# Effect of Admission Time on the Outcomes of Liver Cirrhosis with Acute Upper Gastrointestinal Bleeding: Regular Hours versus Off-Hours Admission

Authors: Yingying Li; Bing Han; Hongyu Li; Tingxue Song; Wenchun Bao; Ran Wang; Zhaohui Bai; Kexin Zheng; Qianqian Li; Xiaozhong Guo; Xingshun Qi
Journal: Canadian Journal of Gastroenterology and Hepatology
 (2018)

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## Abstract

Background and Aims. Acute upper gastrointestinal bleeding (AUGIB) is a lethal complication of liver cirrhosis. We aimed to compare the outcomes of patients with liver cirrhosis and AUGIB who were admitted to hospital on regular hours and off-hours.Methods. This retrospective study screened all cirrhotic patients with AUGIB who were admitted to our hospital from January 2010 to June 2014 for the test cohort and from December 2014 to March 2018 for the validation cohort. A 1:1 propensity score matching analysis was performed to adjust the Child-Pugh and MELD scores. In-hospital mortality, 5-day rebleeding rate, length of stay, and total payment were primary outcomes.Results. Overall, 826 and 173 patients with liver cirrhosis and AUGIB were included in the test and validation cohorts, respectively. After propensity score matching, 226 and 40 patients were included in the test and validation cohorts, respectively. The overall analysis of the test cohort found significantly higher Child-Pugh score (P=0.006), 5-day rebleeding rate (18.69% versus 10.72%, P=0.001), and total payment (¥25,906.83 versus ¥22,017.42, P<0.001) in patients admitted on off-hours. By contrast, the overall analysis of the validation cohort did not find any difference in Child-Pugh score, 5-day rebleeding, in-hospital mortality, length of stay, or hospital payment between patients admitted on regular hours and off-hours. Similarly, the propensity score matching analyses of both test and validation cohorts found no difference in these primary outcomes between the two groups.Conclusions. Off-hours admission might not be negatively associated with the outcomes of patients with liver cirrhosis and AUGIB.


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## Body

## 1. Introduction

Liver cirrhosis is the 13th major cause of death worldwide. Acute upper gastrointestinal bleeding (AUGIB) is a frequent medical emergency with a high incidence of 45-172/100,000 each year in the general population and is a lethal complication of liver cirrhosis leading to an in-hospital mortality of 10% [1, 2]. Due to the acute performance of AUGIB itself, early diagnosis and timely management are needed. Notably, there are general shortage of staff, a potentially lower professional level of staff, and delayed use of endoscopy during weekends and holidays, which may lead to worse outcomes [3, 4]. Previous studies evaluated the effect of admission time on the outcomes of patients with AUGIB, but their findings were inconsistent. Some authors supported the “weekend effect” that patients admitted during weekends had worse outcomes [5–9], such as higher mortality and rebleeding rate, longer length of stay, and increased cost. On the contrary, others suggested no significant difference in the mortality between patients admitted during weekends and weekdays [10–15]. A meta-analysis [16] reported that off-hours admission was significantly associated with an increased mortality and less timely endoscopy in patients with nonvariceal bleeding but not those with variceal bleeding. More recently, another meta-analysis [17] also had similar results. However, there were some limitations in previous studies.First, meta-analyses have shown that geographical variation leads to different weekend effect on outcomes [16, 17]. A study, which included 571 patients suspected with upper gastrointestinal bleeding (UGIB) from 8 participating hospitals in the Netherlands [11], reported that patients admitted on weekends had higher mortality and rebleeding rate than those admitted on weekdays. By contrast, two prospective studies [14, 15] conducted in the United Kingdom found no significant difference in mortality of patients with UGIB between weekend and weekday admission groups. A retrospective study conducted in Korea [12], which included 294 cirrhotic patients with acute variceal bleeding, found no significant difference in the in-hospital mortality between weekend and weekday admission groups. Notably, all studies included in the two meta-analyses were not conducted in China mainland. Considering a geographical difference in the staff schedule and management and outcome of AUGIB, further studies should be performed in China mainland.Second, meta-analyses have also shown that a variation in the source of bleeding leads to different weekend effect on outcomes. All of 4 studies conducted in the United States were based on Nationwide Inpatient Sample, but showed different results [5, 6, 8, 13]. The first study demonstrated that patients with UGIB regardless of source of bleeding admitted on weekends had significantly higher mortality and longer length of stay than those admitted on weekdays [5]. The second study also demonstrated that patients with peptic ulcer hemorrhage admitted on weekends had higher mortality and longer length of stay [6]. The third study further confirmed that patients with nonvariceal UGIB admitted on weekends had higher mortality [8]. However, the fourth study found that the mortality in patients with acute variceal bleeding was similar between weekend and weekday admission groups [13].Third, previous studies usually compared the effect of weekends versus weekdays on the mortality of AUGIB. But the nighttime during weekdays was often ignored from the definition of off-hours. Thus, further studies should refine the interval of off-hours.Herein, we performed a retrospective study to compare the outcomes of patients with liver cirrhosis and AUGIB who were admitted to a large tertiary hospital of Northeastern China on regular hours versus off-hours.


## 2. Methods

### 2.1. Study Design

We reviewed the medical records of cirrhotic patients who were consecutively admitted to the General Hospital of Shenyang Military Area from January 2010 to June 2014 as the test cohort. All patients with a diagnosis of liver cirrhosis and AUGIB were eligible. Additionally, we are prospectively collecting all cirrhotic patients who were admitted to our department and underwent contrast-enhanced CT scans and endoscopy since December 2014. Thus, based on the data during the patients' enrollment and follow-up, a validation cohort of cirrhotic patients with AUGIB between December 2014 and March 2018 was established for the present study. Age and sex were not limited. The source of bleeding was not limited. Patients with liver and other malignancies were excluded. Patients with incomplete case information and unavailable electronic medical records were also excluded. Data from repeated admission was not deliberately excluded. The outcomes we observed included 5-day rebleeding rate, in-hospital mortality, length of hospital stay, and total payment during hospitalizations. This study was approved by the Medical Ethical Committee of our hospital and the ethical approval number was k (2017)42. The patient's informed consent was not required in the retrospective study.


### 2.2. Data Collection

The primary data collected were age, sex, admission time, etiology of liver disease, and laboratory tests (i.e., red blood cell, hemoglobin, white blood cell, platelet count, total bilirubin, direct bilirubin, indirect bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, blood urea nitrogen, creatinine, potassium, sodium, prothrombin time, activated partial thromboplastin time, and international normalized ratio [INR]). The severity of esophageal varices was also collected. Treatment options of AUGIB were collected as follows: endoscopic therapy (i.e., band ligation, sclerotherapy, and histoacryl), Sengstaken Blackmore tube, somatostatin and/or octreotide, blood transfusion, proton pump inhibitors (PPIs), and surgery.


### 2.3. Definitions and Formulas

AUGIB was defined as hematemesis and/or melena within 5 days before our admission or positive occult blood test at the day of admission [18]. Regular hours referred to the interval from 8:00 AM to 17:00 PM at the weekdays (i.e., from Monday to Friday). Otherwise, off-hours were considered, and weekends and public holidays were also considered as off-hours. Child-Pugh score [19] was calculated according to hepatic encephalopathy, ascites, total bilirubin, albumin, and INR. Model for end-stage liver disease (MELD) score=9.57 ×  ln⁡(creatinine[μmol/L]×0.01)  + 3.78 ×  ln⁡(bilirubin[μmol/L]×0.05) + 11.2 ×  ln⁡(INR)  + 0.643 [20]. According to the study by Reverter et al. [21], recalibrated MELD score=-5.312+0.207×MELD. Albumin-bilirubin (ALBI) score=-0.085 × albumin (g/L) + 0.66 ×  log10⁡bilirubin(μmol/L) [22, 23].


### 2.4. Statistical Analyses

Continuous variables were reported as median (range) and were compared using the nonparametric Mann-Whitney U test. Categorical variables were reported as frequency (percentage) and were compared using the chi-square test. Subgroup analyses were also conducted based on the presence of varices on endoscopy (AUGIB with endoscopically confirmed varices and without varices on endoscopy). A 1:1 propensity score matching analysis was performed to adjust the effect of gender, age, Child-Pugh score, MELD score, and recalibrated MELD score on the outcomes. A two-tailed P<0.05 was considered statistically significant. All statistical analyses were performed with IBM SPSS 20.0 (IBM Corp.) statistical package and Stata/SE 12.0 (Stata Corp, College Station, TX) software.


## 2.1. Study Design

We reviewed the medical records of cirrhotic patients who were consecutively admitted to the General Hospital of Shenyang Military Area from January 2010 to June 2014 as the test cohort. All patients with a diagnosis of liver cirrhosis and AUGIB were eligible. Additionally, we are prospectively collecting all cirrhotic patients who were admitted to our department and underwent contrast-enhanced CT scans and endoscopy since December 2014. Thus, based on the data during the patients' enrollment and follow-up, a validation cohort of cirrhotic patients with AUGIB between December 2014 and March 2018 was established for the present study. Age and sex were not limited. The source of bleeding was not limited. Patients with liver and other malignancies were excluded. Patients with incomplete case information and unavailable electronic medical records were also excluded. Data from repeated admission was not deliberately excluded. The outcomes we observed included 5-day rebleeding rate, in-hospital mortality, length of hospital stay, and total payment during hospitalizations. This study was approved by the Medical Ethical Committee of our hospital and the ethical approval number was k (2017)42. The patient's informed consent was not required in the retrospective study.


## 2.2. Data Collection

The primary data collected were age, sex, admission time, etiology of liver disease, and laboratory tests (i.e., red blood cell, hemoglobin, white blood cell, platelet count, total bilirubin, direct bilirubin, indirect bilirubin, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, blood urea nitrogen, creatinine, potassium, sodium, prothrombin time, activated partial thromboplastin time, and international normalized ratio [INR]). The severity of esophageal varices was also collected. Treatment options of AUGIB were collected as follows: endoscopic therapy (i.e., band ligation, sclerotherapy, and histoacryl), Sengstaken Blackmore tube, somatostatin and/or octreotide, blood transfusion, proton pump inhibitors (PPIs), and surgery.


## 2.3. Definitions and Formulas

AUGIB was defined as hematemesis and/or melena within 5 days before our admission or positive occult blood test at the day of admission [18]. Regular hours referred to the interval from 8:00 AM to 17:00 PM at the weekdays (i.e., from Monday to Friday). Otherwise, off-hours were considered, and weekends and public holidays were also considered as off-hours. Child-Pugh score [19] was calculated according to hepatic encephalopathy, ascites, total bilirubin, albumin, and INR. Model for end-stage liver disease (MELD) score=9.57 ×  ln⁡(creatinine[μmol/L]×0.01)  + 3.78 ×  ln⁡(bilirubin[μmol/L]×0.05) + 11.2 ×  ln⁡(INR)  + 0.643 [20]. According to the study by Reverter et al. [21], recalibrated MELD score=-5.312+0.207×MELD. Albumin-bilirubin (ALBI) score=-0.085 × albumin (g/L) + 0.66 ×  log10⁡bilirubin(μmol/L) [22, 23].


## 2.4. Statistical Analyses

Continuous variables were reported as median (range) and were compared using the nonparametric Mann-Whitney U test. Categorical variables were reported as frequency (percentage) and were compared using the chi-square test. Subgroup analyses were also conducted based on the presence of varices on endoscopy (AUGIB with endoscopically confirmed varices and without varices on endoscopy). A 1:1 propensity score matching analysis was performed to adjust the effect of gender, age, Child-Pugh score, MELD score, and recalibrated MELD score on the outcomes. A two-tailed P<0.05 was considered statistically significant. All statistical analyses were performed with IBM SPSS 20.0 (IBM Corp.) statistical package and Stata/SE 12.0 (Stata Corp, College Station, TX) software.


