Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease

Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease Katsuo Tao, Yuichi Ishikawa, Sayo Suzuki, Shota Muraji, Ayako Kuraoka, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4194336/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Fontan-associated liver disease (FALD) may be caused by chronic liver congestion due to high central venous pressure (CVP). Recently, the usefulness of liver native T1 mapping in magnetic resonance imaging (MRI) in adulthood has been reported. Objective To evaluate the usefulness of native liver T1 mapping in children with congenital heart disease (CHD), we investigated the utility of native liver T1 relaxation time (LT1) in pediatric Fontan patients in comparison to other CHDs. Correlations between LT1 and laboratory biomarkers or hemodynamic data were also assessed. Materials and methods A total of 155 patients with CHD (biventricular repair, n = 42; bidirectional Glenn circulation, n = 38; and Fontan circulation, n = 75) underwent blood tests, cardiac catheterization, and cardiac MRI within 48 h. Results Both CVP and LT1 levels were higher in Fontan patients than in bidirectional Glenn and biventricular patients. There were significant correlation in the overall population and weak correlation in Fontan patients between CVP and LT1(correlation coefficient 0.644 [0.541–0.728] and 0.244 [0.0179–0.446], P < 0.001 and 0.035, respectively). Among the laboratory data, the multiple linear regression analysis revealed that the albumin-bilirubin score and alanine aminotransferase were significantly correlated with LT1 in the overall population (both P = 0.015), and the fibrosis-4 index was correlated with LT1 in Fontan patients ( P = 0.019). Conclusion LT1 could be a noninvasive predictor of CVP and a useful marker of liver injury in children with CHD. Fontan-associated liver disease central venous pressure liver native T1 mapping congenital heart disease Figures Figure 1 Figure 2 Figure 3 1. Introduction Chronic liver congestion, represented by high central venous pressure (CVP), is one of the major causes of Fontan-associated liver disease (FALD), and the measurement of CVP is crucial for dealing with FALD [ 1 – 3 ]. The exact prevalence of FALD is not known; however, one case series has reported the incidence of liver cirrhosis to be as high as 43% with a mean follow-up period of 30 years after Fontan surgery [ 2 ]. FALD includes fibrosis, which often leads to cirrhosis, but it is also considered a distinct entity from other causes of liver fibrosis and cirrhosis. As it progresses, hepatocellular carcinoma can also sometimes develop, even at an early age [ 4 ]. Although liver biopsy is considered the gold standard for making the diagnosis, assessing the prognosis, and assisting in therapeutic decisions [ 3 ], it is difficult to repeat such an invasive investigation because of potentially higher risks due to underlying coagulopathy and systemic disease resulting from Fontan anatomy and physiology. Additionally, biopsy findings of the Fontan liver consist of dilated sinusoids and fibrotic changes in the periportal, centrilobular, and portal areas; however, the degree of fibrotic change is poorly associated with clinical characteristics or outcomes because of the potential sampling error in liver biopsy [ 1 ]. Fontan patients undergo abdominal ultrasonography (US) in daily clinical practice [ 4 ]. It is a specific, reliable, and cost-effective first-line imaging modality that has not been studied specifically in Fontan patients, and normative data on FALD are lacking [ 3 ]. Additionally, computed tomography (CT) and magnetic resonance imaging (MRI) are the most sensitive diagnostic tools for evaluating morphological liver changes; however, CT involves radiation exposure [ 3 ]. Staging liver fibrosis in FALD requires a multi-modal approach, but there is no gold standard noninvasive screening tool for FALD [ 5 ]. Recently, some reports on the usefulness of T1 mapping in FALD have been published [ 5 , 6 ]. T1 mapping is a novel MRI technology used to quantify diffuse damage, fibrosis, congestion, edema, and inflammation of the liver parenchyma as well as the heart [ 5 – 7 ]. Shiina et al. reported correlations of liver T1 values in adult Fontan patients with a model for end-stage liver disease (MELD) score or albumin-bilirubin (ALBI) score, which are markers of liver fibrosis [ 5 ]. Ramachandran et al. reported the potential use of liver T1 mapping as a noninvasive biomarker for diffuse liver fibrosis in Fontan patients because of the strong positive correlations between liver native T1 relaxation time (LT1) in adult Fontan patients and magnetic resonance elastography-derived liver stiffness [ 6 ]. In animal experiments in rabbits, Zhiming et al. reported a trend toward increased mean T1 relaxation times in the histologic staging of liver fibrosis [ 8 ]. Despite these preliminary investigations in adult congenital heart disease, LT1 in children with congenital heart disease (CHD) has not been studied. In this study, we investigated the utility of LT1 in Fontan children in comparison to other CHDs. Correlations between LT1 and laboratory biomarkers or hemodynamic data were also assessed. 2. Materials and Methods 2.1. Subjects One hundred fifty-nine patients with CHDs who underwent a blood test, cardiac catheterization, and cardiac MRI within 48 hours at Fukuoka Children’s Hospital from January to December 2021 were enrolled in this study. Patients with an inferior vena cava (IVC) defect (n = 4) were excluded. There were 42 patients with biventricular repair (BVR) and 113 patients with single ventricle repair, among whom 38 had bidirectional Glenn circulation and 75 had Fontan circulation (Table 1). Data reflecting the patients’ clinical status, such as oxygen saturation, blood pressure at the time of admission, laboratory findings, and hemodynamic data from subsequent cardiac catheterization and MRI when available, were retrieved from medical records. In this study, the CVP of patients with bidirectional Glenn circulation indicated IVC pressure. The MELD XI score = 11.76 × Ln (creatinine) + 5.11 × Ln (total bilirubin (t-bil) (µmol/L)) + 9.44, and ALBI score = [(log10 t-bil (µmol/L) × 0.66) + (albumin (g/L) × −0.085)], fibrosis (Fib)-4 Index =(age×aspartate aminotransferase (AST))/(platelet count (PLT) (×10 4 /µl)×√alanine aminotransferase (ALT)), NAFLD (non-alcoholic fatty liver disease) fibrosis score=-1.675 ་ 0.037 × age ་ 0.094 × body mass index (BMI) ་0.99 × AST/ALT − 0.013 × PLT (×10 4 /µL) − 0.66 × albumin (g/L) were determined as objective indicators of hepatic injury [ 9 – 12 ]. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. This retrospective cross-sectional study was approved by the Institutional Review Board of Fukuoka Children’s Hospital (approval No.2021 − 1995). The need for written informed consent was waived owing to the retrospective nature of the study. 2.2 cardiac MRI protocol Cardiac MRI was performed under atmospheric conditions using a 1.5T magnet (Avanto Magneton; Siemens, Erlangen, Germany). T1 quantification was performed during diastole using an ECG-gated Balanced steady-state free precession sequence (true fast imaging with steady precession) at the midventricular short-axis level. We used a 5 (number of heartbeats (nHB) 3 Modified Look-Locker (MOLLI) sequence including inline motion correction, where nHB was three to four heartbeats depending on the heart rate to allow for T1 recovery between the two inversion experiments. Breath-holding or free-breathing was determined according to age and condition. The pulse sequence parameters were as follows: repetition time, 2.5–3.1 ms; echo time, 1.03–1.66 ms; flip angle, 35°; bandwidth, 408–1085 Hz/pixel; matrix, 144 × 144–256 × 256; parallel imaging factor, 2; field of view, 200–350 mm; field of view in phase direction, 84.4–85.7%; slice thickness, 5–8 mm with a gap of 2.5–9.6 mm, slice count, 3; minimum inversion time, 100–106 ms with 80-ms increments. LT1 was calculated in the same section as that of the cardiac MRI myocardial T1 mapping scan. Three regions of interest (ROI) (approximately 30–40 mm 2 ) were carefully drawn, including the liver parenchyma and excluding biliary and vascular tree structures, and a mean value was recorded. (Fig. 1 ) The average T1 value of the three ROIs was defined as a representative patient. To assess the intra-observer agreement of T1 mapping measurements, ten randomly selected data were re-analyzed by the first experienced imager at two-week intervals. The imager was blinded to the clinical outcomes, and the first set of measurements. Two observers (Y.I. and K.T.) drew the ROIs. Post-processing for the native T1, hemodynamic flow data analysis was performed using the CVI42 (Circle Cardiovascular Imaging Inc., Calgary, Canada). 2.3. Statistical analysis All statistical analyses were performed using IBM SPSS Statistics, version 22 (IBM, Armonk, New York, USA). An ANOVA was used to compare the variables of the three groups (biventricular repair group, bidirectional Glenn circulation group, and Fontan circulation group), with the Bonferroni method applied as a post-hoc analysis. A linear regression analysis and Pearson’s correlation coefficient were used to assess the correlations of liver disease biomarkers or hemodynamic data with LT1. Continuous variables are presented as the median and range for non-parametric data. Intra- and interobserver variability was assessed using intra- and interclass correlation coefficients, absolute values, and 95% confidence intervals. P values of < 0.05 were considered to indicate statistical significance. 