Copyright
©The Author(s) 2025.
World J Gastroenterol. Mar 21, 2025; 31(11): 103178
Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.103178
Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.103178
Table 1 Characteristics of study population comparing non-Fontan-associated liver disease with Fontan-associated liver disease, mean ± SD/n (%)
| General and cardiologic characteristics | Total (n = 91) | Non-FALD (n = 10) | FALD (n = 81) | P value |
| Male | 55 (60.4) | 6 (60.0) | 49 (60.5) | NS |
| Age, years | 33.3 ± 8.2 | 31.8 ± 9.7 | 33.4 ± 8.0 | NS |
| Age, years, median (IQR) | 32.0 (27.0-38.0) | 30.0 (22.0-37.0) | 32.0 (28.0-38.0) | |
| BMI, kg/m2, median (IQR) | 23.1 (20.4-25.8) | 25.7 (24.3-26.3) | 22.7 (20.3-25.0) | 0.048 |
| Time since Fontan, years | 24.3 ± 7.7 | 19.3 ± 11.1 | 24.8 ± 7.1 | 0.074 |
| Time since Fontan, years, median (IQR) | 23.0 (19.0-28.0) | 19.0 (9.0-23.0) | 23.0 (19.5-28.0) | |
| Type of congenital heart disease | NS | |||
| Pulmonary atresia or stenosis | 50 (54.9) | 7 (70.0) | 43 (53.1) | |
| Tricuspid atresia | 39 (42.9) | 6 (60.0) | 33 (40.7) | |
| Transposition of great arteries | 34 (37.4) | 5 (50.0) | 29 (35.0) | |
| Doble outlet right ventricle | 15 (16.5) | 0 (0.0) | 15 (18.5) | |
| Doble inlet left ventricle | 13 (14.3) | 0 (0.0) | 13 (16.0) | |
| Left heart/ventricle hypoplasia | 10 (11.0) | 0 (0.0) | 10 (12.4) | |
| Right heart/ventricle hypoplasia | 12 (13.2) | 1 (10.0) | 11 (13.6) | |
| Mitral atresia | 8 (8.8) | 0 (0.0) | 8 (9.9) | |
| Type of surgery | 0.077 | |||
| Atriopulmonary | 19 (21.1) | 0 (0.0) | 19 (23.5) | |
| Bicavopulmonary | ||||
| Intra-atrial lateral conduit | 8 (8.9) | 2 (22.2) | 6 (7.4) | |
| Extracardiac conduit | 63 (70.0) | 7 (77.8) | 56 (69.1) | |
| Fontan conduit stenosis | 35 (38.9) | 0 (0.0) | 35 (43.8) | 0.006 |
| Oxygen saturation, %, median (IQR) | 93.0 (91.0-95.0) | 94.5 (93.0-96.0) | 93.0 (91.0-95.0) | NS |
| Laboratory investigations and serological/clinical scores | ||||
| Hemoglobin, g/dL, median (IQR) | 16.5 (14.8-17.6) | 16.6 (15.4-17.1) | 16.5 (14.5-17.6) | NS |
| Platelet count, × 103/L, median (IQR) | 135.0 (115.0-182.0) | 188.5 (162.0-209.0) | 131.0 (111.0-169.0) | 0.002 |
| Prothrombin, %, median (IQR) | 74.0 (50.0-83.0) | 83.0 (32.0-88.0) | 74.0 (55.0-82.0) | NS |
| INR, median (IQR) | 1.1 (1.1-1.4) | 1.1 (1.1-1.4) | 1.1 (1,1-1.4) | NS |
| AST, UI/L, median (IQR) | 28.0 (24.0-35.0) | 29.0 (22.0-31.0) | 28.0 (24.0-36.0) | NS |
