于SWI_liver的0.594(95%CI: 0.531~0.655)(Z=3.984, P＜0.001)，PTA+HA+Ⅳ-C+LMR×10(AUC=0.937, 95%CI: 0.896~0.966)的诊断效能优于PTA+HA+Ⅳ-C(AUC=0.905, 95%CI: 0.858~0.941)(Z=2.228, P=0.026)。结论 LMR及血清标志物可较准确区分SLF，LMR为一项定量、客观的影像学指标，优于SWIliver，并可提升血清学标志物对临床判定SLF的诊断效能。
- 乙型肝炎, 慢性 /
- 肝硬化 /
- 磁共振成像 /
- 生物标记 /
- 肝肌比 /
- 诊断
Abstract: Objective To investigate the value of liver/muscle ratio (LMR) on susceptibility-weighted imaging (SWI) and serum markers in the diagnosis of the severity of chronic hepatitis B liver fibrosis after grouping based on alanine aminotransferase (ALT) level. Methods A retrospective analysis was performed for 255 patients with chronic hepatitis B who attended Affiliated Hospital of Yan'an University from October 2018 to September 2021, and the patients were divided into severe liver fibrosis group (SLF group) and non-severe liver fibrosis group (non-SLF group). The SLF group was defined as liver stiffness measurement (LSM) > 9.0 kPa and ALT level within the normal range or LSM > 12.0 kPa and ALT level greater than 1-5 times of the upper limit of normal. LMR was calculated by measuring the mean SWI value of the liver (SWI_liver) and the signal intensity of the erector spinae. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two group; the chi-square test was used for comparison of categorical data between two groups. The binary logistic regression analysis was used to investigate the influencing factors for SLF. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of LMR and its combination with serum markers, and the DeLong test was used to compare the difference in the area under the ROC curve (AUC). Results Compared with the non-SLF group, the SLF group had significantly higher ALT (Z=-3.569, P < 0.001), aspartate aminotransferase (AST) (Z=-5.495, P < 0.001), hyaluronic acid (HA) (Z=-6.746, P < 0.001), laminin (LN) (Z=-5.459, P < 0.001), type Ⅳ collagen (Ⅳ-C)(Z=-8.470, P < 0.001), type Ⅲ procollagen (PCⅢ) (Z=-6.326, P < 0.001), aspartate aminotransferase-to-platelet ratio index (Z=-9.004, P < 0.001), and FIB-4 (Z=-8.357, P < 0.001) and significantly lower prothrombin time activity (PTA) (t=10.088, P < 0.001), platelet count (t=9.163, P < 0.001), SWI_liver (t=2.347, P=0.02), and LMR×10 (Z=-4.447, P < 0.001). PTA, HA, Ⅳ-C, and LMR×10 were independent influencing factors for SLF. LMR×10 had an AUC of 0.675 (95% confidence interval [CI]: 0.614-0.732) in the diagnosis of SLF, which was significantly higher than that of SWI_liver (AUC=0.594, 95%CI: 0.531-0.655) (Z=3.984, P < 0.001). PTA+HA+Ⅳ-C+LMR×10 and PTA+HA+Ⅳ-C had an AUC of 0.937 (95%CI: 0.896-0.966) and 0.905 (95%CI: 0.858-0.941), respectively, suggesting that PTA+HA+Ⅳ-C+LMR×10 had a better diagnostic performance than PTA+HA+Ⅳ-C (Z=2.228, P=0.026). Conclusion LMR and serum markers can accurately distinguish SLF after grouping based on ALT level. LMR is a quantitative and objective imaging indicator and is better than SWI_liver, and it can also improve the diagnostic performance of serum markers for SLF in clinical practice.
- Hepatitis B, Chronic /
- Liver Cirrhosis /
- Magnetic Resonance Imaging /
- Biomarkers /
- Liver Muscle Ratio /
- Diagnosis

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图 1 LMR测量示例图

注：a，1例慢性乙型肝炎SLF患者，男性32岁，LMR×10为5.11，ALT为86 U/L，LSM为14 kPa。b，1例慢性乙型肝炎非SLF患者，男性55岁，LMR×10为8.87，ALT为33 U/L，LSM为8.5 kPa。