3. Results Table 1 shows the clinical characteristics of the overall population in this study. With advancing age, patients with a single ventricular repair progress from bidirectional Glenn circulation to Fontan circulation step-by-step. There was also a significant difference in age and BSA among the three groups, but not between the BVR group and the Fontan group (age:8.36 ± 5.45 vs. 10.01 ± 5.62 years, p = 0.32; BSA:0.91 ± 0.41 vs. 1.01 ± 0.41 m 2 , p = 0.57). In the Fontan group, brain natriuretic peptide (BNP) levels tended to be low among the three groups ( p = 0.096), possibly due to ventricular volume reduction after Fontan surgery. Both systole and diastole pressure of the ascending aorta (Asc Ao) were the highest in the BVR group, but there was no significant difference between the BVR and Fontan groups (systole Asc Ao pressure (97.60 ± 16.70 vs. 94.45 ± 12.82 mmHg, p = 0.78), diastole Asc Ao pressure (57.88 ± 11.66 vs. 63.6 ± 10.94 mmHg, p = 1.00). On the other hand, the CVP was the highest in the Fontan group because pulmonary circulation was maintained by the direct return of blood flow from the IVC to the pulmonary artery instead of the atrium. In this study, the CVP of patients with bidirectional Glenn circulation indicated the IVC pressure. Figure 2 shows the LT1 expression in the BVR, bidirectional Glenn, and Fontan groups. The intra- and inter-observer agreement for LT1 was good (intra-/interclass correlation coefficients: 0.926 [0.747–0.981] and 0.973 [0.902–0.993], respectively). The LT1 in the Fontan group was the highest among the three groups, and there was a significant difference in LT1 between the Fontan group and the other two groups. Figure 3 shows a scatter plot of the relationship between CVP and LT1 in the three groups and the overall population. There were significant correlations between CVP and LT1 in the overall population, bidirectional Glenn patients, and Fontan patients (correlation coefficient: 0.644 [0.541–0.728], 0.441 [0.141–0.667], 0.244 [0.0179–0.446], and p < 0.001, 0.013, 0.035, respectively). Table 2 shows the correlation between LT1 and other variables in the overall population. Among the laboratory data, ALT, γ-glutamyl transpeptidase (γ-GTP), t-bil, PLT, and liver fibrosis scores (e.g., the Fib-4 index, MELD XI score, and ALBI score) were significantly correlated with LT1. Additionally, age, BSA, oxygen saturation (SpO 2 ), heart rate (HR), CVP, and systemic flow index (QsI) were significantly correlated with LT1 in the demographic and hemodynamic data. The variables that were correlated with LT1 in the overall population were investigated using a linear regression analysis with a stepwise method. In the final model, CVP, ALT, Fib-4 index, and age were significantly associated with the LT1 expression. Additionally, CVP was most strongly related to LT1 among the four variables (Table 2). The regression equation between LT1 and all four variables was as follows: LT1=523.28་12.32×CVP་1.289×ALT + 135.70×Fib-4 Index-3.62×age. Table 3 shows the correlation between LT1 and other variables in Fontan patients. Additionally, other variables such as age, BSA, duration from Fontan operation, and laboratory findings significantly correlated with LT1 were AST, BNP, and Fib-4 index. In the hemodynamic data, CVP and IVC return were significantly correlated with LT1. Linear regression analysis using stepwise methods revealed that the Fib-4 index was significantly related to LT1. The regression equation between LT1 and Fib-4 index was LT1=642.732་85.861×Fib-4 index. 4. Discussion To the best of our knowledge, this is the first large cohort study on children with CHDs to demonstrate the potential of liver native T1 mapping. We also investigated 75 patients with Fontan circulation among 113 patients who underwent single ventricle repair. FALD is increasingly recognized as a common complication in patients after Fontan operations. Increased CVP and chronic low cardiac output after the Fontan operation cause hepatic congestion and tissue hypoxia, which may instigate fibro genic pathways in the liver [ 13 ]. FALD can range from benign nodular hyperplasia to liver cirrhosis and failure [ 6 ], furthermore, it is often accompanied by hepatocellular carcinoma [ 1 – 5 , 13 – 16 ]. At present, multiple structural and functional liver abnormalities have been identified in patients after Fontan operations, but it is often unclear whether they are incidental or pathological [ 2 ]. Although no healthy control was included in this study, the mean LT1 of healthy controls measured by 1.5-T MRI at our institution was 552 ± 42 ms (n = 23, mean age: 7.2 ± 4.9 years) [ 17 ]. Leah et al. reported that the median LT1 in controls measured by 1.5-T MRI, was 569 ± 39 ms (range, 529–646; n = 12; mean age, 12.2 ± 3.1 years), similar to our control data. In this report, there was no significant association between age and LT1 [ 18 ], but this was not observed in our study, similar to our previous report [ 17 ]. Compared with these control data, the LT1 of the BVR and bidirectional Glenn circulation groups were almost the same as the control data, while the LT1 of the Fontan circulation group was higher in our study. This is consistent with the study by Shiina et al., which reported that, in adults, the LT1 of patients with Fontan circulation was significantly higher than that of the controls and patients with tetralogy of Fallot [ 5 ]. Beigh et al. reported that the LT1 was increased in single ventricular patients both before and after Fontan operations (683 ± 82 ms and 727 ± 49 ms, respectively) in comparison to TGA patients (587 ± 58 ms, P < 0.001) [ 19 ]. The LT1 of all patients with CHD had a significant positive correlation with CVP in addition to ALT and the Fib-4 index (Table 2). According to these results, LT1 is influenced by many factors, including liver fibrosis markers and hemodynamic congestion data represented by CVP. Additionally, the T1 relaxometry time does not unequivocally distinguish fibrosis, congestion, or inflammation [ 5 ]. In previous reports, high CVP and severe atrioventricular valve regurgitation in the early postoperative period were independent predictors of liver cirrhosis and hepatocellular carcinoma [ 16 ]. Therefore, LT1 may be an alternative indicator to CVP and a predictor of liver cirrhosis and hepatocellular carcinoma owing to the strong correlation between CVP and LT1. The LT1 of Fontan patients was correlated with CVP and showed a significant positive correlation with the Fib-4 index. Additionally, the LT1 was weakly correlated with the IVC return flow of Fontan patients. LT1 might represent congestion because both CVP and IVC return flow are positively correlated with LT1 (Table 3). The difference between Fontan patients and all other patients is that the correlation between IVC return flow and LT1 was observed only in Fontan patients. This may be explained by the hemodynamic characteristics of Fontan circulation, where IVC return drains to the pulmonary artery without passing through the atrium. In a previous study, an increased LT1—both before and after the Fontan stages—suggested that intrinsic liver abnormalities occur due to a combination of edema from passive venous congestion early during single ventricle palliation, and that LT1 may be an early marker of liver disease [ 19 ]. In this study, we showed that laboratory data such as ALT and the Fib-4 index might have some clinical implications (Table 2, 3). Strong correlations between LT1 and ALT and the Fib-4 index were observed in the overall population. Additionally, a significant correlation between LT1 and Fib-4 index was observed in Fontan patients. In a previous study, Kogiso et al. reported that the hyaluronic acid level and Fib-4 index were significantly higher in FALD-HCC patients, and that the t-bil level and MELD XI score tended to be higher in FALD-HCC patients [ 16 ]. Shiina et al. reported that MELD XI and ALBI scores were significantly correlated with LT1 [ 5 ]; however, liver biopsy was not performed in the present study. According to the results of our study and previous studies, in daily practice, it may be more appropriate to evaluate FALD using LT1 MRI and blood markers of liver fibrosis in addition to ultrasonography. In a bile duct ligation mouse model, the T1 value was not correlated, but the T2 value, or the difference between pre-enhanced T1 and post-enhanced T1 values, was significantly correlated with the hepatic fibrosis rate [ 20 ]. Another study reported that the T1 mapping-based hepatocyte fraction method was more accurate than the reduction rate for determining the stage of liver fibrosis, suggesting that the calculation of hepatocyte fractions is a superior method for non-invasive liver fibrosis staging [ 21 ]. The methods reported in the two aforementioned papers require contrast medium, which was not used in the present study. While T1 mapping of the liver can be acquired relatively easily and generated inline on the same scanner and at the same time as cardiac MRI, the accuracy of T1 mapping needs to be further validated with liver biopsy and other imaging studies. 5. Study limitations The present study was associated with some limitations. First, we did not perform a liver biopsy and could not explain the mechanism of LT1 elevation based on a histological analysis. Second, none of the patients underwent ultrasonography, and we could not exclude patients with fatty liver, which has an influence on T1 mapping values. 6. Conclusion Liver native T1 relaxation time was correlated with central venous pressure and liver fibrosis markers in children after biventricular repair, bidirectional Glenn, and Fontan procedures. It could be a noninvasive predictor of hemodynamic abnormalities and liver fibrosis in pediatric patients with congenital heart disease. Abbreviations AST: aspartate aminotransferase ALT: alanine aminotransferase ALBI score: albumin-bilirubin score BMI: body mass index BNP: brain natriuretic peptide BSA: body surface area BVR: biventricular repair CHD: congenital heart disease CVP: central venous pressure FALD: Fontan -associated liver disease Fib-4 Index: fibrosis-4 Index HR: heart rate IVC: inferior vena cava LT1: liver native T1 relaxation time MELD Ⅺ score: model for end-stage liver disease Ⅺ score MRI: magnetic resonance imaging NAFLD: non-alcoholic fatty liver disease nHB: number of heart beats PLT: platelet count QsI: systemic flow index SpO 2: oxygen saturation t-bil: total bilirubins γ-GTP: γ-glutamyl transpeptidase Declarations Acknowledgment This research was not supported by any grants from funding agencies in the public, commercial, or not-for-profit sectors. