Prognostic Outcomes by Ishak Fibrosis Score Grouping in Biliary Atresia after Kasai Surgery: A Prospective Study

Prognostic Outcomes by Ishak Fibrosis Score Grouping in Biliary Atresia after Kasai Surgery: A Prospective Study | 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 Prognostic Outcomes by Ishak Fibrosis Score Grouping in Biliary Atresia after Kasai Surgery: A Prospective Study Huang Lu, Hao YongXing, Tang ChengYan, Xia XingRong, Zheng ZeBing, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6640801/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 Objective This study aimed to assess the native liver survival (NLS) of biliary atresia (BA) patients with varying Ishak scores post Kasai portoenterostomy (KPE). Methods A prospective cohort study analyzed 83 BA patients who underwent KPE at the Affiliated Hospital of Zunyi Medical University from 2019 to 2023. Based on postoperative Ishak scores, patients were categorized into the Mild Fibrosis Group (Ishak 1–2, n = 20), the Moderate Fibrosis Group (Ishak 3–4, n = 39), and the Cirrhosis Group (Ishak 5–6, n = 24). Follow-up data, including clinical information and liver function tests, were compared six months postoperatively. Results Baseline characteristics (age, sex, weight) showed no intergroup differences (P > 0.05). Median surgical ages: mild (76 days, IQR 54.8–92), moderate (70 days, IQR 53–87), cirrhosis (90 days, IQR 59–118.5). Generalized estimating equations (GEE) revealed time-dependent declines in ALT, AST, ALP, and Total Bile Acids (TBA) across groups ( P < 0.05), with cirrhosis patients exhibiting higher GGT and bilirubin levels vs. mild fibrosis ( P < 0.05). Three-month Clearance of Jaundice (CoJ) differed significantly: 55.0% (mild) vs . 38.5% (moderate) vs. 8.3% (cirrhosis) (χ²=11.363, P = 0.003). Six-month NLS sharply declined with fibrosis severity: 80.0% (mild) vs. 16.7% (cirrhosis) (χ²=19.714, P < 0.001). Multivariate logistic regression identified lower Ishak scores (OR = 0.463, 95% CI:0.287–0.746) and younger surgical age (OR = 0.965, 95% CI: 0.936–0.994) as independent predictors of survival ( P < 0.05). Conclusion KPE improved liver function, but the Cirrhosis Group had poorer outcomes. Hepatic fibrosis severity correlated negatively with NLS, highlighting the importance of early surgery. Biliary atresia Kasai portoenterostomy liver fibrosis Ishak score Prognostic Figures Figure 1 Figure 2 Figure 3 INTRODUCTION BA is a life-threatening neonatal cholestatic disorder of unknown etiology, characterized by progressive fibro-obliteration of the intra- and extrahepatic bile ducts. This pathological process leads to cholestasis and irreversible hepatic fibrosis, culminating in cirrhosis if untreated. The global prevalence of BA ranges from 1 in 5,000 to 1 in 20,000 live births [ 1 – 2 ]. First-line management involves the Kasai procedure (hepatic portoenterostomy) to restore bile drainage [ 3 ]. However, the surgery fails to establish adequate bile flow in nearly 50% of patients, resulting in persistent intrahepatic ductal fibrosis and progressive fibrosis [ 4 ]. Without timely intervention, BA rapidly progresses to end-stage cirrhosis and liver failure within the first year of life [ 5 ]. Even after technically successful portoenterostomy, over 50% of survivors eventually require liver transplantation (LT) to prevent mortality, necessitating lifelong immunosuppression with associated complications [ 6 ]. Recent advancements in LT techniques have prompted proposals for primary one-stage LT to replace the conventional two-step approach (Kasai procedure followed by LT. This strategy may mitigate secondary surgical trauma and reduce transplant complexity associated with post-Kasai abdominal adhesions [ 7 – 8 ]. A cohort study by Yoeli et al. (N = 3,438 BA patients) demonstrated that children undergoing LT after failed KPE achieved survival rates comparable to those receiving primary one-stage LT, despite the technical challenges of secondary surgery. Notably, delayed LT beyond age 1 year was associated with improved outcomes, likely due to reduced hepatic fibrosis severity and slower disease progression in older recipients. These findings underscore KPE as a critical bridging intervention to optimize LT timing, particularly for patients requiring delayed surgical eligibility [ 9 ]. Accurate identification of prognostic risk factors and development of validated predictive models are critical to inform personalized clinical management in BA. In a multicenter observational study (n = 380), Tomita et al. developed the iBALF scoring system incorporating age, total bilirubin, and platelet count. Patients with iBALF scores > 5.27 demonstrated markedly reduced 1-year NLS(14%-34.7%) compared to lower-score counterparts. These findings suggest that KPE provides limited benefit for high iBALF-score patients, positioning one-stage LT as a potentially preferable initial intervention in this subgroup [ 10 ]. While the iBALF system represents an innovative approach to preoperative risk stratification, its clinical utility remains investigational pending validation through multicenter prospective trials. Current evidence does not justify using iBALF scores as a standalone criteria for one-stage LT selection. Gunadi et al. demonstrated that advanced hepatic fibrosis independently predicts adverse clinical outcomes in BA [ 11 ]. Current histopathological staging systems for liver fibrosis encompass the Scheuer system, METAVIR, and Ishak scoring (0–6 stages), each with distinct diagnostic applications [ 12 , 13 ]. The Ishak system (0–6 stages) is the most widely adopted fibrosis classification framework in multicenter studies, enabling standardized assessment of fibrotic progression in pre- and post-intervention cohorts [ 14 ]. This study aims to evaluate the predictive ability of the Ishak scoring system for 6-month post-KPE NLS through a prospective cohort analysis of 83 cases. It provides a pathological basis for early individualized treatment decision-making after KPE. It also provides new ideas for a standardized prognostic assessment system. METHODS Study population A prospective study was carried out. Patients diagnosed with BA at the Affiliated Hospital of Zunyi Medical University, a tertiary-level hospital in China, between January 1, 2019, and December 31, 2023, were recruited as the study subjects. Inclusion Criteria: (1) Patients were definitively diagnosed with BA at our center through comprehensive evaluations, including laparoscopic exploration and intraoperative cholangiography. The diagnosis was confirmed by the surgical team performing KPE and further validated by histopathological examination. (2) Patients received standardized perioperative management under the care of our multidisciplinary team and completed regular follow-up assessments. (3) Patients had no concurrent congenital hepatobiliary malformations. Exclusion Criteria: (1) Patients whose families opted to discontinue medical care due to life-threatening complications or other critical circumstances. (2) Patients with concurrent congenital gastrointestinal malformations necessitating prioritized surgical intervention. A cohort of 100 patients with BA was initially screened, with 17 excluded per predefined criteria. The final study population comprised 83 children (50 male, 33 female) who underwent KPE and maintained protocol-compliant follow-up (Fig. 1 ). Postoperative liver biopsy specimens, independently evaluated by two senior hepatopathologists using the Ishak scoring system, stratified patients into three histologic severity groups: mild fibrosis (Ishak 1–2, n = 20), moderate fibrosis (Ishak 3–4, n = 39), and severe fibrosis (Ishak 5–6, n = 24), all prospectively monitored per study protocol (Fig. 2 ). Comparative analysis of predefined prognostic biomarkers across subgroups was conducted at the 6-month postoperative interval. Ethical Considerations Ethical approval for this study (KLLY-2021-122) was provided by the Ethical Committee of the Affiliated Hospital of Zunyi Medical University, China. All research was conducted by the Helsinki Declaration. Written informed consent was provided by the parents or legal guardians of all participants. Therapeutic Approach Following diagnostic confirmation of BA via laparoscopic exploration with intraoperative cholangiography, we proceeded with KPE. The surgical protocol included: (1) meticulous excision of the fibrous remnant at the hepatic portal plate; (2) creation of a 30–35 cm Roux-en-Y jejunal limb passed retromesenterically through the transverse mesocolon; (3) hepaticojejunostomy performed with interrupted 5 − 0 polyglactin sutures in a single-layer, extra-mucosal anastomosis technique [ 15 ].Postoperative management comprised: Intravenous cefoperazone-sulbactam(100 mg/kg/day) for 14 days followed by oral amoxicillin-clavulanate (40 mg/kg/day) until 21 days postop; Methylprednisolone pulse therapy initiated on postoperative day 5 (4 mg/kg/day IV), tapered by 1 mg/kg every 72 hours, transitioning to oral prednisolone (2 mg/kg/day) at week 2, with complete cessation by week 16; Adjunctive therapy with ursodeoxycholic acid (20 mg/kg/day) and fat-soluble vitamin supplementation (Vitamins A 5000 IU, D 400 IU, E 15 IU, K 2 mg daily) [ 16 – 17 ]. Follow-up evaluation All patients underwent standardized postoperative surveillance through scheduled outpatient evaluations at 1-, 3-, and 6-month intervals following KPE. Monitoring parameters included anthropometric measures (weight, age), surgical covariates (sex and operative age), serial hepatic biochemistry such as ALT, AST, GGT, total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin(IBIL), and TBA, and the primary clinical endpoint of 6-month NSL. JoC was rigorously defined as achieving serum TBIL ≤ 20 µmol/L (1.17 mg/dL) within the study period [ 16 ]. Attrition Attrition Definition: Participants who failed to complete the protocol-specified 6-month endpoint evaluation due to either: (1) Loss to follow-up (unable to contact despite ≥ 3 documented attempts via phone/email), (2) Geographic relocation beyond catchment area, (3) Mortality (all-cause death verified by civil registry), were classified as attrition cases per CONSORT guidelines. Statistical analysis Statistical analyses were performed using IBM SPSS Statistics 29.0. Continuous variables underwent normality assessment via the Shapiro-Wilk test (α = 0.05). Normally distributed parameters were expressed as mean ± SD, while non-normal distributions were summarized as median [Q1-Q3]. Categorical variables were reported as frequencies (percentages), with group comparisons conducted through χ² or Fisher's exact tests as appropriate.All