Ultrasound-based Dual Elastography for Evaluating the Severity of Drug-induced Liver Injury: One Step Closer to Pathology

doi:10.37015/AUDT.2024.240017

Abstract

Abstract:

Objective: Drug-induced liver injury (DILI) is one of the most challenging forms of liver disorder. We aimed to use ultrasound dual elastography, by combining strain and shear wave imaging, to noninvasively assess liver inflammation and injury severity of DILI.

Methods: 291 DILI patients were included in the prospective multicenter study and divided into training and validation cohorts. All patients received liver biopsy and dual elastography examination. Liver inflammation grading (G0-4) and fibrosis staging (F0-4) were considered as the gold standard of liver injury and G+F ≥ 5 was defined as severe liver injury. Indexes of dual elastography and serological indicators (DESI) were selected and analyzed with multivariable logistic regression to build DESI models for evaluating liver inflammation, and the C score model was built with the same method for diagnosing severe liver injury.

Results: Areas under the receiver operating characteristic curve (AUCs) of the DESI model to assess liver inflammation ≥ G2 were 0.887 and 0.868 in training and validation cohorts, respectively. AUCs of the DESI model in diagnosing ≥ G3 were 0.893 and 0.896 in the two cohorts, respectively. The C score accurately assessed severe liver injury with AUCs of 0.909 and 0.885 in two cohorts. Of the 87 patients with mild clinical severity, 10 (11.49%) had severe pathological injury, which could be identified by C score.

Conclusion: Dual elastography demonstrated high performance in diagnosing liver inflammation and identifying severe pathological liver injury of DILI, making up for the deficiency of serological indicators alone for evaluating DILI severity.

Key words: Drug-induced liver injury; Liver inflammation activity; Dual elastography; Strain elastography; Shear wave elastography

Liyun Xue, PhD, Hui Feng, MD, Fankun Meng, MD, Ying Zheng, MD, Guangwen Cheng, PhD, Yao Zhang, MD, Zhiyong Yin, MD, Jing Wu, MD, Jiabao Zhu, MD, Xueqi Li, MD, Jie Yu, PhD, Ping Liang, PhD, Hong Ding, PhD. Ultrasound-based Dual Elastography for Evaluating the Severity of Drug-induced Liver Injury: One Step Closer to Pathology. Advanced Ultrasound in Diagnosis and Therapy, 2024, 8(3): 106-115.

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Characteristics	Training cohort (n = 232)	Validation cohort (n = 59)	P value
Basic characteristics
Sex (male)	70 (30.17%)	20 (33.90%)	0.580
Age (y)	46.71 ± 11.70	48.42 ± 11.43	0.332
BMI (kg/m²)	22.88 ± 3.01	23.43 ± 3.72	0.241
Laboratory tests at biopsy
Albumin (g/L)	38 (35-51)	38 (34-49)	0.874
Total bilirubin (μmol/L)	20.94 (13.6-89.1)	23.72 (12.9-202)	0.619
Alanine aminotransferase (U/L)	66.53 (35.31-247.20)	47 (35-232)	0.243
Aspartate aminotransferase (U/L)	54.50 (31-263)	53 (27-304)	0.366
Alkaline phosphatase (U/L)	106 (82-353)	105.3 (63-500)	0.160
Gamma-glutamyl transpeptidase (U/L)	99 (51-216)	92 (45-286)	0.332
The percentage of Eosinophil	1.90 (0.05-5.90)	1.30 (0.04-4.60)	0.250
Platelet count	206.50 (168-254)	210 (105-351)	0.534
International normalized ratio	1.01 (0.90-1.40)	1.00 (0.90-1.50)	0.437
Median peak values
Alanine aminotransferase (U/L)	296.50 (70-486)	263 (75-616)	0.529
Alkaline phosphatase (U/L)	321 (92-655)	306 (87-783)	0.460
Total bilirubin (μmol/L)	79.20 (15-436)	85.50 (14-397)	0.224
Median time from DILI onset to liver biopsy (d)	36 (10-92)	29 (9-80)	0.405
Injury type
Hepatocellular	113 (48.71%)	29 (49.15%)	0.933
Mixed	59 (25.43%)	16 (27.12%)
Cholestatic	60 (25.86%)	14 (23.73%)
Histopathologic results of liver biopsy
Inflammation (G)			0.247
0	12	1
1	68	19
2	74	14
3	71	22
4	6	4
Fibrosis (F)			0.804
0	125	32
1	63	14
2	44	13
3	0	0
4	0	0
Medication history
Traditional Chinese medicine and herbal and dietary supplements	91	21	0.995
Anti-infectious agents	20	5
Cardiovascular drugs	24	6
Antineoplastics	6	2
Digestive drugs	16	5
Hormone	9	3
Psychotropics	6	2
Others	23	6
Two or more classes in combination	37	9