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Katsuo Tao and Yuichi Ishikawa. The first draft of the manuscript was written by Katsuo Tao and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Conflict of interest The authors declare that they have no conflict of interest to disclose. Ethical Approval The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. This retrospective cross-sectional study was approved by the Institutional Review Board of Fukuoka Children’s Hospital (approval No.2021-1995; March 17, 2022). All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. References H. Ohuchi (2016) Adult patients with Fontan circulation: What we know and how to manage adults with Fontan circulation? 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Pediatr Radiol 53:1092-1099. https://doi: 10.1007/s00247-022-05560-y Jia-Yi Liu, Zhu-Yuan Ding, Zi-Yi Zhou, et al (2021) Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model. World J Gastroenterol 27: 8156-816. https://doi: 10.3748/wjg.v27.i47.8156 Shen Pan, Xiao-Qi Wang, Qi-Yong Guo (2018) Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging. World J Gastroenterol 24: 2024-2035. https://doi: 10.3748/wjg.v24.i18.2024 Tables Table . 1 Demographic and clinical characteristics of all patients in this study. Characteristics (N=155) BVR (N=42) bidirectional Glenn (N=38) Fontan (N=75) P value three groups Adjusted P value Glenn vs. Fontan Age (year) 7.46 (0.5-18.2) 2.38 (0.83-13.5) 8.83 (1.83-19.9) ＜ 0.001 ＜ 0.001 Male / Female 20/22 23/15 48/27 0.219 0.837 BSA (m 2 ) 0.84 (0.33-1.82) 0.5 (0.34-1.29) 0.89 (0.4-1.92) ＜ 0.001 ＜ 0.001 CVP (mmHg) 3 (1-9) 2 (1-10) 8 (5-13) ＜ 0.001 ＜ 0.001 AscAo pressure (systole) (mmHg) 92 (88-96) 79 (78-80) 86.5 (74-99) 0.001 0.013 AscAo pressure (diastole) (mmHg) 58.5 (57-60) 45.5 (43-48) 47.5 (39-56) ＜ 0.001 ＜ 0.001 LT1 (ms) 572 (359-769) 565 (502-688) 670 (569-767) ＜ 0.001 ＜ 0.001 BNP (pg/mL) 17.8 (5.8-835) 20.3 (5.8-139) 6.9 (5.8-163) 0.096 n.s Values are expressed as median (range). AscAo: ascending aorta, BNP : brain natriuretic peptide, BSA : body surface area, BVR : biventricular repair, CVP : central venous pressure, LT1 : liver T1 relaxation time Table . 2 Correlations between clinical characteristics and liver T1 in all cases Characteristics correlation coefficient P value AST (U/L) 0.112 0.167 ALT (U/L) 0.324 ＜ 0.001 Alb (g/dL) -0.139 0.084 γ-GTP (U/L) 0.394 ＜ 0.001 T-bil (mg/dL) 0.192 0.017 BNP (pg/mL) -0.042 0.603 Fib 4 Index 0.355 ＜ 0.001 MELD XI score 0.285 ＜ 0.001 ALBI score 0.229 0.004 NAFLD fibrosis score -0.149 0.066 Age (year) 0.254 0.001 BSA (m 2 ) 0.264 ＜ 0.001 SpO 2 (%) 0.158 0.049 HR (bpm) -0.207 0.010 CVP (mmHg) 0.644 ＜ 0.001 PAI (mm 2 /m 2 ) -0.057 0.489 QsI (L/min・m 2 ) -0.172 0.033 SPCF （L/min・m 2 ) -0.095 0.242 Characteristics β standardized regression coefficient T value P value Initial model Age (year) -6.27 -0.524 -2.34 0.021 BSA (m 2 ) 47.2 0.287 1.28 0.204 SpO 2 (%) 0.024 0.002 0.028 0.978 HR (bpm) 0.202 0.056 0.571 0.569 CVP (mmHg) 11.9 0.571 7.62 ＜ 0.001 QsI (L/min・m 2 ) 1.22 0.021 0.314 0.754 ALT (U/L) 0.977 0.124 1.77 0.079 γ-GTP (U/L) 0.164 0.088 1.17 0.245 T-bil (mg/dL) -18.3 -0.113 -1.15 0.252 Fib 4 Index 138 0.308 2.58 0.011 MELD XI score 0.305 0.026 0.15 0.014 ALBI score 33.9 0.192 2.87 0.005 Final model CVP (mmHg) 12.1 0.58 9.07 ＜ 0.001 ALT (U/L) 1.22 0.156 2.46 0.015 ALBI score 32.7 0.15 2.45 0.015 Alb : albumin, ALT : alanine aminotransferase, ALBI score : albumin-bilirubin score, AST : aspartate aminotransferase, BNP : brain natriuretic peptide, BSA : body surface area, CVP : central venous pressure, Fib-4 Index : fibrosis-4 Index, HR : heart rate, MELD XI score : model for end-stage liver disease Ⅺ, NAFLD : non-alcoholic fatty liver disease, PAI : pulmonary area index, QsI : systemic flow index, SPCF : systemic pulmonary collateral flow, SpO2 : oxygen saturation, T-bil : total bilirubin, γ-GTP : γ-glutamyl transpeptidase Table .3 Correlations between clinical characteristics and liver T1 in Fontan cases characteristics correlation coefficient P value AST (U/L) -0.177 0.128 ALT (U/L) 0.001 0.996 Alb (g/dL) -0.114 0.329 γ-GTP (U/L) 0.082 0.483 T-bil (mg/dL) 0.036 0.763 BNP (pg/mL) 0.2 0.0853 Fib-4 Index 0.27 0.019 MELD XI score 0.123 0.292 ALBI score 0.0913 0.436 NAFLD fibrosis score 0.069 0.56 Age (year) 0.17 0.144 BSA (m 2 ) 0.197 0.09 SpO2 (%) -0.055 0.639 HR (bpm) -0.129 0.278 CVP (mmHg) 0.244 0.035 PAI (mm 2 /m 2 ) -0.065 0.580 QsI (L/min・m 2 ) 0.065 0.58 SPCF (L/min・m 2 ) 0.083 0.479 IVC return flow (L/min・m 2 ) 0.196 0.091 duration from Fontan operation (year) 0.162 0.164 Characteristics β standardized regression coefficient T value P value Initial model Age (year) -2.85 -0.345 -0.859 0.394 BSA (m 2 ) 16.1 0.145 0.345 0.731 CVP (mmHg) 3.39 0.138 1.01 0.315 IVC return (L/min・m 2 ) 32.7 0.264 1.69 0.095 duration from Fontan operation (year) -0.867 -0.108 -0.221 0.826 AST (U/L) -0.452 -0.082 -0.513 0.61 BNP (pg/ml) 0.465 0.208 1.63 0.107 Fib-4 index 111 0.35 1.74 0.087 Final model Fib 4 index 85.9 0.27 2.40 0.019 Alb : albumin, ALT : alanine aminotransferase, ALBI : albumin-bilirubin, AST : aspartate aminotransferase, BNP : brain natriuretic peptide, BSA : body surface area, CVP : central venous pressure, Fib-4 Index : fibrosis-4 Index, HR : heart rate, IVC : inferior vena cava, MELD XI : model for end-stage liver disease Ⅺ, NAFLD : non-alcoholic fatty liver disease, PAI : pulmonary area index, QsI : systemic flow index, SPCF : systemic pulmonary collateral flow, SpO2 : oxygen saturation, T-bil : total bilirubin, γ-GTP : γ-glutamyl transpeptidase Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4194336","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":286812384,"identity":"edbb7008-9398-4b0c-a3c3-179f0f4d1bdd","order_by":0,"name":"Katsuo Tao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYBACCSglx8bffICBsQFVGIcWZhBlYcwvcSyBJC0ViTMbcgwQWvAByfbzhz/zVEgwbjhw5pvEzx02cgzshw8wWO7ArUWaJ5lNmueMBLPB4d5tkr1n0owZeNISGCTP4NYix5DMxszbJsFmcODsNgnetsOJDRI8BgySbXi08D9m/gzUwmNwIOeZ5F9itEhLJDNIA7VISDbksEkTZYvkjMdmknPOSBgAA9nYWrYtzZgN6JcD+PwicT7x8Yc3FXX1bfzND2++bbOR42c/fPCxJJ4QQwYs4AhkA+LDkg3EaWH+AGMxfiRSyygYBaNgFIwIAADe9UrXx4acTAAAAABJRU5ErkJggg==","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Katsuo","middleName":"","lastName":"Tao","suffix":""},{"id":286812385,"identity":"48ce5d44-75e5-4f5c-b86f-11dd3e4f34cc","order_by":1,"name":"Yuichi Ishikawa","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuichi","middleName":"","lastName":"Ishikawa","suffix":""},{"id":286812386,"identity":"93ebb722-a07c-4e99-9730-0b6077b30197","order_by":2,"name":"Sayo Suzuki","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sayo","middleName":"","lastName":"Suzuki","suffix":""},{"id":286812387,"identity":"a26e3d38-7e2f-4da8-8ef5-02aefa762e84","order_by":3,"name":"Shota Muraji","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shota","middleName":"","lastName":"Muraji","suffix":""},{"id":286812388,"identity":"e5af4415-ef73-44ab-be7d-02866b068031","order_by":4,"name":"Ayako Kuraoka","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ayako","middleName":"","lastName":"Kuraoka","suffix":""},{"id":286812389,"identity":"a2cc5df6-8292-4db4-b759-664db55b49af","order_by":5,"name":"Masaki Sato","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masaki","middleName":"","lastName":"Sato","suffix":""},{"id":286812390,"identity":"5fb642c0-a49c-4b54-aa65-b04b2969772d","order_by":6,"name":"Kenichiro Yamamura","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kenichiro","middleName":"","lastName":"Yamamura","suffix":""},{"id":286812391,"identity":"8afcb0be-c0a7-461a-adf0-b40768959d96","order_by":7,"name":"Kouichi Sagawa","email":"","orcid":"","institution":"Fukuoka Children‘s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kouichi","middleName":"","lastName":"Sagawa","suffix":""}],"badges":[],"createdAt":"2024-03-31 05:59:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4194336/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4194336/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54038680,"identity":"159c8137-4fc1-46aa-8fc9-cd380e700fdc","added_by":"auto","created_at":"2024-04-03 17:16:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":792802,"visible":true,"origin":"","legend":"\u003cp\u003eThe region of interest for liver T1 relaxation time\u003c/p\u003e\n\u003cp\u003eThe region of interest for the liver T1 relaxation time was set in the same slice as the myocardial T1, in the liver parenchyma excluding the bile ducts and blood vessels, and the average of the three planes was used for the study.\u003c/p\u003e","description":"","filename":"Figurepediatriccardiology1.png","url":"https://assets-eu.researchsquare.com/files/rs-4194336/v1/a8a86127f21f0a957c9ceb99.png"},{"id":54038675,"identity":"d17d6e14-07aa-4163-b8ef-044cc63dce1f","added_by":"auto","created_at":"2024-04-03 17:16:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":22768,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of the LT1 and CVP values of the three groups\u003c/p\u003e\n\u003cp\u003eAmong the three groups, both CVP and LT1 were highest in the Fontan group. Additionally, significant differences in CVP and LT1 were observed between the Fontan group and the other two groups.