Predictive Value of Prothrombin Time-International Normalized Ratio Albumin Ratio for QTc Prolongation in Patients with Liver Cirrhosis

Predictive Value of Prothrombin Time-International Normalized Ratio Albumin Ratio for QTc Prolongation in Patients with Liver Cirrhosis | 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 Predictive Value of Prothrombin Time-International Normalized Ratio Albumin Ratio for QTc Prolongation in Patients with Liver Cirrhosis Chen Xing, Yilin Liu, Shanshan Cai This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7608303/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The objective of this study was to investigate the correlation between prothrombin time-international normalized ratio-to-albumin ratio (PTAR) and QTc prolongation among patients with liver cirrhosis. Methods Data from participants with liver cirrhosis were included in this study. The association between PTAR and QTc prolongation was examined using univariate and multivariable logistic regression analyses. The restricted cubic spline (RCS) method was employed for curve fitting and to determine the optimal PTAR threshold for predicting QTc prolongation. Plotting a receiver-operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the based model score, a new model containing the based variables with the PTAR and QTc prolongation. Results An adverse L-shaped curve association between PTAR and QTc prolongation was observed, with an inflection point at 37.40. The odds ratio (OR) for developing QTc prolongation was 1.17 (95% CI: 1.06–1.28, p = 0.001) as PTAR ranged from 0 to 37.40. Interestingly, a threshold of 37.40 was also identified for predicting QTc prolongation. The areas under the curve (AUC) of the ROC plots were 0.646 (0.589, 0.702) for the based model and 0.709 (0.656, 0.762) for the based model + PTAR model (P = 0.002). Conclusion There is a significant inverse L-shaped correlation between PTAR and QTc prolongation in patients with liver cirrhosis. An inflection point at 37.40 was identified, at which PTAR showed predictive value for QTc prolongation. Liver Cirrhosis PTAR QTc Prolongation Logistic regression OR Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Cirrhosis stands as one of the prevailing chronic diseases worldwide, with its incidence witnessing a steady rise each year. Its complications and high mortality rate place a heavy burden on global public health. Liver cirrhosis can develop a range of complex complications, commonly including ascites, gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma (HCC), infection and even death.[ 1 , 2 ] According to WHO survey, it roughly accounts for 1,472,000 deaths worldwide in 2019.[ 3 ] Cirrhotic cardiomyopathy (CCM) is also a relatively common complication, which was initially introduced in 2005 year. Its clinical symptom of circulatory problems arises due to portal hypertension. In individuals with cirrhosis who do not have another underlying heart illness, CCM is defined as early diastolic dysfunction followed by systolic dysfunction with electrophysiological anomalies, and a prolonged QT interval is one of the key symptoms of this.[ 4 – 6 ] The QT interval captures the combined duration of ventricular depolarization and repolarization.[ 7 – 9 ] Given its sensitivity to heart rate fluctuations, a clinically adjusted QT interval (QTc) is employed. Among patients with cirrhosis, the most commonly observed electrophysiological abnormality is the prolongation of the QTc interval, exerting a notable impact on hemodynamic homeostasis in cases of decompensated cirrhosis.[ 10 ] It can predict severe arrhythmias and sudden death.[ 11 ] Numerous studies have indicated that QTc interval prolongation can serve as a predictive marker for cirrhotic mortality, particularly in cases involving digestive hemorrhage.[ 12 – 14 ] Additionally, it is also associated with a worse prognosis in cirrhosis patients.[ 11 ] Haruki and colleagues have developed an innovative liver function index known as the time-international normalized ratio to albumin ratio (PTAR),[ 15 ] which has been applied for prognosis assessment in patients with hepatic cellular carcinoma and sepsis.[ 16 ] It also can be seen as a novel maker assessing the severity of upper gastrointestinal bleeding.[ 17 ] It is noteworthy that PTAR has been established as an independent and significant surrogate prognostic factor associated with adverse outcomes in liver cirrhosis.[ 18 , 19 ] Based on the previous researches and evidences, we postulated that PTAR could play a pivotal role in QTc prolongation. The objective of this investigation was to ascertain the correlation and clinical significance of PTAR in relation to QTc prolongation among liver cirrhosis patients. Methods Study Design and Population A total of 476 cirrhosis patients from April 2017 to April 2018 at Southwest Hospital, Chongqing, China, were preliminarily included in the study. The exclusion criteria includes: patients with cirrhosis with malignancy or cardiac diseases; patients with previously reported arrhythmia or QTc abnormality; patients without complete laboratory data; patients younger than 20 years. Ultimately, 374 participants were included in the current study. The study followed the relevant guidelines and regulations, adhering to the STROBE reporting guideline. This study protocol was approved by the Medical Ethical Committee of our hospital (BIIT2023064KX). Measurement and Definition of QTc prolongation The 12-lead electrocardiogram tests provided automatic calculations for the QTc interval data. The QT interval was determined by measuring from the start of the QRS complex to the end of the T-wave, which is the first return to the isoelectric line. To account for heart rate, the corrected QT (QTc) interval was employed according to Bazett's formula.[ 20 ] Prolonged QTc was regarded as QTc > 450ms for men, QTc > 470ms for women. Variable Collection and Calculation of PTAR We retrospectively collected variables including sex, age, albumin (ALB), international normalized ratio (INR), heart rate (HR), cirrhosis etiology, hemoglobin (HB), aspartate transaminase (AST), potassium (K), sodium (Na), calcium (Ca), prothrombin time (PT), red blood cell count (RBC), white blood cell count (WBC), platelet count (PLT), total bilirubin (TBIL), alkaline phosphatase (ALP), activated partial thromboplastin time (APTT), gamma-glutamyl transferase (GGT), blood urea nitrogen (BUN), and creatinine (Crea), alanine aminotransferase (ALT), diastolic blood pressure (DBP), systolic blood pressure (SBP), Model for End-Stage Liver Disease Score (MELD Score). Venous blood specimens were collected after an overnight fast, and the serum was promptly separated and tested. These values were recorded within the first 24 hours of hospital admission. All data were retrieved from electronic medical records. Additionally, information on patients' conditions, including infections, Child-Pugh grade, ascites severity, cirrhosis etiology, and diabetes mellitus, was gathered at the time of hospital admission. The Child-Pugh score was computed using previous established specification which were categorized into three levels: class A (5–6 scores), class B (7–9 scores), and class C (10–15 scores). The current PTAR was calculated as the ratio of PT-INR to albumin (g/mL). Statistical analysis In current study, PTAR levels were categorized into tertile, with the first tertile serving as the reference group. Baseline characteristics were analyzed using one-way ANOVA or Kruskal-Wallis tests. The chi-square test was applied for categorical variables. To investigate the association between PTAR and QTc prolongation, univariate logistic regression models were employed to estimate the correlation between testing variables and QTc prolongation (QTc > 450ms for men, QTc > 470ms for women). Multivariate logistic regression, using both crude and adjusted models, was employed to assess the relationship between PTAR, considering it both as a continuous variable and as a categorical variable (tertiles), and QTc prolongation. Subgroup analysis was utilized to assess the relationship between PTAR and QTc prolongation based on the gender, etiology, age category (< 60, ≥ 60), infection, degree of ascites and DM presence. To investigate the potential nonlinear relationship between PTAR and QTc prolongation, The restricted cubic spline (RCS) method was used to plot and evaluate both linear and nonlinear relationships between PTAR and QTc prolongation, based on multivariate logistic regression adjusted for age, sex, SBP, DBP, PLT, TBIL, and Na. Subsequently, a two-piece-wise linear regression model was applied using the threshold identified based of recursive algorithm in the RCS plot. A likelihood ratio test was then performed to compare this model with the single-line linear regression model. Finally, we fitted a prediction model to our baseline data on the basis of the variables used in the based model (age, RBC, etiology and TBIL). We referred to this model as the ‘based model’. Then, we developed a new model with the addition of the baseline PTAR, referred to this model as the ‘based model + PTAR model’. We calculated the area under the curve (AUC) of the receiver-operating characteristics (ROC) curve and a 95% CI to compare the predictive power of based model and the based + PTAR model. Results Baseline Characteristics From the original study, we located 476 potential participants from April 2017 to April 2018 in the Southwest Hospital in Chongqing, China. After applying the exclusion criteria, 374 eligible patients (126 female and 248 male) were included in the analysis sample. In Figure 1, the flowchart presents the inclusion and exclusion criteria followed in the study. The baseline characteristics of all subjects according to their PTAR tertiles are presented in Table 1. Patients who had higher PTAR often tended to had a higher HR, BUN, PT, APTT, INR, ALT, AST, ALP, TBIL level; had a more severity of liver function (higher MELD-Scores) and had a longer QT interval. Patients with lower PTAR frequently