| ALT, UI/L, median (IQR) | 33.0 (24.0-43.0) | 35.5 (24.0-42.0) | 32.0 (24.0-44.0) | NS |
| ALP, UI/L, median (IQR) | 82.0 (66.5-105.5) | 82.0 (70.0-89.0) | 81.5 (66.0-108.0) | NS |
| GGT, UI/L, median (IQR) | 78.0 (56.0-121.0) | 66.0 (44.0-110.0) | 79.0 (56.0-121.0) | NS |
| Total bilirubin, mg/dL, median (IQR) | 1.3 (0.9-2.1) | 1.2 (0.8-1.9) | 1.3 (0.9-2.1) | NS |
| Direct bilirubin, mg/dL, median (IQR) | 0.7 (0.6-1.0) | 0.5 (0.3-1.0) | 0.7 (0.6-1.0) | NS |
| Creatinine, mg/dL, median (IQR) | 0.8 (0.7-0.9) | 0.9 (0.7-1.0) | 0.8 (0.7-0.9) | NS |
| Sodium, mEq/L, median (IQR) | 140.0 (138.9-141.0) | 139.0 (139.0-140.0) | 140.0 (138.0-141.0) | NS |
| Albumin, g/dL, median (IQR) | 4.6 (4.4-4.9) | 4.7 (4.5-4.8) | 4.6 (4.3-4.9) | NS |
| Total cholesterol, mg/dL, median (IQR) | 140.0 (121.0-162.0) | 142.5 (138.0-163.0) | 139.0 (118.0-162.0) | NS |
| AFP, ng/mL, median (IQR) | 2.4 (1.5-4.2) | 2.5 (2.4-3.1) | 2.4 (1.5-4.2) | NS |
| NT-proBNP, pg/mL, median (IQR) | 217.0 (100.0-579.0) | 178.5 (60.5-455.5) | 234.0 (107.0-587.0) | NS |
| APRI, median (IQR) | 0.5 (0.4-0.7) | 0.4 (0.2-0.6) | 0.5 (0.4-0.7) | 0.030 |
| FIB-4, median (IQR) | 1.1 (0.9-1.6) | 0.8 (0.6-1.0) | 1.2 (0.9-1.8) | 0.017 |
| Forns index, median (IQR) | 5.7 (4.9-6.8) | 4.5 (3.5-5.2) | 5.8 (5.0-6.9) | 0.005 |
| MELD, median (IQR) | 9 (7-11) | 8 (7-10) | 9 (7-11) | NS |
| MELD-Na, median (IQR) | 10 (7-11) | 8 (7-10) | 10 (7-11) | NS |
| MELD-XI, median (IQR) | 11 (9-13) | 10 (9-13) | 11 (9-13) | NS |
| Child-Pugh | NS | |||
| A (5-6) | 84 (92.3) | 10 (100.0) | 74 (91.4) | |
| B (7-9) | 7 (7.7) | 0 (0.0) | 7 (8.6) | |
| VAST ≥ 2 | 42 (75.0) | 0 (0.0) | 42 (77.8) | < 0.001 |
| Ultrasonography and transient elastography | ||||
| Heterogenous liver echogenicity | 61 (67.8) | 0 (0.0) | 61 (76.3) | < 0.001 |
| Nodular liver surface | 55 (61.8) | 0 (0.0) | 55 (69.6) | < 0.001 |
| Hepatomegaly | 35 (39.3) | 0 (0.0) | 35 (44.3) | 0.005 |
| Abnormal caudate | 49 (55.7) | 0 (0.0) | 49 (62.8) | < 0.001 |
| Liver nodules | 38 (42.2) | 4 (40.0) | 34 (42.5) | NS |
| Portal vein dilation | 7 (8.9) | 0 (0.0) | 7 (9.0) | NS |
| Splenomegaly | 46 (50.5) | 0 (0.0) | 46 (58.8) | < 0.001 |
| Collateral circulation | 17 (18.9) | 0 (0.0) | 17 (21.3) | NS |
| Portosystemic shunts | 6 (6.7) | 0 (0.0) | 6 (7.6) | NS |
| Ascites, grade | NS | |||
| 0 | 75 (83.3) | 10 (100.0) | 65 (81.3) | |
| 1 | 10 (11.1) | 0 (0.0) | 10 (12.5) | |
| 2 | 5 (5.6) | 0 (0.0) | 5 (6.3) | |