\u003c/p\u003e\n\u003cp\u003eBVR, biventricular repair; CVP, central venous pressure; LT1, liver T1 relaxation time\u003c/p\u003e","description":"","filename":"Figurepediatriccardiology2.png","url":"https://assets-eu.researchsquare.com/files/rs-4194336/v1/05dfc0ccde70b7e6432fa698.png"},{"id":54038674,"identity":"2e018634-bfae-4a8e-82cd-54ec78f902c1","added_by":"auto","created_at":"2024-04-03 17:16:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":35917,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of the relationship between CVP and LT1 in the three groups and the overall population\u003c/p\u003e\n\u003cp\u003eThere were significant correlations between CVP and LT1 in the overall population, and between bidirectional Glenn and Fontan patients (correlation coefficients 0.644, 0.399, and 0.244, p\u0026lt;0.001, 0.013, and 0.035, respectively). The regression lines are shown with a dotted line, along with the equation and coefficient of determination (R\u003csup\u003e2\u003c/sup\u003e) in each figure. Additionally, the correlation coefficients (｜r｜) and p-values are shown in each figure.\u003c/p\u003e\n\u003cp\u003eBVR, biventricular repair; LT1, liver T1 relaxation time\u003c/p\u003e","description":"","filename":"Figurepediatriccardiology3.png","url":"https://assets-eu.researchsquare.com/files/rs-4194336/v1/314a81e715000d4b21e2e8fb.png"},{"id":59164737,"identity":"507387a8-07ee-430a-9572-d6e8e5f487ac","added_by":"auto","created_at":"2024-06-27 06:34:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1604294,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4194336/v1/b863411d-9e0a-4573-9731-dbb395efcfc1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eChronic liver congestion, represented by high central venous pressure (CVP), is one of the major causes of Fontan-associated liver disease (FALD), and the measurement of CVP is crucial for dealing with FALD [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The exact prevalence of FALD is not known; however, one case series has reported the incidence of liver cirrhosis to be as high as 43% with a mean follow-up period of 30 years after Fontan surgery [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. FALD includes fibrosis, which often leads to cirrhosis, but it is also considered a distinct entity from other causes of liver fibrosis and cirrhosis. As it progresses, hepatocellular carcinoma can also sometimes develop, even at an early age [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough liver biopsy is considered the gold standard for making the diagnosis, assessing the prognosis, and assisting in therapeutic decisions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], it is difficult to repeat such an invasive investigation because of potentially higher risks due to underlying coagulopathy and systemic disease resulting from Fontan anatomy and physiology. Additionally, biopsy findings of the Fontan liver consist of dilated sinusoids and fibrotic changes in the periportal, centrilobular, and portal areas; however, the degree of fibrotic change is poorly associated with clinical characteristics or outcomes because of the potential sampling error in liver biopsy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFontan patients undergo abdominal ultrasonography (US) in daily clinical practice [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It is a specific, reliable, and cost-effective first-line imaging modality that has not been studied specifically in Fontan patients, and normative data on FALD are lacking [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Additionally, computed tomography (CT) and magnetic resonance imaging (MRI) are the most sensitive diagnostic tools for evaluating morphological liver changes; however, CT involves radiation exposure [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Staging liver fibrosis in FALD requires a multi-modal approach, but there is no gold standard noninvasive screening tool for FALD [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecently, some reports on the usefulness of T1 mapping in FALD have been published [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. T1 mapping is a novel MRI technology used to quantify diffuse damage, fibrosis, congestion, edema, and inflammation of the liver parenchyma as well as the heart [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Shiina et al. reported correlations of liver T1 values in adult Fontan patients with a model for end-stage liver disease (MELD) score or albumin-bilirubin (ALBI) score, which are markers of liver fibrosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Ramachandran et al. reported the potential use of liver T1 mapping as a noninvasive biomarker for diffuse liver fibrosis in Fontan patients because of the strong positive correlations between liver native T1 relaxation time (LT1) in adult Fontan patients and magnetic resonance elastography-derived liver stiffness [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In animal experiments in rabbits, Zhiming et al. reported a trend toward increased mean T1 relaxation times in the histologic staging of liver fibrosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Despite these preliminary investigations in adult congenital heart disease, LT1 in children with congenital heart disease (CHD) has not been studied. In this study, we investigated the utility of LT1 in Fontan children in comparison to other CHDs. Correlations between LT1 and laboratory biomarkers or hemodynamic data were also assessed.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Subjects\u003c/h2\u003e \u003cp\u003eOne hundred fifty-nine patients with CHDs who underwent a blood test, cardiac catheterization, and cardiac MRI within 48 hours at Fukuoka Children\u0026rsquo;s Hospital from January to December 2021 were enrolled in this study. Patients with an inferior vena cava (IVC) defect (n\u0026thinsp;=\u0026thinsp;4) were excluded. There were 42 patients with biventricular repair (BVR) and 113 patients with single ventricle repair, among whom 38 had bidirectional Glenn circulation and 75 had Fontan circulation (Table\u0026nbsp;1). Data reflecting the patients\u0026rsquo; clinical status, such as oxygen saturation, blood pressure at the time of admission, laboratory findings, and hemodynamic data from subsequent cardiac catheterization and MRI when available, were retrieved from medical records. In this study, the CVP of patients with bidirectional Glenn circulation indicated IVC pressure.\u003c/p\u003e \u003cp\u003eThe MELD XI score\u0026thinsp;=\u0026thinsp;11.76 \u0026times; Ln (creatinine)\u0026thinsp;+\u0026thinsp;5.11 \u0026times; Ln (total bilirubin (t-bil) (\u0026micro;mol/L))\u0026thinsp;+\u0026thinsp;9.44, and ALBI score = [(log10 t-bil (\u0026micro;mol/L) \u0026times; 0.66) + (albumin (g/L) \u0026times; \u0026minus;0.085)], fibrosis (Fib)-4 Index =(age\u0026times;aspartate aminotransferase (AST))/(platelet count (PLT) (\u0026times;10\u003csup\u003e4\u003c/sup\u003e/\u0026micro;l)\u0026times;\u0026radic;alanine aminotransferase (ALT)), NAFLD (non-alcoholic fatty liver disease) fibrosis score=-1.675 ་ 0.037 \u0026times; age ་ 0.094 \u0026times; body mass index (BMI) ་0.99 \u0026times; AST/ALT \u0026minus;\u0026thinsp;0.013 \u0026times; PLT (\u0026times;10\u003csup\u003e4\u003c/sup\u003e/\u0026micro;L) \u0026minus;\u0026thinsp;0.66 \u0026times; albumin (g/L) were determined as objective indicators of hepatic injury [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThe study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. This retrospective cross-sectional study was approved by the Institutional Review Board of Fukuoka Children\u0026rsquo;s Hospital (approval No.2021\u0026thinsp;\u0026minus;\u0026thinsp;1995). The need for written informed consent was waived owing to the retrospective nature of the study.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 cardiac MRI protocol\u003c/h2\u003e \u003cp\u003eCardiac MRI was performed under atmospheric conditions using a 1.5T magnet (Avanto Magneton; Siemens, Erlangen, Germany). T1 quantification was performed during diastole using an ECG-gated Balanced steady-state free precession sequence (true fast imaging with steady precession) at the midventricular short-axis level. We used a 5 (number of heartbeats (nHB) 3 Modified Look-Locker (MOLLI) sequence including inline motion correction, where nHB was three to four heartbeats depending on the heart rate to allow for T1 recovery between the two inversion experiments. Breath-holding or free-breathing was determined according to age and condition. The pulse sequence parameters were as follows: repetition time, 2.5\u0026ndash;3.1 ms; echo time, 1.03\u0026ndash;1.66 ms; flip angle, 35\u0026deg;; bandwidth, 408\u0026ndash;1085 Hz/pixel; matrix, 144 \u0026times; 144\u0026ndash;256 \u0026times; 256; parallel imaging factor, 2; field of view, 200\u0026ndash;350 mm; field of view in phase direction, 84.4\u0026ndash;85.7%; slice thickness, 5\u0026ndash;8 mm with a gap of 2.5\u0026ndash;9.6 mm, slice count, 3; minimum inversion time, 100\u0026ndash;106 ms with 80-ms increments.\u003c/p\u003e \u003cp\u003eLT1 was calculated in the same section as that of the cardiac MRI myocardial T1 mapping scan. Three regions of interest (ROI) (approximately 30\u0026ndash;40 mm\u003csup\u003e2\u003c/sup\u003e) were carefully drawn, including the liver parenchyma and excluding biliary and vascular tree structures, and a mean value was recorded. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The average T1 value of the three ROIs was defined as a representative patient. To assess the intra-observer agreement of T1 mapping measurements, ten randomly selected data were re-analyzed by the first experienced imager at two-week intervals. The imager was blinded to the clinical outcomes, and the first set of measurements. Two observers (Y.I. and K.T.) drew the ROIs. Post-processing for the native T1, hemodynamic flow data analysis was performed using the CVI42 (Circle Cardiovascular Imaging Inc., Calgary, Canada).