Liver stiffness reversibly increases during pregnancy and independently predicts preeclampsia

Table 1 Patient characteristics

Parameter	Controls (n = 475)	Preeclampsia (n = 22)	aP value	ICP (n = 40)	aP value
Age (yr)	32.3 ± 5.0	33.4 ± 2.9	0.3069	27.8 ± 4.1	< 0.0001
Gestational age (d)	192 ± 67	169 ± 59	0.1330	237 ± 18	0.0007
Current BMI (kg/m²)	28.0 ± 6.1	29.0 ± 8.6	0.4601	32.0 ± 8.3	0.0001
BMI before pregnancy (kg/m²)	24.7 ± 5.8	25.9 ± 7.8	0.3569	28.4 ± 9.1	0.0002
MAP (kPa)	11.0 ± 1.6	12.1 ± 1.4	0.0279	10.4 ± 2.0	0.2747
Pruritus (present)	2%	0%	0.4948	53%	< 0.0001
Nulliparous	45%	50%	0.6345	37%	0.1883
AST (U/L)	24 ± 23	88 ± 122	< 0.0001	105 ± 122	< 0.0001
ALT (U/L)	15 ± 15	39 ± 35	< 0.0001	174 ± 174	< 0.0001
AP (U/L)	134 ± 126	115 ± 43	0.5955	179 ± 69	0.0382
GGT (U/L)	24 ± 48	35 ± 52	0.4439	32 ± 34	0.3863
Bilirubin total (mg/dL)	0.5 ± 0.3	0.5 ± 0.2	0.5374	0.5 ± 0.3	0.2561
Creatinine (mg/dL)	0.6 ± 0.1	0.6 ± 0.1	0.1308	0.8 ± 0.4	< 0.0001
Urea (mg/dL)	18 ± 5	23 ± 7	0.0006	22 ± 7	0.0001
Uric acid (mg/dL)	3.8 ± 1.1	5.0 ± 1.4	0.0019	5.8 ± 2.5	< 0.0001
Total protein (g/L)	66.1 ± 5.7	63.3 ± 4.3	0.1114	66.9 ± 5.2	0.5143
Albumin (g/L)	36.0 ± 2.2	25.5 ± 15.3	0.0046	36.4 ± 5.5	0.7729
Leukocytes (1/nL)	11.9 ± 4.2	9.6 ± 4.6	0.0599	10.1 ± 3.5	0.0158
Erythrocytes (1/pL)	3.9 ± 0.4	4.2 ± 0.4	0.0390	4.0 ± 0.5	0.4560
Hemoglobin (g/dL)	11.7 ± 1.3	12.4 ± 0.9	0.0632	11.2 ± 1.4	0.0313
Platelets (1/nL)	231 ± 63	173 ± 85	0.0022	231 ± 55	0.9790
INR	0.91 ± 0.03	1.01 ± 0.16	< 0.0001	0.91 ± 0.04	0.6616
Liver size (cm)	13.9 ± 1.8	13.2 ± 1.5	0.0786	14.4 ± 1.1	0.0812
Spleen size (cm)	10.9 ± 1.5	12.4 ± 2.8	< 0.0001	11.4 ± 1.8	0.0954
Diameter VCI (cm)	1.6 ± 0.3	1.8 ± 0.6	0.0075	1.5 ± 0.3	0.1713
Hepatic steatosis in sonography (0-3)	0.2 ± 0.4	0.2 ± 0.5	0.7334	0.4 ± 0.5	0.0174
Liver stiffness (kPa)	5.3 ± 2.0	17.9 ± 20.7	< 0.0001	6.9 ± 2.1	< 0.0001
> 6 kPa	120 (25%)	14 (63%)		23 (58%)
> 8 kPa	30 (6%)	10 (45%)		8 (20%)
> 12.5 kPa	7 (1.5%)	9 (40%)		1 (2.5%)
CAP (dB/m)	226 ± 43	228 ± 47	0.7843	215 ± 40	0.1322

^aP: P-value in comparison vs controls. ICP: Intrahepatic cholestasis of pregnancy; AST: Aspartate transaminase; ALT: Alanine transaminase; BMI: Body mass index; CAP: Controlled attenuation parameter; GGT: Gamma-glutamyltransferase; MAP: Mean arterial pressure; AP: Arterial pressure; INR: International normalized ratio; VCI: Vena cava inferior.

Table 2 Associations with liver stiffness in all women, controls, preeclampsia and cholestasis patients

Spearman correlations	All	Control	Preeclampsia	ICP
General
Gestational age (d)	0.462c	0.499c	-0.372	0.017
Age (yr)	-0.071	-0.035	0.198	-0.249
Current body weight (kg)	0.296c	0.287c	0.195	0.193
Body weight before pregnancy (kg)	0.182c	0.161c	0.315	0.175
Increase in body weight (kg)	0.314c	0.325c	-0.184	0.233
Current BMI (kg/m²)	0.316c	0.313c	0.313	0.169
BMI before pregnancy (kg/m²)	0.188c	0.169c	0.686c	0.175
Increase in BMI (kg/m²)	0.322c	0.328c	-0.118	0.269
MAP (kPa)	0.154c	0.03	0.082	0.464
pruritus	0.194c	-0.034		0.471b
Nulliparous state	0.131b	0.129b	0.287	0.383b
Laboratory
Creatinine (mg/dL)	0.138	0.045	-0.478	0.048
Urea (mg/dL)	0.064	-0.068	-0.459	0.063
AST (U/L)	0.267c	0.04	0.588a	0.325a
ALT (U/L)	0.286c	0.103	0.354	0.28
AP (U/L)	0.297c	0.313c	-0.091	0.128
GGT (U/L)	0.228b	0.164	0.717b	-0.038
Bilirubin total (mg/dL)	0.027	-0.128	0.754b	0.257
Uric acid (mg/dL)	0.283c	0.152	-0.157	0.059
Total protein (g/L)	-0.201a	-0.350c	-0.018	-0.018
Albumin (g/L)	-0.199	-0.195	-0.5	-0.21
Leukocytes (1/nL)	-0.346c	-0.205a	-0.834c	-0.595c
Erythrocytes (1/pL)	0.169a	0.133	-0.473	0.181
Hemoglobin (g/dL)	0.024	0.073	-0.767b	0.064
Platelets (1/nL)	-0.132	0.025	-0.790b	-0.480b
Quick-test (%)	-0.029	0.086	-0.814b	0.017
INR	-0.013	-0.132	0.802b	-0.038
Bile acid (µmol/L)	0.698c	0.393		0.698c
Sonography
Liver size (cm)	0.031	0.027	0.357	-0.247
Spleen size (cm)	0.167b	0.112a	0.587b	-0.071
Diameter VCI (cm)	-0.009	-0.035	0.387	0.144
Level of hepatic steatosis (0-3)	0.211c	0.186c	0.343	0.309
CAP (dB/m)	0.075	0.081	0.775c	0.02
Cumulative estimated fetus weight (g)	0.244a	0.223

^aP < 0.05;

^bP < 0.01;

^cP < 0.001. ICP: Intrahepatic cholestasis of pregnancy; AST: Aspartate transaminase; ALT: Alanine transaminase; BMI: Body mass index; CAP: Controlled attenuation parameter; GGT: Gamma-glutamyltransferase; MAP: Mean arterial pressure; AP: Arterial pressure; INR: International normalized ratio; VCI: Vena cava inferior.