Cardiopulmonary changes and its association with clinical features in noncirrhotic portal hypertension

Table 1 Baseline characteristics of the cohort

Baseline characteristics	Overall cohort (n = 42)	NCPH (n = 32)	Preclinical NCPH (n = 10)	P value1
Age (years)	52 (41-61)	52 (43 – 62)	49 (40-59)	0.5
Gender, male (%)	26 (62)	20 (63)	6 (60)	0.9
Body mass index (kg/m2)	24.1 (22.1-26.8)	24.0 (22.6-26.8)	25.3 (19.0-26.6)	0.2
Heart rate (bpm)	69 (62-74)	69 (63-74)	69 (60-74)	0.5
Systolic blood pressure (mmHg)	116 (104-127)	114 (103-125)	126 (115-132)	0.2
Diastolic blood pressure (mmHg)	67 (60-71)	62 (59-72)	68 (68-70)	0.3
Oxygen saturation (%)	97 (96-98)	98 (96-99)	97 (96-98)	0.6
Smoking status				0.05
Current or previous smoker, n (%)	15 (36)	14 (44)	1 (10)
Non-smoker, n (%)	27 (64)	18 (56)	9 (90)
Underlying disorder				< 0.01
Immunodeficiency, n (%)	17 (40)	9 (28)	8 (80)
Autoimmune disorders, n (%)	2 (5)	2 (6)
Hematological disorders, n (%)	4 (10)	3 (9)	1 (10)
Exposure to medication, n (%)	4 (10)	4 (13)
Genetic disorders, n (%)	3 (7)	2 (6)	1 (10)
CVID and exposure to drugs, n (%)	1 (2)	1 (3)
Undiagnosed, n (%)	11 (26)	11 (35)
Medication use
Beta blockers, n (%)	17 (40)	17 (53)
Diuretics, n (%)	13 (31)	11 (34)	2 (20)	0.4
Antihypertensives, n (%)	6 (14)	5 (16)	1 (10)	0.4
Antidiabetics including insulin, n (%)	6 (14)	5 (16)	1 (10)	0.4
Immunomodulators, n (%)	12 (29)	7 (22)	5 (50)	0.08
Haemoglobin (g/dL)	12.9 (11.1-14.4)	12.7 (11.0-14.1)	13.3 (12.8-15.4)	0.06
Sodium (mEq/L)	138 (138-140)	138 (138-141)	139 (138-139)	0.6
Creatinine (mg/dL)	0.8 (0.7-0.9)	0.8 (0.7-0.9)	0.8 (0.7 – 1.0)	0.9
Albumin (g/dL)	3.9 (3.7-4.2)	3.9 (3.7-4.2)	4.1 (3.6-4.2)	0.7
C-reactive protein (mg/dL)	2.2 (1.0-4.5)	2.3 (1.2-4.9)	1.7 (1.0 – 3.0)	0.09
Prothrombin time (seconds)	14.2 (13.1-15.0)	14.4 (13.6-15.3)	12.9 (12.7-13.8)	< 0.01
International normalized ratio	1.1 (0.9-1.2)	1.1 (1.0-1.2)	1.0 (0.9-1.0)	< 0.01
Platelet count (109/L)	94 (62-153)	77.5 (53.8-134)	171 (128-246)	0.02
Alanine aminotransferase, AST (U/L)	45 (25-60)	40 (26-59)	45 (25-77)	0.6
Aspartate aminotransferase, ALT (U/L)	46 (31-62)	44 (31-60)	46.5 (31.3-75.3)	0.6
AST/ALT ratio	1.1 (0.9-1.3)	1.1 (0.9-1.3)	1.1 (1.0-1.2)	0.9
Fibrosis-4 index	3.4 (1.9-6.3)	4.1 (2.7-7.4)	1.5 (1.4-2.6)	< 0.01
MELD-Na	9 (8-10)	9 (8-10)	8 (7-10)	0.06
Liver stiffness measurement (kPa)	8.6 (6.0-13.5)	11.6 (7.7-14.5)	5.3 (4.3-6.1)	< 0.01
Hepatic venous pressure gradient (mmHg)2	6 (4-11)	10 (5-15)	4 (3-5)	< 0.01

¹P values show a comparison among those with and without portal hypertension cohort using either Student’s t-test or the Mann-Whitney U test for continuous variables and corrected χ² test or a 2-sided Fisher’s exact test for categorical variables.

²30 patients (23 with portal hypertension and 7 without portal hypertension) underwent transjugular portal pressure measurement.

Data presented as median (IQR), mean (SD) or n (%). MELD-Na: Model for end-stage liver disease-sodium; CVID: Common variable immunodeficiency; NCPH: Noncirrhotic portal hypertension; AST/ALT: Aspartate aminotransferase to alanine aminotransferase.