prone to have higher HB, RBC, PLT, ALB, potassium, calcium level. The lower the level of PTAR, the less likely to develop ascite. Otherwise, Child-Pugh scores increased with higher PTAR levels (all P < 0.05). Association between PTAR and QTc prolongation We performed a univariate logistic regression to determine risk factors associated with QTc prolongation in the entire study population. The analysis revealed that sex, etiology, TBIL, and PTAR were strongly correlated with QTc prolongation, each with a p-value of less than 0.05 (Table S1). In both crude and adjusted multivariate logistic regressions (Table 2), significant associations (p < 0.001) between PTAR and QTc prolongation were observed, regardless of continuous or categorical format. In the crude model, every one-unit rise in PTAR showed a 5% association with QTc prolongation (Odds ratio (OR)=1.05, 95% CI: 1.03~1.07, p< 0.001). Compared to patients with lower PTAR levels (Q1: 21.56-32.67), the OR for QTc prolongation in model 3 (adjusted for age, sex, SBP, DBP, PLT, TBIL, and Na) were 3.12 (95% CI: 1.74-5.61, p < 0.001) for Q2 (32.71-43.07) and 4.05 (95% CI: 2.19-7.52, p < 0.001) for Q3 (43.14-93.61) (Table 2). The RCS curve suggested that the relationship between PTAR and QTc prolongation presented an inverse L-shaped curve (Figure 2), a non-linear (p =0.014) relationship was observed between PTAR and QTc prolongation. Using a recursive algorithm, a PTAR threshold of 37.40 was identified. As the PTAR level increased from 0 to 37.40, the OR for QTc prolongation gradually rose, eventually plateauing beyond this threshold. A two-piecewise linear regression model revealed that for PTAR levels below 37.40, the OR was 1.17 (95% CI: 1.06-1.28, p = 0.001). For PTAR levels above 37.40, the p-value was 0.422, indicating no significant linear relationship between PTAR and QTc prolongation when PTAR was larger than 37.40 (Table 3). Subgroup Analyses To investigate the relationship between PTAR levels and QTc prolongation, stratifying subgroup analyses was conducted according to age (< 60, ≥ 60), sex, etiology, infection, diabetes, degree of ascites and Child-Pugh classification (Figure 3). Effect size of QTc prolongation on the level of PTAR in subgroups remained consistent. There were no significant interactions found in the subgroups. ROC curves for the incidence of QTc prolongation The AUC of the ROC curves (95% CI) were 0.646 (0.589, 0.702) for the based model, 0.709 (0.656, 0.762) for the based model + PTAR model (P = 0.002). Both markers were significant predictors for QTc prolongation (Figure 4). Discussion In this cross-sectional study of cirrhotic patients, an inverse L-shaped association between PTAR and QTc prolongation was observed, with an inflection point close to 37.40. Specifically, the risk of prolonged QTc with increasing PTAR in those with a PTAR level of < 37.40, whereas the risk of prolonged QTc no longer increased with rising PTAR in those with a PTAR level of ≥ 37.40. Both stratified and multivariate logistic regression analysis presented the correlation between PTAR and QTc prolongation remained robust, even after accounting for other confounding factors. We fitted predictive models for QTc prolongation based on previously published literature using relevant predictive factors, with and without the addition of the PTAR. As shown, the predictive accuracy was improved by including the PTAR. A large amount of research has demonstrated that QTc prolongation is associated with severity of the liver function as well as a poor prognosis, including severe cardiac arrhythmia, various complications and even some sudden death in cirrhotic patients.[ 11 , 15 , 21 ] According to previous studies, there are some biochemical markers and syndromes that might reveal how severe liver cirrhosis is, such as ALB, BUN, PT, APTT, INR, ALT, AST, ALP, TBIL, calcium, ascite, portal hypertension, Child-Pugh, MELD-score and so on.[ 22 , 23 ] Among these researches, we noted the malnutrition and chronic diseases are likely to be linked to low albumin levels, and mortality will inevitably be associated with them as well.[ 24 , 25 ] Patients with UGIB can also utilize serum albumin for risk stratification.[ 26 ] It is possible for albumin distribution to be altered by a history of critical diseases.[ 27 , 28 ] In patients with severe medical conditions, the PT-INR serves as a valuable predictor of mortality since it tends to happen in patients with coagulopathy.[ 29 , 30 ] Moreover, both albumin and INR abnormalities have been widely reported to be closely related to higher risk of mortality in critical patients with sepsis, in particular in intensive care.[ 31 , 32 ] Haruki et al developed a novel objective accessible parameter PTAR, evaluating liver functional and pointed out that this excellent indicator had excellent performance in reflecting outcome of liver condition after liver resection in patients with liver cancer.[ 15 ] Additionally, Ming et al.'s subsequent study pointed out the potential of PTAR as a valuable tool for early detection of critical conditions and the assessment of adverse prognoses in cirrhotic patients.[ 33 ] With involvement of just two common laboratory parameters, PTAR is characterized by its simplicity, easy accessibility, and objectivity. The PTAR level may exhibit greater stability compared to single albumin and INR levels due to its ability to maintain a balance between the two, less influenced by diverse physiological and pathological conditions. Apart from the above advantages, it is more simpler to compute and utilize in clinical settings than other models, such as AIBL, SIRS, Child-Pugh, and MELD, and it performed better at accurately predicting prognosis.[ 16 ] Even in some extreme conditions, as Faigel DO et al had illustrated the episodes of ‘Torsade de pointes’ in cirrhotic patients when QTc ≥ 500ms, however, these events commonly occur concomitantly with the usage of medications known to induce QT interval prolongation.[ 34 ] Therefore, PTAR might be a reliable biomarker for predicting QTc prolongation in liver cirrhosis patients. Clinicians may employ this noninvasive biomarker to early identification the occurrence of QTc prolongation, screening these patients for cardiovascular complications, preventing the development of QTc prolongation through early intervention and adjusting the treatment plan promptly. In addition, the early identification of QTc prolongation has significant guiding value for drug selection. For liver cirrhosis patients with prolonged QTc intervals, special caution is needed when using drugs. Therefore, drugs that may further prolong the QTc interval, such as certain antiarrhythmic drugs, antipsychotic drugs, macrolide antibiotics, and quinolone antibiotics, should be avoided. Although the potential mechanism of the correlation between PTAR and QTc prolongation is remained to be explored, our findings seem biologically plausible based on the available evidence. First, albumin is regarded to be related to a variety of inflammatory responses and negatively correlates with the degree of systemic inflammatory response. As a series of findings shown that inflammation can often found in progressive cirrhosis and closely related to poor prognosis, involving ascites or edema, hepatic encephalopathy, gastrointestinal bleeding, leading to mortality finally.[ 35 , 36 ] Moreover, the pivotal role of systemic inflammation in the progression of HBV-associated cirrhosis is widely recognized, Ming et al revealed lower serum albumin might reflect the status of inflammatory in decompensated cirrhosis patients and correlated with decreased liver functional reserve, representing liver functional severe damage.[ 33 ] Meanwhile, the INR not only serves as a reflection of the liver's synthetic function, but also the impairment of liver function because of the relationship between deterioration of the coagulation system and aggravation of the liver function.[ 37 ] Professor Ming. then pointed out that the combination of elevated INR and decreased albumin contributed to high PTAR which may specifically denote the positively association with severity of liver status and the degree of inflammation. Furthermore, aggravating liver function was tend to be accompanied by distinctly systemic hemodynamic instability,[ 10 ] especially in end-stage liver disease. This circulatory modulation appears to drive cardiac dysfunction, causing adrenergic hyperactivity, activating the sympathetic nervous system,[ 38 ] and causing QTc prolongation to develop.[ 21 ] Therefore, based on previous pathological theories and our present results, we guess the PTAR and QTc prolongation may have potential relationship. Second, It has been assumed that abnormal ventricular repolarization is supported by exposure of some cardiotoxins due to the liver dysfunction and reduction of inactivation of toxic substances, such as endotoxin, nitricoxide and various cytokines. Sina et al found out nitricoxide (NO) and endogenous opioids play an significant part in the mechanism of the prolonged QTc in an animal experiment.