statistical tests were two-tailed, with P < 0.05 considered significant. Repeated measures data were analyzed using GEE. The primary analysis utilized the Full Analysis Set (FAS) following the intention-to-treat (ITT) principle, with missing data assumed to be missing at random (MAR). To evaluate the robustness of findings, a sensitivity analysis was conducted by applying the same GEE method after multiple imputation (MI) of missing values. Logistic regression analysis was employed to identify factors associated with 6-month native liver survival (NLS) and to construct a predictive model. Potential predictors were initially screened through univariate logistic regression (α = 0.1), with three clinically established prognostic variables (ALT, TBA, and sex) forced into the model(supplementary materials Table S5 ). The final multivariable model included 9 variables. Collinearity diagnostics indicated no substantial multicollinearity (variance inflation factor (VIF) range: 1.3–4.2; tolerance values > 0.3). Forward stepwise selection was used for variable selection, and parameter estimate stability was assessed via sensitivity analysis using the full-model approach. RESULTS 1. Baseline characteristics The study cohort comprised 83 eligible patients stratified by Ishak fibrosis staging into Mild fibrosis (1-2, n=20), moderate fibrosis(3-4, n=39), and cirrhosis (5-6, n=24) groups, with baseline demographics demonstrating comparable distributions across groups: median ages 76 (IQR 54.8-92), 70 (53-87), and 90 days (59-118.5) respectively (Kruskal-Wallis P=0.313); female predominance decreasing from 50.0% to 29.2% (χ²=2.01, P= 0.363); mean weights 5.3±1.6, 4.9±1.0, and 5.4±1.1kg (ANOVA P =0.363). Biochemical profiling revealed significant intergroup variance in bilirubin metabolism: TBIL escalated from 159 ± 35 μmol/L (mild) to 195 ± 53 μmol/L (cirrhosis) ( P =0.043), paralleled by DBIL increases (88.4 vs. 102.6 μmol/L, P =0.024), while IBIL showed marginal significance (68.8-84.6 μmol/L, P =0.055). Hepatic enzymes, including ALT (78-91 U/L), AST (102-117 U/L), GGT (210-255 U/L), and ALP (350-420 IU/L), exhibited nonsignificant trends (all P >0.05), with TBA remaining comparable (35.2-38.7 μmol/L, P =0.544). Table 1. Comparison of Baseline Characteristics Across Ishak Groups Baseline clinical characteristics Mild fibrosis(n=20) Moderate fibrosis(n=39) cirrhosis(n=24) P Socio-demographic Age (days) 76(54.8-92) 70(53-87) 90(59-118.5) 0.313 Female sex(%) 10(50.0) 16(41.0) 7(29.2) 0.363 Weight(kg) 5.3±1.6 4.9±1.0 5.4±1.1 0.363 Hepatic Panel ALT 121(101.5-183.5) 158.5(83.8-205.5) 161(90.3-205.8) 0.677 AST 208.5(174.3-294.2) 263(156.5-351.3) 250(182.3-383.0) 0.674 GGT 347(189-720.8) 374(164-891) 409(221-1064) 0.409 ALP 691.7±164.4 667.4±215.4 783.2±317.5 0.187 TBIL 159(141-186) 168(141-221) 195(159-230) 0.043 DBIL 88.4(78.9-103.7) 90.8(76.4-116.9) 102.6(93-124.1) 0.024 IBIL 68.8(64.0-84.7) 79.6(65.2-106.8) 84.6(74.0-104.4) 0.055 TBA 155.8±56.6 152.2±56.9 170.6±58.6 0.544 Note: bold values represent P < 0.05. Abbreviations :TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; TBA, total bile acids; T0: Baseline; T1-T3: Postoperative follow-up at 1, 3, and 6 months. 2. Comparison of liver function indices across Ishak Groups GEE was used to compare changes in liver function indicators among the three groups. Gamma or Gaussian distributions were selected as the probability distribution types (gamma for GGT, Gaussian for others), with exchangeable working correlation matrices. Both unadjusted and adjusted models (controlling for gender and age at surgery) were employed to analyze the main effects of group and time. For GGT, the unadjusted GEE model revealed a significant main effect of time on GGT levels across all groups ( P < 0.05), and the Mild Fibrosis Group exhibited significantly lower GGT levels than the Cirrhosis Group. Results from the adjusted model were consistent (Table 2, supplementary materials Table S1, Figure 3A). Similarly, TBIL, DBIL, and IBIL showed significant time effects ( P < 0.001) and group differences between Mild Fibrosis and Cirrhosis groups ( P < 0.05), with lower bilirubin levels in the former. Adjusted analyses yielded concordant findings (Table 2, supplementary materials Table S1, Figure 3 B-D). ALT, AST, ALP, and TBA analyses indicated significant time effects ( P < 0.05) but no group differences. Collectively, all groups showed reduced liver function indices within six months post-K, though the Cirrhosis Group had persistently higher GGT and bilirubin levels, indicating poorer improvement(supplementary materials Table S2). Sensitivity analyses using GEE revealed distinct biomarker dynamics: cholestatic markers (GGT, bilirubin) exhibited fibrosis-dependent associations, with GGT demonstrating robust correlations in cirrhosis subgroups (6.7% β attenuation post-adjustment) and moderate fibrosis showing a dose-response trend (P = 0.051), while TBIL/DBIL associations attenuated significantly (18.5-24.4%) after covariate adjustment. In contrast, hepatocellular enzymes (ALT, ALP) showed strong time-dependent declines (Wald χ² >29.87, P 0.3). Temporal trajectories remained stable across models, indicating uniform postoperative recovery patterns regardless of Ishak classification (detailed statistics in Supplementary Tables S3-S4). Table 2 Results of the GEE analysis for Comparison of liver function Item Unadjusted model Adjusted model β 95%CI P β 95%CI P Lower Upper Lower Upper GGT Group Mild fibrosis Reference Reference Moderate fibrosis 0.198 -0.113 0.510 0.212 0.192 -0.119 0.502 0.227 Cirrhosis 0.419 0.063 0.775 0.021 0.394 0.041 0.747 0.029 Time T0 Reference Reference T1 0.658 0.485 0.831 ＜ 0.001 0.660 0.485 0.834 ＜ 0.001 T2 0.409 0.220 0.598 ＜ 0.001 0.421 0.231 0.610 ＜ 0.001 T3 -0.284 -0.544 -0.023 0.033 -0.277 -0.540 -0.014 0.039 TBIL Group Mild fibrosis Reference Reference Moderate fibrosis 26.635 -11.754 65.023 0.174 25.313 -13.945 64.570 0.206 cirrhosis 62.032 20.482 103.582 0.003 48.455 9.118 87.792 0.016 Time T0 Reference Reference T1 -65.533 -85.288 -45.777 ＜ 0.001 -64.143 -83.514 -44.773 ＜ 0.001 T2 -62.818 -91.722 -33.914 ＜ 0.001 -61.041 -89.618 -32.464 ＜ 0.001 T3 -93.237 -128.917 -57.558 ＜ 0.001 -90.612 -125.871 -55.353 ＜ 0.001 DBIL Group Mild fibrosis Reference Reference Moderate fibrosis 12.573 -6.063 31.208 0.186 12.088 -6.859 31.035 0.211 cirrhosis 33.234 12.727 53.740 0.001 26.925 7.382 46.469 0.007 Time T0 Reference Reference T1 -30.324 -40.618 -20.029 ＜ 0.001 -29.627 -39.807 -19.447 ＜ 0.001 T2 -31.947 -47.111 -16.783 ＜ 0.001 -31.086 -46.135 -16.037 ＜ 0.001 T3 -51.113 -68.203 -34.024 ＜ 0.001 -49.875 -66.826 -32.923 ＜ 0.001 IBIL Group Mild fibrosis Reference Reference Moderate fibrosis 13.795 -6.700 34.290 0.187 13.109 -7.882 33.920 0.222 cirrhosis 27.989 6.385 49.594 0.011 21.016 0.552 41.480 0.044 Time T0 Reference Reference T1 -35.409 -45.871 -24.948 ＜ 0.001 -34.706 -44.907 -24.504 ＜ 0.001 T2 -30.980 -45.758 -16.203 ＜ 0.001 -30.011 -44.590 -15.432 ＜ 0.001 T3 -43.326 -63.706 -22.946 ＜ 0.001 -41.999 -62.085 -21.913 ＜ 0.001 Note: a indicates adjusted for gender and age at surgery, bold values represent P < 0.05. Abbreviations :TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; T0: Baseline; T1-T3: Postoperative follow-up at 1, 3, and 6 months. 3. Comparison of 3-month JoC among the three groups A significant difference in 3-month JoC rates was observed across the three groups (χ² = 11.363, P = 0.003), with rates of 55.0% in the Mild Fibrosis group, 38.5% in the Moderate Fibrosis group, and 8.3% in the Cirrhosis group. Post hoc pairwise comparisons indicated that while the difference between the Mild and Moderate Fibrosis groups was not statistically significant (55.0% vs. 38.5%; χ² = 1.467, P = 0.226), the Moderate Fibrosis group exhibited a significantly higher JoC rate than the Cirrhosis group (38.5% vs. 8.3%; χ² = 6.845, P = 0.009), and the Mild Fibrosis group demonstrated markedly higher JoC rates compared to the Cirrhosis group (55.0% vs. 8.3%; χ² = 11.413, P < 0.001). Table 3 Comparison of 3-month JoC among the three groups Group JoC n χ 2 P Mild 55.0% 20 11.363 0.003 Moderate 38.5% 39 Cirrhosis 8.3% 24 Post hoc analysis Mild vs. Moderate 55.0% vs. 38.5% 20 vs. 39 1.467 0.226 Moderate vs. Cirrhosis 38.5% vs. 8.3% 39 vs. 24 6.845 0.009 Mild vs. Cirrhosis 55.0% vs. 8.3% 20 vs. 24 11.413 <0.001 Note: bold values represent P < 0.05. 4. Comparison of 6-month NLS Rates A significant difference in 6-month NLS rates was observed among the three groups (χ² = 19.714, P < 0.001). The Mild Fibrosis Group had the highest survival rate (80.0%), significantly exceeding the Cirrhosis Group (16.7%; χ² = 17.649, P < 0.001). The Moderate Fibrosis Group demonstrated an intermediate survival rate (61.5%), which was not statistically different from the Mild Fibrosis Group (χ² = 2.064, P = 0.151) but markedly higher than the Cirrhosis Group (χ² = 12.115, P < 0.001). Post hoc pairwise comparisons further confirmed these trends: survival rates differed significantly between the Mild and Cirrhosis Groups (80.0% vs. 16.7%; P < 0.001) and between the Moderate and Cirrhosis Groups (61.5% vs. 16.7%; P < 0.001), whereas the Low- vs. Moderate Group comparison did not reach significance (80.0% vs. 61.5%; P = 0.151). These findings indicate a significant negative correlation between prognostic risk scores and NLS, with the Cirrhosis Group associated with the poorest outcomes (Table 4). Table 4 Comparison of 6-month NLS between the three groups Group NLS n χ 2 P Mild 80.0% 20 19.714 <0.001 Moderate 61.5% 39 Cirrhosis 16.7% 24 Post hoc analysis Mild vs. Moderate 80.0% vs. 61.5% 20 vs. 9 2.064 0.151 Moderate vs. Cirrhosis 61.5% vs. 16.7% 39 vs. 24 12.115 <0.001 Mild vs. Cirrhosis 80.0% vs. 16.7% 20 vs. 24 17.649 <0.001 Note: bold values represent P < 0.05. 