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Statistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using IBM SPSS Statistics, version 22 (IBM, Armonk, New York, USA). An ANOVA was used to compare the variables of the three groups (biventricular repair group, bidirectional Glenn circulation group, and Fontan circulation group), with the Bonferroni method applied as a post-hoc analysis. A linear regression analysis and Pearson\u0026rsquo;s correlation coefficient were used to assess the correlations of liver disease biomarkers or hemodynamic data with LT1. Continuous variables are presented as the median and range for non-parametric data. Intra- and interobserver variability was assessed using intra- and interclass correlation coefficients, absolute values, and 95% confidence intervals. P values of \u0026lt;\u0026thinsp;0.05 were considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eTable\u0026nbsp;1 shows the clinical characteristics of the overall population in this study. With advancing age, patients with a single ventricular repair progress from bidirectional Glenn circulation to Fontan circulation step-by-step. There was also a significant difference in age and BSA among the three groups, but not between the BVR group and the Fontan group (age:8.36\u0026thinsp;\u0026plusmn;\u0026thinsp;5.45 vs. 10.01\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62 years, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.32; BSA:0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 vs. 1.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 m\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.57). In the Fontan group, brain natriuretic peptide (BNP) levels tended to be low among the three groups (\u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.096), possibly due to ventricular volume reduction after Fontan surgery. Both systole and diastole pressure of the ascending aorta (Asc Ao) were the highest in the BVR group, but there was no significant difference between the BVR and Fontan groups (systole Asc Ao pressure (97.60\u0026thinsp;\u0026plusmn;\u0026thinsp;16.70 vs. 94.45\u0026thinsp;\u0026plusmn;\u0026thinsp;12.82 mmHg, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.78), diastole Asc Ao pressure (57.88\u0026thinsp;\u0026plusmn;\u0026thinsp;11.66 vs. 63.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.94 mmHg, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;1.00). On the other hand, the CVP was the highest in the Fontan group because pulmonary circulation was maintained by the direct return of blood flow from the IVC to the pulmonary artery instead of the atrium. In this study, the CVP of patients with bidirectional Glenn circulation indicated the IVC pressure.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the LT1 expression in the BVR, bidirectional Glenn, and Fontan groups. The intra- and inter-observer agreement for LT1 was good (intra-/interclass correlation coefficients: 0.926 [0.747\u0026ndash;0.981] and 0.973 [0.902\u0026ndash;0.993], respectively). The LT1 in the Fontan group was the highest among the three groups, and there was a significant difference in LT1 between the Fontan group and the other two groups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows a scatter plot of the relationship between CVP and LT1 in the three groups and the overall population. There were significant correlations between CVP and LT1 in the overall population, bidirectional Glenn patients, and Fontan patients (correlation coefficient: 0.644 [0.541\u0026ndash;0.728], 0.441 [0.141\u0026ndash;0.667], 0.244 [0.0179\u0026ndash;0.446], and \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001, 0.013, 0.035, respectively).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;2 shows the correlation between LT1 and other variables in the overall population. Among the laboratory data, ALT, γ-glutamyl transpeptidase (γ-GTP), t-bil, PLT, and liver fibrosis scores (e.g., the Fib-4 index, MELD XI score, and ALBI score) were significantly correlated with LT1. Additionally, age, BSA, oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e), heart rate (HR), CVP, and systemic flow index (QsI) were significantly correlated with LT1 in the demographic and hemodynamic data.\u003c/p\u003e \u003cp\u003eThe variables that were correlated with LT1 in the overall population were investigated using a linear regression analysis with a stepwise method. In the final model, CVP, ALT, Fib-4 index, and age were significantly associated with the LT1 expression. Additionally, CVP was most strongly related to LT1 among the four variables (Table\u0026nbsp;2). The regression equation between LT1 and all four variables was as follows: LT1=523.28་12.32\u0026times;CVP་1.289\u0026times;ALT\u0026thinsp;+\u0026thinsp;135.70\u0026times;Fib-4 Index-3.62\u0026times;age.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;3 shows the correlation between LT1 and other variables in Fontan patients. Additionally, other variables such as age, BSA, duration from Fontan operation, and laboratory findings significantly correlated with LT1 were AST, BNP, and Fib-4 index. In the hemodynamic data, CVP and IVC return were significantly correlated with LT1. Linear regression analysis using stepwise methods revealed that the Fib-4 index was significantly related to LT1. The regression equation between LT1 and Fib-4 index was LT1=642.732་85.861\u0026times;Fib-4 index.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first large cohort study on children with CHDs to demonstrate the potential of liver native T1 mapping. We also investigated 75 patients with Fontan circulation among 113 patients who underwent single ventricle repair.\u003c/p\u003e \u003cp\u003eFALD is increasingly recognized as a common complication in patients after Fontan operations. Increased CVP and chronic low cardiac output after the Fontan operation cause hepatic congestion and tissue hypoxia, which may instigate fibro genic pathways in the liver [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. FALD can range from benign nodular hyperplasia to liver cirrhosis and failure [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], furthermore, it is often accompanied by hepatocellular carcinoma [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. At present, multiple structural and functional liver abnormalities have been identified in patients after Fontan operations, but it is often unclear whether they are incidental or pathological [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlthough no healthy control was included in this study, the mean LT1 of healthy controls measured by 1.5-T MRI at our institution was 552\u0026thinsp;\u0026plusmn;\u0026thinsp;42 ms (n\u0026thinsp;=\u0026thinsp;23, mean age: 7.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9 years) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Leah et al. reported that the median LT1 in controls measured by 1.5-T MRI, was 569\u0026thinsp;\u0026plusmn;\u0026thinsp;39 ms (range, 529\u0026ndash;646; n\u0026thinsp;=\u0026thinsp;12; mean age, 12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 years), similar to our control data. In this report, there was no significant association between age and LT1 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], but this was not observed in our study, similar to our previous report [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Compared with these control data, the LT1 of the BVR and bidirectional Glenn circulation groups were almost the same as the control data, while the LT1 of the Fontan circulation group was higher in our study. This is consistent with the study by Shiina et al., which reported that, in adults, the LT1 of patients with Fontan circulation was significantly higher than that of the controls and patients with tetralogy of Fallot [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Beigh et al. reported that the LT1 was increased in single ventricular patients both before and after Fontan operations (683\u0026thinsp;\u0026plusmn;\u0026thinsp;82 ms and 727\u0026thinsp;\u0026plusmn;\u0026thinsp;49 ms, respectively) in comparison to TGA patients (587\u0026thinsp;\u0026plusmn;\u0026thinsp;58 ms, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe LT1 of all patients with CHD had a significant positive correlation with CVP in addition to ALT and the Fib-4 index (Table\u0026nbsp;2). According to these results, LT1 is influenced by many factors, including liver fibrosis markers and hemodynamic congestion data represented by CVP. Additionally, the T1 relaxometry time does not unequivocally distinguish fibrosis, congestion, or inflammation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In previous reports, high CVP and severe atrioventricular valve regurgitation in the early postoperative period were independent predictors of liver cirrhosis and hepatocellular carcinoma [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, LT1 may be an alternative indicator to CVP and a predictor of liver cirrhosis and hepatocellular carcinoma owing to the strong correlation between CVP and LT1.