[ 39 ] Our study has several limitations. Firstly, given the cross-sectional study design, it is important to note that while a correlation between PTAR and QTc prolongation was established, causal relationships cannot be inferred, requiring a prospective study to further investigation. Additionally, we extracted the size of sample only from single tertiary hospital. Therefore, taking a large sample size and multi-centric study into account is urgently ed in the future. There's no denying that, the potential bias in patient selection could not be avoided. Finally, recalls and self-reporting bias may happened since some patients had complicated medical conditions and may have taken more medications. As a result, the pertinent information on recent drug usage were tend to be insufficient and then may be likely to affect the occurrence of QTc prolongation. Conclusion In summary, this study presents an adverse L-shaped connection between PTAR and prolonged QTc among cirrhotic patients. An inflection point of 37.40 of PTAR was determined using recursive algorithm, which segmented PTAR into category which showed a good prediction precision. This index is easily measurable and applicable in clinical practice without requiring specific techniques or the use of multiple variables to calculate it. These findings highlight the usefulness of this simple index to early identify individuals with cirrhosis at high risk of developing a OTc prolongation event. Maybe in the future, well-designed, multicenter and Prospective study should be proposed to further investigate the role of PTAR in cirrhosis patients. Declarations Ethics approval and consent to participate Ethical approval was obtained from the Medical Ethics Committee of the First Affiliated Hospital of Army Medical University (approval number BIIT2023064KX), and the ethics committee waived the requirement for informed consent due to the retrospective nature of the study and the use of de-identified clinical data. Our study adhered to the Declaration of Helsinki in this respect. Consent for publication Not applicable. Competing interests No conflicts of interest exists among the authors. Authors’ Contributions - CX and SS C conceived the idea - CX and YLL collected the data, conducted the analysis, and wrote the main manuscript text. Data Availability The datasets generated and analysed during the current study are available in the GitHub repository at https://github.com/xingchen19931017/liver-cirrhosis-originaldata. Funding Not available. Acknowledgement Not available. References Huang DQ, Terrault NA, Tacke F, et al. Global epidemiology of cirrhosis - aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol 2023. Liu Y-B, Chen M-K. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022;28(41):5910-5930. 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Am J Gastroenterol 1995;90(5):822-824. Cazzaniga M, Dionigi E, Gobbo G, et al. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol 2022;1600-0641:147-154. Bajaj JS, OʼLeary JG, Tandon P, et al. Nosocomial Infections Are Frequent and Negatively Impact Outcomes in Hospitalized Patients With Cirrhosis. Hepatology 2022;1572-0241:1020-1029. Vanerio G, Jos Association cdtojoNS. International Normalized Ratio Variability: A Measure of Anticoagulation Quality or a Powerful Mortality Predictor. J Stroke 2015;24(10):2223-2228. Izzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, et al. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology (Baltimore, Md) 2020;71(1):334-345. Tavakoli S, Hajrasouliha A, Jabehdar-Maralani P, Ebrahimi F, Solhpour A, Sadeghipour H, et al. Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: the roles of nitric oxide and endogenous opioid peptides. Eur J Pharmacol 2007;46(3):432-439. Tables Table 1. Baseline characteristics according to PTAR in liver cirrhosis patients Variables Total T1 T2 T3 P-Value (n=374) (n=125) (n=124) (n=125) Sex, n (%) 0.493 Male 248 (66.3) 80 (64) 80 (64.5) 88 (70.4) Female 126 (33.7) 45 (36) 44 (35.5) 37 (29.6) Age (years) 56.7 ± 11.6 56.5 ± 11.1 56.7 ± 12.5 57.0 ± 11.4 0.936 SBP (mmHg) 116.4 ± 15.6 117.9 ± 15.4 117.6 ± 16.4 113.6 ± 14.6 0.05 DBP (mmHg) 70.1 ± 11.2 71.5 ± 10.9 69.8 ± 11.5 68.8 ± 11.1 0.151 HR (beats/min) 81.5 ± 13.2 78.4 ± 11.1 83.0 ± 14.0 83.1 ± 13.8 0.005 Etiology, n (%) 0.124 Virus 235 (62.8) 82 (65.6) 79 (63.7) 74 (59.2) Alcoholic+Virus 72 (19.3) 16 (12.8) 26 (21) 30 (24) Autoimmune 25 ( 6.7) 7 (5.6) 7 (5.6) 11 (8.8) Others 42 (11.2) 20 (16) 12 (9.7) 10 (8) Hb (g/L) 100.6 ± 26.3 113.6 ± 25.0 93.4 ± 24.5 94.8 ± 24.8 < 0.001 ALB (g/L) 32.6 ± 6.5 39.2 ± 4.0 32.3 ± 3.6 26.4 ± 3.7 < 0.001 AST (U/L) 62.2 ± 78.1 45.4 ± 61.7 57.2 ± 66.7 83.8 ± 96.8 < 0.001 K (mmol/L) 3.8 ± 0.5 3.9 ± 0.4 3.8 ± 0.4 3.7 ± 0.5 0.004 Na (mmol/L) 138.5 ± 4.5 139.9 ± 3.1 138.3 ± 4.5 137.4 ± 5.3 < 0.001 Ca (mmol/L) 2.1 ± 0.2 2.3 ± 0.1 2.1 ± 0.1 2.0 ± 0.1 < 0.001 PT (s) 14.6 ± 2.6 12.8 ± 1.0 14.1 ± 1.4 16.9 ± 2.8 < 0.001 APTT (s) 39.0 ± 9.8 32.2 ± 4.4 37.8 ± 6.5 47.1 ± 10.6 < 0.001 INR 1.2 ± 0.2 1.1 ± 0.1 1.2 ± 0.1 1.4 ± 0.2 < 0.001 Degree of ascite, n (%) < 0.001 NO 229 (61.2) 104 (83.2) 74 (59.7) 51 (40.8) Mild 28 ( 7.5) 4 (3.2) 10 (8.1) 14 (11.2) Moderate−severe 117 (31.3) 17 (13.6) 40 (32.3) 60 (48) Classification of child, n (%) < 0.001 Class A 163 (43.6) 101 (80.8) 54 (43.5) 8 (6.4) Class B-C 211 (56.4) 24 (19.2) 70 (56.5) 117 (93.6) MELD Scores 10.4 ± 4.7 8.1 ± 3.3 9.5 ± 4.0 13.5 ± 4.9 < 0.001 QT interval 402.9 ± 41.9 402.1 ± 33.5 401.0 ± 45.7 405.7 ± 45.5 0.647 DM, n (%) 0.872 No 319 (85.3) 107 (85.6) 107 (86.3) 105 (84) Yes 55 (14.7) 18 (14.4) 17 (13.7) 20 (16) Infection, n (%) 0.872 No 319 (85.3) 107 (85.6) 107 (86.3) 105 (84) Yes 55 (14.7) 18 (14.4) 17 (13.7) 20 (16) RBC (10 12 /L) 3.4 (3.0, 4.0) 3.9 (3.5, 4.4) 3.3 (2.8, 3.9) 3.1 (2.7, 3.5) < 0.001 WBC (10 9 /L) 3.2 (2.3, 4.9) 3.3 (2.3, 4.5) 3.0 (2.0, 4.4) 3.5 (2.5, 5.6) 0.01 PLT (10 9 /L) 64.0 (40.0, 106.5) 76.0 (51.0, 123.0) 62.5 (40.8, 105.0) 56.0 (36.0, 87.0) 0.002 TBIL (umol/L) 27.4 (17.8, 44.3) 20.2 (15.3, 28.9) 25.6 (17.3, 36.5) 44.3 (28.8, 72.7) < 0.001 ALT (U/L) 26.4 (18.9, 42.8) 24.2 (18.5, 34.8) 24.2 (15.5, 40.5) 31.8 (21.6, 52.6) < 0.001 ALP (U/L) 110.5 (81.0, 152.8) 100.7 (79.0, 146.3) 107.5 (81.8, 149.1) 126.0 (86.0, 170.0) 0.012 GGT (U/L) 45.0 (26.0, 92.0) 45.0 (29.0, 82.0) 45.5 (24.8, 98.2) 44.0 (24.0, 92.0) 0.811 BUN (mmol/L) 5.3 (4.2, 7.4) 5.3 (4.4, 6.5) 5.0 (4.0, 7.0) 6.0 (4.3, 8.5) 0.009 Cr (umol/L) 65.2 (56.6, 79.0) 65.5 (59.0, 81.2) 64.2 (55.8, 78.2) 65.4 (56.1, 77.3) 0.434 Data are shown as mean±SD, median (IQR), or n (%). Abbreviations: T, Tertiles; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; WBC, White blood cell; RBC, Red blood cell; PLT, Platelet; TBIL, Total Bilirubin; DBIL, Direct Bilirubin;IBIL, Indirect Bilirubin; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase; ALP, Alkaline Phosphatase; GGT, gamma-Glutamyl Transpeptidase; BUN, Blood urea nitrogen; MELD, Model for end-stage liver disease. Table 2. Multivariate regression analysis of the association between PTAR and QTc prolongation QTcprolongation Variable CrudeModel ModelI ModelII ModelIII OR(95%CI) P-value OR(95%CI) P-value OR(95%CI) P-value OR(95%CI) P-value PTAR 1.05 (1.03~1.07) <0.001 1.05 (1.03~1.07) <0.001 1.05 (1.03~1.07) <0.001 1.04 (1.02~1.07) <0.001 PTAR,Tertiles T1 (21.56~32.67) Ref. Ref. Ref. Ref. T2 (32.71~43.07) 3.35 (1.92~5.84) <0.001 3.53 (1.99~6.25) <0.001 3.47 (1.95~6.18) <0.001 3.12 (1.74~5.61) <0.001 T3 (43.14~93.61) 5.01 (2.86~8.75) <0.001 5.02 (2.84~8.88) <0.001 5.24 (2.94~9.36) <0.001 4.05 (2.19~7.52) <0.001 P for trend <0.001 <0.001 <0.001 <0.001 Abbreviations: Q, Tertiles; OR, odds ratio; CI, confidence interval; PTAR, INR/ALB; Ref: reference. Model I was adjusted for age+sex; Model II was adjusted for age+sex+SBP+DBP; Model III was adjusted for age+sex+SBP+DBP+PLT+TBIL+Na; Only 99% of the data is displayed. Table 3. Threshold effect analysis of the relationship of PTAR with QTc prolongation PTAR AdjustedModel OR(95%CI) p-value ＜37.40 1.17 (1.06~1.28) 0.001 ≥ 37.40 1.01 (0.98~1.05) 0.422 Log-likelihood ratio test 0.003 Abbreviations: OR, odds ratio; CI, confidence interval; PTAR, INR/ALB. Adjusted for age+sex+SBP+DBP+PLT+TBIL+Na. Only 99% of the data is displayed. Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":88217,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/7835e3a945afb76056d83071.png"},{"id":96242559,"identity":"11c3d2f9-5c74-45f5-ae60-84c31379cea8","added_by":"auto","created_at":"2025-11-19 07:13:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":72436,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between PTAR and QTc prolongation.Note: the figure displays the estimated risk of QTc prolongation as a solid line, accompanied by a shaded region representing the point-wise 95% confidence interval, which has been adjusted for age+sex+SBP+DBP+PLT+TBIL+Na.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/62908ff1175b5555ae1add88.png"},{"id":96242829,"identity":"6bccd4b9-7be5-441e-ad50-863031057608","added_by":"auto","created_at":"2025-11-19 07:14:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":129632,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analyses of the association between PTAR and QTc prolongation. Adjusted for age+sex+SBP+DBP+PLT+TBIL+Na.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/3366ba8b4abf4340e490f19b.png"},{"id":96243832,"identity":"4bd1a7df-115f-4a9c-83af-1ad934b795a9","added_by":"auto","created_at":"2025-11-19 07:17:07","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":63590,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver-operating characteristic curves (ROC) based model (Model 1) and the based + PTAR model (Model 2) . The estimates of the area under the ROC curves and their 95% confidence intervals (CI) compare the model 1 and the model 2 and the risk of QTc prolongation.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/c0a23648d935f78b8d124c9b.png"},{"id":97135982,"identity":"adcc2737-c163-41fc-b1ca-8baff3595e6a","added_by":"auto","created_at":"2025-12-01 09:54:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1254595,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/85c63794-a6a6-4bac-b3f9-0eb9728ac60f.pdf"},{"id":96242344,"identity":"80bfe81c-4326-45cc-b2a1-64c6e2ed9823","added_by":"auto","created_at":"2025-11-19 07:12:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16906,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/2743bc9adc7edae6ea932a91.docx"},{"id":95905393,"identity":"e8136bc1-a4f7-431d-ad4c-47ab263df610","added_by":"auto","created_at":"2025-11-14 09:22:03","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":18388,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/64ca3754daca809cc2163e48.docx"},{"id":95905424,"identity":"b3b58fd4-e450-4720-8f84-dba83ffa4501","added_by":"auto","created_at":"2025-11-14 09:22:05","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":89045026,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.tif","url":"https://assets-eu.researchsquare.com/files/rs-7608303/v1/3f78ddbc6941dea25ae4345f.