## 3. Results

### 3.1. Test Cohort

#### 3.1.1. Patients’ Characteristics

Between January 2010 and June 2014, a total of 826 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table1. Median age was 55.27 years (range: 6.28 to 95.13). Among them, 564 (68.3%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=208, 25.2%) and alcohol abuse (n=219, 26.5%). A majority of patients had Child-Pugh class B (339/776, 51.4%). Median MELD score at admission was 6.37 (-7.52 to 38.22). Five hundred and twenty-two patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 32 (6.1%), 24 (4.6%), 54 (10.3%), and 412 (78.9%) patients, respectively. As for the treatment of AUGIB, 508 (61.5%) patients underwent endoscopic therapy, 20 (2.4%) patients underwent Sengstaken Blackmore tube placement, 750 (90.8%) patients received somatostatin and/or octreotide, 544 (65.9%) patients received blood transfusion, 813 (98.4%) patients received PPIs, and 8 (1.0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in 4 patients, because some of their medical records were missing. Five-day rebleeding rate was 14.0% (115/822). In-hospital mortality was 5.7% (47/826). Median length of hospital stay was 11.23 days (range: 0.06 to 100.55). Total payment was ¥23,120.87 (range: 1,287.54 to 226,872.93).Table 1
Characteristics of patients with liver cirrhosis and AUGIB in test cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 826 55.27 (6.28-95.13) 486 54.54 (20.88-95.13) 340 55.95 (6.28-84.56) 0.074 Sex (male) 826 564 (68.3%) 486 337 (69.3%) 340 227 (66.8%) 0.434 Etiology of Liver Diseases 826  486  340  0.387 HBV  208 (25.2%)  126 (25.9%)  82 (24.1%) HCV  51 (6.2%)  32 (6.6%)  19 (5.6%) HBV + HCV  6 (0.7%)  2 (0.4%)  4 (1.2%) Alcohol Abuse  219 (26.5%)  125 (25.7%)  94 (27.7%) HBV + Alcohol Abuse  64 (7.7%)  42 (8.6%)  22 (6.5%) HCV + Alcohol Abuse  13 (1.6%)  7 (1.4%)  6 (1.8%) HBV + HCV + Alcohol Abuse  2 (0.2%)  1 (0.2%)  1 (0.3%) Drug Related  35 (4.2%)  23 (4.7%)  12 (3.5%) Autoimmune Liver Diseases  56 (6.8%)  26 (5.4%)  30 (8.8%) Other or Unclear Etiology  172 (20.8%)  102 (21%)  70 (20.6%) Laboratory Tests Red Blood Cell (1012/L) 822 2.56 (0.93-5.49) 482 2.61 (0.93-5.49) 340 2.49 (1.05-5.10) 0.250 Hemoglobin (g/L) 822 72.00 (23.00-180.00) 482 73.00 (23.00-164.00) 340 71.00 (23.00-180.00) 0.512 White Blood Cell (109/L) 822 4.70 (0.40-46.10) 482 4.20 (0.80-33.50) 340 5.30 (0.90-46.10) <0.001 Platelet Count (109/L) 822 75.00 (9.00-842.00) 482 74.00 (9.00-842.00) 340 77.50 (17.00-775.00) 0.429 Total Bilirubin (umol/L) 820 20.30 (3.30-679.10) 480 20.10 (4.10-679.10) 340 20.50 (3.30-250.80) 0.598 Direct Bilirubin (umol/L) 820 8.30 (0.50-413.80) 480 8.20 (1.30-413.80) 340 8.50 (0.50-195.20) 0.916 Indirect Bilirubin (umol/L) 820 11.75 (1.30-265.30) 480 11.50 (1.30-265.30) 340 12.05 (2.00-126.60) 0.436 Albumin (g/L) 796 30.40 (9.60-49.30) 469 31.00 (9.60-49.30) 327 29.30 (10.00-48.00) <0.001 Alanine Aminotransferase (U/L) 818 23.00 (5.00-1064.00) 479 23.00 (5.00-730.00) 339 24.00 (5.00-1064.00) 0.403 Aspartate Aminotransferase (U/L) 818 31.00 (7.00-1487.00) 479 31.00 (7.00-1399.00) 339 32.00 (8.00-1487.00) 0.255 Alkaline Phosphatase (U/L) 818 73.00 (1.30-889.00) 479 74.00 (17.44-889.00) 339 72.00 (1.30-688.00) 0.535 Gamma-glutamyl Transpeptidase (U/L) 818 35.00 (5.00-1168.00) 479 35.00 (5.00-1168.00) 339 37.00 (6.00-755.00) 0.945 Blood Urea Nitrogen (mmol/L) 792 7.71 (1.58-42.83) 465 7.06 (1.58-42.83) 327 8.21 (1.96-37.67) <0.001 Serum Creatinine (umol/L) 791 61.00 (20.00-919.00) 465 60.00 (20.00-919.00) 326 61.00 (24.00-327.00) 0.284 Potassium (mmol/L) 810 4.06 (2.13-7.87) 473 4.00 (2.13-7.07) 337 4.12 (2.79-7.78) <0.001 Sodium (mmol/L) 810 138.80 (83.00-160.80) 473 139.10 (83.00-160.80) 337 138.50 (116.40-152.40) 0.055 PT (seconds) 794 16.20 (10.80-62.80) 465 15.90 (10.80-62.80) 329 16.50 (11.00-49.50) 0.034 APTT (seconds) 791 40.30 (25.70-180.00) 463 40.50 (25.7-180.00) 328 39.95 (27.30-97.20) 0.452 INR 791 1.31 (0.77-7.96) 463 1.28 (0.77-7.96) 328 1.35 (0.79-5.94) 0.040 Child-Pugh Score 776 7.00 (5.00-15.00) 455 7.00 (5.00-15.00) 321 7.00 (5.00-15.00) 0.006 Child-Pugh A/B/C 776 234 (30.2%)/339(51.4%)/143 (18.4%) 455 160 (35.2%)/216(47.5%)/79 (17.3%) 321 74 (23.1%)/183(57.0%)/64 (19.9%) 0.001 MELD Score 772 6.37 (-7.52-38.22) 453 5.87 (-7.52-38.22) 319 7.06 (-7.44-37.65) 0.067 Recalibrated MELD Score 772 -4.00 (-6.87-2.60) 453 -4.10 (-6.87-2.60) 319 -3.85 (-6.85-2.48) 0.067 ALBI Score 793 -1.70 (-3.31-0.22) 467 -1.77 (-3.31-0.03) 326 -1.59 (-3.13-0.22) <0.001 Esophageal Varices (No/Mild/Moderate/Severe) 522 32 (6.1%)/24 (4.6%)/54 (10.3%)/412 (78.9%) 309 20 (6.5%)/17 (5.5%)/32(10.4%)/240 (77.6%) 213 12 (5.6%)/7 (3.3%)/22 (10.3%)/172 (80.8%) 0.650 Treatment Endoscopic Treatment 826 508 (61.5%) 486 310 (63.8%) 340 198 (58.2%) 0.107 Sengstaken Blakemore 826 20 (2.4%) 486 12 (2.5%) 340 8 (2.4%) 0.915 Somatostatin and/or Octreotide 826 750 (90.8%) 486 435 (80.5%) 340 315 (92.7%) 0.124 Blood Transfusion 826 544 (65.9%) 486 295 (60.7%) 340 249 (73.3%) <0.001 PPIs 826 813 (98.4%) 486 477 (98.2%) 340 336 (98.8%) 0.443 Surgery 826 8 (1.0%) 486 2 (0.4%) 340 6 (1.8%) 0.051 5-day Re-bleeding After Treatment 822 115 (14.0%) 485 52 (10.7%) 337 63 (18.7%) 0.001 Death During Hospitalization 826 47 (5.7%) 486 25 (5.1%) 340 22(6.5%) 0.418 Length of Stay (days) 826 11.23 (0.06-100.55) 486 11.27 (0.06-78.00) 340 11.13 (0.09-100.55) 0.830 Total Payment (¥) 826 23,120.87 (1,287.54-226,872.93) 486 22,017.42 (1,683.37-126,413.58) 340 25,906.83 (1,287.54-226,872.93) <0.001 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


#### 3.1.2. Outcome

Patients admitted on off-hours had lower serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P<0.001), prothrombin time (P=0.034), INR (P=0.040), Child-Pugh score (P=0.006), and ALBI score (P<0.001) than those admitted on regular hours (Table1). As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion than those admitted on regular hours (73.3% versus 60.7%, P<0.001). Among the different departments of our hospital, there was no significant difference in the selection of most treatment options for AUGIB between patients admitted on regular hours and off-hours (Supplementary Table 1). As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (18.7% versus 10.7%, P=0.001) and a larger amount of payment (¥25,906.83 versus ¥22,017.42, P<0.001). In-hospital mortality was not significantly different between the two groups (P=0.418). Length of stay was not significantly different between the two groups (P=0.830).


#### 3.1.3. Subgroup Analyses

The origin of bleeding could be evaluated in 611 patients in the test cohort. They included 591 patients with endoscopically confirmed esophageal and/or gastric varices and 20 patients without varices at endoscopy (Supplementary Table2).Among the patients with endoscopically confirmed varices, patients admitted on off-hours were older (P=0.015) and had lower red blood cell (P=0.026) and serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P=0.001), prothrombin time (P=0.027), INR (P=0.04), Child-Pugh score (P<0.001), MELD score (P=0.023), recalibrated MELD score (P=0.023), and ALBI score (P<0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (75.5% versus 59.5%, P<0.001) and surgery (2.1% versus 0.3%, P=0.027) than those admitted on regular hours. As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (16.5% versus 10.6%, P=0.038) and a larger amount of payment (¥29,361.51 versus ¥23,864.24, P<0.001). In-hospital mortality and length of stay were not significantly different between the two groups (P=0.094 and P=0.856, respectively).Among the patients without varices at endoscopy, no significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between patients admitted on regular hours and off-hours (P>0.05, in all comparisons). As for the outcomes, none died. Five-day rebleeding rate, length of stay, and total payment were not significantly different between the two groups (P=0.117, P=0.869, and P=0.187, respectively).


#### 3.1.4. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 226 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table2. Median age was 54.51 years (range: 6.28 to 81.62). Among them, 144 (63.7%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=58, 25.7%) and alcohol abuse (n=50, 22. 1%). A majority of patients had Child-Pugh class B (n=121, 53.5%). Median MELD score at admission was 6.12 (-7.14 to 21.56). No, mild, moderate, and severe esophageal varices were observed in 11 (4.9%), 19 (4.4%), 23 (10.2%), and 182 (80.5%) patients, respectively. As for the treatment of AUGIB, 191 (84.5%) patients underwent endoscopic therapy, 8 (3.5%) patients underwent Sengstaken Blackmore tube placement, 218 (96.5%) patients received somatostatin and/or octreotide, 159 (70.4%) patients received blood transfusion, all patients received PPIs, and 1 (0.4%) patient underwent surgery. Five-day rebleeding rate was 14.2% (n=32). In-hospital mortality was 2.2% (n=5). Median length of hospital stay was 12.835 days (range: 2.76 to 78.00). Median total payment was ¥28,633.075 (range: 2,776.55 to 143,048.30).Table 2
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in test cohort.
Variables  Propensity matching patients  P value Overall (n=226) Regular hours (n=113) Off-hours (n=113) Age (years) 54.51 (6.28-81.62) 54.41 (29.85-81.62) 54.60 (6.28-78.66) 0.829 Sex (male) 144 (63.7%) 73 (64.6%) 71 (62.8%) 0.782 Etiology of Liver Diseases    0.612 HBV 58 (25.7%) 29 (25.7%) 29 (25.7%) HCV 14 (6.2%) 7 (6.2%) 7 (6.2%) HBV+ HCV 1 (0.4%) 1 (0.9%) 0 (0%) Alcohol Abuse 50 (22.1%) 26 (23.0%) 24 (21.2%) HBV+ Alcohol Abuse 26 (11.5%) 15 (13.3%) 11 (9.7%) HCV+ Alcohol Abuse 3 (1.3%) 0 (0%) 3 (2.7%) HBV+ HCV+ Alcohol Abuse 1 (0.4%) 0 (0%) 1 (0.9%) Drug Related 10 (4.4%) 5 (4.4%) 5 (4.4%) Autoimmune Liver Diseases 12 (5.3%) 5 (4.4%) 7 (6.2%) Other or Unclear Etiology 51 (22.6%) 25 (22.1%) 26 (23.0%) Laboratory Tests Red Blood Cell (1012/L) 2.54 (0.98-5.49) 2.60 (0.98-5.49) 2.53 (1.15-4.68) 0.989 Hemoglobin (g/L) 71.50 (23.00-157.00) 72.00 (23.00-157.00) 71.00 (23.00-133.00) 0.901 White Blood Cell (109/L) 4.30 (1.00-26.30) 4.10 (1.10-26.30) 4.40 (1.00-17.50) 0.239 Platelet Count (109/L) 74.00 (17.00-435.00) 72.00 (27.00-303.00) 79.00 (17.00-435.00) 0.538 Total Bilirubin (umol/L) 18.80 (3.30-187.40) 19.00 (6.10-90.40) 18.40 (3.30-187.40) 0.669 Direct Bilirubin (umol/L) 7.50 (0.50-151.60) 7.50 (1.30-56.30) 7.20 (0.50-151.60) 0.384 Indirect Bilirubin (umol/L) 11.35 (2.40-56.80) 11.20 (3.20-41.10) 11.40 (2.40-56.80) 0.771 Albumin (g/L) 30.10 (10.00-49.30) 30.48 (10.50-49.30) 29.40 (10.00-45.60) 0.580 Alanine Aminotransferase (U/L) 23.00 (5.00-234.00) 23.00 (6.00-234.00) 23.00 (5.00-154.00) 0.896 Aspartate Aminotransferase (U/L) 31.00 (9.00-263.00) 31.00 (12.00-263.00) 31.00 (9.00-175.00) 0.872 Alkaline Phosphatase (U/L) 74.00 (17.44-707.00) 77.00 (17.44-707.00) 71.00 (21.00-685.00) 0.282 Gamma-glutamyl Transpeptidase (U/L) 36.00 (8.00-1168.00) 45.00 (8.00-1168.00) 33.00 (9.00-737.00) 0.354 Blood Urea Nitrogen (mmol/L) 7.62 (1.96-34.00) 7.66 (2.04-34.00) 7.61 (1.96-28.10) 0.989 Serum Creatinine (umol/L) 60.00 (28.00-234.00) 60.00 (28.00-225.70) 59.00 (30.50-234.00) 0.655 Potassium (mmol/L) 4.06 (2.90-5.50) 4.05 (3.00-5.50) 4.08 (2.90-5.50) 0.285 Sodium (mmol/L) 138.50 (128.00-150.00) 138.30 (130.40-148.00) 138.50 (128.00-150.00) 0.773 PT (seconds) 15.80 (11.00-46.30) 15.60 (12.10-36.10) 16.00 (11.00-46.30) 0.912 APTT (seconds) 39.55 (27.30-66.80) 40.10 (28.20-66.80) 38.50 (27.30-63.90) 0.253 INR 1.28 (0.79-4.77) 1.26 (0.90-3.57) 1.29 (0.79-4.77) 0.950 Child-Pugh Score 7.00 (5.00-13.00) 7.00 (5.00-12.00) 7.00 (5.00-13.00) 0.891 Child-Pugh A/B/C 72 (31.9%)/121 (53.5%)/33 (14.6%) 35 (31.0%)/64 (56.6%)/14 (12.4%) 37 (32.7%)/57 (50.5%)/19 (16.8%) 0.544 MELD Score 6.12 (-7.14-21.56) 6.12 (-5.03-20.16) 5.68 (-7.14-21.56) 0.733 Recalibrated MELD Score -4.05 (-6.79 - -0.85) -4.04 (-6.35 - -1.14) -4.14 (-6.79 - -0.85) 0.733 ALBI Score -1.70 (-3.23-0.22) -1.70 (-3.23 - -0.43) -1.69 (-3.06-0.22) 0.767 Esophageal Varices(No/Mild/Moderate/Severe) 11 (4.9%)/10 (4.4%)/23(10.2%)/182 (80.5%) 5 (4.4%)/5 (4.4%)/11(9.8%)/92 (81.4%) 6 (5.3%)/5 (4.4%)/12(10.6%)/90 (79.7%) 0.984 Treatment Endoscopic Treatment 191 (84.5%) 96 (85.0%) 95 (84.1%) 0.854 Sengstaken Blakemore 8 (3.5%) 5 (4.4%) 3 (2.7%) 0.472 Somatostatin and/or Octreotide 218 (96.5%) 107 (94.7%) 111 (98.2%) 0.150 Blood Transfusion 159 (70.4%) 80 (70.8%) 79 (69.9%) 0.884 PPIs 226 (100%) 113 (100%) 113 (100%) NA Surgery 1 (0.4%) 1 (0.9%) 0 (0%) 0.316 5-day Re-bleeding After Treatment 32 (14.2%) 14 (12.4%) 18 (15.9%) 0.445 Death During Hospitalization 5 (2.2%) 2 (1.8%) 3 (2.7%) 0.651 Length of Stay (days) 12.835 (2.76-78.00) 12.97 (3.91-78.00) 12.41 (2.76-45.26) 0.229 Total Payment (¥) 28,633.075 (2,776.55-143,048.30) 26,733.81 (2,776.55-115,201.67) 29,361.51 (5,856.09-143,048.30) 0.390 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT, prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: Proton pump inhibitors; ¥, Renminbi.