\u003c/p\u003e \u003cp\u003eThe LT1 of Fontan patients was correlated with CVP and showed a significant positive correlation with the Fib-4 index. Additionally, the LT1 was weakly correlated with the IVC return flow of Fontan patients. LT1 might represent congestion because both CVP and IVC return flow are positively correlated with LT1 (Table\u0026nbsp;3). The difference between Fontan patients and all other patients is that the correlation between IVC return flow and LT1 was observed only in Fontan patients. This may be explained by the hemodynamic characteristics of Fontan circulation, where IVC return drains to the pulmonary artery without passing through the atrium. In a previous study, an increased LT1\u0026mdash;both before and after the Fontan stages\u0026mdash;suggested that intrinsic liver abnormalities occur due to a combination of edema from passive venous congestion early during single ventricle palliation, and that LT1 may be an early marker of liver disease [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we showed that laboratory data such as ALT and the Fib-4 index might have some clinical implications (Table\u0026nbsp;2, 3). Strong correlations between LT1 and ALT and the Fib-4 index were observed in the overall population. Additionally, a significant correlation between LT1 and Fib-4 index was observed in Fontan patients. In a previous study, Kogiso et al. reported that the hyaluronic acid level and Fib-4 index were significantly higher in FALD-HCC patients, and that the t-bil level and MELD XI score tended to be higher in FALD-HCC patients [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Shiina et al. reported that MELD XI and ALBI scores were significantly correlated with LT1 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]; however, liver biopsy was not performed in the present study. According to the results of our study and previous studies, in daily practice, it may be more appropriate to evaluate FALD using LT1 MRI and blood markers of liver fibrosis in addition to ultrasonography.\u003c/p\u003e \u003cp\u003eIn a bile duct ligation mouse model, the T1 value was not correlated, but the T2 value, or the difference between pre-enhanced T1 and post-enhanced T1 values, was significantly correlated with the hepatic fibrosis rate [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Another study reported that the T1 mapping-based hepatocyte fraction method was more accurate than the reduction rate for determining the stage of liver fibrosis, suggesting that the calculation of hepatocyte fractions is a superior method for non-invasive liver fibrosis staging [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The methods reported in the two aforementioned papers require contrast medium, which was not used in the present study. While T1 mapping of the liver can be acquired relatively easily and generated inline on the same scanner and at the same time as cardiac MRI, the accuracy of T1 mapping needs to be further validated with liver biopsy and other imaging studies.\u003c/p\u003e"},{"header":"5. Study limitations","content":"\u003cp\u003eThe present study was associated with some limitations. First, we did not perform a liver biopsy and could not explain the mechanism of LT1 elevation based on a histological analysis. Second, none of the patients underwent ultrasonography, and we could not exclude patients with fatty liver, which has an influence on T1 mapping values.\u003c/p\u003e"},{"header":"6. Conclusion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eLiver native T1 relaxation time was correlated with central venous pressure and liver fibrosis markers in children after biventricular repair, bidirectional Glenn, and Fontan procedures. It could be a noninvasive predictor of hemodynamic abnormalities and liver fibrosis in pediatric patients with congenital heart disease.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAST: aspartate aminotransferase\u003c/p\u003e\n\u003cp\u003eALT: alanine aminotransferase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eALBI score:\u0026nbsp;albumin-bilirubin\u0026nbsp;score\u003c/p\u003e\n\u003cp\u003eBMI: body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBNP:\u0026nbsp;brain natriuretic peptide\u003c/p\u003e\n\u003cp\u003eBSA: body surface area\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBVR: biventricular repair\u003c/p\u003e\n\u003cp\u003eCHD: congenital heart disease\u003c/p\u003e\n\u003cp\u003eCVP: central venous pressure\u003c/p\u003e\n\u003cp\u003eFALD: Fontan -associated liver disease\u003c/p\u003e\n\u003cp\u003eFib-4 Index: fibrosis-4 Index\u003c/p\u003e\n\u003cp\u003eHR: heart rate\u003c/p\u003e\n\u003cp\u003eIVC: inferior vena cava \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLT1: liver native T1 relaxation time\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMELD\u0026nbsp;Ⅺ\u0026nbsp;score:\u0026nbsp;model for end-stage liver disease\u0026nbsp;Ⅺ\u0026nbsp;score\u003c/p\u003e\n\u003cp\u003eMRI: magnetic resonance imaging\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNAFLD: non-alcoholic fatty liver disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003enHB:\u0026nbsp;number of heart beats\u003c/p\u003e\n\u003cp\u003ePLT: platelet count\u003c/p\u003e\n\u003cp\u003eQsI: systemic flow index\u003c/p\u003e\n\u003cp\u003eSpO\u003csub\u003e2:\u0026nbsp;\u003c/sub\u003eoxygen saturation\u003c/p\u003e\n\u003cp\u003et-bil:\u0026nbsp;total\u0026nbsp;bilirubins\u003c/p\u003e\n\u003cp\u003e\u0026gamma;-GTP: \u0026gamma;-glutamyl transpeptidase\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was not supported by any grants from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor Contributions\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Katsuo Tao and Yuichi Ishikawa. The first draft of the manuscript was written by Katsuo Tao and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest to disclose.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003eThe study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.\u003c/p\u003e\u003cp\u003eThis retrospective cross-sectional study was approved by the Institutional Review Board of Fukuoka Children\u0026rsquo;s Hospital (approval No.2021-1995; \u0026nbsp;March 17, 2022).\u003c/p\u003e\n\u003cp\u003eAll authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003eH. Ohuchi (2016) Adult patients with Fontan circulation: What we know and how to manage adults with Fontan circulation? Journal of Cardiology 68:181\u0026ndash;189. https://doi: 10.1016/j.jjcc.2016.04.001\u003c/li\u003e\n\u003cli\u003ePundi K, Pundi KN, Kamath PS, et al (2016) Liver Disease in Patients After the Fontan Operation. Am J Cardiol 117:456-460. https://doi: 10.1016/j.amjcard.2015.11.014\u003c/li\u003e\n\u003cli\u003eCurt J Daniels, Elisa A Bradley, Mike J Landzberg, et al (2017) Fontan-Associated Liver Disease. Fontan-Associated Liver Disease: Proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC, J Am Coll Cardiol 70:3173-3194. https://doi: 10.1016/j.jacc.2017.10.045\u003c/li\u003e\n\u003cli\u003eGiulia Perucca, Charlotte de Lange, St\u0026eacute;phanie Franchi-Abella, et al (2021) Radiologic follow-up in Fontan-associated liver disease in Europe: European Society of Paediatric Radiology survey demonstrates the need for a consensus protocol. Pediatric Radiology 51:2607\u0026ndash;2610. https://doi: 10.1007/s00247-021-05172-y \u003c/li\u003e\n\u003cli\u003eYumi Shiina, Kei Inai, Ryoko Ohashi, and Michinobu Nagao (2021) Potential of Liver T1 Mapping for the Detection of Fontan-associated Liver Disease in Adults. Magn Reson Med Sci 20; 295\u0026ndash;30. https://doi: 10.2463/mrms.mp.2020-0063\u003c/li\u003e\n\u003cli\u003ePreeti Ramachandran, Suraj D. Serai, Gruschen R. Veldtman, et al (2019) Assessment of liver T1 mapping in Fontan patients and its correlation with magnetic resonance elastography‑derived liver stiffness. Abdominal Radiology 44:2403\u0026ndash;2408. https://doi: 10.1007/s00261-019-01990-9\u003c/li\u003e\n\u003cli\u003eJinning Li, Huanhuan Liu, Caiyuan Zhang, et al (2020) Native T1 mapping compared to ultrasonography elastography for staging and monitoring liver fibrosis: an animal study of repeatability, reproducibility, and accuracy. Eur Radiol 30:337\u0026ndash;345. https://doi: 10.1007/s00330-019-06335-0\u003c/li\u003e\n\u003cli\u003eZhiming Li, Jihong Sun, Xi Hu, et al (2016) Assessment of Liver Fibrosis by Variable Flip Angle T1 Mapping at 3.0T. J. MAGN. RESON. IMAGING 43:698\u0026ndash;703. https://doi: 10.1002/jmri.25030\u003c/li\u003e\n\u003cli\u003eFragaki M, Sifaki-Pistolla D, Orfanoudaki E, Kouroumalis E (2019) Comparative evaluation of ALBI, MELD, and Child-Pugh scores in prognosis of cirrhosis: is ALBI the new alternative? Ann Gastroenterol 32:626\u0026ndash;632. https://doi: 10.20524/aog.2019.0417\u003c/li\u003e\n\u003cli\u003eDeng M, Ng SWY, Cheung ST, Chong CCN (2020) Clinical application of Albumin-Bilirubin (ALBI) score: the current status. Surgeon 18:178\u0026ndash;186. https://doi: 10.1016/j.surge.2019.09.002 \u003c/li\u003e\n\u003cli\u003eMitsutaka Nakashima, Satoru Sakuragi, Toru Miyoshi, et al (2021) Fibrosis-4 index reflects right ventricular function and prognosis in heart failure with preserved ejection fraction. ESC Heart Fail 8: 2240\u0026ndash;2247 https://doi: 10.1002/ehf2.13317\u003c/li\u003e\n\u003cli\u003eNengguang Fan, Xiaoying Ding, Qin Zhen, et al (2021) Association of the Non-Alcoholic Fatty Liver Disease Fibrosis Score with subclinical myocardial remodeling in patients with type 2 diabetes: A cross-sectional study in China. J Diabetes Investig 12:1035-1041. https://doi: 10.1111/jdi.13430\u003c/li\u003e\n\u003cli\u003eJack Rychik, Andrew M. Atz, et al (2019) Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association. Circulation 140:e243-e284 https://doi: 10.1161/CIR.0000000000000696\u003c/li\u003e\n\u003cli\u003eNandwana SB, Olaiya B, Cox K, Sahu A, Mittal P (2018) Abdominal imaging surveillance in adult patients after Fontan procedure: risk of chronic liver disease and hepatocellular carcinoma. Curr Probl Diagn Radiol 47:19\u0026ndash;22. https://doi: 10.1067/j.cpradiol.2017.04.00\u003c/li\u003e\n\u003cli\u003eAsrani SK, Warnes CA, Kamath PS (2013) Hepatocellular carcinoma after the Fontan procedure. N Engl J Med 368:1756\u0026ndash;1757. https://doi: 10.1056/NEJMc1214222\u003c/li\u003e\n\u003cli\u003eKogiso T, Sagawa T, Taniai M, Shimada E, Inai K, Shinohara T, et al (2022) Risk factors for Fontan-associated hepatocellular carcinoma. PLoS ONE 17: e0270230. https://doi: 10.1371/journal.pone.0270230 \u003c/li\u003e\n\u003cli\u003eIshikawa Y, Urabe H, Yamada Y, et al (2023) Normal Ventricular and Regional Blood Flow Volumes and Native T1 Values in Healthy Japanese Children Obtained from Comprehensive Cardiovascular Magnetic Resonance Imaging. Int Heart J 64(4):663-671. https://doi: 10.1536/ihj.23-022\u003c/li\u003e\n\u003cli\u003eLeah A. Gilligan \u0026amp; Jonathan R. Dillman \u0026amp; Jean A. Tkach \u0026amp; Stavra A. Xanthakos \u0026amp; Jacqueline K (2019) Gill1 \u0026amp; Andrew T. Trout. Magnetic resonance imaging T1 relaxation times for the liver, pancreas and spleen in healthy children at 1.5 and 3 tesla. Pediatr Radiol 49:1018\u0026ndash;1024. https://doi: 10.1007/s00247-019-04411-7\u003c/li\u003e\n\u003cli\u003eMirza V. R. Beigh, Kiera B. E. Pajunen, Joseph J. Pagano, et al (2023) T1 mapping of the myocardium and liver in the single ventricle population. Pediatr Radiol 53:1092-1099. https://doi: 10.1007/s00247-022-05560-y \u003c/li\u003e\n\u003cli\u003eJia-Yi Liu, Zhu-Yuan Ding, Zi-Yi Zhou, et al (2021) Multiparameter magnetic resonance imaging of liver fibrosis in a bile duct ligation mouse model. World J Gastroenterol 27: 8156-816. https://doi: 10.3748/wjg.v27.i47.8156\u003c/li\u003e\n\u003cli\u003eShen Pan, Xiao-Qi Wang, Qi-Yong Guo (2018) Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging. World J Gastroenterol 24: 2024-2035. https://doi: 10.3748/wjg.v24.i18.2024\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e Demographic and clinical characteristics of all patients in this study.