| Liver stiffness, kPa, median (IQR) | 25.3 (20.3-33.0) | 14.6 (11.4-18.5) | 27.7 (21.9-34.3) | < 0.001 |
Table 2 Characteristics of study population comparing non-advanced Fontan-associated liver disease with advanced Fontan-associated liver disease, mean ± SD/n (%)
| General and cardiologic characteristics | Total (n = 74) | Non-advanced FALD (n = 20) | Advanced FALD (n = 54) | P value |
| Male | 45 (60.8) | 11 (55.0) | 34 (63.9) | NS |
| Age, years | 33.0 ± 7.5 | 32.2 ± 8.9 | 33.2 ± 7.0 | NS |
| Age, years, median (IQR) | 32.0 (28.0-38.0) | 32.5 (23.0-39.0) | 32.0 (28.0-37.0) | |
| BMI, kg/m2, median (IQR) | 22.4 (20.3-25.7) | 24.3 (20.3-26.0) | 22.2 (19.6-24.9) | NS |
| Time since Fontan, median (IQR) | 23.0 (19.0-27.5) | 21.0 (18.0-28.0) | 23.0 (20.0-27.0) | NS |
| Type of congenital heart disease | NS | |||
| Pulmonary atresia or stenosis | 41 (55.4) | 10 (50.0) | 31 (57.4) | |
| Tricuspid atresia | 31 (41.9) | 11 (55.0) | 20 (37.0) | |
| Transposition of great arteries | 26 (35.1) | 7 (35.0) | 19 (35.2) | |
| Doble outlet right ventricle | 12 (16.2) | 3 (15.0) | 9 (16.7) | |
| Doble inlet left ventricle | 8 (10.8) | 1 (5.0) | 7 (13.0) | |
| Left heart/ventricle hypoplasia | 10 (13.5) | 2 (10.0) | 8 (14.8) | |
| Right heart/ventricle hypoplasia | 12 (16.2) | 2 (10.0) | 10 (18.5) | |
| Mitral atresia | 7 (9.5) | 1 (5.0) | 6 (11.1) | |
| Type of surgery | NS | |||
| Atriopulmonary | 16 (21.9) | 3 (15.8) | 13 (24.1) | |
| Bicavopulmonary | ||||
| Intra-atrial lateral conduit | 6 (8.2) | 2 (10.5) | 4 (7.4) | |
| Extracardiac conduit | 51 (69.9) | 14 (73.7) | 37 (68.5) | |
| Fontan conduit stenosis | 30 (41.1) | 4 (20.0) | 26 (49.1) | 0.033 |
| Oxygen saturation, %, median (IQR) | 92.0 (91.0-95.0) | 94.0 (92.5-96.0) | 92.0 (90.0-94.0) | 0.007 |
| Laboratory investigations and serological/clinical scores | ||||
| Hemoglobin, g/dL, median (IQR) | 16.3 (14.5-17.6) | 16.2 (14.5-17.0) | 16.3 (14.5-17.6) | NS |
| Platelet count, × 103/L, median (IQR) | 130.0 (111.0-169.0) | 162.0 (142.0-198.0) | 120.0 (97.0-150.0) | < 0.001 |
| Prothrombin, %, median (IQR) | 73.0 (50.0-82.5) | 73.0 (34.5-87.9) | 72.5 (51.0-81.0) | NS |
| INR, median (IQR) | 1.1 (1.1-1.4) | 1.1 (1.1-1.4) | 1.2 (1.1-1.4) | NS |
| AST, UI/L, median (IQR) | 28.0 (23.5-33.0) | 29.0 (23.0-36.0) | 28.0 (23.5-32.0) | NS |
| ALT, UI/L, median (IQR) | 31.5 (23.5-43.0) | 34.0 (22.5-44.0) | 31.0 (24.0-42.0) | NS |