5. Multivariable regression analysis of 6-month postoperative survival outcomes Univariable logistic regression identified Ishak fibrosis stage as the strongest predictor ( P <0.001), with surgical age, TBIL, and AST also significant ( P <0.05) (detailed results in Supplementary Table S5).The multivariable regression model demonstrated that Ishak score (OR=0.463, P =0.002) was independently associated with poorer prognosis, whereas younger age at surgery (OR=0.965, P =0.020) showed a protective effect. Other clinical parameters, including gender (OR=1.608, P =0.481), ALT (OR=1.003, P =0.513), AST (OR=0.994, P =0.133), GGT (OR=0.999, P =0.269), ALP (OR=0.999, P =0.511), TBIL (OR=0.816, P =0.704), and TBA(OR=1.008, P =0.288), did not demonstrate statistically significant associations with survival outcomes in the adjusted analysis (all P >0.05; Table 5). Forward stepwise regression validated Ishak fibrosis score (OR=0.450, P90% of univariable effect magnitudes. The Ishak score dominated prognostic stratification, reinforcing histopathological staging and surgical timing as primary determinants(detailed results in Supplementary Table S6). Table 5 Multivariable analysis of factors associated with 6-month survival after surgery Factors OR 95 ％ CI P Lower Upper Ishak Score 0.463 0.287 0.746 0.002 sex 1.608 0.429 6.032 0.481 Surgical age (days) 0.965 0.936 0.994 0.020 ALT 1.003 0.993 1.014 0.513 AST 0.994 0.986 1.002 0.133 GGT 0.999 0.998 1.001 0.269 ALP 0.999 0.996 1.002 0.511 TBIL 0.816 0.286 2.329 0.704 TBA 1.008 0.993 1.023 0.288 Note: bold values represent P < 0.05. Abbreviations :TBIL, total bilirubin; TBA, total bile acids. Discussion BA is the leading cause of pediatric end-stage liver disease and the primary indication for LT in children, although the optimal therapeutic strategy remains controversial [18]. In most centers, the standard approach involves sequential therapy with the KPE, followed by LT if jaundice persists or irreversible cirrhosis develops [19]. In contrast, some centers advocate for primary LT as the initial intervention [20]. Developing a validated prognostic model for BA to guide individualized treatment planning before or early after the KPE could significantly alleviate the socioeconomic burden on families and healthcare systems, offering substantial clinical value [21]. Analyzing prognostic indicators across Ishak fibrosis subgroups in BA patients, this study developed a predictive model for early postoperative outcomes. As Ishak fibrosis scores increased, the Cirrhosis group demonstrated significantly lower 6-month native liver survival rates compared to the Mild andModerate groups. Concurrently, these patients exhibited reduced 3-month CoJ, indicating impaired surgical outcomes and delayed hepatic functional recovery. Higher Ishak scores correlated with shortened native liver survival duration, persistent cholestasis, and overall poorer prognosis. The timing of surgical intervention, particularly in relation to patient age at the KPE, has been established as a critical prognostic determinant [22]. Although our study found no statistically significant differences in operative ages across the three subgroups, multivariable logistic regression analysis identified older age at surgery as an independent risk factor for 6-month NLS. This finding aligns with existing evidence demonstrating that early intervention improves biliary drainage efficiency, thereby mitigating cholestatic hepatocyte injury and decelerating fibrogenesis [23,24]. Our results further substantiate the clinical imperative for timely surgical management, providing quantitative evidence to guide optimal intervention timing in BA management. Biochemical analysis revealed progressive elevation of TBIL, DBIL, and IBIL with advancing fibrosis stages. Although TBA showed no statistically significant intergroup differences, a trend toward higher values was observed in the Cirrhosis cohort. These findings align with previous reports [25], suggesting that advanced fibrosis disrupts biliary excretion pathways, leading to systemic bilirubin accumulation and worsening hepatic synthetic dysfunction [26]. While GGT levels are typically elevated in BA, normal values may occasionally occur as documented in prior reports [27]. Our data specifically revealed that postoperative GGT levels in the mild fibrosis group were significantly lower than those in the cirrhosis group. Although preoperative levels of ALT, AST, and ALP showed no statistically significant differences among the Ishak subgroups.Following KPE, all subgroups exhibited progressive improvement in liver function parameters during follow-up monitoring. However, when analyzed through the lens of Ishak histopathological staging, patients in cirrhosis subgroups demonstrated slower recovery rates for bilirubin normalization compared to mild subgroups, despite achieving absolute biochemical improvements. This suggests that while the KPE provides functional benefit across disease stages. This study has several limitations. As a single-center retrospective cohort with a limited sample size, potential selection bias may constrain the generalizability of findings. Furthermore, the 6-month postoperative observation window following KPE precluded longitudinal assessment of long-term outcomes. Future investigations will employ multicenter prospective designs with extended surveillance periods. In conclusion, the Ishak score can serve as a risk stratification tool to guide clinicians in implementing intensified postoperative monitoring for high-risk infants (Ishak ≥5) and initiating early multidisciplinary team collaboration for liver transplantation. This facilitates the provision of individualized prognostic counseling to families, particularly emphasizing the elevated probability of requiring sequential liver transplantation in high-risk subgroups, thereby promoting shared clinical decision-making. These findings further suggest that such patients may be direct candidates for primary liver transplantation, avoiding ineffective surgical interventions. Although liver biopsy remains the pathological gold standard for assessing hepatic fibrosis staging [28] and could theoretically inform first-stage transplantation decisions for infants with high Ishak scores (≥5), its inherent limitations - including invasive nature, sampling errors, diagnostic variability, and unavoidable complications (e.g., pain, hemorrhage, infection) - preclude routine preoperative utilization [29]. Non-invasive hepatic stiffness measurement techniques, notably transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and shear-wave elastography (SWE), have gained clinical adoption for BA fibrosis evaluation due to their operational simplicity, cost-effectiveness, and high patient acceptability [30-32]. However, current non-invasive modalities demonstrate limited efficacy in discriminating fibrosis stages and lack internationally standardized cutoff values [33], substantially constraining their utility in surgical decision-making. Future research should prioritize the integration of multimodal imaging biomarkers with machine learning algorithms. Emerging methodologies in computational histopathology analysis and dynamic fibrosis modeling [34-36] hold promise for developing virtual staging platforms, potentially revolutionizing preoperative assessment paradigms. Declarations CONFLICTS OF INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. FUNDING INFORMATION 1. Science and Technology Department of Guizhou Province(Qian Kehe basic character [2021])normal 555). 2. Medical Research Union Found for High-quality health development of Guizhou Province(2024GZYXKYJJXM0063). 3. Guizhou Moutai Hospital 2022 Grant for Scientific Research and Talent Cultivation(MTyk2022-19). Author Contribution Huang Lu: Writing – Original Draft, ValidationHao YongXing: ResourcesTang ChengYan: Data Curation, Xia XingRong: ConceptualizationZheng ZeBing: InvestigationDu Qing: MethodologyZhou WanKang: VisualizationZhu DaiWei: SoftwareLi ZePing: SupervisionLeng Mengdan​​: Formal Analysis​Liu YuanMei: Writing – Review & Editing​Jin Zhu: Project Administration, Funding Acquisition References Tam PKH, Wells RG, Tang CSM et al (2024) Biliary atresia. Nat Reviews Disease Primers 10(1):47 Hellen DJ, Karpen SJ (2023) Genetic Contributions to Biliary Atresia: A Developmental Cholangiopathy. Semin Liver Dis 43(3):323–335 Lendahl U, Lui VCH, Chung PHY et al (2021) Biliary Atresia - emerging diagnostic and therapy opportunities. EBioMedicine 74:103689 Ye C, Zhu J, Wang J et al (2022) Single-cell and spatial transcriptomics reveal the fibrosis-related immune landscape of biliary atresia. 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Hepatobiliary Surg Nutr 13(6):1019–1021 Wang P, Zhang HY, Yang J et al (2023) Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China. Int J Surg 109(12):4009–4017 Lu X, Jiang J, Shen Z et al (2023) Effect of Adjuvant Steroid Therapy in Type 3 Biliary Atresia: A Single-Center, Open-Label, Randomized Controlled Trial. Ann Surg 277(6):e1200–e1207 LeeVan E, Matsuoka L, Cao S, Groshen S, Alexopoulos S (2019) Biliary-Enteric Drainage vs. Primary Liver Transplant as Initial Treatment for Children With Biliary Atresia. JAMA Surg 154(1):26–32 Venkat V, Ng VL, Magee JC et al (2020) Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age. Hepatol Commun 4(12):1824–1834 Ge L, Zhan J, Gao W, Zhao S, Xu X, Dou R (2020) Relevant factors for early liver transplantation after Kasai portoenterostomy. BMC Pediatr 20(1):484 Okubo R, Nio M, Sasaki H (2020) Japanese Biliary Atresia Society. Impacts of Early Kasai Portoenterostomy on Short-Term and Long-Term Outcomes of Biliary Atresia. Hepatol Commun 5(2):234–243 Davenport M, Makin E, Ong EG, Sharif K, Dawrant M, Alizai N (2025) The Outcome of a Centralization Program in Biliary Atresia: Twenty Years and Beyond. Ann Surg 281(4):608–614 Kahan AM, Holley AG, Horns J et al (2025) The Age-stratified Cost of Biliary Atresia: A MarketScan®-Based Cost Analysis. J Pediatr Surg 60(5):162244 Liu F, Yeung F, Chung PHY (2022) The outcome of Kasai portoenterostomy after day 70 of life. Front Pediatr 10:1015806 Harpavat S, Garcia-Prats JA, Anaya C et al (2020) Diagnostic Yield of Newborn Screening for Biliary Atresia Using Direct or Conjugated Bilirubin Measurements. JAMA 323(12):1141–1150 Vimalesvaran S, Souza LN, Deheragoda M et al (2021) Outcomes of adults who received liver transplant as young children. EClinicalMedicine 38:100987 Shankar S, Bolia RS, Foo HW et al (2020) Normal gamma glutamyl transferase levels at presentation predict poor outcome in biliary atresia[J]. J Pediatr Gastroenterol Nutr 70(3):350–355 Neuberger J, Patel J, Caldwell H et al (2020) Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology. Gut 69(8):1382–1403 Chowdhury AB, Mehta KJ (2023) Liver biopsy for assessment of chronic liver diseases: a synopsis. Clin Exp Med 23(2):273–285 Molleston JP, Goodrich NP, Ye W, Leung DH, Sokol RJ, Shneider BL (2025) Prospective Analysis of Liver Stiffness Measurement by Vibration Controlled Transient Elastography as a Predictor of Outcomes in Biliary Atresia. Gastroenterology 168(2):393–395 Yan YL, Xing X, Wang Y, Wang XZ, Wang Z, Yang L (2022) Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in autoimmune hepatitis-primary biliary cholangitis overlap syndrome. World J Gastroenterol 28(18):2021–2033 Liguori A, Zoncapè M, Casazza G, Easterbrook P, Tsochatzis EA (2025) Staging liver fibrosis and cirrhosis using non-invasive tests in people with chronic hepatitis B to inform WHO 2024 guidelines: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 10(4):332–349 Vannier MW, Wang G (2021) Histomorphometry of Biliary Atresia with Phase-Contrast CT Microscopy Yields Unique Insights. Radiology 299(3):611–612 Li Q, Wang F, Chen Y et al (2022) Virtual liver needle biopsy from reconstructed three-dimensional histopathological images: Quantification of sampling error. Comput Biol Med 147:105764 Marti-Aguado D, Fernández-Patón M, Alfaro-Cervello C et al (2021) Digital Pathology Enables Automated and Quantitative Assessment of Inflammatory Activity in Patients with Chronic Liver Disease. Biomolecules 11(12):1808 Marri UK, Das P, Shalimar, Kalaivani M, Srivastava DN, Madhusudhan KS (2021) Noninvasive Staging of Liver Fibrosis Using 5-Minute Delayed Dual-Energy CT: Comparison with US Elastography and Correlation with Histologic Findings. Radiology 298(3):600–608 Additional Declarations No competing interests reported. Supplementary Files supplementarymaterialsTableS1S6.