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics (N=155)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003eBVR\u003c/p\u003e\n \u003cp\u003e(N=42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003ebidirectional Glenn\u003c/p\u003e\n \u003cp\u003e(N=38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003eFontan\u003c/p\u003e\n \u003cp\u003e(N=75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003cp\u003ethree groups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003eAdjusted\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003cp\u003eGlenn vs. Fontan\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eAge \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e7.46\u003c/p\u003e\n \u003cp\u003e(0.5-18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003cp\u003e(0.83-13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e8.83\u003c/p\u003e\n \u003cp\u003e(1.83-19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eMale / Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e20/22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e23/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e48/27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e0.837\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eBSA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003cp\u003e(0.33-1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003cp\u003e(0.34-1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003cp\u003e(0.4-1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; \u0026nbsp; \u0026nbsp;(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e(1-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e(1-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e(5-13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eAscAo pressure\u003c/p\u003e\n \u003cp\u003e(systole) \u0026nbsp; (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003cp\u003e(88-96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003cp\u003e(78-80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e86.5\u003c/p\u003e\n \u003cp\u003e(74-99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eAscAo pressure\u003c/p\u003e\n \u003cp\u003e(diastole) \u0026nbsp;(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e58.5\u003c/p\u003e\n \u003cp\u003e(57-60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e45.5\u003c/p\u003e\n \u003cp\u003e(43-48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e47.5\u003c/p\u003e\n \u003cp\u003e(39-56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eLT1 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(ms)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e572\u003c/p\u003e\n \u003cp\u003e(359-769)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e565\u003c/p\u003e\n \u003cp\u003e(502-688)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e670\u003c/p\u003e\n \u003cp\u003e(569-767)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.654867256637168%\" valign=\"top\"\u003e\n \u003cp\u003eBNP \u0026nbsp; \u0026nbsp; \u0026nbsp;(pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.106194690265486%\" valign=\"top\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003cp\u003e(5.8-835)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.460176991150444%\" valign=\"top\"\u003e\n \u003cp\u003e20.3\u003c/p\u003e\n \u003cp\u003e(5.8-139)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003cp\u003e(5.8-163)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.982300884955752%\" valign=\"top\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.398230088495575%\" valign=\"top\"\u003e\n \u003cp\u003en.s\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Values are expressed as median (range).\u003c/p\u003e\n\u003cp\u003eAscAo: ascending aorta, BNP : brain natriuretic peptide, BSA : body surface area, BVR : biventricular repair, CVP : central venous pressure, LT1 : liver T1 relaxation time\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e Correlations between clinical characteristics and liver T1 in all cases\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"548\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003ecorrelation coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eAST \u0026nbsp;(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eALT \u0026nbsp;(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eAlb (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gamma;-GTP (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eT-bil \u0026nbsp;(mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eBNP \u0026nbsp; (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.603\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eFib 4 Index \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eMELD\u0026nbsp;XI\u0026nbsp;score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eALBI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eNAFLD\u0026nbsp;fibrosis\u0026nbsp;score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.066\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eAge \u0026nbsp; \u0026nbsp; \u0026nbsp; (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eBSA \u0026nbsp; (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e \u0026nbsp; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eHR \u0026nbsp; (bpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.010\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e0.644\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003ePAI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(mm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e) \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.489\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eQsI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"36.13138686131387%\" valign=\"top\"\u003e\n \u003cp\u003eSPCF \u0026nbsp; （L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.42335766423358%\" valign=\"top\"\u003e\n \u003cp\u003e-0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003estandardized regression coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003eT value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eAge \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e-6.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e-0.524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e-2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eBSA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e47.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.978\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eHR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(bpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.571\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.569\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; \u0026nbsp; \u0026nbsp;(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e11.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.571\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e7.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eQsI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.754\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eALT \u0026nbsp; \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gamma;-GTP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.245\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eT-bil \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e-18.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e-0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e-1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eFib 4 Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e2.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eMELD\u0026nbsp;XI\u0026nbsp;score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eALBI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e33.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e2.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinal model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e9.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eALT \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e1.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e2.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"28.268551236749115%\" valign=\"top\"\u003e\n \u003cp\u003eALBI score \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e32.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e2.