#### 3.1.5. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 113 patients were matched on each group (Table2). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.445, P=0.651, P=0.229, and P=0.390, respectively).


#### 3.1.6. Subgroup Analyses after Propensity Score Matching

After a 1:1 propensity score matching analysis, 140 patients with endoscopically confirmed varices were matched on each group (Supplementary Table3). Patients admitted on off-hours had higher white blood cell (P=0.007), blood urea nitrogen (P=0.01), and potassium (P=0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (77.1% versus 58.6%, P=0.001) and surgery (2.9% versus 0%, P=0.044) than those admitted on regular hours. As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.306, P=0.409, P=0.421, and P=0.058, respectively).


### 3.2. Validation Cohort

#### 3.2.1. Patients’ Characteristics

Between December 2014 and March 2018, a total of 173 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table3. Median age was 56.60 years (range: 20.57 to 88.73). Among them, 121 (69.9%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=47, 27.2%) and alcohol abuse (n=55, 31.8%). A majority of patients had Child-Pugh class B (94/169, 55.6%). Median MELD score at admission was 7.22 (-3.16 to 23.19). One hundred and fifty-one patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 9 (6.0%), 23 (15.2%), 26 (17.2%), and 93 (61.6%) patients, respectively. The origin of bleeding could be evaluated in 162 patients, of whom only 4 did not have esophageal and/or gastric varices. As for the treatment of AUGIB, 139 (80.3%) patients underwent endoscopic therapy, 1 (0.6%) patients underwent Sengstaken Blackmore tube placement, 160 (92.5%) patients received somatostatin and/or octreotide, 88 (50.9%) patients received blood transfusion, 173 (100%) patients received PPIs, and 0 (0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in one patient. Five-day rebleeding rate was 7.6% (13/172). In-hospital mortality was 2.3% (4/173). Median length of hospital stay was 10.10 days (range: 0.12 to 32.94). Total payment was ¥24,328.31 (range: 3,427.24 to 98,215.78).Table 3
Characteristics of patients with liver cirrhosis and AUGIB in validation cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 173 56.60 (20.57-88.73) 131 56.60 (20.57-75.73) 42 56.56 (33.42-88.73) 0.683 Sex (male) 173 121 (69.9%) 131 91 (69.5%) 42 30 (71.4%) 0.809 Etiology of Liver Diseases 173  131  42  0.830 HBV  47 (27.2%)  37 (28.2%)  10 (23.8%) HCV  17 (9.8%)  12 (9.2%)  5 (11.9%) Alcohol Abuse  55 (31.8%)  41 (31.3%)  14 (33.3%) HBV + Alcohol Abuse  3 (1.7%)  2 (1.5%)  1 (2.4%) HBV + HCV + Alcohol Abuse  1 (0.6%)  1 (0.8%)  0 (0%) Drug Related  1 (0.6%)  1 (0.8%)  0 (0%) Autoimmune Liver Diseases  3 (1.7%)  3 (2.3%)  0 (0%) Other or Unclear Etiology  46 (26.6%)  34 (25.9%)  12 (28.6%) Laboratory Tests Red Blood Cell (1012/L) 173 2.70 (1.32-5.11) 131 2.70 (1.32-5.11) 42 2.62 (1.56-4.14) 0.372 Hemoglobin (g/L) 173 73.00 (31.00-156.00) 131 73.00 (31.00-156.00) 42 73.50 (38.00-130.00) 0.575 White Blood Cell (109/L) 173 4.20 (1.00-23.10) 131 4.10 (1.00-23.10) 42 4.35 (1.70-14.90) 0.368 Platelet Count (109/L) 173 71.00 (18.00-457.00) 131 73.00 (18.00-377.00) 42 68.50 (23.00-457.00) 0.980 Total Bilirubin (umol/L) 172 20.80 (5.20-210.00) 131 21.60 (5.20-210.00) 41 18.30 (6.70-106.10) 0.587 Direct Bilirubin (umol/L) 172 8.70 (2.00-146.90) 131 9.00 (2.00-146.90) 41 8.30 (2.50-60.10) 0.643 Indirect Bilirubin (umol/L) 172 10.65 (2.60-79.90) 131 11.40 (2.60-69.20) 41 9.80 (4.20-79.90) 0.801 Albumin (g/L) 171 29.40 (17.00-50.70) 130 29.65 (17.20-50.70) 41 29.40 (17.00-41.00) 0.693 Alanine Aminotransferase (U/L) 172 20.70 (5.00-275.36) 131 20.98 (6.00-140.00) 41 17.17 (5.00-275.36) 0.504 Aspartate Aminotransferase (U/L) 172 27.00 (9.63-310.39) 131 27.50 (9.63-278.00) 41 26.11 (10.00-310.39) 0.801 Alkaline Phosphatase (U/L) 172 78.23 (24.02-378.66) 131 75.66 (24.02-378.66) 41 79.75 (46.24-197.00) 0.981 Gamma-glutamyl Transpeptidase (U/L) 172 31.98 (7.54-1227.00) 131 29.61 (7.54-1227.00) 41 40.53 (7.69-295.00) 0.346 Blood Urea Nitrogen (mmol/L) 172 7.60 (2.17-47.25) 131 7.40 (2.17-47.25) 41 7.96 (2.47-20.15) 0.993 Serum Creatinine (umol/L) 172 69.145 (34.40-267.63) 131 67.03 (34.40-267.63) 41 74.21 (34.90-144.98) 0.116 Potassium (mmol/L) 173 3.95 (2.48-5.54) 131 3.95 (2.48-5.54) 42 3.97 (3.12-5.49) 0.876 Sodium (mmol/L) 173 138.50 (124.00-152.90) 131 138.40 (130.40-152.90) 42 138.80 (124.00-145.70) 0.544 PT (seconds) 171 16.10 (10.50-27.40) 131 16.10 (11.60-27.40) 40 16.05 (10.50-27.20) 0.606 APTT (seconds) 170 37.85 (19.40-59.70) 131 37.90 (27.50-59.70) 39 37.40 (19.40-52.10) 0.542 INR 170 1.32 (0.91-2.55) 131 1.33 (1.01-2.55) 39 1.31 (0.91-2.50) 0.681 Child-Pugh Score 169 8.00 (5.00-15.00) 130 8.00 (5.00-12.00) 39 7.00 (5.00-12.00) 0.603 Child-Pugh A/B/C 169 51 (30.2%)/94 (55.6%)/24 (14.2%) 130 37 (28.5%)/75 (57.7%)/18 (13.8%) 39 14 (35.9%)/19 (48.7%)/6 (15.4%) 0.596 MELD Score 170 7.22 (-3.16-23.19) 131 7.26 (-3.16-20.70) 39 7.22 (-2.38-23.19) 0.671 Recalibrated MELD Score 170 -3.82 (-5.97- -0.51) 131 -3.81 (-5.97- -1.03) 39 -3.82 (-5.80- -0.51) 0.671 ALBI Score 171 -1.63 (-3.40- -0.11) 130 -1.62 (-3.40- -0.11) 41 -1.68 (-2.70- -0.49) 0.675 Esophageal Varices (No/Mild/Moderate/Severe) 151 9 (6.0%)/23 (15.2%)/26 (17.2%)/93 (61.6%) 116 6 (5.2%)/18 (15.5%)/20 (17.2)/72 (61.1%) 35 3 (8.6%)/5 (14.3%)/6(17.1%)/21 (60.0%) 0.965 Treatment Endoscopic Treatment 173 139 (80.3%) 131 104 (79.4%) 42 35 (83.3%) 0.576 Sengstaken Blakemore 173 1 (0.6%) 131 0 (0%) 42 1 (2.4%) 0.077 Somatostatin and/or Octreotide 173 160 (92.5%) 131 119 (90.8%) 42 41 (97.6%) 0.147 Blood Transfusion 173 88 (50.9%) 131 62 (47.3%) 42 26 (61.9%) 0.100 PPIs 173 173 (100%) 131 131 (100%) 42 42 (100%) NA Surgery 173 0 (0%) 131 0 (0%) 42 0 (0%) NA 5-day Re-bleeding After Treatment 172 13 (7.6%) 130 9 (6.9%) 42 4 (9.5%) 0.579 Death During Hospitalization 173 4 (2.3%) 131 3 (2.3%) 42 1 (2.4%) 0.973 Length of Stay (days) 173 10.10 (0.12-32.94) 131 10.10 (0.12-32.94) 42 10.28 (5.02-31.06) 0.335 Total Payment (¥) 173 24,328.31 (3,427.24-98,215.78) 131 22,685.20 (3,427.24-98,215.78) 42 25,213.81 (9,970.37-81,125.52) 0.166 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


#### 3.2.2. Outcomes

No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.579, P=0.973, P=0.335, and P=0.166, respectively) (Table3).


#### 3.2.3. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 40 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table4. Median age was 56.86 years (range: 20.57 to 75.64). Among them, 28 (70%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=9, 22.5%) and alcohol abuse (n=14, 35%). A majority of patients had Child-Pugh class B (n=22, 55%). Median MELD score at admission was 5.82 (range: -2.38 to 23.19). No, mild, moderate, and severe esophageal varices were observed in 2 (5%), 5 (12.5%), 6 (15%), and 27 (67.5%) patients, respectively. As for the treatment of AUGIB, 38 (95%) patients underwent endoscopic therapy, no patient underwent Sengstaken Blackmore tube placement, 39 (97.5%) patients received somatostatin and/or octreotide, 21 (52.5%) patients received blood transfusion, all patients received PPIs, and no patient underwent surgery. Five-day rebleeding rate was 12.5% (n=5). In-hospital mortality was 2.5% (n=1). Median length of hospital stay was 11.95 days (range: 5.73 to 31.06). Median total payment was ¥24,961.33 (range: 11,212.15 to 81,125.52).Table 4
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in validation cohort.
Variables  Propensity matching patients  P value Overall (n=40) Regular hours (n=20) Off-hours (n=20) Age (years) 56.86 (20.57-75.64) 60.64 (20.57-75.64) 55.52 (35.18-74.33) 0.160 Sex (male) 28 (70%) 13 (65%) 15 (75%) 0.490 Etiology of Liver Diseases    0.622 HBV 9 (22.5%) 4 (20%) 5 (25%) HCV 4 (10%) 2 (10%) 2 (10%) Alcohol Abuse 14 (35%) 7 (35%) 7 (35%) Drug Related 2 (5%) 0 (0%) 2 (10%) Autoimmune Liver Diseases 1 (2.5%) 1 (5%) 0 (0%) Other or Unclear Etiology 10 (25%) 6 (30%) 4 (20%) Laboratory Tests Red Blood Cell (1012/L) 2.625 (1.65-3.89) 2.58 (1.69-3.89) 2.705 (1.65-3.78) 0.968 Hemoglobin (g/L) 74.50 (38.00-126.00) 77.00 (53.00-122.00) 72.50 (38.00-126.00) 0.473 White Blood Cell (109/L) 4.40 (1.80-14.90) 4.40 (2.20-11.70) 4.35 (1.80-14.90) 0.839 Platelet Count (109/L) 72.50 (27.00-301.00) 72.50 (27.00-301.00) 72.00 (32.00-145.00) 0.978 Total Bilirubin (umol/L) 18.10 (5.50-106.10) 16.85 (5.50-50.90) 18.10 (8.50-106.10) 0.256 Direct Bilirubin (umol/L) 7.85 (2.20-60.10) 7.10 (2.20-41.50) 7.95 (3.00-60.10) 0.675 Indirect Bilirubin (umol/L) 9.50 (2.80-46.00) 8.55 (2.80-22.10) 10.00 (5.40-46.00) 0.148 Albumin (g/L) 30.65 (18.00-39.20) 30.85 (19.00-38.60) 30.00 (18.00-39.20) 1 Alanine Aminotransferase (U/L) 21.805 (6.79-88.77) 21.805 (9.44-72.47) 20.415 (6.79-88.77) 0.756 Aspartate Aminotransferase (U/L) 25.635 (10.74-136.00) 28.38 (11.00-88.79) 25.635 (10.74-136.00) 0.978 Alkaline Phosphatase (U/L) 80.10 (40.34-234.00) 80.94 (40.34-234.00) 78.245 (46.24-149.45) 0.705 Gamma-glutamyl Transpeptidase (U/L) 41.245 (7.69-295.00) 40.48 (13.71-254.00) 42.765 (7.69-295.00) 0.935 Blood Urea Nitrogen (mmol/L) 7.395 (2.98-18.83) 7.055 (2.98-18.83) 8.40 (4.65-18.72) 0.245 Serum Creatinine (umol/L) 70.11 (34.90-143.10) 66.68 (42.60-95.20) 74.255 (34.90-143.10) 0.117 Potassium (mmol/L) 3.95 (3.10-4.66) 3.88 (3.10-4.66) 3.98 (3.27-4.59) 0.330 Sodium (mmol/L) 139.10 (124.00-145.70) 138.50 (135.00-141.40) 139.45 (124.00-145.70) 0.279 PT (seconds) 15.80 (13.30-24.50) 15.40 (13.30-23.90) 16.05 (13.50-24.50) 0.417 APTT (seconds) 36.25 (30.80-47.50) 35.90 (30.80-45.20) 37.15 (32.20-47.50) 0.351 INR 1.275 (1.02-2.19) 1.255 (1.08-2.08) 1.31 (1.02-2.19) 0.516 Child-Pugh Score 8.00 (5.00-12.00) 8.00 (5.00-12.00) 7.00 (5.00-12.00) 0.836 Child-Pugh A/B/C 14 (35%)/22 (55%)/4 (10%) 7 (35%)/12 (60%)/1 (5%) 7 (35%)/10 (50%)/3 (15%) 0.544 MELD Score 5.82 (-2.38-23.19) 5.51 (-1.04-14.75) 6.51 (-2.38-23.19) 0.245 Recalibrated MELD Score -4.11 (-5.80- -0.51) -4.17 (-5.53- -2.26) -3.96 (-5.80- -0.51) 0.245 ALBI Score -1.67 (-2.62- -0.49) -1.73 (-2.44- -0.49) -1.67 (-2.62- -0.60) 0.787 Esophageal Varices (No/Mild/Moderate/Severe) 2 (5%)/5 (12.5%)/6 (15%)/27 (67.5%) 1 (5%)/3 (15%)/3 (15%)/13 (65%) 1 (5%)/2 (10%)/3 (15%)/14 (70%) 0.971 Treatment Endoscopic Treatment 38 (95%) 19 (95%) 19 (95%) 1 Sengstaken Blakemore 0 (0%) 0(0%) 0(0%) NA Somatostatin 39 (97.5%) 20 (100%) 19 (95%) 0.311 Blood Transfusion 21 (52.5%) 9 (45%) 12 (60%) 0.342 PPIs 40 (100%) 20 (100%) 20 (100%) NA Surgery 0 (0%) 0 (0%) 0 (0%) NA 5-day Re-bleeding After Treatment 5 (12.5%) 2 (10%) 3 (15%) 0.633 Death During Hospitalization 1 (2.5%) 0 (0%) 1 (5%) 0.311 Length of Stay (days) 11.95 (5.73-31.06) 11.95 (5.73-21.95) 11.28 (7.52-31.06) 0.441 Total Payment (¥) 24,961.33 (11,212.15-81,125.52) 25,985.45 (15,513.68-56,952.12) 24,961.33 (11,212.15-81,125.52) 0.829 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: Prothrombin time; APTT: activated partial thromboplastin time; INR, International normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