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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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-6640801","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":458597153,"identity":"01a7553f-0465-43c5-90dc-be70933f53cd","order_by":0,"name":"Huang Lu","email":"","orcid":"","institution":"Guizhou Children’s Hospital, Affiliated Hospital of Zunyi Medical University","correspondingAuthor":false,"prefix":"","firstName":"Huang","middleName":"","lastName":"Lu","suffix":""},{"id":458597154,"identity":"87e30d01-ba1e-4ee7-be77-768b1e9501ef","order_by":1,"name":"Hao YongXing","email":"","orcid":"","institution":"Guizhou Children’s 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Zhu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBAC9mYGBmYGBgkeNvbmgw8+QAQN8GphhGixkOPnOZZsOIMoLQ1gLRXGkjN8zKR5iNLSznv4c2GbROKGGwwG0jZ/tiU2sDdvk2CouYPHYXwJxjNBWm43JBjn8NxObOA5VibBcOwZHi08Bsm8IC13DhxIzpEAapHIMZNgbDiMV8thsJYbiQ2HLQyAWuTf4Nci2Mxj2AzUAvR+MjD0EkC28ODXIs3MY8zMc04CFMjMjD0Hbhu38aQVWyQcw62Fj/+M8WeesjpgVPZ///Hjz23ZfvbDG298qMGtBROwgYgEEjSMglEwCkbBKMAEAAOfUc7EUYjoAAAAAElFTkSuQmCC","orcid":"","institution":"Guizhou Children’s Hospital, Affiliated Hospital of Zunyi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jin","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2025-05-11 16:53:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6640801/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6640801/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83211369,"identity":"06ea3d31-c2aa-4ee6-a37a-5d0db6840742","added_by":"auto","created_at":"2025-05-21 08:34:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":23276,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT Flow Diagram of Participant Recruitment, Exclusion Criteria Application, and 6-Month Follow-up Completion\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6640801/v1/20491d9d75b2f2bf268e3fd2.png"},{"id":83211373,"identity":"ec0f707a-82fe-412e-85d2-0d02c710b433","added_by":"auto","created_at":"2025-05-21 08:34:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":872924,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological Staging of BA Using Ishak Fibrosis Scoring System.Schematic of Ishak scoring criteria: Stage 1: No fibrous septa Stage, 2: Single short fibrous septum, Stage 3: 2-3 bridging septa, Stage 4: ≥4 incomplete septa, Stage 5: ≥4 septa with 1-3 pseudolobules, Stage 6: \u0026gt;3 pseudolobules with architectural distortion.Mild fibrosis (Ishak 1-2): A (×40), B (×100), Moderate fibrosis (Ishak 3-4): C (×100), D (×100), cirrhosis (Ishak 5-6): E (×40), F (×40).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6640801/v1/34d9de2bb85430706b7b1810.png"},{"id":83214178,"identity":"dc893ba0-0e96-4651-806b-816d071c8e24","added_by":"auto","created_at":"2025-05-21 08:50:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":42845,"visible":true,"origin":"","legend":"\u003cp\u003eLongitudinal Changes in GGT, TBIL, DBIL, and IBIL Levels— GEE Analysis Across Patient Groups.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6640801/v1/59ea77434d25870b20bbae38.png"},{"id":84115402,"identity":"8b863c0d-7147-4941-b7d0-ecbd70584f5f","added_by":"auto","created_at":"2025-06-07 06:31:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2063988,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6640801/v1/bb2b19d9-e9e5-4df1-af99-ae601c9ba49f.pdf"},{"id":83211368,"identity":"6dd811af-aff2-4d37-853d-97ac2e82281e","added_by":"auto","created_at":"2025-05-21 08:34:44","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":38728,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarymaterialsTableS1S6.docx","url":"https://assets-eu.researchsquare.com/files/rs-6640801/v1/a7861eff51abd38a578d3708.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prognostic Outcomes by Ishak Fibrosis Score Grouping in Biliary Atresia after Kasai Surgery: A Prospective Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBA is a life-threatening neonatal cholestatic disorder of unknown etiology, characterized by progressive fibro-obliteration of the intra- and extrahepatic bile ducts. This pathological process leads to cholestasis and irreversible hepatic fibrosis, culminating in cirrhosis if untreated. The global prevalence of BA ranges from 1 in 5,000 to 1 in 20,000 live births [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. First-line management involves the Kasai procedure (hepatic portoenterostomy) to restore bile drainage [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the surgery fails to establish adequate bile flow in nearly 50% of patients, resulting in persistent intrahepatic ductal fibrosis and progressive fibrosis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Without timely intervention, BA rapidly progresses to end-stage cirrhosis and liver failure within the first year of life [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Even after technically successful portoenterostomy, over 50% of survivors eventually require liver transplantation (LT) to prevent mortality, necessitating lifelong immunosuppression with associated complications [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Recent advancements in LT techniques have prompted proposals for primary one-stage LT to replace the conventional two-step approach (Kasai procedure followed by LT. This strategy may mitigate secondary surgical trauma and reduce transplant complexity associated with post-Kasai abdominal adhesions [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA cohort study by Yoeli et al. (N\u0026thinsp;=\u0026thinsp;3,438 BA patients) demonstrated that children undergoing LT after failed KPE achieved survival rates comparable to those receiving primary one-stage LT, despite the technical challenges of secondary surgery. Notably, delayed LT beyond age 1 year was associated with improved outcomes, likely due to reduced hepatic fibrosis severity and slower disease progression in older recipients. These findings underscore KPE as a critical bridging intervention to optimize LT timing, particularly for patients requiring delayed surgical eligibility [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Accurate identification of prognostic risk factors and development of validated predictive models are critical to inform personalized clinical management in BA. In a multicenter observational study (n\u0026thinsp;=\u0026thinsp;380), Tomita et al. developed the iBALF scoring system incorporating age, total bilirubin, and platelet count. Patients with iBALF scores\u0026thinsp;\u0026gt;\u0026thinsp;5.27 demonstrated markedly reduced 1-year NLS(14%-34.7%) compared to lower-score counterparts. These findings suggest that KPE provides limited benefit for high iBALF-score patients, positioning one-stage LT as a potentially preferable initial intervention in this subgroup [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. While the iBALF system represents an innovative approach to preoperative risk stratification, its clinical utility remains investigational pending validation through multicenter prospective trials. Current evidence does not justify using iBALF scores as a standalone criteria for one-stage LT selection. Gunadi et al. demonstrated that advanced hepatic fibrosis independently predicts adverse clinical outcomes in BA [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrent histopathological staging systems for liver fibrosis encompass the Scheuer system, METAVIR, and Ishak scoring (0\u0026ndash;6 stages), each with distinct diagnostic applications [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The Ishak system (0\u0026ndash;6 stages) is the most widely adopted fibrosis classification framework in multicenter studies, enabling standardized assessment of fibrotic progression in pre- and post-intervention cohorts [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aims to evaluate the predictive ability of the Ishak scoring system for 6-month post-KPE NLS through a prospective cohort analysis of 83 cases. It provides a pathological basis for early individualized treatment decision-making after KPE. It also provides new ideas for a standardized prognostic assessment system.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eA prospective study was carried out. Patients diagnosed with BA at the Affiliated Hospital of Zunyi Medical University, a tertiary-level hospital in China, between January 1, 2019, and December 31, 2023, were recruited as the study subjects.\u003c/p\u003e \u003cp\u003eInclusion Criteria: (1) Patients were definitively diagnosed with BA at our center through comprehensive evaluations, including laparoscopic exploration and intraoperative cholangiography. The diagnosis was confirmed by the surgical team performing KPE and further validated by histopathological examination. (2) Patients received standardized perioperative management under the care of our multidisciplinary team and completed regular follow-up assessments. (3) Patients had no concurrent congenital hepatobiliary malformations.\u003c/p\u003e \u003cp\u003eExclusion Criteria: (1) Patients whose families opted to discontinue medical care due to life-threatening complications or other critical circumstances. (2) Patients with concurrent congenital gastrointestinal malformations necessitating prioritized surgical intervention.