| ALP, UI/L, median (IQR) | 81.0 (66.0-108.0) | 73.5 (62.5-84.0) | 87.0 (66.0-114.0) | NS |
| GGT, UI/L, median (IQR) | 77.0 (54.5-124.0) | 62.5 (43.0-89.5) | 80.5 (60.0-140.0) | 0.025 |
| Total bilirubin, mg/dL, median (IQR) | 1.4 (0.9-2.1) | 0.9 (0.7-1.8) | 1.5 (1.0-2.2) | 0.030 |
| Direct bilirubin, mg/dL, median (IQR) | 0.7 (0.6-1.0) | 0.6 (0.4-1.0) | 0.7 (0.6-1.0) | NS |
| Creatinine, mg/dL, median (IQR) | 0.8 (0.7-0.9) | 0.9 (0.7-0.9) | 0.8 (0.7-0.9) | NS |
| Sodium, mEq/L, median (IQR) | 140.0 (138.9-141.0) | 140.0 (139.0-142.0) | 140.0 (138.0-141.0) | NS |
| Albumin, g/dL, median (IQR) | 4.6 (4.3-4.9) | 4.7 (4.5-4.8) | 4.6 (4.3-4.9) | NS |
| Total cholesterol, mg/dL, median (IQR) | 139.0 (122.0-161.5) | 142.5 (129.0-150.5) | 137.5 (118.5-163.5) | NS |
| AFP, ng/mL, median (IQR) | 2.4 (1.6-4.4) | 2.4 (2.0-3.1) | 2.3 (1.5-4.9) | NS |
| NT-proBNP, pg/mL, median (IQR) | 223.0 (100.0-579.0) | 181.0 (82.0-453.0) | 246.0 (107.0-737.0) | NS |
| APRI, median (IQR) | 0.51 (0.37-0.71) | 0.40 (0.33-0.63) | 0.53 (0.39-0.77) | 0.024 |
| FIB-4, median (IQR) | 1.1 (0.9-1.7) | 1.0 (0.7-1.3) | 1.2 (0.9-1.9) | 0.028 |
| Forns index, median (IQR) | 5.7 (5.0-6.8) | 5.0 (4.3-5.6) | 6.3 (5.4-7.2) | < 0.001 |
| MELD, median (IQR) | 9 (7-11) | 8 (7-9) | 10 (8-11) | 0.024 |
| MELD-Na, median (IQR) | 10 (8-12) | 7 (7-9) | 10 (8-12) | 0.007 |
| MELD-XI, median (IQR) | 12 (9-13) | 10 (9-13) | 12 (10-14) | 0.040 |
| Child-Pugh | 0.084 | |||
| A (5-6) | 67 (90.5) | 20 (100.0) | 47 (87.0) | |
| B (7-9) | 7 (9.5) | 0 (0.0) | 7 (13.0) | |
| VAST ≥ 2 | 42 (75.0) | 0 (0.0) | 42 (93.4) | < 0.001 |
| Ultrasonography and transient elastography | ||||
| Heterogenous liver echogenicity | 46 (63.0) | 7 (35.0) | 39 (73.6) | 0.006 |
| Nodular liver surface | 44 (60.3) | 6 (30.0) | 38 (71.7) | 0.003 |
| Hepatomegaly | 30 (40.5) | 3 (15.0) | 27 (50.0) | 0.008 |
| Abnormal caudate | 42 (57.5) | 5 (25.0) | 37 (69.8) | 0.001 |
| Portal vein dilation | 7 (9.6) | 1 (5.0) | 6 (11.3) | NS |
| Splenomegaly | 46 (62.2) | 0 (0.0) | 46 (85.2) | < 0.001 |
| Collateral circulation | 17 (23.0) | 0 (0.0) | 17 (31.5) | 0.004 |
| Portosystemic shunts | 6 (8.1) | 0 (0.0) | 6 (11.1) | NS |
| Ascites, grade | NS | |||
| 0 | 59 (79.7) | 19 (95.9) | 40 (74.1) | |
| 1 | 10 (13.5) | 1 (5.0) | 9 (16.7) | |
| 2 | 5 (6.8) | 0 (0.0) | 5 (9.3) | |
| Liver stiffness, kPa, median (IQR) | 26.8 (20.3-34.3) | 19.0 (13.0-30.0) | 29.5 (22.6-36.4) | 0.001 |
Table 3 Multivariate risk factor analysis for the development of Fontan-associated liver disease