#### 3.2.4. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 20 patients were matched on each group (Table4). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.633, P=0.311, P=0.441, and P=0.829, respectively).


## 3.1. Test Cohort

### 3.1.1. Patients’ Characteristics

Between January 2010 and June 2014, a total of 826 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table1. Median age was 55.27 years (range: 6.28 to 95.13). Among them, 564 (68.3%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=208, 25.2%) and alcohol abuse (n=219, 26.5%). A majority of patients had Child-Pugh class B (339/776, 51.4%). Median MELD score at admission was 6.37 (-7.52 to 38.22). Five hundred and twenty-two patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 32 (6.1%), 24 (4.6%), 54 (10.3%), and 412 (78.9%) patients, respectively. As for the treatment of AUGIB, 508 (61.5%) patients underwent endoscopic therapy, 20 (2.4%) patients underwent Sengstaken Blackmore tube placement, 750 (90.8%) patients received somatostatin and/or octreotide, 544 (65.9%) patients received blood transfusion, 813 (98.4%) patients received PPIs, and 8 (1.0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in 4 patients, because some of their medical records were missing. Five-day rebleeding rate was 14.0% (115/822). In-hospital mortality was 5.7% (47/826). Median length of hospital stay was 11.23 days (range: 0.06 to 100.55). Total payment was ¥23,120.87 (range: 1,287.54 to 226,872.93).Table 1
Characteristics of patients with liver cirrhosis and AUGIB in test cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 826 55.27 (6.28-95.13) 486 54.54 (20.88-95.13) 340 55.95 (6.28-84.56) 0.074 Sex (male) 826 564 (68.3%) 486 337 (69.3%) 340 227 (66.8%) 0.434 Etiology of Liver Diseases 826  486  340  0.387 HBV  208 (25.2%)  126 (25.9%)  82 (24.1%) HCV  51 (6.2%)  32 (6.6%)  19 (5.6%) HBV + HCV  6 (0.7%)  2 (0.4%)  4 (1.2%) Alcohol Abuse  219 (26.5%)  125 (25.7%)  94 (27.7%) HBV + Alcohol Abuse  64 (7.7%)  42 (8.6%)  22 (6.5%) HCV + Alcohol Abuse  13 (1.6%)  7 (1.4%)  6 (1.8%) HBV + HCV + Alcohol Abuse  2 (0.2%)  1 (0.2%)  1 (0.3%) Drug Related  35 (4.2%)  23 (4.7%)  12 (3.5%) Autoimmune Liver Diseases  56 (6.8%)  26 (5.4%)  30 (8.8%) Other or Unclear Etiology  172 (20.8%)  102 (21%)  70 (20.6%) Laboratory Tests Red Blood Cell (1012/L) 822 2.56 (0.93-5.49) 482 2.61 (0.93-5.49) 340 2.49 (1.05-5.10) 0.250 Hemoglobin (g/L) 822 72.00 (23.00-180.00) 482 73.00 (23.00-164.00) 340 71.00 (23.00-180.00) 0.512 White Blood Cell (109/L) 822 4.70 (0.40-46.10) 482 4.20 (0.80-33.50) 340 5.30 (0.90-46.10) <0.001 Platelet Count (109/L) 822 75.00 (9.00-842.00) 482 74.00 (9.00-842.00) 340 77.50 (17.00-775.00) 0.429 Total Bilirubin (umol/L) 820 20.30 (3.30-679.10) 480 20.10 (4.10-679.10) 340 20.50 (3.30-250.80) 0.598 Direct Bilirubin (umol/L) 820 8.30 (0.50-413.80) 480 8.20 (1.30-413.80) 340 8.50 (0.50-195.20) 0.916 Indirect Bilirubin (umol/L) 820 11.75 (1.30-265.30) 480 11.50 (1.30-265.30) 340 12.05 (2.00-126.60) 0.436 Albumin (g/L) 796 30.40 (9.60-49.30) 469 31.00 (9.60-49.30) 327 29.30 (10.00-48.00) <0.001 Alanine Aminotransferase (U/L) 818 23.00 (5.00-1064.00) 479 23.00 (5.00-730.00) 339 24.00 (5.00-1064.00) 0.403 Aspartate Aminotransferase (U/L) 818 31.00 (7.00-1487.00) 479 31.00 (7.00-1399.00) 339 32.00 (8.00-1487.00) 0.255 Alkaline Phosphatase (U/L) 818 73.00 (1.30-889.00) 479 74.00 (17.44-889.00) 339 72.00 (1.30-688.00) 0.535 Gamma-glutamyl Transpeptidase (U/L) 818 35.00 (5.00-1168.00) 479 35.00 (5.00-1168.00) 339 37.00 (6.00-755.00) 0.945 Blood Urea Nitrogen (mmol/L) 792 7.71 (1.58-42.83) 465 7.06 (1.58-42.83) 327 8.21 (1.96-37.67) <0.001 Serum Creatinine (umol/L) 791 61.00 (20.00-919.00) 465 60.00 (20.00-919.00) 326 61.00 (24.00-327.00) 0.284 Potassium (mmol/L) 810 4.06 (2.13-7.87) 473 4.00 (2.13-7.07) 337 4.12 (2.79-7.78) <0.001 Sodium (mmol/L) 810 138.80 (83.00-160.80) 473 139.10 (83.00-160.80) 337 138.50 (116.40-152.40) 0.055 PT (seconds) 794 16.20 (10.80-62.80) 465 15.90 (10.80-62.80) 329 16.50 (11.00-49.50) 0.034 APTT (seconds) 791 40.30 (25.70-180.00) 463 40.50 (25.7-180.00) 328 39.95 (27.30-97.20) 0.452 INR 791 1.31 (0.77-7.96) 463 1.28 (0.77-7.96) 328 1.35 (0.79-5.94) 0.040 Child-Pugh Score 776 7.00 (5.00-15.00) 455 7.00 (5.00-15.00) 321 7.00 (5.00-15.00) 0.006 Child-Pugh A/B/C 776 234 (30.2%)/339(51.4%)/143 (18.4%) 455 160 (35.2%)/216(47.5%)/79 (17.3%) 321 74 (23.1%)/183(57.0%)/64 (19.9%) 0.001 MELD Score 772 6.37 (-7.52-38.22) 453 5.87 (-7.52-38.22) 319 7.06 (-7.44-37.65) 0.067 Recalibrated MELD Score 772 -4.00 (-6.87-2.60) 453 -4.10 (-6.87-2.60) 319 -3.85 (-6.85-2.48) 0.067 ALBI Score 793 -1.70 (-3.31-0.22) 467 -1.77 (-3.31-0.03) 326 -1.59 (-3.13-0.22) <0.001 Esophageal Varices (No/Mild/Moderate/Severe) 522 32 (6.1%)/24 (4.6%)/54 (10.3%)/412 (78.9%) 309 20 (6.5%)/17 (5.5%)/32(10.4%)/240 (77.6%) 213 12 (5.6%)/7 (3.3%)/22 (10.3%)/172 (80.8%) 0.650 Treatment Endoscopic Treatment 826 508 (61.5%) 486 310 (63.8%) 340 198 (58.2%) 0.107 Sengstaken Blakemore 826 20 (2.4%) 486 12 (2.5%) 340 8 (2.4%) 0.915 Somatostatin and/or Octreotide 826 750 (90.8%) 486 435 (80.5%) 340 315 (92.7%) 0.124 Blood Transfusion 826 544 (65.9%) 486 295 (60.7%) 340 249 (73.3%) <0.001 PPIs 826 813 (98.4%) 486 477 (98.2%) 340 336 (98.8%) 0.443 Surgery 826 8 (1.0%) 486 2 (0.4%) 340 6 (1.8%) 0.051 5-day Re-bleeding After Treatment 822 115 (14.0%) 485 52 (10.7%) 337 63 (18.7%) 0.001 Death During Hospitalization 826 47 (5.7%) 486 25 (5.1%) 340 22(6.5%) 0.418 Length of Stay (days) 826 11.23 (0.06-100.55) 486 11.27 (0.06-78.00) 340 11.13 (0.09-100.55) 0.830 Total Payment (¥) 826 23,120.87 (1,287.54-226,872.93) 486 22,017.42 (1,683.37-126,413.58) 340 25,906.83 (1,287.54-226,872.93) <0.001 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


### 3.1.2. Outcome

Patients admitted on off-hours had lower serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P<0.001), prothrombin time (P=0.034), INR (P=0.040), Child-Pugh score (P=0.006), and ALBI score (P<0.001) than those admitted on regular hours (Table1). As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion than those admitted on regular hours (73.3% versus 60.7%, P<0.001). Among the different departments of our hospital, there was no significant difference in the selection of most treatment options for AUGIB between patients admitted on regular hours and off-hours (Supplementary Table 1). As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (18.7% versus 10.7%, P=0.001) and a larger amount of payment (¥25,906.83 versus ¥22,017.42, P<0.001). In-hospital mortality was not significantly different between the two groups (P=0.418). Length of stay was not significantly different between the two groups (P=0.830).


### 3.1.3. Subgroup Analyses

The origin of bleeding could be evaluated in 611 patients in the test cohort. They included 591 patients with endoscopically confirmed esophageal and/or gastric varices and 20 patients without varices at endoscopy (Supplementary Table2).Among the patients with endoscopically confirmed varices, patients admitted on off-hours were older (P=0.015) and had lower red blood cell (P=0.026) and serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P=0.001), prothrombin time (P=0.027), INR (P=0.04), Child-Pugh score (P<0.001), MELD score (P=0.023), recalibrated MELD score (P=0.023), and ALBI score (P<0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (75.5% versus 59.5%, P<0.001) and surgery (2.1% versus 0.3%, P=0.027) than those admitted on regular hours. As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (16.5% versus 10.6%, P=0.038) and a larger amount of payment (¥29,361.51 versus ¥23,864.24, P<0.001). In-hospital mortality and length of stay were not significantly different between the two groups (P=0.094 and P=0.856, respectively).Among the patients without varices at endoscopy, no significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between patients admitted on regular hours and off-hours (P>0.05, in all comparisons). As for the outcomes, none died. Five-day rebleeding rate, length of stay, and total payment were not significantly different between the two groups (P=0.117, P=0.869, and P=0.187, respectively).