\u003c/p\u003e \u003cp\u003eA cohort of 100 patients with BA was initially screened, with 17 excluded per predefined criteria. The final study population comprised 83 children (50 male, 33 female) who underwent KPE and maintained protocol-compliant follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Postoperative liver biopsy specimens, independently evaluated by two senior hepatopathologists using the Ishak scoring system, stratified patients into three histologic severity groups: mild fibrosis (Ishak 1\u0026ndash;2, n\u0026thinsp;=\u0026thinsp;20), moderate fibrosis (Ishak 3\u0026ndash;4, n\u0026thinsp;=\u0026thinsp;39), and severe fibrosis (Ishak 5\u0026ndash;6, n\u0026thinsp;=\u0026thinsp;24), all prospectively monitored per study protocol (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Comparative analysis of predefined prognostic biomarkers across subgroups was conducted at the 6-month postoperative interval.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003e \u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cp\u003e for this study (KLLY-2021-122) was provided by the Ethical Committee of the Affiliated Hospital of Zunyi Medical University, China. All research was conducted by the Helsinki Declaration. Written informed consent was provided by the parents or legal guardians of all participants.\u003c/p\u003e \u003c/p\u003e\n\u003ch3\u003eTherapeutic Approach\u003c/h3\u003e\n\u003cp\u003eFollowing diagnostic confirmation of BA via laparoscopic exploration with intraoperative cholangiography, we proceeded with KPE. The surgical protocol included: (1) meticulous excision of the fibrous remnant at the hepatic portal plate; (2) creation of a 30\u0026ndash;35 cm Roux-en-Y jejunal limb passed retromesenterically through the transverse mesocolon; (3) hepaticojejunostomy performed with interrupted 5\u0026thinsp;\u0026minus;\u0026thinsp;0 polyglactin sutures in a single-layer, extra-mucosal anastomosis technique [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].Postoperative management comprised: Intravenous cefoperazone-sulbactam(100 mg/kg/day) for 14 days followed by oral amoxicillin-clavulanate (40 mg/kg/day) until 21 days postop; Methylprednisolone pulse therapy initiated on postoperative day 5 (4 mg/kg/day IV), tapered by 1 mg/kg every 72 hours, transitioning to oral prednisolone (2 mg/kg/day) at week 2, with complete cessation by week 16; Adjunctive therapy with ursodeoxycholic acid (20 mg/kg/day) and fat-soluble vitamin supplementation (Vitamins A 5000 IU, D 400 IU, E 15 IU, K 2 mg daily) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eFollow-up evaluation\u003c/h3\u003e\n\u003cp\u003eAll patients underwent standardized postoperative surveillance through scheduled outpatient evaluations at 1-, 3-, and 6-month intervals following KPE. Monitoring parameters included anthropometric measures (weight, age), surgical covariates (sex and operative age), serial hepatic biochemistry such as ALT, AST, GGT, total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin(IBIL), and TBA, and the primary clinical endpoint of 6-month NSL. JoC was rigorously defined as achieving serum TBIL\u0026thinsp;\u0026le;\u0026thinsp;20 \u0026micro;mol/L (1.17 mg/dL) within the study period [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eAttrition\u003c/h3\u003e\n\u003cp\u003e Attrition Definition: Participants who failed to complete the protocol-specified 6-month endpoint evaluation due to either: (1) Loss to follow-up (unable to contact despite \u0026ge;\u0026thinsp;3 documented attempts via phone/email), (2) Geographic relocation beyond catchment area, (3) Mortality (all-cause death verified by civil registry), were classified as attrition cases per CONSORT guidelines.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics 29.0. Continuous variables underwent normality assessment via the Shapiro-Wilk test (α\u0026thinsp;=\u0026thinsp;0.05). Normally distributed parameters were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, while non-normal distributions were summarized as median [Q1-Q3]. Categorical variables were reported as frequencies (percentages), with group comparisons conducted through χ\u0026sup2; or Fisher's exact tests as appropriate.All statistical tests were two-tailed, with \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant.\u003c/p\u003e \u003cp\u003eRepeated measures data were analyzed using GEE. The primary analysis utilized the Full Analysis Set (FAS) following the intention-to-treat (ITT) principle, with missing data assumed to be missing at random (MAR). To evaluate the robustness of findings, a sensitivity analysis was conducted by applying the same GEE method after multiple imputation (MI) of missing values.\u003c/p\u003e \u003cp\u003eLogistic regression analysis was employed to identify factors associated with 6-month native liver survival (NLS) and to construct a predictive model. Potential predictors were initially screened through univariate logistic regression (α\u0026thinsp;=\u0026thinsp;0.1), with three clinically established prognostic variables (ALT, TBA, and sex) forced into the model(supplementary materials \u003cb\u003eTable S5\u003c/b\u003e). The final multivariable model included 9 variables. Collinearity diagnostics indicated no substantial multicollinearity (variance inflation factor (VIF) range: 1.3\u0026ndash;4.2; tolerance values\u0026thinsp;\u0026gt;\u0026thinsp;0.3). Forward stepwise selection was used for variable selection, and parameter estimate stability was assessed via sensitivity analysis using the full-model approach.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003e1. Baseline characteristics\u003c/p\u003e\n\u003cp\u003eThe study cohort comprised 83 eligible patients stratified by Ishak fibrosis staging into Mild fibrosis (1-2, n=20), moderate fibrosis(3-4, n=39), and cirrhosis (5-6, n=24) groups, with baseline demographics demonstrating comparable distributions across groups: median ages 76 (IQR 54.8-92), 70 (53-87), and 90 days (59-118.5) respectively (Kruskal-Wallis P=0.313); female predominance decreasing from 50.0% to 29.2% (\u0026chi;\u0026sup2;=2.01, \u003cem\u003eP=\u003c/em\u003e0.363); mean weights 5.3\u0026plusmn;1.6, 4.9\u0026plusmn;1.0, and 5.4\u0026plusmn;1.1kg (ANOVA \u003cem\u003eP\u003c/em\u003e=0.363). Biochemical profiling revealed significant intergroup variance in bilirubin metabolism: TBIL escalated from 159 \u0026plusmn; 35 \u0026mu;mol/L (mild) to 195 \u0026plusmn; 53 \u0026mu;mol/L (cirrhosis) (\u003cem\u003eP\u003c/em\u003e=0.043), paralleled by DBIL increases (88.4 \u003cem\u003evs.\u003c/em\u003e 102.6 \u0026mu;mol/L, \u003cem\u003eP\u003c/em\u003e=0.024), while IBIL showed marginal significance (68.8-84.6 \u0026mu;mol/L, \u003cem\u003eP\u003c/em\u003e=0.055). Hepatic enzymes, including ALT (78-91 U/L), AST (102-117 U/L), GGT (210-255 U/L), and ALP (350-420 IU/L), exhibited nonsignificant trends (all \u003cem\u003eP\u003c/em\u003e\u0026gt;0.05), with TBA remaining comparable (35.2-38.7 \u0026mu;mol/L, \u003cem\u003eP\u003c/em\u003e=0.544).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eComparison of Baseline Characteristics Across Ishak Groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"588\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eclinical characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild fibrosis(n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate fibrosis(n=39)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecirrhosis(n=24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSocio-demographic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eAge (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e76(54.8-92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e70(53-87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e90(59-118.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eFemale sex(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e10(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e16(41.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e7(29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eWeight(kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e5.3\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e4.9\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e5.4\u0026plusmn;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHepatic Panel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e121(101.5-183.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e158.5(83.8-205.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e161(90.3-205.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.677\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e208.5(174.3-294.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e263(156.5-351.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e250(182.3-383.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.674\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eGGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e347(189-720.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e374(164-891)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e409(221-1064)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eALP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e691.7\u0026plusmn;164.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e667.4\u0026plusmn;215.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e783.2\u0026plusmn;317.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e159(141-186)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e168(141-221)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e195(159-230)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eDBIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e88.4(78.9-103.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e90.8(76.4-116.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e102.6(93-124.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eIBIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e68.8(64.0-84.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e79.6(65.2-106.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e84.6(74.0-104.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eTBA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 130px;\"\u003e\n \u003cp\u003e155.8\u0026plusmn;56.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 124px;\"\u003e\n \u003cp\u003e152.2\u0026plusmn;56.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e170.6\u0026plusmn;58.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 63px;\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e bold values represent P \u0026lt; 0.05. \u003cstrong\u003eAbbreviations\u003c/strong\u003e:TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; TBA, total bile acids; T0: Baseline; T1-T3: Postoperative follow-up at 1, 3, and 6 months.