Item	AUC (95% CI)	Sensitivity (%)	Specificity (%)	+LR	-LR	P value
≥G2
Training cohort
DESI	0.887 (0.841-0.933)	82.00	87.84	6.17	0.28	/
A index	0.790 (0.728-0.853)	56.29	86.42	4.15	0.51	0.000
Vs	0.820 (0.761-0.870)	80.13	71.60	2.82	0.82	0.003
LFI	0.605 (0.535-0.672)	79.47	39.51	1.31	0.52	<0.001
Validation cohort
DESI	0.868 (0.777-0.960)	85.44	86.30	7.99	0.33	/
A index	0.757 (0.626-0.887)	94.44	56.52	2.17	0.098	0.027
Vs	0.806 (0.682-0.898)	86.11	73.91	3.3	0.19	0.158
LFI	0.667 (0.533-0.785)	30.56	95.65	7.03	0.73	0.009
≥G3
Training cohort
DESI	0.893 (0.842-0.945)	84.72	89.13	7.79	0.17	/
A index	0.815 (0.757-0.873)	75.32	72.26	2.72	0.34	0.005
Vs	0.821 (0.762-0.881)	77.92	79.35	3.77	0.28	0.014
LFI	0.622 (0.553- 0.688)	36.36	88.39	3.13	0.72	<0.001
Validation cohort
DESI	0.896 (0.808-0.984)	90.91	83.78	5.61	0.11	/
A index	0.765 (0.646-0.884)	90.91	51.35	1.87	0.18	0.020
Vs	0.809 (0.686-0.900)	81.82	75.68	3.36	0.24	0.124
LFI	0.686 (0.551-0.800)	54.55	83.78	3.36	0.54	0.006

Clinical severity grading	Pathological severity		C score^#
Clinical severity grading	G+F<5^*	G+F≥5^*	C score^#
Mild (n = 87)	77	10	1.77 ± 0.62, P = 0.029
Moderate (n = 162)	146	16	2.25 ± 0.86, P = 0.034
Severe (n = 42)	35	7	4.30 ± 1.41

Item	G+F<5	G+F≥5	AUC (95%CI)	P value^*	Sensitivity (%)	Specificity (%)	+LR	-LR
Training cohort
C score	0.70 ± 0.36	4.34 ± 1.69	0.909 (0.853-0.965)	/	84.62	86.96	6.49	0.18
A index	1.18 ± 0.32	1.55 ± 0.27	0.797 (0.736-0.849)	0.001	81.48	67.32	2.49	0.28
F index	1.65 ± 0.67	2.40 ± 0.57	0.755 (0.691-0.812)	0.000	96.30	45.37	1.76	0.082
Validation cohort
C score	3.22±0.53	7.11±0.86	0.885 (0.783-0.987)	/	80.00	92.59	10.8	0.22
A index	1.20±0.31	1.32±0.14	0646 (0.511-0.766)	0.007	80.00	48.15	1.54	0.42
F index	1.61±0.61	1.99±0.20	0.728 (0.596-0.836)	0.047	60.00	66.67	1.80	0.60