### 3.1.4. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 226 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table2. Median age was 54.51 years (range: 6.28 to 81.62). Among them, 144 (63.7%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=58, 25.7%) and alcohol abuse (n=50, 22. 1%). A majority of patients had Child-Pugh class B (n=121, 53.5%). Median MELD score at admission was 6.12 (-7.14 to 21.56). No, mild, moderate, and severe esophageal varices were observed in 11 (4.9%), 19 (4.4%), 23 (10.2%), and 182 (80.5%) patients, respectively. As for the treatment of AUGIB, 191 (84.5%) patients underwent endoscopic therapy, 8 (3.5%) patients underwent Sengstaken Blackmore tube placement, 218 (96.5%) patients received somatostatin and/or octreotide, 159 (70.4%) patients received blood transfusion, all patients received PPIs, and 1 (0.4%) patient underwent surgery. Five-day rebleeding rate was 14.2% (n=32). In-hospital mortality was 2.2% (n=5). Median length of hospital stay was 12.835 days (range: 2.76 to 78.00). Median total payment was ¥28,633.075 (range: 2,776.55 to 143,048.30).Table 2
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in test cohort.
Variables  Propensity matching patients  P value Overall (n=226) Regular hours (n=113) Off-hours (n=113) Age (years) 54.51 (6.28-81.62) 54.41 (29.85-81.62) 54.60 (6.28-78.66) 0.829 Sex (male) 144 (63.7%) 73 (64.6%) 71 (62.8%) 0.782 Etiology of Liver Diseases    0.612 HBV 58 (25.7%) 29 (25.7%) 29 (25.7%) HCV 14 (6.2%) 7 (6.2%) 7 (6.2%) HBV+ HCV 1 (0.4%) 1 (0.9%) 0 (0%) Alcohol Abuse 50 (22.1%) 26 (23.0%) 24 (21.2%) HBV+ Alcohol Abuse 26 (11.5%) 15 (13.3%) 11 (9.7%) HCV+ Alcohol Abuse 3 (1.3%) 0 (0%) 3 (2.7%) HBV+ HCV+ Alcohol Abuse 1 (0.4%) 0 (0%) 1 (0.9%) Drug Related 10 (4.4%) 5 (4.4%) 5 (4.4%) Autoimmune Liver Diseases 12 (5.3%) 5 (4.4%) 7 (6.2%) Other or Unclear Etiology 51 (22.6%) 25 (22.1%) 26 (23.0%) Laboratory Tests Red Blood Cell (1012/L) 2.54 (0.98-5.49) 2.60 (0.98-5.49) 2.53 (1.15-4.68) 0.989 Hemoglobin (g/L) 71.50 (23.00-157.00) 72.00 (23.00-157.00) 71.00 (23.00-133.00) 0.901 White Blood Cell (109/L) 4.30 (1.00-26.30) 4.10 (1.10-26.30) 4.40 (1.00-17.50) 0.239 Platelet Count (109/L) 74.00 (17.00-435.00) 72.00 (27.00-303.00) 79.00 (17.00-435.00) 0.538 Total Bilirubin (umol/L) 18.80 (3.30-187.40) 19.00 (6.10-90.40) 18.40 (3.30-187.40) 0.669 Direct Bilirubin (umol/L) 7.50 (0.50-151.60) 7.50 (1.30-56.30) 7.20 (0.50-151.60) 0.384 Indirect Bilirubin (umol/L) 11.35 (2.40-56.80) 11.20 (3.20-41.10) 11.40 (2.40-56.80) 0.771 Albumin (g/L) 30.10 (10.00-49.30) 30.48 (10.50-49.30) 29.40 (10.00-45.60) 0.580 Alanine Aminotransferase (U/L) 23.00 (5.00-234.00) 23.00 (6.00-234.00) 23.00 (5.00-154.00) 0.896 Aspartate Aminotransferase (U/L) 31.00 (9.00-263.00) 31.00 (12.00-263.00) 31.00 (9.00-175.00) 0.872 Alkaline Phosphatase (U/L) 74.00 (17.44-707.00) 77.00 (17.44-707.00) 71.00 (21.00-685.00) 0.282 Gamma-glutamyl Transpeptidase (U/L) 36.00 (8.00-1168.00) 45.00 (8.00-1168.00) 33.00 (9.00-737.00) 0.354 Blood Urea Nitrogen (mmol/L) 7.62 (1.96-34.00) 7.66 (2.04-34.00) 7.61 (1.96-28.10) 0.989 Serum Creatinine (umol/L) 60.00 (28.00-234.00) 60.00 (28.00-225.70) 59.00 (30.50-234.00) 0.655 Potassium (mmol/L) 4.06 (2.90-5.50) 4.05 (3.00-5.50) 4.08 (2.90-5.50) 0.285 Sodium (mmol/L) 138.50 (128.00-150.00) 138.30 (130.40-148.00) 138.50 (128.00-150.00) 0.773 PT (seconds) 15.80 (11.00-46.30) 15.60 (12.10-36.10) 16.00 (11.00-46.30) 0.912 APTT (seconds) 39.55 (27.30-66.80) 40.10 (28.20-66.80) 38.50 (27.30-63.90) 0.253 INR 1.28 (0.79-4.77) 1.26 (0.90-3.57) 1.29 (0.79-4.77) 0.950 Child-Pugh Score 7.00 (5.00-13.00) 7.00 (5.00-12.00) 7.00 (5.00-13.00) 0.891 Child-Pugh A/B/C 72 (31.9%)/121 (53.5%)/33 (14.6%) 35 (31.0%)/64 (56.6%)/14 (12.4%) 37 (32.7%)/57 (50.5%)/19 (16.8%) 0.544 MELD Score 6.12 (-7.14-21.56) 6.12 (-5.03-20.16) 5.68 (-7.14-21.56) 0.733 Recalibrated MELD Score -4.05 (-6.79 - -0.85) -4.04 (-6.35 - -1.14) -4.14 (-6.79 - -0.85) 0.733 ALBI Score -1.70 (-3.23-0.22) -1.70 (-3.23 - -0.43) -1.69 (-3.06-0.22) 0.767 Esophageal Varices(No/Mild/Moderate/Severe) 11 (4.9%)/10 (4.4%)/23(10.2%)/182 (80.5%) 5 (4.4%)/5 (4.4%)/11(9.8%)/92 (81.4%) 6 (5.3%)/5 (4.4%)/12(10.6%)/90 (79.7%) 0.984 Treatment Endoscopic Treatment 191 (84.5%) 96 (85.0%) 95 (84.1%) 0.854 Sengstaken Blakemore 8 (3.5%) 5 (4.4%) 3 (2.7%) 0.472 Somatostatin and/or Octreotide 218 (96.5%) 107 (94.7%) 111 (98.2%) 0.150 Blood Transfusion 159 (70.4%) 80 (70.8%) 79 (69.9%) 0.884 PPIs 226 (100%) 113 (100%) 113 (100%) NA Surgery 1 (0.4%) 1 (0.9%) 0 (0%) 0.316 5-day Re-bleeding After Treatment 32 (14.2%) 14 (12.4%) 18 (15.9%) 0.445 Death During Hospitalization 5 (2.2%) 2 (1.8%) 3 (2.7%) 0.651 Length of Stay (days) 12.835 (2.76-78.00) 12.97 (3.91-78.00) 12.41 (2.76-45.26) 0.229 Total Payment (¥) 28,633.075 (2,776.55-143,048.30) 26,733.81 (2,776.55-115,201.67) 29,361.51 (5,856.09-143,048.30) 0.390 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT, prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: Proton pump inhibitors; ¥, Renminbi.


### 3.1.5. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 113 patients were matched on each group (Table2). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.445, P=0.651, P=0.229, and P=0.390, respectively).


### 3.1.6. Subgroup Analyses after Propensity Score Matching

After a 1:1 propensity score matching analysis, 140 patients with endoscopically confirmed varices were matched on each group (Supplementary Table3). Patients admitted on off-hours had higher white blood cell (P=0.007), blood urea nitrogen (P=0.01), and potassium (P=0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (77.1% versus 58.6%, P=0.001) and surgery (2.9% versus 0%, P=0.044) than those admitted on regular hours. As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.306, P=0.409, P=0.421, and P=0.058, respectively).


## 3.1.1. Patients’ Characteristics

Between January 2010 and June 2014, a total of 826 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table1. Median age was 55.27 years (range: 6.28 to 95.13). Among them, 564 (68.3%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=208, 25.2%) and alcohol abuse (n=219, 26.5%). A majority of patients had Child-Pugh class B (339/776, 51.4%). Median MELD score at admission was 6.37 (-7.52 to 38.22). Five hundred and twenty-two patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 32 (6.1%), 24 (4.6%), 54 (10.3%), and 412 (78.9%) patients, respectively. As for the treatment of AUGIB, 508 (61.5%) patients underwent endoscopic therapy, 20 (2.4%) patients underwent Sengstaken Blackmore tube placement, 750 (90.8%) patients received somatostatin and/or octreotide, 544 (65.9%) patients received blood transfusion, 813 (98.4%) patients received PPIs, and 8 (1.0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in 4 patients, because some of their medical records were missing. Five-day rebleeding rate was 14.0% (115/822). In-hospital mortality was 5.7% (47/826). Median length of hospital stay was 11.23 days (range: 0.06 to 100.55). Total payment was ¥23,120.87 (range: 1,287.54 to 226,872.93).Table 1
Characteristics of patients with liver cirrhosis and AUGIB in test cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 826 55.27 (6.28-95.13) 486 54.54 (20.88-95.13) 340 55.95 (6.28-84.56) 0.074 Sex (male) 826 564 (68.3%) 486 337 (69.3%) 340 227 (66.8%) 0.434 Etiology of Liver Diseases 826  486  340  0.387 HBV  208 (25.2%)  126 (25.9%)  82 (24.1%) HCV  51 (6.2%)  32 (6.6%)  19 (5.6%) HBV + HCV  6 (0.7%)  2 (0.4%)  4 (1.2%) Alcohol Abuse  219 (26.5%)  125 (25.7%)  94 (27.7%) HBV + Alcohol Abuse  64 (7.7%)  42 (8.6%)  22 (6.5%) HCV + Alcohol Abuse  13 (1.6%)  7 (1.4%)  6 (1.8%) HBV + HCV + Alcohol Abuse  2 (0.2%)  1 (0.2%)  1 (0.3%) Drug Related  35 (4.2%)  23 (4.7%)  12 (3.5%) Autoimmune Liver Diseases  56 (6.8%)  26 (5.4%)  30 (8.8%) Other or Unclear Etiology  172 (20.8%)  102 (21%)  70 (20.6%) Laboratory Tests Red Blood Cell (1012/L) 822 2.56 (0.93-5.49) 482 2.61 (0.93-5.49) 340 2.49 (1.05-5.10) 0.250 Hemoglobin (g/L) 822 72.00 (23.00-180.00) 482 73.00 (23.00-164.00) 340 71.00 (23.00-180.00) 0.512 White Blood Cell (109/L) 822 4.70 (0.40-46.10) 482 4.20 (0.80-33.50) 340 5.30 (0.90-46.10) <0.001 Platelet Count (109/L) 822 75.00 (9.00-842.00) 482 74.00 (9.00-842.00) 340 77.50 (17.00-775.00) 0.429 Total Bilirubin (umol/L) 820 20.30 (3.30-679.10) 480 20.10 (4.10-679.10) 340 20.50 (3.30-250.80) 0.598 Direct Bilirubin (umol/L) 820 8.30 (0.50-413.80) 480 8.20 (1.30-413.80) 340 8.50 (0.50-195.20) 0.916 Indirect Bilirubin (umol/L) 820 11.75 (1.30-265.30) 480 11.50 (1.30-265.30) 340 12.05 (2.00-126.60) 0.436 Albumin (g/L) 796 30.40 (9.60-49.30) 469 31.00 (9.60-49.30) 327 29.30 (10.00-48.00) <0.001 Alanine Aminotransferase (U/L) 818 23.00 (5.00-1064.00) 479 23.00 (5.00-730.00) 339 24.00 (5.00-1064.00) 0.403 Aspartate Aminotransferase (U/L) 818 31.00 (7.00-1487.00) 479 31.00 (7.00-1399.00) 339 32.00 (8.00-1487.00) 0.255 Alkaline Phosphatase (U/L) 818 73.00 (1.30-889.00) 479 74.00 (17.44-889.00) 339 72.00 (1.30-688.00) 0.535 Gamma-glutamyl Transpeptidase (U/L) 818 35.00 (5.00-1168.00) 479 35.00 (5.00-1168.00) 339 37.00 (6.00-755.00) 0.945 Blood Urea Nitrogen (mmol/L) 792 7.71 (1.58-42.83) 465 7.06 (1.58-42.83) 327 8.21 (1.96-37.67) <0.001 Serum Creatinine (umol/L) 791 61.00 (20.00-919.00) 465 60.00 (20.00-919.00) 326 61.00 (24.00-327.00) 0.284 Potassium (mmol/L) 810 4.06 (2.13-7.87) 473 4.00 (2.13-7.07) 337 4.12 (2.79-7.78) <0.001 Sodium (mmol/L) 810 138.80 (83.00-160.80) 473 139.10 (83.00-160.80) 337 138.50 (116.40-152.40) 0.055 PT (seconds) 794 16.20 (10.80-62.80) 465 15.90 (10.80-62.80) 329 16.50 (11.00-49.50) 0.034 APTT (seconds) 791 40.30 (25.70-180.00) 463 40.50 (25.7-180.00) 328 39.95 (27.30-97.20) 0.452 INR 791 1.31 (0.77-7.96) 463 1.28 (0.77-7.96) 328 1.35 (0.79-5.94) 0.040 Child-Pugh Score 776 7.00 (5.00-15.00) 455 7.00 (5.00-15.00) 321 7.00 (5.00-15.00) 0.006 Child-Pugh A/B/C 776 234 (30.2%)/339(51.4%)/143 (18.4%) 455 160 (35.2%)/216(47.5%)/79 (17.3%) 321 74 (23.1%)/183(57.0%)/64 (19.9%) 0.001 MELD Score 772 6.37 (-7.52-38.22) 453 5.87 (-7.52-38.22) 319 7.06 (-7.44-37.65) 0.067 Recalibrated MELD Score 772 -4.00 (-6.87-2.60) 453 -4.10 (-6.87-2.60) 319 -3.85 (-6.85-2.48) 0.067 ALBI Score 793 -1.70 (-3.31-0.22) 467 -1.77 (-3.31-0.03) 326 -1.59 (-3.13-0.22) <0.001 Esophageal Varices (No/Mild/Moderate/Severe) 522 32 (6.1%)/24 (4.6%)/54 (10.3%)/412 (78.9%) 309 20 (6.5%)/17 (5.5%)/32(10.4%)/240 (77.6%) 213 12 (5.6%)/7 (3.3%)/22 (10.3%)/172 (80.8%) 0.650 Treatment Endoscopic Treatment 826 508 (61.5%) 486 310 (63.8%) 340 198 (58.2%) 0.107 Sengstaken Blakemore 826 20 (2.4%) 486 12 (2.5%) 340 8 (2.4%) 0.915 Somatostatin and/or Octreotide 826 750 (90.8%) 486 435 (80.5%) 340 315 (92.7%) 0.124 Blood Transfusion 826 544 (65.9%) 486 295 (60.7%) 340 249 (73.3%) <0.001 PPIs 826 813 (98.4%) 486 477 (98.2%) 340 336 (98.8%) 0.443 Surgery 826 8 (1.0%) 486 2 (0.4%) 340 6 (1.8%) 0.051 5-day Re-bleeding After Treatment 822 115 (14.0%) 485 52 (10.7%) 337 63 (18.7%) 0.001 Death During Hospitalization 826 47 (5.7%) 486 25 (5.1%) 340 22(6.5%) 0.418 Length of Stay (days) 826 11.23 (0.06-100.55) 486 11.27 (0.06-78.00) 340 11.13 (0.09-100.55) 0.830 Total Payment (¥) 826 23,120.87 (1,287.54-226,872.93) 486 22,017.42 (1,683.37-126,413.58) 340 25,906.83 (1,287.54-226,872.93) <0.001 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


## 3.1.2. Outcome

Patients admitted on off-hours had lower serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P<0.001), prothrombin time (P=0.034), INR (P=0.040), Child-Pugh score (P=0.006), and ALBI score (P<0.001) than those admitted on regular hours (Table1). As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion than those admitted on regular hours (73.3% versus 60.7%, P<0.001). Among the different departments of our hospital, there was no significant difference in the selection of most treatment options for AUGIB between patients admitted on regular hours and off-hours (Supplementary Table 1). As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (18.7% versus 10.7%, P=0.001) and a larger amount of payment (¥25,906.83 versus ¥22,017.42, P<0.001). In-hospital mortality was not significantly different between the two groups (P=0.418). Length of stay was not significantly different between the two groups (P=0.830).