\u003c/p\u003e\n\u003cp\u003e2. Comparison of liver function indices across Ishak Groups\u003c/p\u003e\n\u003cp\u003eGEE was used to compare changes in liver function indicators among the three groups. Gamma or Gaussian distributions were selected as the probability distribution types (gamma for GGT, Gaussian for others), with exchangeable working correlation matrices. Both unadjusted and adjusted models (controlling for gender and age at surgery) were employed to analyze the main effects of group and time.\u003c/p\u003e\n\u003cp\u003eFor GGT, the unadjusted GEE model revealed a significant main effect of time on GGT levels across all groups (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), and the Mild Fibrosis Group exhibited significantly lower GGT levels than the Cirrhosis Group. Results from the adjusted model were consistent (Table 2, supplementary materials Table S1, Figure 3A).\u003c/p\u003e\n\u003cp\u003eSimilarly, TBIL, DBIL, and IBIL showed significant time effects (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and group differences between Mild Fibrosis and Cirrhosis groups (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), with lower bilirubin levels in the former. Adjusted analyses yielded concordant findings (Table 2, supplementary materials Table S1, Figure 3 B-D).\u003c/p\u003e\n\u003cp\u003eALT, AST, ALP, and TBA analyses indicated significant time effects (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05) but no group differences. Collectively, all groups showed reduced liver function indices within six months post-K, though the Cirrhosis Group had persistently higher GGT and bilirubin levels, indicating poorer improvement(supplementary materials Table S2).\u003c/p\u003e\n\u003cp\u003eSensitivity analyses using GEE revealed distinct biomarker dynamics: cholestatic markers (GGT, bilirubin) exhibited fibrosis-dependent associations, with GGT demonstrating robust correlations in cirrhosis subgroups (6.7% \u0026beta; attenuation post-adjustment) and moderate fibrosis showing a dose-response trend (P = 0.051), while TBIL/DBIL associations attenuated significantly (18.5-24.4%) after covariate adjustment. In contrast, hepatocellular enzymes (ALT, ALP) showed strong time-dependent declines (Wald \u0026chi;\u0026sup2; \u0026gt;29.87, P \u0026lt; 0.001) independent of baseline fibrosis stratification, with no intergroup differences persisting post-adjustment (all P \u0026gt; 0.3). Temporal trajectories remained stable across models, indicating uniform postoperative recovery patterns regardless of Ishak classification (detailed statistics in Supplementary Tables S3-S4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u0026nbsp;\u003c/strong\u003eResults of the GEE analysis for Comparison of liver function\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"106%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eItem\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted model\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGGT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eMild fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eModerate fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.502\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.658\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.834\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.284\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.039\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBIL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eMild fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eModerate fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e26.635\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-11.754\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e65.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e25.313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-13.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e64.570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e62.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e103.582\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e48.455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e9.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e87.792\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-65.533\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-85.288\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-45.777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-64.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-83.514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-44.773\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-62.818\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-91.722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-33.914\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-61.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-89.618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-32.464\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-93.237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-128.917\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-57.558\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-90.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-125.871\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-55.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBIL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eMild fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eModerate fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12.573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-6.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e31.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-6.859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e31.035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.211\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e33.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e12.727\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e53.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e26.925\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e7.382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e46.469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-30.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-40.618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-20.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-29.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-39.807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-19.447\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-31.947\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-47.111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-16.783\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-31.086\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-46.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-16.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-51.113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-68.203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-34.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-49.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-66.826\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-32.923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBIL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eMild fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eModerate fibrosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e13.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-6.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e34.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e13.109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-7.882\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e33.920\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e27.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e6.385\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e49.594\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e21.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.552\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e41.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.044\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 42px;\"\u003e\n \u003cp\u003eReference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-35.409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-45.871\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-24.948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-34.706\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-44.907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-24.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-30.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-45.758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-16.203\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-30.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-44.590\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-15.432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-43.326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-63.706\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-22.946\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e＜\u003c/strong\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e-41.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e-62.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-21.913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\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 \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e a indicates adjusted for gender and age at surgery, bold values represent \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05. \u003cstrong\u003eAbbreviations\u003c/strong\u003e:TBIL, total bilirubin; DBIL, direct bilirubin; IBIL, indirect bilirubin; \u0026nbsp;T0: Baseline; T1-T3: Postoperative follow-up at 1, 3, and 6 months.\u003c/p\u003e\n\u003cp\u003e3. \u0026nbsp;Comparison of 3-month JoC among the three groups\u003c/p\u003e\n\u003cp\u003eA significant difference in 3-month JoC rates was observed across the three groups (\u0026chi;\u0026sup2; = 11.363, \u003cem\u003eP\u003c/em\u003e = 0.003), with rates of 55.0% in the Mild Fibrosis group, 38.5% in the Moderate Fibrosis group, and 8.3% in the Cirrhosis group. Post hoc pairwise comparisons indicated that while the difference between the Mild and Moderate Fibrosis groups was not statistically significant (55.0% \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e38.5%; \u0026chi;\u0026sup2; = 1.467, \u003cem\u003eP\u003c/em\u003e = 0.226), the Moderate Fibrosis group exhibited a significantly higher JoC rate than the Cirrhosis group (38.5%\u003cem\u003e\u0026nbsp;vs.\u003c/em\u003e 8.3%; \u0026chi;\u0026sup2; = 6.845, \u003cem\u003eP\u003c/em\u003e = 0.009), and the Mild Fibrosis group demonstrated markedly higher JoC rates compared to the Cirrhosis group (55.0% \u003cem\u003evs.