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Predictive Value of Prothrombin Time-International Normalized Ratio Albumin Ratio for QTc Prolongation in Patients with Liver Cirrhosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCirrhosis stands as one of the prevailing chronic diseases worldwide, with its incidence witnessing a steady rise each year. Its complications and high mortality rate place a heavy burden on global public health. Liver cirrhosis can develop a range of complex complications, commonly including ascites, gastrointestinal bleeding, hepatic encephalopathy, hepatocellular carcinoma (HCC), infection and even death.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] According to WHO survey, it roughly accounts for 1,472,000 deaths worldwide in 2019.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Cirrhotic cardiomyopathy (CCM) is also a relatively common complication, which was initially introduced in 2005 year. Its clinical symptom of circulatory problems arises due to portal hypertension. In individuals with cirrhosis who do not have another underlying heart illness, CCM is defined as early diastolic dysfunction followed by systolic dysfunction with electrophysiological anomalies, and a prolonged QT interval is one of the key symptoms of this.[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe QT interval captures the combined duration of ventricular depolarization and repolarization.[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Given its sensitivity to heart rate fluctuations, a clinically adjusted QT interval (QTc) is employed. Among patients with cirrhosis, the most commonly observed electrophysiological abnormality is the prolongation of the QTc interval, exerting a notable impact on hemodynamic homeostasis in cases of decompensated cirrhosis.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] It can predict severe arrhythmias and sudden death.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Numerous studies have indicated that QTc interval prolongation can serve as a predictive marker for cirrhotic mortality, particularly in cases involving digestive hemorrhage.[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Additionally, it is also associated with a worse prognosis in cirrhosis patients.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eHaruki and colleagues have developed an innovative liver function index known as the time-international normalized ratio to albumin ratio (PTAR),[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] which has been applied for prognosis assessment in patients with hepatic cellular carcinoma and sepsis.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] It also can be seen as a novel maker assessing the severity of upper gastrointestinal bleeding.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] It is noteworthy that PTAR has been established as an independent and significant surrogate prognostic factor associated with adverse outcomes in liver cirrhosis.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Based on the previous researches and evidences, we postulated that PTAR could play a pivotal role in QTc prolongation. The objective of this investigation was to ascertain the correlation and clinical significance of PTAR in relation to QTc prolongation among liver cirrhosis patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and Population\u003c/h2\u003e\u003cp\u003eA total of 476 cirrhosis patients from April 2017 to April 2018 at Southwest Hospital, Chongqing, China, were preliminarily included in the study. The exclusion criteria includes: patients with cirrhosis with malignancy or cardiac diseases; patients with previously reported arrhythmia or QTc abnormality; patients without complete laboratory data; patients younger than 20 years. Ultimately, 374 participants were included in the current study.\u003c/p\u003e\u003cp\u003e The study followed the relevant guidelines and regulations, adhering to the STROBE reporting guideline. This study protocol was approved by the Medical Ethical Committee of our hospital (BIIT2023064KX).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMeasurement and Definition of QTc prolongation\u003c/h3\u003e\n\u003cp\u003eThe 12-lead electrocardiogram tests provided automatic calculations for the QTc interval data. The QT interval was determined by measuring from the start of the QRS complex to the end of the T-wave, which is the first return to the isoelectric line. To account for heart rate, the corrected QT (QTc) interval was employed according to Bazett's formula.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Prolonged QTc was regarded as QTc\u0026thinsp;\u0026gt;\u0026thinsp;450ms for men, QTc\u0026thinsp;\u0026gt;\u0026thinsp;470ms for women.\u003c/p\u003e\n\u003ch3\u003eVariable Collection and Calculation of PTAR\u003c/h3\u003e\n\u003cp\u003eWe retrospectively collected variables including sex, age, albumin (ALB), international normalized ratio (INR), heart rate (HR), cirrhosis etiology, hemoglobin (HB), aspartate transaminase (AST), potassium (K), sodium (Na), calcium (Ca), prothrombin time (PT), red blood cell count (RBC), white blood cell count (WBC), platelet count (PLT), total bilirubin (TBIL), alkaline phosphatase (ALP), activated partial thromboplastin time (APTT), gamma-glutamyl transferase (GGT), blood urea nitrogen (BUN), and creatinine (Crea), alanine aminotransferase (ALT), diastolic blood pressure (DBP), systolic blood pressure (SBP), Model for End-Stage Liver Disease Score (MELD Score). Venous blood specimens were collected after an overnight fast, and the serum was promptly separated and tested. These values were recorded within the first 24 hours of hospital admission. All data were retrieved from electronic medical records. Additionally, information on patients' conditions, including infections, Child-Pugh grade, ascites severity, cirrhosis etiology, and diabetes mellitus, was gathered at the time of hospital admission. The Child-Pugh score was computed using previous established specification which were categorized into three levels: class A (5\u0026ndash;6 scores), class B (7\u0026ndash;9 scores), and class C (10\u0026ndash;15 scores). The current PTAR was calculated as the ratio of PT-INR to albumin (g/mL).\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eIn current study, PTAR levels were categorized into tertile, with the first tertile serving as the reference group. Baseline characteristics were analyzed using one-way ANOVA or Kruskal-Wallis tests. The chi-square test was applied for categorical variables. To investigate the association between PTAR and QTc prolongation, univariate logistic regression models were employed to estimate the correlation between testing variables and QTc prolongation (QTc\u0026thinsp;\u0026gt;\u0026thinsp;450ms for men, QTc\u0026thinsp;\u0026gt;\u0026thinsp;470ms for women). Multivariate logistic regression, using both crude and adjusted models, was employed to assess the relationship between PTAR, considering it both as a continuous variable and as a categorical variable (tertiles), and QTc prolongation. Subgroup analysis was utilized to assess the relationship between PTAR and QTc prolongation based on the gender, etiology, age category (\u0026lt;\u0026thinsp;60, \u0026ge; 60), infection, degree of ascites and DM presence. To investigate the potential nonlinear relationship between PTAR and QTc prolongation, The restricted cubic spline (RCS) method was used to plot and evaluate both linear and nonlinear relationships between PTAR and QTc prolongation, based on multivariate logistic regression adjusted for age, sex, SBP, DBP, PLT, TBIL, and Na. Subsequently, a two-piece-wise linear regression model was applied using the threshold identified based of recursive algorithm in the RCS plot. A likelihood ratio test was then performed to compare this model with the single-line linear regression model.\u003c/p\u003e\u003cp\u003eFinally, we fitted a prediction model to our baseline data on the basis of the variables used in the based model (age, RBC, etiology and TBIL). We referred to this model as the \u0026lsquo;based model\u0026rsquo;. Then, we developed a new model with the addition of the baseline PTAR, referred to this model as the \u0026lsquo;based model\u0026thinsp;+\u0026thinsp;PTAR model\u0026rsquo;. We calculated the area under the curve (AUC) of the receiver-operating characteristics (ROC) curve and a 95% CI to compare the predictive power of based model and the based\u0026thinsp;+\u0026thinsp;PTAR model.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom the original study, we located 476 potential participants from April 2017 to April 2018 in the Southwest Hospital in Chongqing, China. After applying the exclusion criteria, 374 eligible patients (126 female and 248 male) were included in the analysis sample. In Figure 1, the flowchart presents the inclusion and exclusion criteria followed in the study. The baseline characteristics of all subjects according to their PTAR tertiles are presented in Table 1. Patients who had higher PTAR often tended to had a higher HR, BUN, PT, APTT, INR, ALT, AST, ALP, TBIL level; had a more severity of liver function (higher MELD-Scores) and had a longer QT interval. Patients with lower PTAR frequently prone to have higher HB, RBC, PLT, ALB, potassium, calcium level. The lower the level of PTAR, the less likely to develop ascite. Otherwise, Child-Pugh scores increased with higher PTAR levels (all P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssociation between PTAR and QTc prolongation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe performed a univariate logistic regression to determine risk factors associated with QTc prolongation in the entire study population. The analysis revealed that sex, etiology, TBIL, and PTAR were strongly correlated with QTc prolongation, each with a p-value of less than 0.05 (Table S1). In both crude and adjusted multivariate logistic regressions (Table 2), significant associations (p \u0026lt; 0.001) between PTAR and QTc prolongation were