## 3.1.3. Subgroup Analyses

The origin of bleeding could be evaluated in 611 patients in the test cohort. They included 591 patients with endoscopically confirmed esophageal and/or gastric varices and 20 patients without varices at endoscopy (Supplementary Table2).Among the patients with endoscopically confirmed varices, patients admitted on off-hours were older (P=0.015) and had lower red blood cell (P=0.026) and serum albumin (P<0.001) and higher white blood cell (P<0.001), blood urea nitrogen (P<0.001), potassium (P=0.001), prothrombin time (P=0.027), INR (P=0.04), Child-Pugh score (P<0.001), MELD score (P=0.023), recalibrated MELD score (P=0.023), and ALBI score (P<0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (75.5% versus 59.5%, P<0.001) and surgery (2.1% versus 0.3%, P=0.027) than those admitted on regular hours. As for the outcomes, patients admitted on off-hours had a higher 5-day rebleeding rate (16.5% versus 10.6%, P=0.038) and a larger amount of payment (¥29,361.51 versus ¥23,864.24, P<0.001). In-hospital mortality and length of stay were not significantly different between the two groups (P=0.094 and P=0.856, respectively).Among the patients without varices at endoscopy, no significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between patients admitted on regular hours and off-hours (P>0.05, in all comparisons). As for the outcomes, none died. Five-day rebleeding rate, length of stay, and total payment were not significantly different between the two groups (P=0.117, P=0.869, and P=0.187, respectively).


## 3.1.4. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 226 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table2. Median age was 54.51 years (range: 6.28 to 81.62). Among them, 144 (63.7%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=58, 25.7%) and alcohol abuse (n=50, 22. 1%). A majority of patients had Child-Pugh class B (n=121, 53.5%). Median MELD score at admission was 6.12 (-7.14 to 21.56). No, mild, moderate, and severe esophageal varices were observed in 11 (4.9%), 19 (4.4%), 23 (10.2%), and 182 (80.5%) patients, respectively. As for the treatment of AUGIB, 191 (84.5%) patients underwent endoscopic therapy, 8 (3.5%) patients underwent Sengstaken Blackmore tube placement, 218 (96.5%) patients received somatostatin and/or octreotide, 159 (70.4%) patients received blood transfusion, all patients received PPIs, and 1 (0.4%) patient underwent surgery. Five-day rebleeding rate was 14.2% (n=32). In-hospital mortality was 2.2% (n=5). Median length of hospital stay was 12.835 days (range: 2.76 to 78.00). Median total payment was ¥28,633.075 (range: 2,776.55 to 143,048.30).Table 2
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in test cohort.
Variables  Propensity matching patients  P value Overall (n=226) Regular hours (n=113) Off-hours (n=113) Age (years) 54.51 (6.28-81.62) 54.41 (29.85-81.62) 54.60 (6.28-78.66) 0.829 Sex (male) 144 (63.7%) 73 (64.6%) 71 (62.8%) 0.782 Etiology of Liver Diseases    0.612 HBV 58 (25.7%) 29 (25.7%) 29 (25.7%) HCV 14 (6.2%) 7 (6.2%) 7 (6.2%) HBV+ HCV 1 (0.4%) 1 (0.9%) 0 (0%) Alcohol Abuse 50 (22.1%) 26 (23.0%) 24 (21.2%) HBV+ Alcohol Abuse 26 (11.5%) 15 (13.3%) 11 (9.7%) HCV+ Alcohol Abuse 3 (1.3%) 0 (0%) 3 (2.7%) HBV+ HCV+ Alcohol Abuse 1 (0.4%) 0 (0%) 1 (0.9%) Drug Related 10 (4.4%) 5 (4.4%) 5 (4.4%) Autoimmune Liver Diseases 12 (5.3%) 5 (4.4%) 7 (6.2%) Other or Unclear Etiology 51 (22.6%) 25 (22.1%) 26 (23.0%) Laboratory Tests Red Blood Cell (1012/L) 2.54 (0.98-5.49) 2.60 (0.98-5.49) 2.53 (1.15-4.68) 0.989 Hemoglobin (g/L) 71.50 (23.00-157.00) 72.00 (23.00-157.00) 71.00 (23.00-133.00) 0.901 White Blood Cell (109/L) 4.30 (1.00-26.30) 4.10 (1.10-26.30) 4.40 (1.00-17.50) 0.239 Platelet Count (109/L) 74.00 (17.00-435.00) 72.00 (27.00-303.00) 79.00 (17.00-435.00) 0.538 Total Bilirubin (umol/L) 18.80 (3.30-187.40) 19.00 (6.10-90.40) 18.40 (3.30-187.40) 0.669 Direct Bilirubin (umol/L) 7.50 (0.50-151.60) 7.50 (1.30-56.30) 7.20 (0.50-151.60) 0.384 Indirect Bilirubin (umol/L) 11.35 (2.40-56.80) 11.20 (3.20-41.10) 11.40 (2.40-56.80) 0.771 Albumin (g/L) 30.10 (10.00-49.30) 30.48 (10.50-49.30) 29.40 (10.00-45.60) 0.580 Alanine Aminotransferase (U/L) 23.00 (5.00-234.00) 23.00 (6.00-234.00) 23.00 (5.00-154.00) 0.896 Aspartate Aminotransferase (U/L) 31.00 (9.00-263.00) 31.00 (12.00-263.00) 31.00 (9.00-175.00) 0.872 Alkaline Phosphatase (U/L) 74.00 (17.44-707.00) 77.00 (17.44-707.00) 71.00 (21.00-685.00) 0.282 Gamma-glutamyl Transpeptidase (U/L) 36.00 (8.00-1168.00) 45.00 (8.00-1168.00) 33.00 (9.00-737.00) 0.354 Blood Urea Nitrogen (mmol/L) 7.62 (1.96-34.00) 7.66 (2.04-34.00) 7.61 (1.96-28.10) 0.989 Serum Creatinine (umol/L) 60.00 (28.00-234.00) 60.00 (28.00-225.70) 59.00 (30.50-234.00) 0.655 Potassium (mmol/L) 4.06 (2.90-5.50) 4.05 (3.00-5.50) 4.08 (2.90-5.50) 0.285 Sodium (mmol/L) 138.50 (128.00-150.00) 138.30 (130.40-148.00) 138.50 (128.00-150.00) 0.773 PT (seconds) 15.80 (11.00-46.30) 15.60 (12.10-36.10) 16.00 (11.00-46.30) 0.912 APTT (seconds) 39.55 (27.30-66.80) 40.10 (28.20-66.80) 38.50 (27.30-63.90) 0.253 INR 1.28 (0.79-4.77) 1.26 (0.90-3.57) 1.29 (0.79-4.77) 0.950 Child-Pugh Score 7.00 (5.00-13.00) 7.00 (5.00-12.00) 7.00 (5.00-13.00) 0.891 Child-Pugh A/B/C 72 (31.9%)/121 (53.5%)/33 (14.6%) 35 (31.0%)/64 (56.6%)/14 (12.4%) 37 (32.7%)/57 (50.5%)/19 (16.8%) 0.544 MELD Score 6.12 (-7.14-21.56) 6.12 (-5.03-20.16) 5.68 (-7.14-21.56) 0.733 Recalibrated MELD Score -4.05 (-6.79 - -0.85) -4.04 (-6.35 - -1.14) -4.14 (-6.79 - -0.85) 0.733 ALBI Score -1.70 (-3.23-0.22) -1.70 (-3.23 - -0.43) -1.69 (-3.06-0.22) 0.767 Esophageal Varices(No/Mild/Moderate/Severe) 11 (4.9%)/10 (4.4%)/23(10.2%)/182 (80.5%) 5 (4.4%)/5 (4.4%)/11(9.8%)/92 (81.4%) 6 (5.3%)/5 (4.4%)/12(10.6%)/90 (79.7%) 0.984 Treatment Endoscopic Treatment 191 (84.5%) 96 (85.0%) 95 (84.1%) 0.854 Sengstaken Blakemore 8 (3.5%) 5 (4.4%) 3 (2.7%) 0.472 Somatostatin and/or Octreotide 218 (96.5%) 107 (94.7%) 111 (98.2%) 0.150 Blood Transfusion 159 (70.4%) 80 (70.8%) 79 (69.9%) 0.884 PPIs 226 (100%) 113 (100%) 113 (100%) NA Surgery 1 (0.4%) 1 (0.9%) 0 (0%) 0.316 5-day Re-bleeding After Treatment 32 (14.2%) 14 (12.4%) 18 (15.9%) 0.445 Death During Hospitalization 5 (2.2%) 2 (1.8%) 3 (2.7%) 0.651 Length of Stay (days) 12.835 (2.76-78.00) 12.97 (3.91-78.00) 12.41 (2.76-45.26) 0.229 Total Payment (¥) 28,633.075 (2,776.55-143,048.30) 26,733.81 (2,776.55-115,201.67) 29,361.51 (5,856.09-143,048.30) 0.390 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT, prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: Proton pump inhibitors; ¥, Renminbi.


## 3.1.5. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 113 patients were matched on each group (Table2). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.445, P=0.651, P=0.229, and P=0.390, respectively).


## 3.1.6. Subgroup Analyses after Propensity Score Matching

After a 1:1 propensity score matching analysis, 140 patients with endoscopically confirmed varices were matched on each group (Supplementary Table3). Patients admitted on off-hours had higher white blood cell (P=0.007), blood urea nitrogen (P=0.01), and potassium (P=0.001) than those admitted on regular hours. As for the interventions, patients admitted on off-hours had a higher proportion of blood transfusion (77.1% versus 58.6%, P=0.001) and surgery (2.9% versus 0%, P=0.044) than those admitted on regular hours. As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.306, P=0.409, P=0.421, and P=0.058, respectively).