Table 2 Factors associated with shunting

Characteristics	Shunt present (n = 17)	Shunt absent (n = 21)	P value1
Age (years)	51 (39-61)	49 (41-57)	0.7
Male gender, n (%)	8 (47)	16 (76)	0.09
Body mass index (kg/m2)	24.1 (23.4-28.7)	23.5 (21.9-25.7)	0.04
Heart rate (bpm)	70 (63-78)	68 (60-70)	0.1
Systolic blood pressure (mmHg)	116 (101-124)	116 (105-127)	0.6
Diastolic blood pressure (mmHg)	61 (60-69)	68 (62-70)	0.2
Oxygen saturation (%)	97 (96-98)	98 (97-99)	0.08
Had features of portal hypertension (%)2	15 (88)	13 (62)	0.1
Smoking status			0.6
Current or previous smoker, n (%)	5 (29)	8 (38)
Non-smoker, n (%)	12 (71)	13 (62)
Underlying disorder			< 0.01
Immunodeficiency, n (%)	3 (18)	13 (62)
Autoimmune disorders, n (%)	1 (5)	1 (5)
Hematological disorders, n (%)	2 (12)	1 (5)
Exposure to medication, n (%)	2 (12)	2 (9)
Genetic disorders, n (%)	3 (18)
CVID and exposure to drugs, n (%)		1 (5)
Undiagnosed, n (%)	6 (35)	3 (14)
Medication use
Beta blockers, n (%)	8 (47)	8 (38)	0.7
Diuretics, n (%)	5 (29)	5 (24)	0.7
Antihypertensives, n (%)	2 (12)	3 (14)	0.9
Antidiabetics including insulin, n (%)	4 (24)	1 (5)	0.2
Immunomodulators, n (%)	3 (18)	9 (43)	0.2
Sodium (mEq/L)	138 (138-140)	138 (138-139)	0.3
Creatinine (mg/dL)	0.8 (0.7-0.9)	0.8 (0.7-0.9)	0.6
Albumin (g/dL)	3.9 (3.8-4.2)	3.9 (3.6-4.2)	0.6
Haemoglobin (g/dL)	13.5 (10.8-14.2)	12.9 (11.8-14.4)	0.6
C-reactive protein (mg/dL)	2.3 (1.4-3.6)	1.9 (1.0-5.2)	0.1
Prothrombin time (seconds)	14.2 (13.4-15.4)	14.1 (13.0-14.5)	0.2
International normalized ratio	1.1 (1.0-1.2)	1.1 (0.9-1.1)	0.2
Platelet count (109/L)	85 (65-146)	97 (60-144)	0.8
Alanine aminotransferase, ALT (U/L)	32 (25-53)	45 (26-76)	0.2
Aspartate aminotransferase, AST (U/L)	42 (32-49)	46 (30-71)	0.7
Chenodeoxycholic acid (nmol/mL)	6.1 (2.0-14.5)	4.1 (1.2-1.0)	0.1
Cholic acid (nmol/mL)	4.8 (1.8-11.1)	1.3 (0.7-10.4)	0.7
Deoxycholic acid (nmol/mL)	1.7 (0.8-9.1)	0.9 (0.1-2.4)	0.09
Ursodeoxycholic acid (nmol/mL)	0.4 (0.2-1.7)	0.3 (0.1-0.7)	0.2
Primary bile acid (nmol/mL)	14.2 (3.8-26.0)	5.1 (2.0-18.7)	0.3
Secondary bile acid (nmol/mL)	1.7 (1.2-11.6)	1.3 (0.3-2.4)	0.08
Total Bile acid (nmol/mL)	15.9 (5.2-33.0)	7.5 (4.4-22.2)	0.2
Spleen length (cm)	16.2 (12.7-20.0)	15.8 (12.6-18.7)	0.8
Wedged hepatic venous pressure (mmHg)3	23 (14-27)	19 (14-26)	0.6
Free hepatic vein pressure (mmHg)3	13 (10-15)	11 (9-15)	0.4
Hepatic venous pressure gradient (mmHg)3	8 (5-11)	6 (3-14)	0.6
AST/ALT ratio	1.3 (1.0-1.4)	1.0 (0.8-1.1)	0.04
FIB-4 index	3.7 (2.0-5.0)	3.3 (1.6-6.6)	0.9
MELD-Na	10.0 (8.0-10.0)	8.0 (7.0-10.0)	0.7
Liver stiffness measurement (kPa)	12.4 (7.2-16.8)	7.1 (5.4-10.3)	0.03

¹P values show a comparison among the groups using either Student’s t-test or the Mann-Whitney U test for continuous variables and corrected χ² test or a 2-sided Fisher’s exact test for categorical variables.

²Features of portal hypertension were defined by presence of gastric, esophageal, or ectopic varices, portal hypertensive gastropathy, or the presence of ascites or portosystemic shunting in imaging.

³30 patients (14 with shunt and 16 without shunt) underwent transjugular portal pressure measurement.

Data presented as median (IQR), mean (SD) or n (%). MELD-Na: Model for end-stage liver disease-sodium; CVID: Common variable immunodeficiency; AST/ALT: Aspartate aminotransferase to alanine aminotransferase.