observed, regardless of continuous or categorical format. In the crude model, every one-unit rise in PTAR showed a 5% association with QTc prolongation (Odds ratio (OR)=1.05, 95% CI: 1.03~1.07, p\u0026lt; 0.001). Compared to patients with lower PTAR levels (Q1: 21.56-32.67), the OR for QTc prolongation in model 3 (adjusted for age, sex, SBP, DBP, PLT, TBIL, and Na) were 3.12 (95% CI: 1.74-5.61, p \u0026lt; 0.001) for Q2 (32.71-43.07) and 4.05 (95% CI: 2.19-7.52, p \u0026lt; 0.001) for Q3 (43.14-93.61) (Table 2). The RCS curve suggested that the relationship between PTAR and QTc prolongation presented an inverse L-shaped curve (Figure 2), a non-linear (p =0.014) relationship was observed between PTAR and QTc prolongation. Using a recursive algorithm, a PTAR threshold of 37.40 was identified. As the PTAR level increased from 0 to 37.40, the OR for QTc prolongation gradually rose, eventually plateauing beyond this threshold. A two-piecewise linear regression model revealed that for PTAR levels below 37.40, the OR was 1.17 (95% CI: 1.06-1.28, p = 0.001). For PTAR levels above 37.40, the p-value was 0.422, indicating no significant linear relationship between PTAR and QTc prolongation when PTAR was larger than 37.40 (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup Analyses\u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo investigate the relationship between PTAR levels and QTc prolongation, stratifying subgroup analyses was conducted according to age (\u0026lt; 60, ≥ 60), sex, etiology, infection, diabetes, degree of ascites and Child-Pugh classification (Figure 3). Effect size of QTc prolongation on the level of PTAR in subgroups remained consistent. There were no significant interactions found in the subgroups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC curves for the incidence of QTc prolongation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe AUC of the ROC curves (95% CI) were 0.646 (0.589, 0.702) for the based model, 0.709 (0.656, 0.762) for the based model + PTAR model (P = 0.002). Both markers were significant predictors for QTc prolongation (Figure 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this cross-sectional study of cirrhotic patients, an inverse L-shaped association between PTAR and QTc prolongation was observed, with an inflection point close to 37.40. Specifically, the risk of prolonged QTc with increasing PTAR in those with a PTAR level of \u0026lt;\u0026thinsp;37.40, whereas the risk of prolonged QTc no longer increased with rising PTAR in those with a PTAR level of \u0026ge;\u0026thinsp;37.40. Both stratified and multivariate logistic regression analysis presented the correlation between PTAR and QTc prolongation remained robust, even after accounting for other confounding factors. We fitted predictive models for QTc prolongation based on previously published literature using relevant predictive factors, with and without the addition of the PTAR. As shown, the predictive accuracy was improved by including the PTAR.\u003c/p\u003e\u003cp\u003eA large amount of research has demonstrated that QTc prolongation is associated with severity of the liver function as well as a poor prognosis, including severe cardiac arrhythmia, various complications and even some sudden death in cirrhotic patients.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] According to previous studies, there are some biochemical markers and syndromes that might reveal how severe liver cirrhosis is, such as ALB, BUN, PT, APTT, INR, ALT, AST, ALP, TBIL, calcium, ascite, portal hypertension, Child-Pugh, MELD-score and so on.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Among these researches, we noted the malnutrition and chronic diseases are likely to be linked to low albumin levels, and mortality will inevitably be associated with them as well.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Patients with UGIB can also utilize serum albumin for risk stratification.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] It is possible for albumin distribution to be altered by a history of critical diseases.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] In patients with severe medical conditions, the PT-INR serves as a valuable predictor of mortality since it tends to happen in patients with coagulopathy.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] Moreover, both albumin and INR abnormalities have been widely reported to be closely related to higher risk of mortality in critical patients with sepsis, in particular in intensive care.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] Haruki et al developed a novel objective accessible parameter PTAR, evaluating liver functional and pointed out that this excellent indicator had excellent performance in reflecting outcome of liver condition after liver resection in patients with liver cancer.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Additionally, Ming et al.'s subsequent study pointed out the potential of PTAR as a valuable tool for early detection of critical conditions and the assessment of adverse prognoses in cirrhotic patients.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] With involvement of just two common laboratory parameters, PTAR is characterized by its simplicity, easy accessibility, and objectivity. The PTAR level may exhibit greater stability compared to single albumin and INR levels due to its ability to maintain a balance between the two, less influenced by diverse physiological and pathological conditions. Apart from the above advantages, it is more simpler to compute and utilize in clinical settings than other models, such as AIBL, SIRS, Child-Pugh, and MELD, and it performed better at accurately predicting prognosis.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Even in some extreme conditions, as Faigel DO et al had illustrated the episodes of \u0026lsquo;Torsade de pointes\u0026rsquo; in cirrhotic patients when QTc\u0026thinsp;\u0026ge;\u0026thinsp;500ms, however, these events commonly occur concomitantly with the usage of medications known to induce QT interval prolongation.[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Therefore, PTAR might be a reliable biomarker for predicting QTc prolongation in liver cirrhosis patients. Clinicians may employ this noninvasive biomarker to early identification the occurrence of QTc prolongation, screening these patients for cardiovascular complications, preventing the development of QTc prolongation through early intervention and adjusting the treatment plan promptly. In addition, the early identification of QTc prolongation has significant guiding value for drug selection. For liver cirrhosis patients with prolonged QTc intervals, special caution is needed when using drugs. Therefore, drugs that may further prolong the QTc interval, such as certain antiarrhythmic drugs, antipsychotic drugs, macrolide antibiotics, and quinolone antibiotics, should be avoided.\u003c/p\u003e\u003cp\u003eAlthough the potential mechanism of the correlation between PTAR and QTc prolongation is remained to be explored, our findings seem biologically plausible based on the available evidence. First, albumin is regarded to be related to a variety of inflammatory responses and negatively correlates with the degree of systemic inflammatory response. As a series of findings shown that inflammation can often found in progressive cirrhosis and closely related to poor prognosis, involving ascites or edema, hepatic encephalopathy, gastrointestinal bleeding, leading to mortality finally.[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] Moreover, the pivotal role of systemic inflammation in the progression of HBV-associated cirrhosis is widely recognized, Ming et al revealed lower serum albumin might reflect the status of inflammatory in decompensated cirrhosis patients and correlated with decreased liver functional reserve, representing liver functional severe damage.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] Meanwhile, the INR not only serves as a reflection of the liver's synthetic function, but also the impairment of liver function because of the relationship between deterioration of the coagulation system and aggravation of the liver function.[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] Professor Ming. then pointed out that the combination of elevated INR and decreased albumin contributed to high PTAR which may specifically denote the positively association with severity of liver status and the degree of inflammation. Furthermore, aggravating liver function was tend to be accompanied by distinctly systemic hemodynamic instability,[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] especially in end-stage liver disease. This circulatory modulation appears to drive cardiac dysfunction, causing adrenergic hyperactivity, activating the sympathetic nervous system,[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e] and causing QTc prolongation to develop.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Therefore, based on previous pathological theories and our present results, we guess the PTAR and QTc prolongation may have potential relationship. Second, It has been assumed that abnormal ventricular repolarization is supported by exposure of some cardiotoxins due to the liver dysfunction and reduction of inactivation of toxic substances, such as endotoxin, nitricoxide and various cytokines. Sina et al found out nitricoxide (NO) and endogenous opioids play an significant part in the mechanism of the prolonged QTc in an animal experiment.