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.017667844522968%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.015\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Alb : albumin, ALT : alanine aminotransferase, ALBI score : albumin-bilirubin score,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAST : aspartate aminotransferase, BNP : brain natriuretic peptide, BSA : body surface area,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCVP : central venous pressure,\u0026nbsp;Fib-4 Index : fibrosis-4 Index,\u0026nbsp;HR : heart rate, MELD\u0026nbsp;XI\u0026nbsp;score :\u0026nbsp;model for end-stage liver disease\u0026nbsp;Ⅺ,\u0026nbsp;NAFLD :\u0026nbsp;non-alcoholic fatty liver disease,\u0026nbsp;PAI : pulmonary area index, QsI : systemic flow index, SPCF : systemic pulmonary collateral flow, SpO2 : oxygen saturation, T-bil : total bilirubin,\u0026nbsp;\u0026gamma;-GTP : \u0026gamma;-glutamyl transpeptidase\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable\u003c/strong\u003e\u003cstrong\u003e.3\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e Correlations between clinical characteristics and liver T1 in Fontan cases\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"548\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003echaracteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003ecorrelation coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eAST \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e-0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.128\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eALT \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eAlb \u0026nbsp; \u0026nbsp; \u0026nbsp; (g/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e-0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.329\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026gamma;-GTP \u0026nbsp; \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.483\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eT-bil \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eBNP \u0026nbsp; \u0026nbsp; \u0026nbsp; (pg/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.0853\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eFib-4 Index \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eMELD\u0026nbsp;XI\u0026nbsp;score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.292\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eALBI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.0913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.436\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eNAFLD\u0026nbsp;fibrosis\u0026nbsp;score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.069\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eAge \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eBSA \u0026nbsp; \u0026nbsp; \u0026nbsp; (m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eSpO2 \u0026nbsp; \u0026nbsp; \u0026nbsp; (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e-0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.639\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eHR \u0026nbsp; \u0026nbsp; \u0026nbsp; (bpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e-0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.278\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003ePAI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(mm\u003csup\u003e2\u003c/sup\u003e/m\u003csup\u003e2\u003c/sup\u003e) \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e-0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eQsI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eSPCF \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.479\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eIVC return flow\u0026nbsp; \u0026nbsp; \u0026nbsp;(L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"43.065693430656935%\" valign=\"top\"\u003e\n \u003cp\u003eduration from Fontan operation \u0026nbsp;(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"34.48905109489051%\" valign=\"top\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.445255474452555%\" valign=\"top\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026beta;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003estandardized regression coefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003eT value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eAge \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e-2.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e-0.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e-0.859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eBSA \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(m\u003csup\u003e2\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eCVP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e3.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e1.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eIVC return \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (L/min・m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e32.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e1.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eduration from Fontan operation \u0026nbsp;(year) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e-0.867\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e-0.108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e-0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.826\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eAST \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; (U/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e-0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e-0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e-0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eBNP \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e1.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eFib-4 index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e1.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinal model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"40.459363957597176%\" valign=\"top\"\u003e\n \u003cp\u003eFib 4 index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.540636042402827%\" valign=\"top\"\u003e\n \u003cp\u003e85.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.67844522968198%\" valign=\"top\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e2.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.66077738515901%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Alb : albumin, ALT : alanine aminotransferase, ALBI : albumin-bilirubin,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAST : aspartate aminotransferase, BNP : brain natriuretic peptide, BSA : body surface area,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCVP : central venous pressure, Fib-4 Index : fibrosis-4 Index, HR : heart rate, IVC : inferior vena cava, MELD XI : model for end-stage liver disease Ⅺ, NAFLD : non-alcoholic fatty liver disease,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePAI : pulmonary area index, QsI : systemic flow index, SPCF : systemic pulmonary collateral flow, SpO2 : oxygen saturation, T-bil : total bilirubin, \u0026gamma;-GTP : \u0026gamma;-glutamyl transpeptidase\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Fontan-associated liver disease, central venous pressure, liver native T1 mapping, congenital heart disease","lastPublishedDoi":"10.21203/rs.3.rs-4194336/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4194336/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFontan-associated liver disease (FALD) may be caused by chronic liver congestion due to high central venous pressure (CVP). Recently, the usefulness of liver native T1 mapping in magnetic resonance imaging (MRI) in adulthood has been reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the usefulness of native liver T1 mapping in children with congenital heart disease (CHD), we investigated the utility of native liver T1 relaxation time (LT1) in pediatric Fontan patients in comparison to other CHDs. Correlations between LT1 and laboratory biomarkers or hemodynamic data were also assessed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 155 patients with CHD (biventricular repair, n = 42; bidirectional Glenn circulation, n = 38; and Fontan circulation, n = 75) underwent blood tests, cardiac catheterization, and cardiac MRI within 48 h.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBoth CVP and LT1 levels were higher in Fontan patients than in bidirectional Glenn and biventricular patients. There were significant correlation in the overall population and weak correlation in Fontan patients between CVP and LT1(correlation coefficient 0.644 [0.541–0.728] and 0.244 [0.0179–0.446], \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001 and 0.035, respectively). Among the laboratory data, the multiple linear regression analysis revealed that the albumin-bilirubin score and alanine aminotransferase were significantly correlated with LT1 in the overall population (both \u003cem\u003eP\u003c/em\u003e = 0.015), and the fibrosis-4 index was correlated with LT1 in Fontan patients (\u003cem\u003eP\u003c/em\u003e = 0.019).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLT1 could be a noninvasive predictor of CVP and a useful marker of liver injury in children with CHD.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Native liver T1 mapping on magnetic resonance imaging for an evaluation of congestive liver injury in children with congenital heart disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-03 17:15:56","doi":"10.21203/rs.3.rs-4194336/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4321ca10-3dc5-4c49-95f4-7c5e7850a139","owner":[],"postedDate":"April 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-27T06:26:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-03 17:15:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4194336","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4194336","identity":"rs-4194336","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}