## 3.2. Validation Cohort

### 3.2.1. Patients’ Characteristics

Between December 2014 and March 2018, a total of 173 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table3. Median age was 56.60 years (range: 20.57 to 88.73). Among them, 121 (69.9%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=47, 27.2%) and alcohol abuse (n=55, 31.8%). A majority of patients had Child-Pugh class B (94/169, 55.6%). Median MELD score at admission was 7.22 (-3.16 to 23.19). One hundred and fifty-one patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 9 (6.0%), 23 (15.2%), 26 (17.2%), and 93 (61.6%) patients, respectively. The origin of bleeding could be evaluated in 162 patients, of whom only 4 did not have esophageal and/or gastric varices. As for the treatment of AUGIB, 139 (80.3%) patients underwent endoscopic therapy, 1 (0.6%) patients underwent Sengstaken Blackmore tube placement, 160 (92.5%) patients received somatostatin and/or octreotide, 88 (50.9%) patients received blood transfusion, 173 (100%) patients received PPIs, and 0 (0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in one patient. Five-day rebleeding rate was 7.6% (13/172). In-hospital mortality was 2.3% (4/173). Median length of hospital stay was 10.10 days (range: 0.12 to 32.94). Total payment was ¥24,328.31 (range: 3,427.24 to 98,215.78).Table 3
Characteristics of patients with liver cirrhosis and AUGIB in validation cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 173 56.60 (20.57-88.73) 131 56.60 (20.57-75.73) 42 56.56 (33.42-88.73) 0.683 Sex (male) 173 121 (69.9%) 131 91 (69.5%) 42 30 (71.4%) 0.809 Etiology of Liver Diseases 173  131  42  0.830 HBV  47 (27.2%)  37 (28.2%)  10 (23.8%) HCV  17 (9.8%)  12 (9.2%)  5 (11.9%) Alcohol Abuse  55 (31.8%)  41 (31.3%)  14 (33.3%) HBV + Alcohol Abuse  3 (1.7%)  2 (1.5%)  1 (2.4%) HBV + HCV + Alcohol Abuse  1 (0.6%)  1 (0.8%)  0 (0%) Drug Related  1 (0.6%)  1 (0.8%)  0 (0%) Autoimmune Liver Diseases  3 (1.7%)  3 (2.3%)  0 (0%) Other or Unclear Etiology  46 (26.6%)  34 (25.9%)  12 (28.6%) Laboratory Tests Red Blood Cell (1012/L) 173 2.70 (1.32-5.11) 131 2.70 (1.32-5.11) 42 2.62 (1.56-4.14) 0.372 Hemoglobin (g/L) 173 73.00 (31.00-156.00) 131 73.00 (31.00-156.00) 42 73.50 (38.00-130.00) 0.575 White Blood Cell (109/L) 173 4.20 (1.00-23.10) 131 4.10 (1.00-23.10) 42 4.35 (1.70-14.90) 0.368 Platelet Count (109/L) 173 71.00 (18.00-457.00) 131 73.00 (18.00-377.00) 42 68.50 (23.00-457.00) 0.980 Total Bilirubin (umol/L) 172 20.80 (5.20-210.00) 131 21.60 (5.20-210.00) 41 18.30 (6.70-106.10) 0.587 Direct Bilirubin (umol/L) 172 8.70 (2.00-146.90) 131 9.00 (2.00-146.90) 41 8.30 (2.50-60.10) 0.643 Indirect Bilirubin (umol/L) 172 10.65 (2.60-79.90) 131 11.40 (2.60-69.20) 41 9.80 (4.20-79.90) 0.801 Albumin (g/L) 171 29.40 (17.00-50.70) 130 29.65 (17.20-50.70) 41 29.40 (17.00-41.00) 0.693 Alanine Aminotransferase (U/L) 172 20.70 (5.00-275.36) 131 20.98 (6.00-140.00) 41 17.17 (5.00-275.36) 0.504 Aspartate Aminotransferase (U/L) 172 27.00 (9.63-310.39) 131 27.50 (9.63-278.00) 41 26.11 (10.00-310.39) 0.801 Alkaline Phosphatase (U/L) 172 78.23 (24.02-378.66) 131 75.66 (24.02-378.66) 41 79.75 (46.24-197.00) 0.981 Gamma-glutamyl Transpeptidase (U/L) 172 31.98 (7.54-1227.00) 131 29.61 (7.54-1227.00) 41 40.53 (7.69-295.00) 0.346 Blood Urea Nitrogen (mmol/L) 172 7.60 (2.17-47.25) 131 7.40 (2.17-47.25) 41 7.96 (2.47-20.15) 0.993 Serum Creatinine (umol/L) 172 69.145 (34.40-267.63) 131 67.03 (34.40-267.63) 41 74.21 (34.90-144.98) 0.116 Potassium (mmol/L) 173 3.95 (2.48-5.54) 131 3.95 (2.48-5.54) 42 3.97 (3.12-5.49) 0.876 Sodium (mmol/L) 173 138.50 (124.00-152.90) 131 138.40 (130.40-152.90) 42 138.80 (124.00-145.70) 0.544 PT (seconds) 171 16.10 (10.50-27.40) 131 16.10 (11.60-27.40) 40 16.05 (10.50-27.20) 0.606 APTT (seconds) 170 37.85 (19.40-59.70) 131 37.90 (27.50-59.70) 39 37.40 (19.40-52.10) 0.542 INR 170 1.32 (0.91-2.55) 131 1.33 (1.01-2.55) 39 1.31 (0.91-2.50) 0.681 Child-Pugh Score 169 8.00 (5.00-15.00) 130 8.00 (5.00-12.00) 39 7.00 (5.00-12.00) 0.603 Child-Pugh A/B/C 169 51 (30.2%)/94 (55.6%)/24 (14.2%) 130 37 (28.5%)/75 (57.7%)/18 (13.8%) 39 14 (35.9%)/19 (48.7%)/6 (15.4%) 0.596 MELD Score 170 7.22 (-3.16-23.19) 131 7.26 (-3.16-20.70) 39 7.22 (-2.38-23.19) 0.671 Recalibrated MELD Score 170 -3.82 (-5.97- -0.51) 131 -3.81 (-5.97- -1.03) 39 -3.82 (-5.80- -0.51) 0.671 ALBI Score 171 -1.63 (-3.40- -0.11) 130 -1.62 (-3.40- -0.11) 41 -1.68 (-2.70- -0.49) 0.675 Esophageal Varices (No/Mild/Moderate/Severe) 151 9 (6.0%)/23 (15.2%)/26 (17.2%)/93 (61.6%) 116 6 (5.2%)/18 (15.5%)/20 (17.2)/72 (61.1%) 35 3 (8.6%)/5 (14.3%)/6(17.1%)/21 (60.0%) 0.965 Treatment Endoscopic Treatment 173 139 (80.3%) 131 104 (79.4%) 42 35 (83.3%) 0.576 Sengstaken Blakemore 173 1 (0.6%) 131 0 (0%) 42 1 (2.4%) 0.077 Somatostatin and/or Octreotide 173 160 (92.5%) 131 119 (90.8%) 42 41 (97.6%) 0.147 Blood Transfusion 173 88 (50.9%) 131 62 (47.3%) 42 26 (61.9%) 0.100 PPIs 173 173 (100%) 131 131 (100%) 42 42 (100%) NA Surgery 173 0 (0%) 131 0 (0%) 42 0 (0%) NA 5-day Re-bleeding After Treatment 172 13 (7.6%) 130 9 (6.9%) 42 4 (9.5%) 0.579 Death During Hospitalization 173 4 (2.3%) 131 3 (2.3%) 42 1 (2.4%) 0.973 Length of Stay (days) 173 10.10 (0.12-32.94) 131 10.10 (0.12-32.94) 42 10.28 (5.02-31.06) 0.335 Total Payment (¥) 173 24,328.31 (3,427.24-98,215.78) 131 22,685.20 (3,427.24-98,215.78) 42 25,213.81 (9,970.37-81,125.52) 0.166 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


### 3.2.2. Outcomes

No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.579, P=0.973, P=0.335, and P=0.166, respectively) (Table3).


### 3.2.3. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 40 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table4. Median age was 56.86 years (range: 20.57 to 75.64). Among them, 28 (70%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=9, 22.5%) and alcohol abuse (n=14, 35%). A majority of patients had Child-Pugh class B (n=22, 55%). Median MELD score at admission was 5.82 (range: -2.38 to 23.19). No, mild, moderate, and severe esophageal varices were observed in 2 (5%), 5 (12.5%), 6 (15%), and 27 (67.5%) patients, respectively. As for the treatment of AUGIB, 38 (95%) patients underwent endoscopic therapy, no patient underwent Sengstaken Blackmore tube placement, 39 (97.5%) patients received somatostatin and/or octreotide, 21 (52.5%) patients received blood transfusion, all patients received PPIs, and no patient underwent surgery. Five-day rebleeding rate was 12.5% (n=5). In-hospital mortality was 2.5% (n=1). Median length of hospital stay was 11.95 days (range: 5.73 to 31.06). Median total payment was ¥24,961.33 (range: 11,212.15 to 81,125.52).Table 4
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in validation cohort.
Variables  Propensity matching patients  P value Overall (n=40) Regular hours (n=20) Off-hours (n=20) Age (years) 56.86 (20.57-75.64) 60.64 (20.57-75.64) 55.52 (35.18-74.33) 0.160 Sex (male) 28 (70%) 13 (65%) 15 (75%) 0.490 Etiology of Liver Diseases    0.622 HBV 9 (22.5%) 4 (20%) 5 (25%) HCV 4 (10%) 2 (10%) 2 (10%) Alcohol Abuse 14 (35%) 7 (35%) 7 (35%) Drug Related 2 (5%) 0 (0%) 2 (10%) Autoimmune Liver Diseases 1 (2.5%) 1 (5%) 0 (0%) Other or Unclear Etiology 10 (25%) 6 (30%) 4 (20%) Laboratory Tests Red Blood Cell (1012/L) 2.625 (1.65-3.89) 2.58 (1.69-3.89) 2.705 (1.65-3.78) 0.968 Hemoglobin (g/L) 74.50 (38.00-126.00) 77.00 (53.00-122.00) 72.50 (38.00-126.00) 0.473 White Blood Cell (109/L) 4.40 (1.80-14.90) 4.40 (2.20-11.70) 4.35 (1.80-14.90) 0.839 Platelet Count (109/L) 72.50 (27.00-301.00) 72.50 (27.00-301.00) 72.00 (32.00-145.00) 0.978 Total Bilirubin (umol/L) 18.10 (5.50-106.10) 16.85 (5.50-50.90) 18.10 (8.50-106.10) 0.256 Direct Bilirubin (umol/L) 7.85 (2.20-60.10) 7.10 (2.20-41.50) 7.95 (3.00-60.10) 0.675 Indirect Bilirubin (umol/L) 9.50 (2.80-46.00) 8.55 (2.80-22.10) 10.00 (5.40-46.00) 0.148 Albumin (g/L) 30.65 (18.00-39.20) 30.85 (19.00-38.60) 30.00 (18.00-39.20) 1 Alanine Aminotransferase (U/L) 21.805 (6.79-88.77) 21.805 (9.44-72.47) 20.415 (6.79-88.77) 0.756 Aspartate Aminotransferase (U/L) 25.635 (10.74-136.00) 28.38 (11.00-88.79) 25.635 (10.74-136.00) 0.978 Alkaline Phosphatase (U/L) 80.10 (40.34-234.00) 80.94 (40.34-234.00) 78.245 (46.24-149.45) 0.705 Gamma-glutamyl Transpeptidase (U/L) 41.245 (7.69-295.00) 40.48 (13.71-254.00) 42.765 (7.69-295.00) 0.935 Blood Urea Nitrogen (mmol/L) 7.395 (2.98-18.83) 7.055 (2.98-18.83) 8.40 (4.65-18.72) 0.245 Serum Creatinine (umol/L) 70.11 (34.90-143.10) 66.68 (42.60-95.20) 74.255 (34.90-143.10) 0.117 Potassium (mmol/L) 3.95 (3.10-4.66) 3.88 (3.10-4.66) 3.98 (3.27-4.59) 0.330 Sodium (mmol/L) 139.10 (124.00-145.70) 138.50 (135.00-141.40) 139.45 (124.00-145.70) 0.279 PT (seconds) 15.80 (13.30-24.50) 15.40 (13.30-23.90) 16.05 (13.50-24.50) 0.417 APTT (seconds) 36.25 (30.80-47.50) 35.90 (30.80-45.20) 37.15 (32.20-47.50) 0.351 INR 1.275 (1.02-2.19) 1.255 (1.08-2.08) 1.31 (1.02-2.19) 0.516 Child-Pugh Score 8.00 (5.00-12.00) 8.00 (5.00-12.00) 7.00 (5.00-12.00) 0.836 Child-Pugh A/B/C 14 (35%)/22 (55%)/4 (10%) 7 (35%)/12 (60%)/1 (5%) 7 (35%)/10 (50%)/3 (15%) 0.544 MELD Score 5.82 (-2.38-23.19) 5.51 (-1.04-14.75) 6.51 (-2.38-23.19) 0.245 Recalibrated MELD Score -4.11 (-5.80- -0.51) -4.17 (-5.53- -2.26) -3.96 (-5.80- -0.51) 0.245 ALBI Score -1.67 (-2.62- -0.49) -1.73 (-2.44- -0.49) -1.67 (-2.62- -0.60) 0.787 Esophageal Varices (No/Mild/Moderate/Severe) 2 (5%)/5 (12.5%)/6 (15%)/27 (67.5%) 1 (5%)/3 (15%)/3 (15%)/13 (65%) 1 (5%)/2 (10%)/3 (15%)/14 (70%) 0.971 Treatment Endoscopic Treatment 38 (95%) 19 (95%) 19 (95%) 1 Sengstaken Blakemore 0 (0%) 0(0%) 0(0%) NA Somatostatin 39 (97.5%) 20 (100%) 19 (95%) 0.311 Blood Transfusion 21 (52.5%) 9 (45%) 12 (60%) 0.342 PPIs 40 (100%) 20 (100%) 20 (100%) NA Surgery 0 (0%) 0 (0%) 0 (0%) NA 5-day Re-bleeding After Treatment 5 (12.5%) 2 (10%) 3 (15%) 0.633 Death During Hospitalization 1 (2.5%) 0 (0%) 1 (5%) 0.311 Length of Stay (days) 11.95 (5.73-31.06) 11.95 (5.73-21.95) 11.28 (7.52-31.06) 0.441 Total Payment (¥) 24,961.33 (11,212.15-81,125.52) 25,985.45 (15,513.68-56,952.12) 24,961.33 (11,212.15-81,125.52) 0.829 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: Prothrombin time; APTT: activated partial thromboplastin time; INR, International normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


### 3.2.4. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 20 patients were matched on each group (Table4). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.633, P=0.311, P=0.441, and P=0.829, respectively).