[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eOur study has several limitations. Firstly, given the cross-sectional study design, it is important to note that while a correlation between PTAR and QTc prolongation was established, causal relationships cannot be inferred, requiring a prospective study to further investigation. Additionally, we extracted the size of sample only from single tertiary hospital. Therefore, taking a large sample size and multi-centric study into account is urgently ed in the future. There's no denying that, the potential bias in patient selection could not be avoided. Finally, recalls and self-reporting bias may happened since some patients had complicated medical conditions and may have taken more medications. As a result, the pertinent information on recent drug usage were tend to be insufficient and then may be likely to affect the occurrence of QTc prolongation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study presents an adverse L-shaped connection between PTAR and prolonged QTc among cirrhotic patients. An inflection point of 37.40 of PTAR was determined using recursive algorithm, which segmented PTAR into category which showed a good prediction precision. This index is easily measurable and applicable in clinical practice without requiring specific techniques or the use of multiple variables to calculate it. These findings highlight the usefulness of this simple index to early identify individuals with cirrhosis at high risk of developing a OTc prolongation event. Maybe in the future, well-designed, multicenter and Prospective study should be proposed to further investigate the role of PTAR in cirrhosis patients.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was obtained from the Medical Ethics Committee of the First Affiliated Hospital of Army Medical University (approval number BIIT2023064KX), and the ethics committee waived the requirement for informed consent due to the retrospective nature of the study and the use of de-identified clinical data. Our study adhered to the Declaration of Helsinki in this respect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflicts of interest exists among the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003ccode\u003e-\u0026nbsp;\u003c/code\u003eCX and SS C conceived the idea\u003c/p\u003e\n\u003cp\u003e\u003ccode\u003e-\u0026nbsp;\u003c/code\u003eCX and YLL collected the data, conducted the analysis, and wrote the main manuscript text.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are available in the GitHub repository at https://github.com/xingchen19931017/liver-cirrhosis-originaldata.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot available.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHuang DQ, Terrault NA, Tacke F, et al. Global epidemiology of cirrhosis - aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol 2023.\u003c/li\u003e\n \u003cli\u003eLiu Y-B, Chen M-K. Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions. World J Gastroenterol 2022;28(41):5910-5930.\u003c/li\u003e\n \u003cli\u003eGlobal burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396(10258):1204-1222.\u003c/li\u003e\n \u003cli\u003eShahvaran SA, Menyh\u0026aacute;rt O, Csedrik L, et al. Diagnosis and Prevalence of Cirrhotic Cardiomyopathy: A Systematic Review and Meta-analysis. Curr Probl Cardiol 2021;46(10):100821.\u003c/li\u003e\n \u003cli\u003eIzzy MJ, VanWagner LB. Current Concepts of Cirrhotic Cardiomyopathy. Clin Liver Dis 2021;25(2):471-481.\u003c/li\u003e\n \u003cli\u003eBodys-Pełka A, Kusztal M, Raszeja-Wyszomirska J, et al. What\u0026apos;s New in Cirrhotic Cardiomyopathy?-Review Article. J Pers Med 2021;11(12).\u003c/li\u003e\n \u003cli\u003eLiu H, Jayakumar S, Traboulsi M, et al. Cirrhotic cardiomyopathy: Implications for liver transplantation. Liver Transpl 2017;23(6):826-835.\u003c/li\u003e\n \u003cli\u003eRaval Z, Harinstein M, Skaro A, et al. Cardiovascular risk assessment of the liver transplant candidate. Liver Transpl 2011;58(3):223-231.\u003c/li\u003e\n \u003cli\u003eBernardi M, Maggioli C, Dibra V, et al. QT interval prolongation in liver cirrhosis: innocent bystander or serious threat? J Hepatol 2012;6(1):57-66.\u003c/li\u003e\n \u003cli\u003eM\u0026oslash;ller S, Henriksen JJ. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. J Hepatol 2002;87(1):9-15.\u003c/li\u003e\n \u003cli\u003eBernardi M, Calandra S, Colantoni A, et al. Q-T interval prolongation in cirrhosis: prevalence, relationship with severity, and etiology of the disease and possible pathogenetic factors. J Hepatol 1998;27(1):28-34.\u003c/li\u003e\n \u003cli\u003eTrevisani F, Di Micoli A, Zambruni A, et al. QT interval prolongation by acute gastrointestinal bleeding in patients with cirrhosis. Gut 2012;32(10):1510-1515.\u003c/li\u003e\n \u003cli\u003eLee S, Park M, Park K, et al. Corrected QT interval on the electrocardiogram after liver transplantation: Surrogate marker of poor clinical outcomes? Sci Rep 2018;13(10).\u003c/li\u003e\n \u003cli\u003eKo J, Koshy A, Han H, et al. Effect of liver transplantation on QT-interval prolongation and impact on mortality. Liver Transpl 2021;326:158-163.\u003c/li\u003e\n \u003cli\u003eHaruki K, Shiba H, Saito N, et al. Risk stratification using a novel liver functional reserve score of combination prothrombin time-international normalized ratio to albumin ratio and albumin in patients with hepatocellular carcinoma. J Hepatol 2018;164(3):404-410.\u003c/li\u003e\n \u003cli\u003eWang S, Ding S, Luo H, et al. International Normalized Ratio to Albumin Ratio (PTAR): An Objective Risk Stratification Tool in Patients with Sepsis. J Infect Dis 2021;14:1829-1841.\u003c/li\u003e\n \u003cli\u003eChoi J, Lee J, Lee S, et al. International Normalized Ratio-to-Albumin Ratio as a Novel Marker of Upper Gastrointestinal Bleeding Severity. Sci Rep 2022;2022:1172540.\u003c/li\u003e\n \u003cli\u003eGao F, Cai M, Lin M, et al. Prognostic value of international normalized ratio to albumin ratio among critically ill patients with cirrhosis. Liver Int 2019;31(7):824-831.\u003c/li\u003e\n \u003cli\u003eLongheval G, Vereerstraeten P, Thiry P, et al. Predictive models of short- and long-term survival in patients with nonbiliary cirrhosis. Liver Transpl 2003;9(3):260-267.\u003c/li\u003e\n \u003cli\u003eRoboz G, Ritchie E, Carlin R, et al. Prevalence, management, and clinical consequences of QT interval prolongation during treatment with arsenic trioxide. Cancer Chemother Pharmacol 2014;32(33):3723-3728.\u003c/li\u003e\n \u003cli\u003eZambruni A, Trevisani F, Di Micoli A, et al. Effect of chronic beta-blockade on QT interval in patients with liver cirrhosis. J Hepatol 2008;48(3):415-421.\u003c/li\u003e\n \u003cli\u003eBiselli M, Gramenzi A, Lenzi B, et al. Development and Validation of a Scoring System That Includes Corrected QT Interval for Risk Analysis of Patients With Cirrhosis and Gastrointestinal Bleeding. Liver Int 2019;17(7):1388-1397.e1381.\u003c/li\u003e\n \u003cli\u003eOu M, Tian Y, Zhuang G, et al. QTc interval prolongation in liver cirrhosis with upper gastrointestinal bleeding. J Gastroenterol 2021;156(2):68-75.\u003c/li\u003e\n \u003cli\u003eJeng L, Chan W, Teng C, et al. Prognostic Significance of Serum Albumin Level and Albumin-Based Mono- and Combination Biomarkers in Patients with Hepatocellular Carcinoma. Sci Rep 2023;15(4).\u003c/li\u003e\n \u003cli\u003eXi W, Wu C, Liang Y, et al. Analysis of malnutrition factors for inpatients with chronic kidney disease. J Clin Nutr 2022;9:1002498.\u003c/li\u003e\n \u003cli\u003eGonz\u0026aacute;lez-Gonz\u0026aacute;lez JA, V\u0026aacute;zquez-Elizondo G, Monreal-Robles R, et al. Hypoalbuminemia in the outcome of patients with non-variceal upper gastrointestinal bleeding. J Gastroenterol 2022;37(4):431-440.\u003c/li\u003e\n \u003cli\u003eVincent J, Russell J, Jacob M, et al. Albumin administration in the acutely ill: what is new and where next? Crit Care 2014;18(4):231.\u003c/li\u003e\n \u003cli\u003eCao Y, Su Y, Guo C, et al. Albumin Level is Associated with Short-Term and Long-Term Outcomes in Sepsis Patients Admitted in the ICU: A Large Public Database Retrospective Research. J Crit Care 2023;15:263-273.\u003c/li\u003e\n \u003cli\u003eSchupp T, Weidner K, Rusnak J, et al. Diagnostic and Prognostic Significance of the Prothrombin Time/International Normalized Ratio in Sepsis and Septic Shock. J Crit Care 2022;28:10760296221137893.\u003c/li\u003e\n \u003cli\u003eLiu L, Ying M, Chen S, et al. The association between prothrombin time-international normalized ratio and long-term mortality in patients with coronary artery disease: a large cohort retrospective study with 44,662 patients. J Clin Cardiol 2021;1471-2261:1-10.\u003c/li\u003e\n \u003cli\u003eYin M, Si L, Qin W, et al. Predictive Value of Serum Albumin Level for the Prognosis of Severe Sepsis Without Exogenous Human Albumin Administration: A Prospective Cohort Study. Crit Care Med 2018;33(12):687-694.\u003c/li\u003e\n \u003cli\u003eLyons P, Micek S, Hampton N, et al. Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality. J Crit Care Med 2018;46(5):736-742.\u003c/li\u003e\n \u003cli\u003eCai M, Han Z, He X, et al. Usefulness of International Normalized Ratio to Albumin Ratio for Evaluation of Mortality in Hepatitis B Virus-Associated Decompensated Cirrhosis. J Med Sci 2021;2021:6664574.\u003c/li\u003e\n \u003cli\u003eFaigel D, Metz D, Kochman M, et al. Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol 1995;90(5):822-824.\u003c/li\u003e\n \u003cli\u003eCazzaniga M, Dionigi E, Gobbo G, et al. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol 2022;1600-0641:147-154.\u003c/li\u003e\n \u003cli\u003eBajaj JS, OʼLeary JG, Tandon P, et al. Nosocomial Infections Are Frequent and Negatively Impact Outcomes in Hospitalized Patients With Cirrhosis. Hepatology 2022;1572-0241:1020-1029.\u003c/li\u003e\n \u003cli\u003eVanerio G, Jos Association cdtojoNS. International Normalized Ratio Variability: A Measure of Anticoagulation Quality or a Powerful Mortality Predictor. J Stroke 2015;24(10):2223-2228.\u003c/li\u003e\n \u003cli\u003eIzzy M, VanWagner LB, Lin G, Altieri M, Findlay JY, Oh JK, et al. Redefining Cirrhotic Cardiomyopathy for the Modern Era. Hepatology (Baltimore, Md) 2020;71(1):334-345.\u003c/li\u003e\n \u003cli\u003eTavakoli S, Hajrasouliha A, Jabehdar-Maralani P, Ebrahimi F, Solhpour A, Sadeghipour H, et al. Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: the roles of nitric oxide and endogenous opioid peptides. Eur J Pharmacol 2007;46(3):432-439.