| Variable | Multivariate analysis | |
| OR (95%CI) | P value | |
| Age | NS | |
| Time since Fontan surgery | NS | |
| Forns index | 2.59 (1.04-6.46) | 0.042 |
| Liver stiffness measurement | 1.34 (1.10-1.64) | 0.003 |
Table 4 Multivariate risk factor analysis for the development of advanced Fontan-associated liver disease
| Variable | Multivariate analysis | |
| OR (95%CI) | P value | |
| Age | NS | |
| Time since Fontan surgery | NS | |
| Conduit stenosis | NS | |
| Oxygen saturation | 0.68 (0.51-0.92) | 0.013 |
| Liver stiffness measurement | 1.10 (1.01-1.19) | 0.023 |
Table 5 Definition of liver stiffness measurement by transient elastography cut-off values for Fontan-associated liver disease
| LSM cut-off value | Sensitivity | Specificity | PPV | NPV | Accuracy | |
| Rule-out cut-off | < 15 | 0.969 | 0.500 | 0.926 | 0.714 | 0.907 |
| Optimal cut-off | 20 | 0.923 | 0.800 | 0.968 | 0.615 | 0.907 |
| Rule-in cut-off | ≥ 25 | 0.615 | 1.000 | 1.000 | 0.286 | 0.667 |
Table 6 Definition of liver stiffness measurement by transient elastography cut-off values for advanced Fontan-associated liver disease
| LSM cut-off value | Sensitivity | Specificity | PPV | NPV | Accuracy | |
| Rule-out cut-off | < 20 | 0.957 | 0.474 | 0.815 | 0.818 | 0.815 |
| Optimal cut-off | 25 | 0.696 | 0.684 | 0.842 | 0.481 | 0.691 |
| Rule-in cut-off | ≥ 40 | 0.196 | 0.947 | 0.900 | 0.327 | 0.415 |
Table 7 Multivariate analysis for mortality
| Variable | Multivariate analysis | |
| OR (95%CI) | P value | |
| Time since Fontan surgery | 1.36 (1.04-1.79) | 0.026 |
| Liver stiffness measurement | 1.23 (1.02-1.47) | 0.026 |
Table 8 Multivariate analysis for clinically relevant events
| Variable | Multivariate analysis | |
| OR (95%CI) | P value | |
| Time since Fontan surgery | 1.14 (1.03-1.26) | 0.010 |
| MELD-XI score | 1.40 (1.04-1.89) | 0.028 |
| Liver stiffness measurement | 1.07 (1.01-1.13) | 0.021 |
- Citation: Cuadros M, Abadía M, Castillo P, Martín-Arranz MD, Gonzalo N, Romero M, García-Sánchez A, García-Samaniego J, Olveira A, Ruiz-Cantador J, González-Fernández Ó, Ponz I, Merás P, Merino C, Rodríguez-Chaverri A, Balbacid E, Froilán C. Role of transient elastography in the diagnosis and prognosis of Fontan-associated liver disease. World J Gastroenterol 2025; 31(11): 103178
- URL: https://www.wjgnet.com/1007-9327/full/v31/i11/103178.htm
- DOI: https://dx.doi.org/10.3748/wjg.v31.i11.103178