Transient elastography compared to liver biopsy and morphometry for predicting fibrosis in pediatric chronic liver disease: Does etiology matter?

Table 1 Basic clinical characteristics of the studied groups

Parameter	HCV	AIH	Wilson disease	P value
	(n = 50)	(n = 20)	(n = 20)
Age (yr)	8.50 ± 3.51	8.98 ± 2.98	12.05 ± 4.25	0.003
Sex [male, n (%)]	39 (78)	7 (35)	13 (65)	0.003
Jaundice, n (%)	0 (0)	18 (90)	5 (25)	< 0.0001
Abdominal enlargement, n (%)	0 (0)	5 (25)	15 (75)	< 0.0001
Liver US, n (%)				< 0.0001
Normal	50 (100)	0 (0)	1 (5)
Enlarged	0 (0)	20 (100)	13 (65)
Shrunken	0 (0)	0 (0)	6 (30)
Splenomegaly US, n (%)	0 (0)	16 (80)	20 (100)	< 0.0001
Total bilirubin (mg/dL)	0.97 ± 0.24	7.70 ± 3.72	3.37 ± 2.85	< 0.0001
Direct bilirubin (mg/dL)	0.24 ± 0.17	5.58 ± 3.24	1.8 ± 1.30	< 0.0001
Albumin (g/dL)	4.40 ± 0.61	3.71 ± 1.71	3.55 ± 0.71	< 0.0001
Aspartate transaminase (U/L)	27.21 ± 14.75	225.10 ± 21.7	76.59 ± 68.43	< 0.0001
Alanine transaminase (U/L)	29.52 ± 14.93	218.65 ± 14.2	87.05 ± 56.26	< 0.0001
Gamma-glutamyl transpeptidase (U/L)	28.66 ± 13.80	52.50 ± 19.22	51.25 ± 37.89	< 0.0001
Alkaline phosphatase (U/L)	127.82 ± 74.13	122.25 ± 45.03	222.30 ± 134.23	< 0.0001
Prothrombin time (s)	13.2 ± 1.1	14.87 ± 3.13	16.18 ± 5.31	0.003
Activity grade, n (%)				< 0.0001
Minimal (A1-A3)	40 (80)	6 (30)	0 (0)
Mild (A4-A8)	8 (16)	8 (40)	18 (90)
Moderate (A9-A12)	2 (4)	6 (30)	2 (10)
Fibrosis category, n (%)				< 0.0001
Absent (F0)	4 (8)	0 (0)	0 (0)
Mild (F1)	32 (64)	1 (5)	0 (0)
Moderate (F2-F3)	14 (28)	7 (35)	6 (30)
Severe (F4-F6)	0 (0)	12 (60)	14 (70)
Fibrosis area fraction (%)	2.72 ± 1.66	17.41 ± 9.24	12.68 ± 4.59	< 0.0001
Liver stiffness (kPa)	5.75 ±1.81	22.13 ± 14.23	20.05 ± 10.57	< 0.0001

AIH: Autoimmune hepatitis; HCV: Hepatitis C virus; US: Ultrasonography.

Table 2 Clinical performance of liver stiffness in predicting individual Ishak fibrosis stages in all the patients

Ishak fibrosis stage	Cut-off (kPa)	AUROC	P value	Sensitivity	Specificity	PPV	NPV
≥ F1	4.75	0.807	0.039	81.4	75.0	98.6	15.7
≥ F2	6.65	0.947	< 0.0001	88.7	86.5	90.4	84.2
≥ F3	8.25	0.960	< 0.0001	89.5	90.4	87.2	92.2
≥ F4	13.0	0.993	< 0.0001	100	96.9	92.9	100
≥ F5	18.0	0.985	< 0.0001	100	97.2	90.0	100
F6	29.5	0.941	< 0.0001	85.7	91.6	46.2	98.7

AUROC: Area under receiver operating characteristic curve; PPV: Positive predictive value; NPV: Negative predictive value.

Table 3 Area under receiver operating characteristic curve for liver stiffness in predicting individual Ishak fibrosis stages in the different etiological groups

Ishak fibrosis stage	HCV		AIH		Wilson disease
	AUROC	P value	AUROC	P value	AUROC	P value
≥ F1	0.698	0.192	NA	--	NA	--
≥ F2	0.870	< 0.0001	1.000	< 0.0001	NA	--
≥ F3	0.799	0.049	1.000	< 0.0001	1.000	< 0.0001
≥ F4	NA	--	0.958	0.001	1.000	< 0.0001
≥ F5	NA	--	0.927	0.002	1.000	< 0.0001
F6	NA	--	0.828	0.047	0.837	0.044

AIH: Autoimmune hepatitis; AUROC: Area under receiver operating characteristic; HCV: Hepatitis C virus.

Table 4 Liver stiffness measurement in every fibrosis stage by the disease group

Ishak fibrosis stage	All patients	HCV	AIH	Wilson disease
	(n = 90)	(n = 50)	(n = 20)	(n = 20)
	kPa	kPa	kPa	kPa
F0	5.10 ± 2.61	5.10 ± 2.61	--	--
F1	5.10 ± 1.45	5.13 ± 1.45	3.70	--
F2	7.32 ± 1.4	7.33 ± 1.32	7.50 ± 0.71	6.00
F3	9.88 ± 4.33	7.43 ± 1.73	16.15 ± 7.23	8.30 ± 0.84
F4	18.58 ± 8.57	--	21.43 ± 12.19	15.75 ± 0.96
F5	31.25 ± 10.38	--	36.08 ± 16.19	28.49 ± 4.93
F6	31.71 ± 6.13	--	32.75 ± 3.63	30.33 ± 9.87

AIH: Autoimmune hepatitis; HCV: Hepatitis C virus.

Table 5 Correlation of liver stiffness with age, laboratory, and histopathological parameters of the studied patients

Parameter	Correlation
	r	P value
Age (yr)	0.267	0.011
Total bilirubin (mg/dL)	0.433	< 0.0001
Direct bilirubin (mg/dL)	0.506	< 0.0001
Albumin (g/dL)	-0.419	< 0.0001
Alanine transaminase (U/L)	0.622	< 0.0001
Aspartate transaminase (U/L)	0.559	< 0.0001
Alkaline phosphatase (U/L)	0.261	0.013
gamma-glutamyl transpeptidase (U/L)	0.559	< 0.0001
Prothrombin time (s)	0.322	0.002
Ishak activity grade	0.760	< 0.0001
Ishak fibrosis stage	0.879	< 0.0001