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Baseline characteristics according to PTAR in liver cirrhosis patients\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"939\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=374)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=125)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=124)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=125)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.493\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e248 (66.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e80 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e80 (64.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e88 (70.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e126 (33.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e45 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e44 (35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e37 (29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e56.7 \u0026plusmn; 11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e56.5 \u0026plusmn; 11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e56.7 \u0026plusmn; 12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e57.0 \u0026plusmn; 11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.936\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e116.4 \u0026plusmn; 15.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e117.9 \u0026plusmn; 15.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e117.6 \u0026plusmn; 16.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e113.6 \u0026plusmn; 14.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBP (mmHg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e70.1 \u0026plusmn; 11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e71.5 \u0026plusmn; 10.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e69.8 \u0026plusmn; 11.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e68.8 \u0026plusmn; 11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (beats/min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e81.5 \u0026plusmn; 13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e78.4 \u0026plusmn; 11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e83.0 \u0026plusmn; 14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e83.1 \u0026plusmn; 13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eVirus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e235 (62.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e82 (65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e79 (63.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e74 (59.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eAlcoholic+Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e72 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e16 (12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e26 (21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e30 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eAutoimmune\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e25 ( 6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e7 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e7 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e11 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e42 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e20 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e12 (9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e10 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHb (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e100.6 \u0026plusmn; 26.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e113.6 \u0026plusmn; 25.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e93.4 \u0026plusmn; 24.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e94.8 \u0026plusmn; 24.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALB (g/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e32.6 \u0026plusmn; 6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e39.2 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e32.3 \u0026plusmn; 3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e26.4 \u0026plusmn; 3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e62.2 \u0026plusmn; 78.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e45.4 \u0026plusmn; 61.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e57.2 \u0026plusmn; 66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e83.8 \u0026plusmn; 96.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eK (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.8 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.9 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.8 \u0026plusmn; 0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.7 \u0026plusmn; 0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNa (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e138.5 \u0026plusmn; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e139.9 \u0026plusmn; 3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e138.3 \u0026plusmn; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e137.4 \u0026plusmn; 5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e2.1 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e2.3 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e2.1 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e2.0 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePT (s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e14.6 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e12.8 \u0026plusmn; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e14.1 \u0026plusmn; 1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e16.9 \u0026plusmn; 2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPTT (s)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e39.0 \u0026plusmn; 9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e32.2 \u0026plusmn; 4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e37.8 \u0026plusmn; 6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e47.1 \u0026plusmn; 10.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eINR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e1.2 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e1.1 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e1.2 \u0026plusmn; 0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e1.4 \u0026plusmn; 0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDegree of ascite, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eNO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e229 (61.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e104 (83.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e74 (59.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e51 (40.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e28 ( 7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e4 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e10 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e14 (11.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eModerate\u0026minus;severe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e117 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e17 (13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e40 (32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e60 (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClassification of child, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eClass A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e163 (43.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e101 (80.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e54 (43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e8 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eClass B-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e211 (56.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e24 (19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e70 (56.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e117 (93.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMELD Scores\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e10.4 \u0026plusmn; 4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e8.1 \u0026plusmn; 3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e9.5 \u0026plusmn; 4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e13.5 \u0026plusmn; 4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQT interval\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e402.9 \u0026plusmn; 41.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e402.1 \u0026plusmn; 33.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e401.0 \u0026plusmn; 45.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e405.7 \u0026plusmn; 45.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDM, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e319 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e107 (85.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e107 (86.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e105 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e55 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e18 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e17 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e20 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfection, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.872\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e319 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e107 (85.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e107 (86.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e105 (84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e55 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e18 (14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e17 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e20 (16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRBC (10\u003csup\u003e12\u003c/sup\u003e/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.4 (3.0, 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.9 (3.5, 4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.3 (2.8, 3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.1 (2.7, 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e /L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.2 (2.3, 4.