Table 3 Factors associated with right ventricular systolic pressure

Variables	Correlation1, r	P value
Age	0.31	0.04
Oxygen saturation (%)	-0.33	0.03
Cardiac output (L/min)	0.33	0.04
Cardiac index (L/min/m2)	0.29	0.07
LV mass index (gm/m2)	0.31	0.05
LA volume (mL)	0.51	< 0.01
LA volume index (mL/m2)	0.5	0.01
RA volume (mL)	0.37	0.02
RA volume index (mL/m2)	0.42	< 0.01
Septal MV E/e’	0.28	0.08
Lateral MV E/e’	0.39	0.01
TAPSE (mm)	0.35	0.04
IVC diameter (mm)	0.32	0.04
AST/ALT ratio	0.33	0.03
Liver stiffness measurement (kPa)	0.04	0.7
Wedged hepatic venous pressure (mmHg)2	0.09	0.6
Free hepatic vein pressure (mmHg)2	0.43	0.02
Hepatic venous pressure gradient (mmHg)2	-0.08	0.6

¹Spearman correlation.

²30 patients underwent transjugular portal pressure measurement.

LV: Left ventricle; TAPSE: Tricuspid annular plane systolic excursion; IVC: Inferior vena cava; AST/ALT: Aspartate aminotransferase to alanine aminotransferase; LA: Left atrial; RA: Right atrial.

Table 4 Features among those with and without portal hypertension (excluding smokers and beta blocker users)

Baseline characteristics	NCPH (n = 7)	Preclinical NCPH (n = 9)	P value1
Age (years)	51 (42-63)	46 (39-57)	0.6
Male gender, n (%)	4 (57)	5 (56)	0.8
Body mass index (kg/m2)	25.8 (23.3-31.6)	25.1 (18.6-25.7)	0.09
Heart rate (bpm)	70 (67-80)	70 (65-75)	0.2
Systolic blood pressure (mmHg)	116 (113-128)	124 (114-129)	0.7
Diastolic blood pressure (mmHg)	67 (55-71)	68 (68-69)	0.5
Oxygen saturation (%)	96 (96-98)	97 (96-97)	0.7
Sodium (mEq/L)	139 (138-140)	139 (138-139)	0.9
Creatinine (mg/dL)	0.8 (0.7-0.8)	0.8 (0.7-1.0)	0.7
Albumin (g/dL)	3.9 (3.8-3.9)	4.1 (3.5-4.2)	0.9
Haemoglobin (g/dL)	12.7 (11.9-14.1)	13 (12.8-15.7)	0.3
C-reactive protein (mg/dL)	1.2 (0.6-3.9)	1.5 (1.0-2.6)	0.4
Left ventricular ejection fraction (%)	60 (59-62)	62 (62-65)	0.1
Cardiac output (L/min)	5.6 (5.2-7.8)	5.2 (4.4-6.0)	0.3
Cardiac index (L/min/m2)	2.9 (2.7-3.8)	2.8 (2.7-3.0)	0.5
LV diastolic volume (mL)	146 (133-164)	97 (89-121)	0.02
LV diastolic volume index (mL/m2)	69 (64-86)	57 (48-59)	0.04
LV mass index (gm/m2)	84.9 (80.5-98.3)	68.4 (64.1-86.5)	0.3
LV global longitudinal strain (%)	-22.7 (-24.4--19.0)	-21.6 (-22.3--19.9)	0.9
RV free wall strain (%)	-24.6 (-26.9--23.5)	-25.9 (-28.9--24.3)	0.6
RVSP (mmHg)	26 (24-38)	27 (25-30)	0.3
LA volume (ml)	80 (73-85)	46 (34-59)	0.03
LA volume index (mL/m2)	37 (35-44)	23 (22-29)	0.04
RA volume (mL)	57 (52-64)	28 (26-43)	0.09
RA volume index (mL/m2)	26 (26-30)	16 (13-20)	0.1
Septal MV E/e’	10.0 (8.1-11.7)	7.4 (6.5-8.8)	0.1
Lateral MV E/e’	7.8 (6.5-9.8)	4.9 (4.5-6.9)	0.1
Septal e’ (cm/s)	9 (8-11)	11 (10-11)	0.4
Lateral e’ (cm/s)	12 (12-15)	15 (10-15)	0.8
TAPSE (mm)	25 (22-26)	24 (23-25)	0.9
Mitral E to A ratio	1.2 (0.8-1.2)	1.4 (1.1-1.5)	0.9
IVC diameter (mm)	23.0 (16.8-30.8)	20.0 (12.0-21.0)	0.1

¹P values show a comparison among the groups using either student’s t-test or the Mann-Whitney U test for continuous variables and corrected χ² test or a 2-sided Fisher’s exact test for categorical variables.

Data presented as median (IQR), mean (SD) or n (%). LVID: Left ventricular internal diameter; LV: Left ventricle; RV: Right ventricular; RVSP: Right ventricular systolic pressure; LA: Left atrial; RA: Right atrial; TAPSE: Tricuspid annular plane systolic excursion; IVC: Inferior vena cava; NCPH: Noncirrhotic portal hypertension.