\u003c/em\u003e 8.3%; \u0026chi;\u0026sup2; = 11.413, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Comparison of 3-month JoC among the three groups\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"468\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJoC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e55.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e11.363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e38.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e8.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003ePost hoc analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eMild \u003cem\u003evs.\u0026nbsp;\u003c/em\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e55.0%\u003cem\u003evs.\u0026nbsp;\u003c/em\u003e38.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e20 \u003cem\u003evs.\u003c/em\u003e 39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e1.467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eModerate \u003cem\u003evs.\u003c/em\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e38.5% \u003cem\u003evs.\u003c/em\u003e 8.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e39 \u003cem\u003evs.\u003c/em\u003e 24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e6.845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003eMild \u003cem\u003evs.\u0026nbsp;\u003c/em\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e55.0% \u003cem\u003evs.\u003c/em\u003e 8.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e20 \u003cem\u003evs.\u003c/em\u003e 24\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e11.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 60px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e bold values represent \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e4. \u0026nbsp;Comparison of 6-month NLS Rates\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA significant difference in 6-month NLS rates was observed among the three groups (\u0026chi;\u0026sup2; = 19.714, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001). The Mild Fibrosis Group had the highest survival rate (80.0%), significantly exceeding the Cirrhosis Group (16.7%; \u0026chi;\u0026sup2; = 17.649, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001). The Moderate Fibrosis Group demonstrated an intermediate survival rate (61.5%), which was not statistically different from the Mild Fibrosis Group (\u0026chi;\u0026sup2; = 2.064, \u003cem\u003eP\u003c/em\u003e = 0.151) but markedly higher than the Cirrhosis Group (\u0026chi;\u0026sup2; = 12.115, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). Post hoc pairwise comparisons further confirmed these trends: survival rates differed significantly between the Mild and Cirrhosis Groups (80.0% \u003cem\u003evs.\u003c/em\u003e 16.7%; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and between the Moderate and Cirrhosis Groups (61.5%\u003cem\u003e\u0026nbsp;vs.\u003c/em\u003e 16.7%; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), whereas the Low- \u003cem\u003evs.\u003c/em\u003e Moderate Group comparison did not reach significance (80.0%\u003cem\u003e\u0026nbsp;vs.\u0026nbsp;\u003c/em\u003e61.5%; \u003cem\u003eP\u003c/em\u003e = 0.151). These findings indicate a significant negative correlation between prognostic risk scores and NLS, with the Cirrhosis Group associated with the poorest outcomes (Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e Comparison of 6-month NLS between the three groups\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"468\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNLS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e80.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e19.714\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e61.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003ePost hoc analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eMild \u003cem\u003evs.\u0026nbsp;\u003c/em\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e80.0% \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e61.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e20 \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eModerate \u003cem\u003evs.\u003c/em\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e61.5% \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e39 \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e12.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 148px;\"\u003e\n \u003cp\u003eMild\u003cem\u003e\u0026nbsp;vs.\u0026nbsp;\u003c/em\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 129px;\"\u003e\n \u003cp\u003e80.0% \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e16.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 72px;\"\u003e\n \u003cp\u003e20 \u003cem\u003evs.\u0026nbsp;\u003c/em\u003e24\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e17.649\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e bold values represent \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e5. \u0026nbsp;Multivariable regression analysis of 6-month postoperative survival outcomes\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp; Univariable logistic regression identified Ishak fibrosis stage as the strongest predictor ( \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), with surgical age, TBIL, and AST also significant (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05) (detailed results in Supplementary Table S5).The multivariable regression model demonstrated that Ishak score (OR=0.463, \u003cem\u003eP\u003c/em\u003e=0.002) was independently associated with poorer prognosis, whereas younger age at surgery (OR=0.965, \u003cem\u003eP\u003c/em\u003e=0.020) showed a protective effect. Other clinical parameters, including gender (OR=1.608, \u003cem\u003eP\u003c/em\u003e=0.481), ALT (OR=1.003, \u003cem\u003eP\u003c/em\u003e=0.513), AST (OR=0.994, \u003cem\u003eP\u003c/em\u003e=0.133), GGT (OR=0.999, \u003cem\u003eP\u003c/em\u003e=0.269), ALP (OR=0.999, \u003cem\u003eP\u003c/em\u003e=0.511), TBIL (OR=0.816, \u003cem\u003eP\u003c/em\u003e=0.704), and TBA(OR=1.008, \u003cem\u003eP\u003c/em\u003e=0.288), did not demonstrate statistically significant associations with survival outcomes in the adjusted analysis (all \u003cem\u003eP\u003c/em\u003e\u0026gt;0.05; Table 5).\u003c/p\u003e\n\u003cp\u003eForward stepwise regression validated Ishak fibrosis score (OR=0.450, P\u0026lt;0.001) and surgical age (P=0.003) as robust outcome predictors, retaining \u0026gt;90% of univariable effect magnitudes. The Ishak score dominated prognostic stratification, \u0026nbsp;reinforcing histopathological staging and surgical timing as primary determinants(detailed results in Supplementary Table S6).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5\u003c/strong\u003e\u0026nbsp; Multivariable analysis of factors associated with 6-month survival after surgery\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"547\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 227px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95\u003c/strong\u003e\u003cstrong\u003e％\u003c/strong\u003e\u003cstrong\u003eCI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eLower\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003eUpper\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eIshak Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.463\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.746\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e1.608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.429\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e6.032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.481\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eSurgical age (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.965\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.936\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e1.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.994\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.133\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eGGT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.998\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.269\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eALP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.511\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e0.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e2.329\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.704\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003eTBA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e1.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e0.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 114px;\"\u003e\n \u003cp\u003e1.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eNote:\u003c/strong\u003e bold values represent \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.05. \u003cstrong\u003eAbbreviations\u003c/strong\u003e:TBIL, total bilirubin; TBA, total bile acids.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBA is the leading cause of pediatric end-stage liver disease and the primary indication for LT in children, although the optimal therapeutic strategy remains controversial [18]. In most centers, the standard approach involves sequential therapy with the KPE, followed by LT if jaundice persists or irreversible cirrhosis develops [19]. In contrast, some centers advocate for primary LT as the initial intervention [20]. Developing a validated prognostic model for BA to guide individualized treatment planning before or early after the KPE could significantly alleviate the socioeconomic burden on families and healthcare systems, offering substantial clinical value [21]. Analyzing prognostic indicators across Ishak fibrosis subgroups in BA patients, this study developed a predictive model for early postoperative outcomes.\u003c/p\u003e\n\u003cp\u003eAs Ishak fibrosis scores increased, the\u0026nbsp;Cirrhosis\u0026nbsp;group demonstrated significantly lower 6-month native liver survival rates compared to\u0026nbsp;the Mild andModerate groups. Concurrently, these patients exhibited reduced 3-month CoJ, indicating impaired surgical outcomes and delayed hepatic functional recovery. Higher Ishak scores correlated with shortened native liver survival duration, persistent cholestasis, and overall poorer prognosis.