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.3 (2.3, 4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.0 (2.0, 4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e3.5 (2.5, 5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLT (10\u003csup\u003e9\u0026nbsp;\u003c/sup\u003e/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e64.0 (40.0, 106.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e76.0 (51.0, 123.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e62.5 (40.8, 105.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e56.0 (36.0, 87.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTBIL (umol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e27.4 (17.8, 44.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e20.2 (15.3, 28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e25.6 (17.3, 36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e44.3 (28.8, 72.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e26.4 (18.9, 42.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e24.2 (18.5, 34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e24.2 (15.5, 40.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e31.8 (21.6, 52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALP (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e110.5 (81.0, 152.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e100.7 (79.0, 146.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e107.5 (81.8, 149.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e126.0 (86.0, 170.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGGT (U/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e45.0 (26.0, 92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e45.0 (29.0, 82.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e45.5 (24.8, 98.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e44.0 (24.0, 92.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.811\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBUN (mmol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e5.3 (4.2, 7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e5.3 (4.4, 6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e5.0 (4.0, 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e6.0 (4.3, 8.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 240px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCr (umol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e65.2 (56.6, 79.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e65.5 (59.0, 81.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e64.2 (55.8, 78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e65.4 (56.1, 77.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.434\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\u003eData are shown as mean\u0026plusmn;SD, median (IQR), or n (%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbbreviations: T, Tertiles; SBP, Systolic blood pressure; DBP, Diastolic blood pressure; WBC, White blood cell; RBC, Red blood cell; PLT, Platelet;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTBIL, Total Bilirubin; DBIL, Direct Bilirubin;IBIL, Indirect Bilirubin; ALT, Alanine Aminotransferase; AST, Aspartate Aminotransferase;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eALP, Alkaline Phosphatase; GGT, gamma-Glutamyl Transpeptidase; BUN, Blood urea nitrogen; MELD, Model for end-stage liver disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eMultivariate regression analysis of the association between PTAR and QTc prolongation\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"939\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\" style=\"width: 65px;\"\u003e\n \u003cp\u003eQTcprolongation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 63px;\"\u003e\n \u003cp\u003eCrudeModel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 63px;\"\u003e\n \u003cp\u003eModelI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 63px;\"\u003e\n \u003cp\u003eModelII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 65px;\"\u003e\n \u003cp\u003eModelIII\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003ePTAR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e1.05 (1.03~1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e1.05 (1.03~1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e1.05 (1.03~1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e1.04 (1.02~1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003ePTAR,Tertiles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003eT1 (21.56~32.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003eRef.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003eT2 (32.71~43.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e3.35 (1.92~5.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e3.53 (1.99~6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e3.47 (1.95~6.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e3.12 (1.74~5.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003eT3 (43.14~93.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e5.01 (2.86~8.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e5.02 (2.84~8.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e5.24 (2.94~9.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e4.05 (2.19~7.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 133px;\"\u003e\n \u003cp\u003eP for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 126px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\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\u003eAbbreviations: Q, Tertiles; OR, odds ratio; CI, confidence interval; PTAR, INR/ALB; Ref: reference.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eModel I was adjusted for age+sex;\u003c/p\u003e\n\u003cp\u003eModel II was adjusted for age+sex+SBP+DBP;\u003c/p\u003e\n\u003cp\u003eModel III was adjusted for age+sex+SBP+DBP+PLT+TBIL+Na; Only 99% of the data is displayed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eThreshold effect analysis of the relationship of PTAR with QTc prolongation\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"940\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 440px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTAR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjustedModel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 440px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 323px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR(95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 440px;\"\u003e\n \u003cp\u003e＜37.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 323px;\"\u003e\n \u003cp\u003e1.17 (1.06~1.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 440px;\"\u003e\n \u003cp\u003e\u0026ge; 37.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 323px;\"\u003e\n \u003cp\u003e1.01 (0.98~1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 440px;\"\u003e\n \u003cp\u003eLog-likelihood ratio test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 323px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e0.003\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\u003eAbbreviations: OR, odds ratio; CI, confidence interval; PTAR, INR/ALB. Adjusted for age+sex+SBP+DBP+PLT+TBIL+Na. Only 99% of the data is displayed.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Liver Cirrhosis, PTAR, QTc Prolongation, Logistic regression, OR","lastPublishedDoi":"10.21203/rs.3.rs-7608303/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7608303/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe objective of this study was to investigate the correlation between prothrombin time-international normalized ratio-to-albumin ratio (PTAR) and QTc prolongation among patients with liver cirrhosis.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eData from participants with liver cirrhosis were included in this study. The association between PTAR and QTc prolongation was examined using univariate and multivariable logistic regression analyses. The restricted cubic spline (RCS) method was employed for curve fitting and to determine the optimal PTAR threshold for predicting QTc prolongation. Plotting a receiver-operating characteristics (ROC) curve to compare a prediction model fitted on the variables used in the based model score, a new model containing the based variables with the PTAR and QTc prolongation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eAn adverse L-shaped curve association between PTAR and QTc prolongation was observed, with an inflection point at 37.40. The odds ratio (OR) for developing QTc prolongation was 1.17 (95% CI: 1.06\u0026ndash;1.28, p\u0026thinsp;=\u0026thinsp;0.001) as PTAR ranged from 0 to 37.40. Interestingly, a threshold of 37.40 was also identified for predicting QTc prolongation. The areas under the curve (AUC) of the ROC plots were 0.646 (0.589, 0.702) for the based model and 0.709 (0.656, 0.762) for the based model\u0026thinsp;+\u0026thinsp;PTAR model (P\u0026thinsp;=\u0026thinsp;0.002).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThere is a significant inverse L-shaped correlation between PTAR and QTc prolongation in patients with liver cirrhosis. An inflection point at 37.40 was identified, at which PTAR showed predictive value for QTc prolongation.\u003c/p\u003e","manuscriptTitle":"Predictive Value of Prothrombin Time-International Normalized Ratio Albumin Ratio for QTc Prolongation in Patients with Liver Cirrhosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-14 09:21:58","doi":"10.21203/rs.3.rs-7608303/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":"835015a6-4d9c-4f9c-94ed-3245cd321efe","owner":[],"postedDate":"November 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-25T10:53:49+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-14 09:21:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7608303","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7608303","identity":"rs-7608303","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}