Figure 1. Sample figure of LMR measurements

下载: 全尺寸图片幻灯片

图 2 不同程度纤维化SWI_liver、LMR的均值差异

Figure 2. Estimation plot of SWI_liver and LMR for different degree of fibrosis

下载: 全尺寸图片幻灯片

图 3 MRI参数及血清学诊断SLF的ROC曲线

注：a，SWI_liver与LMR×10的ROC曲线；b，联合PTA、HA、Ⅳ-C与联合PTA、HA、Ⅳ-C、LMR×10的ROC曲线。

Figure 3. ROC curve of MRI parameters and serology in the diagnosis of SLF

下载: 全尺寸图片幻灯片

表 1 不同程度纤维化患者基本特征、血清学及影像学特征比较

Table 1. Comparison of basic features, serological and imaging features of different degrees of fibrosis

项目	非SLF组(n=178)	SLF组(n=77)	统计值	P值
男性[例(%)]	108(60.67)	45(58.44)	χ²=0.112	0.738
年龄(岁)	47.40±11.19	50.12±10.56	t=-1.810	0.070
BMI(kg/m²)	24.02±2.94	23.49±3.98	t=1.162	0.247
PTA(%)	90.43±14.57	70.18±14.56	t=10.088	＜0.001
PLT(×10⁹/L)	175.50±65.81	94.66±61.97	t=9.163	＜0.001
ALT(U/L)	22.0(16.0~34.3)	32.0(22.0~46.5)	Z=-3.569	＜0.001
AST(U/L)	23.0(19.0~30.0)	34.0(25.5~44.0)	Z=-5.495	＜0.001
HA(ng/mL)	116.90(72.45~182.60)	263.42(136.15~427.72)	Z=-6.746	＜0.001
LN(ng/mL)	69.64 (53.25~84.39)	99.16(73.84~147.48)	Z=-5.459	＜0.001
Ⅳ-C(S/CO)	42.05(28.69~58.67)	91.99(64.64~131.93)	Z=-8.470	＜0.001
PCⅢ(ng/mL)	6.28(4.08~8.75)	10.18(6.97~14.27)	Z=-6.326	＜0.001
LSM(kPa)	5.60(4.50~6.93)	16.20(11.85~21.30)	Z=-12.543	＜0.001
SWI_liver	258.45±55.24	240.84±54.47	t=2.347	0.020
LMR×10	8.30(7.00~9.13)	7.10(6.25~8.50)	Z=-4.447	＜0.001
APRI	0.40(0.29~0.60)	1.12(0.73~1.97)	Z=-9.004	＜0.001
FIB-4	1.42(0.96~2.13)	3.70(2.16~7.19)	Z=-8.357	＜0.001

下载: 导出CSV

表 2 二元Logistic回归分析SLF的影响因素

Table 2. Binary Logistic regression analysis of SLF

变量	B值	SE	Wald	OR(95%CI)	P值
PTA	-0.069	0.021	10.251	0.93(0.90~0.97)	0.001
HA	0.007	0.002	13.262	1.01(1.00~1.01)	＜0.001
Ⅳ-C	0.036	0.036	15.115	1.04(1.02~1.06)	＜0.001
LMR×10	-0.949	0.219	18.867	0.39(0.25~0.59)	＜0.001

下载: 导出CSV

表 3 MRI参数及血清学诊断SLF的效能

Table 3. Efficacy of MRI parameters and serology in the diagnosis of SLF

参数	AUC	95%CI	最佳截断值	敏感度(%)	特异度(%)	Z值	P值
SWI_liver	0.594	0.531~0.655	257.43	71.43	52.81	2.396	0.017
LMR×10	0.675	0.614~0.732	0.79	64.94	61.80	4.918	＜0.001
PTA+HA+Ⅳ-C	0.905	0.858~0.941	0.39	72.31	94.74	17.840	＜0.001
PTA+HA+Ⅳ-C+LMR×10	0.937	0.896~0.966	0.28	86.15	86.18	26.161	＜0.001

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