\u003c/p\u003e\n\u003cp\u003eThe timing of surgical intervention, particularly in relation to patient age at the KPE, has been established as a critical prognostic determinant [22]. Although our study found no statistically significant differences in operative ages across the three subgroups, multivariable logistic regression analysis identified older age at surgery as an independent risk factor for 6-month NLS. This finding aligns with existing evidence demonstrating that early intervention improves biliary drainage efficiency, thereby mitigating cholestatic hepatocyte injury and decelerating fibrogenesis [23,24]. Our results further substantiate the clinical imperative for timely surgical management, providing quantitative evidence to guide optimal intervention timing in BA management.\u003c/p\u003e\n\u003cp\u003eBiochemical analysis revealed progressive elevation of TBIL, DBIL, and IBIL with advancing fibrosis stages. Although TBA showed no statistically significant intergroup differences, a trend toward higher values was observed in the\u0026nbsp;Cirrhosis\u0026nbsp;cohort. These findings align with previous reports [25], suggesting that advanced fibrosis disrupts biliary excretion pathways, leading to systemic bilirubin accumulation and worsening hepatic synthetic dysfunction [26].\u003c/p\u003e\n\u003cp\u003eWhile GGT levels are typically elevated in BA, normal values may occasionally occur as documented in prior reports [27]. Our data specifically revealed that postoperative GGT levels in the mild fibrosis group were significantly lower than those in the cirrhosis group. Although preoperative levels of ALT, AST, and ALP showed no statistically significant differences among the Ishak subgroups.Following KPE, all subgroups exhibited progressive improvement in liver function parameters during follow-up monitoring. However, when analyzed through the lens of Ishak histopathological staging, patients in cirrhosis subgroups demonstrated slower recovery rates for bilirubin normalization compared to mild subgroups, despite achieving absolute biochemical improvements. This suggests that while the KPE provides functional benefit across disease stages.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. As a single-center retrospective cohort with a limited sample size, potential selection bias may constrain the generalizability of findings. Furthermore, the 6-month postoperative observation window following KPE precluded longitudinal assessment of long-term outcomes. Future investigations will employ multicenter prospective designs with extended surveillance periods.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the Ishak score can serve as a risk stratification tool to guide clinicians in implementing intensified postoperative monitoring for high-risk infants (Ishak ≥5) and initiating early multidisciplinary team collaboration for liver transplantation. This facilitates the provision of individualized prognostic counseling to families, particularly emphasizing the elevated probability of requiring sequential liver transplantation in high-risk subgroups, thereby promoting shared clinical decision-making. These findings further suggest that such patients may be direct candidates for primary liver transplantation, avoiding ineffective surgical interventions. Although liver biopsy remains the pathological gold standard for assessing hepatic fibrosis staging [28] and could theoretically inform first-stage transplantation decisions for infants with high Ishak scores (≥5), its inherent limitations - including invasive nature, sampling errors, diagnostic variability, and unavoidable complications (e.g., pain, hemorrhage, infection) - preclude routine preoperative utilization [29]. Non-invasive hepatic stiffness measurement techniques, notably transient elastography (TE), acoustic radiation force impulse imaging (ARFI), and shear-wave elastography (SWE), have gained clinical adoption for BA fibrosis evaluation due to their operational simplicity, cost-effectiveness, and high patient acceptability [30-32]. However, current non-invasive modalities demonstrate limited efficacy in discriminating fibrosis stages and lack internationally standardized cutoff values [33], substantially constraining their utility in surgical decision-making.\u003c/p\u003e\n\u003cp\u003eFuture research should prioritize the integration of multimodal imaging biomarkers with machine learning algorithms. Emerging methodologies in computational histopathology analysis and dynamic fibrosis modeling [34-36] hold promise for developing virtual staging platforms, potentially revolutionizing preoperative assessment paradigms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCONFLICTS OF INTEREST\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFUNDING INFORMATION\u003c/h2\u003e \u003cp\u003e1. Science and Technology Department of Guizhou Province(Qian Kehe basic character [2021])normal 555).\u003c/p\u003e \u003cp\u003e2. Medical Research Union Found for High-quality health development of Guizhou Province(2024GZYXKYJJXM0063).\u003c/p\u003e \u003cp\u003e3. Guizhou Moutai Hospital 2022 Grant for Scientific Research and Talent Cultivation(MTyk2022-19).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHuang Lu: Writing \u0026ndash; Original Draft, ValidationHao YongXing: ResourcesTang ChengYan: Data Curation, Xia XingRong: ConceptualizationZheng ZeBing: InvestigationDu Qing: MethodologyZhou WanKang: VisualizationZhu DaiWei: SoftwareLi ZePing: SupervisionLeng Mengdan​​: Formal Analysis​Liu YuanMei: Writing \u0026ndash; Review \u0026amp; Editing​Jin Zhu: Project Administration, Funding Acquisition\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTam PKH, Wells RG, Tang CSM et al (2024) Biliary atresia. 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Liver Transpl 28(3):483\u0026ndash;492\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang J, Xu Y, Chen Z et al (2020) Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia. Cell 183(7):1867\u0026ndash;1883e26\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhan JH, Chen YJ (2021) Advantages and disadvantages of Kasai operation and liver transplantation for biliary atresia[J]. J Clin Pediatr Surg 20(2):101\u0026ndash;106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDavenport M, Superina R (2024) Primary Liver Transplant in Biliary Atresia: The Case for and Against. J Pediatr Surg 59(8):1418\u0026ndash;1426\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoeli D, Choudhury RA, Sundaram SS et al (2022) Primary \u003cem\u003evs.\u003c/em\u003e salvage liver transplantation for biliary atresia: A retrospective cohort study. 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J Hepatol 22(6):696\u0026ndash;699\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang X, Lv C, Wang B et al (2024) The utility of P-I-R classification in predicting the on-treatment histological and clinical outcomes of patients with hepatitis B and advanced liver fibrosis. Hepatology 79(2):425\u0026ndash;437\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhan J, Liu S, Li T, Li X (2024) Kasai procedure or liver transplantation: how should we choose in biliary atresia? Hepatobiliary Surg Nutr 13(6):1019\u0026ndash;1021\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang P, Zhang HY, Yang J et al (2023) Severity assessment to guide empiric antibiotic therapy for cholangitis in children after Kasai portoenterostomy: a multicenter prospective randomized control trial in China. 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Radiology 298(3):600\u0026ndash;608\u003c/span\u003e\u003c/li\u003e\u003c/ol\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":"Biliary atresia, Kasai portoenterostomy, liver fibrosis, Ishak score, Prognostic","lastPublishedDoi":"10.21203/rs.3.rs-6640801/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6640801/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study aimed to assess the native liver survival (NLS) of biliary atresia (BA) patients with varying Ishak scores post Kasai portoenterostomy (KPE).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA prospective cohort study analyzed 83 BA patients who underwent KPE at the Affiliated Hospital of Zunyi Medical University from 2019 to 2023. Based on postoperative Ishak scores, patients were categorized into the Mild Fibrosis Group (Ishak 1\u0026ndash;2, n\u0026thinsp;=\u0026thinsp;20), the Moderate Fibrosis Group (Ishak 3\u0026ndash;4, n\u0026thinsp;=\u0026thinsp;39), and the Cirrhosis Group (Ishak 5\u0026ndash;6, n\u0026thinsp;=\u0026thinsp;24). Follow-up data, including clinical information and liver function tests, were compared six months postoperatively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBaseline characteristics (age, sex, weight) showed no intergroup differences (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Median surgical ages: mild (76 days, IQR 54.8\u0026ndash;92), moderate (70 days, IQR 53\u0026ndash;87), cirrhosis (90 days, IQR 59\u0026ndash;118.5). Generalized estimating equations (GEE) revealed time-dependent declines in ALT, AST, ALP, and Total Bile Acids (TBA) across groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with cirrhosis patients exhibiting higher GGT and bilirubin levels \u003cem\u003evs.\u003c/em\u003e mild fibrosis (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05). Three-month Clearance of Jaundice (CoJ) differed significantly: 55.0% (mild) \u003cem\u003evs\u003c/em\u003e. 38.5% (moderate) \u003cem\u003evs.\u003c/em\u003e 8.3% (cirrhosis) (χ\u0026sup2;=11.363, \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.003). Six-month NLS sharply declined with fibrosis severity: 80.0% (mild) \u003cem\u003evs.\u003c/em\u003e16.7% (cirrhosis) (χ\u0026sup2;=19.714, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate logistic regression identified lower Ishak scores (OR\u0026thinsp;=\u0026thinsp;0.463, 95% CI:0.287\u0026ndash;0.746) and younger surgical age (OR\u0026thinsp;=\u0026thinsp;0.965, 95% CI: 0.936\u0026ndash;0.994) as independent predictors of survival (\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eKPE improved liver function, but the Cirrhosis Group had poorer outcomes. Hepatic fibrosis severity correlated negatively with NLS, highlighting the importance of early surgery.\u003c/p\u003e","manuscriptTitle":"Prognostic Outcomes by Ishak Fibrosis Score Grouping in Biliary Atresia after Kasai Surgery: A Prospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-21 08:34:40","doi":"10.21203/rs.3.rs-6640801/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":"50464ad6-46b8-45a9-a671-36740e8d7a80","owner":[],"postedDate":"May 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-07T06:23:26+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-21 08:34:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6640801","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6640801","identity":"rs-6640801","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}