## 3.2.1. Patients’ Characteristics

Between December 2014 and March 2018, a total of 173 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table3. Median age was 56.60 years (range: 20.57 to 88.73). Among them, 121 (69.9%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=47, 27.2%) and alcohol abuse (n=55, 31.8%). A majority of patients had Child-Pugh class B (94/169, 55.6%). Median MELD score at admission was 7.22 (-3.16 to 23.19). One hundred and fifty-one patients underwent endoscopy. No, mild, moderate, and severe esophageal varices were observed in 9 (6.0%), 23 (15.2%), 26 (17.2%), and 93 (61.6%) patients, respectively. The origin of bleeding could be evaluated in 162 patients, of whom only 4 did not have esophageal and/or gastric varices. As for the treatment of AUGIB, 139 (80.3%) patients underwent endoscopic therapy, 1 (0.6%) patients underwent Sengstaken Blackmore tube placement, 160 (92.5%) patients received somatostatin and/or octreotide, 88 (50.9%) patients received blood transfusion, 173 (100%) patients received PPIs, and 0 (0%) patients underwent surgery. Information regarding 5-day rebleeding was unavailable in one patient. Five-day rebleeding rate was 7.6% (13/172). In-hospital mortality was 2.3% (4/173). Median length of hospital stay was 10.10 days (range: 0.12 to 32.94). Total payment was ¥24,328.31 (range: 3,427.24 to 98,215.78).Table 3
Characteristics of patients with liver cirrhosis and AUGIB in validation cohort.
Variables No. Pts Overall No. Pts Regular hours No. Pts Off-hours P value Age (years) 173 56.60 (20.57-88.73) 131 56.60 (20.57-75.73) 42 56.56 (33.42-88.73) 0.683 Sex (male) 173 121 (69.9%) 131 91 (69.5%) 42 30 (71.4%) 0.809 Etiology of Liver Diseases 173  131  42  0.830 HBV  47 (27.2%)  37 (28.2%)  10 (23.8%) HCV  17 (9.8%)  12 (9.2%)  5 (11.9%) Alcohol Abuse  55 (31.8%)  41 (31.3%)  14 (33.3%) HBV + Alcohol Abuse  3 (1.7%)  2 (1.5%)  1 (2.4%) HBV + HCV + Alcohol Abuse  1 (0.6%)  1 (0.8%)  0 (0%) Drug Related  1 (0.6%)  1 (0.8%)  0 (0%) Autoimmune Liver Diseases  3 (1.7%)  3 (2.3%)  0 (0%) Other or Unclear Etiology  46 (26.6%)  34 (25.9%)  12 (28.6%) Laboratory Tests Red Blood Cell (1012/L) 173 2.70 (1.32-5.11) 131 2.70 (1.32-5.11) 42 2.62 (1.56-4.14) 0.372 Hemoglobin (g/L) 173 73.00 (31.00-156.00) 131 73.00 (31.00-156.00) 42 73.50 (38.00-130.00) 0.575 White Blood Cell (109/L) 173 4.20 (1.00-23.10) 131 4.10 (1.00-23.10) 42 4.35 (1.70-14.90) 0.368 Platelet Count (109/L) 173 71.00 (18.00-457.00) 131 73.00 (18.00-377.00) 42 68.50 (23.00-457.00) 0.980 Total Bilirubin (umol/L) 172 20.80 (5.20-210.00) 131 21.60 (5.20-210.00) 41 18.30 (6.70-106.10) 0.587 Direct Bilirubin (umol/L) 172 8.70 (2.00-146.90) 131 9.00 (2.00-146.90) 41 8.30 (2.50-60.10) 0.643 Indirect Bilirubin (umol/L) 172 10.65 (2.60-79.90) 131 11.40 (2.60-69.20) 41 9.80 (4.20-79.90) 0.801 Albumin (g/L) 171 29.40 (17.00-50.70) 130 29.65 (17.20-50.70) 41 29.40 (17.00-41.00) 0.693 Alanine Aminotransferase (U/L) 172 20.70 (5.00-275.36) 131 20.98 (6.00-140.00) 41 17.17 (5.00-275.36) 0.504 Aspartate Aminotransferase (U/L) 172 27.00 (9.63-310.39) 131 27.50 (9.63-278.00) 41 26.11 (10.00-310.39) 0.801 Alkaline Phosphatase (U/L) 172 78.23 (24.02-378.66) 131 75.66 (24.02-378.66) 41 79.75 (46.24-197.00) 0.981 Gamma-glutamyl Transpeptidase (U/L) 172 31.98 (7.54-1227.00) 131 29.61 (7.54-1227.00) 41 40.53 (7.69-295.00) 0.346 Blood Urea Nitrogen (mmol/L) 172 7.60 (2.17-47.25) 131 7.40 (2.17-47.25) 41 7.96 (2.47-20.15) 0.993 Serum Creatinine (umol/L) 172 69.145 (34.40-267.63) 131 67.03 (34.40-267.63) 41 74.21 (34.90-144.98) 0.116 Potassium (mmol/L) 173 3.95 (2.48-5.54) 131 3.95 (2.48-5.54) 42 3.97 (3.12-5.49) 0.876 Sodium (mmol/L) 173 138.50 (124.00-152.90) 131 138.40 (130.40-152.90) 42 138.80 (124.00-145.70) 0.544 PT (seconds) 171 16.10 (10.50-27.40) 131 16.10 (11.60-27.40) 40 16.05 (10.50-27.20) 0.606 APTT (seconds) 170 37.85 (19.40-59.70) 131 37.90 (27.50-59.70) 39 37.40 (19.40-52.10) 0.542 INR 170 1.32 (0.91-2.55) 131 1.33 (1.01-2.55) 39 1.31 (0.91-2.50) 0.681 Child-Pugh Score 169 8.00 (5.00-15.00) 130 8.00 (5.00-12.00) 39 7.00 (5.00-12.00) 0.603 Child-Pugh A/B/C 169 51 (30.2%)/94 (55.6%)/24 (14.2%) 130 37 (28.5%)/75 (57.7%)/18 (13.8%) 39 14 (35.9%)/19 (48.7%)/6 (15.4%) 0.596 MELD Score 170 7.22 (-3.16-23.19) 131 7.26 (-3.16-20.70) 39 7.22 (-2.38-23.19) 0.671 Recalibrated MELD Score 170 -3.82 (-5.97- -0.51) 131 -3.81 (-5.97- -1.03) 39 -3.82 (-5.80- -0.51) 0.671 ALBI Score 171 -1.63 (-3.40- -0.11) 130 -1.62 (-3.40- -0.11) 41 -1.68 (-2.70- -0.49) 0.675 Esophageal Varices (No/Mild/Moderate/Severe) 151 9 (6.0%)/23 (15.2%)/26 (17.2%)/93 (61.6%) 116 6 (5.2%)/18 (15.5%)/20 (17.2)/72 (61.1%) 35 3 (8.6%)/5 (14.3%)/6(17.1%)/21 (60.0%) 0.965 Treatment Endoscopic Treatment 173 139 (80.3%) 131 104 (79.4%) 42 35 (83.3%) 0.576 Sengstaken Blakemore 173 1 (0.6%) 131 0 (0%) 42 1 (2.4%) 0.077 Somatostatin and/or Octreotide 173 160 (92.5%) 131 119 (90.8%) 42 41 (97.6%) 0.147 Blood Transfusion 173 88 (50.9%) 131 62 (47.3%) 42 26 (61.9%) 0.100 PPIs 173 173 (100%) 131 131 (100%) 42 42 (100%) NA Surgery 173 0 (0%) 131 0 (0%) 42 0 (0%) NA 5-day Re-bleeding After Treatment 172 13 (7.6%) 130 9 (6.9%) 42 4 (9.5%) 0.579 Death During Hospitalization 173 4 (2.3%) 131 3 (2.3%) 42 1 (2.4%) 0.973 Length of Stay (days) 173 10.10 (0.12-32.94) 131 10.10 (0.12-32.94) 42 10.28 (5.02-31.06) 0.335 Total Payment (¥) 173 24,328.31 (3,427.24-98,215.78) 131 22,685.20 (3,427.24-98,215.78) 42 25,213.81 (9,970.37-81,125.52) 0.166 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: prothrombin time; APTT: activated partial thromboplastin time; INR: international normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


## 3.2.2. Outcomes

No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.579, P=0.973, P=0.335, and P=0.166, respectively) (Table3).


## 3.2.3. Patients’ Characteristics after Propensity Score Matching

After a 1:1 propensity score matching analysis, a total of 40 patients with liver cirrhosis and AUGIB were included. Baseline patient characteristics are described in Table4. Median age was 56.86 years (range: 20.57 to 75.64). Among them, 28 (70%) patients were male. Major etiology of liver diseases included hepatitis B virus infection (n=9, 22.5%) and alcohol abuse (n=14, 35%). A majority of patients had Child-Pugh class B (n=22, 55%). Median MELD score at admission was 5.82 (range: -2.38 to 23.19). No, mild, moderate, and severe esophageal varices were observed in 2 (5%), 5 (12.5%), 6 (15%), and 27 (67.5%) patients, respectively. As for the treatment of AUGIB, 38 (95%) patients underwent endoscopic therapy, no patient underwent Sengstaken Blackmore tube placement, 39 (97.5%) patients received somatostatin and/or octreotide, 21 (52.5%) patients received blood transfusion, all patients received PPIs, and no patient underwent surgery. Five-day rebleeding rate was 12.5% (n=5). In-hospital mortality was 2.5% (n=1). Median length of hospital stay was 11.95 days (range: 5.73 to 31.06). Median total payment was ¥24,961.33 (range: 11,212.15 to 81,125.52).Table 4
Characteristics of patients with liver cirrhosis and AUGIB after propensity matching in validation cohort.
Variables  Propensity matching patients  P value Overall (n=40) Regular hours (n=20) Off-hours (n=20) Age (years) 56.86 (20.57-75.64) 60.64 (20.57-75.64) 55.52 (35.18-74.33) 0.160 Sex (male) 28 (70%) 13 (65%) 15 (75%) 0.490 Etiology of Liver Diseases    0.622 HBV 9 (22.5%) 4 (20%) 5 (25%) HCV 4 (10%) 2 (10%) 2 (10%) Alcohol Abuse 14 (35%) 7 (35%) 7 (35%) Drug Related 2 (5%) 0 (0%) 2 (10%) Autoimmune Liver Diseases 1 (2.5%) 1 (5%) 0 (0%) Other or Unclear Etiology 10 (25%) 6 (30%) 4 (20%) Laboratory Tests Red Blood Cell (1012/L) 2.625 (1.65-3.89) 2.58 (1.69-3.89) 2.705 (1.65-3.78) 0.968 Hemoglobin (g/L) 74.50 (38.00-126.00) 77.00 (53.00-122.00) 72.50 (38.00-126.00) 0.473 White Blood Cell (109/L) 4.40 (1.80-14.90) 4.40 (2.20-11.70) 4.35 (1.80-14.90) 0.839 Platelet Count (109/L) 72.50 (27.00-301.00) 72.50 (27.00-301.00) 72.00 (32.00-145.00) 0.978 Total Bilirubin (umol/L) 18.10 (5.50-106.10) 16.85 (5.50-50.90) 18.10 (8.50-106.10) 0.256 Direct Bilirubin (umol/L) 7.85 (2.20-60.10) 7.10 (2.20-41.50) 7.95 (3.00-60.10) 0.675 Indirect Bilirubin (umol/L) 9.50 (2.80-46.00) 8.55 (2.80-22.10) 10.00 (5.40-46.00) 0.148 Albumin (g/L) 30.65 (18.00-39.20) 30.85 (19.00-38.60) 30.00 (18.00-39.20) 1 Alanine Aminotransferase (U/L) 21.805 (6.79-88.77) 21.805 (9.44-72.47) 20.415 (6.79-88.77) 0.756 Aspartate Aminotransferase (U/L) 25.635 (10.74-136.00) 28.38 (11.00-88.79) 25.635 (10.74-136.00) 0.978 Alkaline Phosphatase (U/L) 80.10 (40.34-234.00) 80.94 (40.34-234.00) 78.245 (46.24-149.45) 0.705 Gamma-glutamyl Transpeptidase (U/L) 41.245 (7.69-295.00) 40.48 (13.71-254.00) 42.765 (7.69-295.00) 0.935 Blood Urea Nitrogen (mmol/L) 7.395 (2.98-18.83) 7.055 (2.98-18.83) 8.40 (4.65-18.72) 0.245 Serum Creatinine (umol/L) 70.11 (34.90-143.10) 66.68 (42.60-95.20) 74.255 (34.90-143.10) 0.117 Potassium (mmol/L) 3.95 (3.10-4.66) 3.88 (3.10-4.66) 3.98 (3.27-4.59) 0.330 Sodium (mmol/L) 139.10 (124.00-145.70) 138.50 (135.00-141.40) 139.45 (124.00-145.70) 0.279 PT (seconds) 15.80 (13.30-24.50) 15.40 (13.30-23.90) 16.05 (13.50-24.50) 0.417 APTT (seconds) 36.25 (30.80-47.50) 35.90 (30.80-45.20) 37.15 (32.20-47.50) 0.351 INR 1.275 (1.02-2.19) 1.255 (1.08-2.08) 1.31 (1.02-2.19) 0.516 Child-Pugh Score 8.00 (5.00-12.00) 8.00 (5.00-12.00) 7.00 (5.00-12.00) 0.836 Child-Pugh A/B/C 14 (35%)/22 (55%)/4 (10%) 7 (35%)/12 (60%)/1 (5%) 7 (35%)/10 (50%)/3 (15%) 0.544 MELD Score 5.82 (-2.38-23.19) 5.51 (-1.04-14.75) 6.51 (-2.38-23.19) 0.245 Recalibrated MELD Score -4.11 (-5.80- -0.51) -4.17 (-5.53- -2.26) -3.96 (-5.80- -0.51) 0.245 ALBI Score -1.67 (-2.62- -0.49) -1.73 (-2.44- -0.49) -1.67 (-2.62- -0.60) 0.787 Esophageal Varices (No/Mild/Moderate/Severe) 2 (5%)/5 (12.5%)/6 (15%)/27 (67.5%) 1 (5%)/3 (15%)/3 (15%)/13 (65%) 1 (5%)/2 (10%)/3 (15%)/14 (70%) 0.971 Treatment Endoscopic Treatment 38 (95%) 19 (95%) 19 (95%) 1 Sengstaken Blakemore 0 (0%) 0(0%) 0(0%) NA Somatostatin 39 (97.5%) 20 (100%) 19 (95%) 0.311 Blood Transfusion 21 (52.5%) 9 (45%) 12 (60%) 0.342 PPIs 40 (100%) 20 (100%) 20 (100%) NA Surgery 0 (0%) 0 (0%) 0 (0%) NA 5-day Re-bleeding After Treatment 5 (12.5%) 2 (10%) 3 (15%) 0.633 Death During Hospitalization 1 (2.5%) 0 (0%) 1 (5%) 0.311 Length of Stay (days) 11.95 (5.73-31.06) 11.95 (5.73-21.95) 11.28 (7.52-31.06) 0.441 Total Payment (¥) 24,961.33 (11,212.15-81,125.52) 25,985.45 (15,513.68-56,952.12) 24,961.33 (11,212.15-81,125.52) 0.829 Data are expressed as median (range) or frequency (percentage). Abbreviations. AUGIB: acute upper gastrointestinal bleeding; HBV: Hepatitis B virus; HCV: Hepatitis C virus; PT: Prothrombin time; APTT: activated partial thromboplastin time; INR, International normalized ratio; MELD: model for end-stage liver disease; ALBI: albumin-bilirubin; PPIs: proton pump inhibitors; ¥: Renminbi.


## 3.2.4. Outcomes after Propensity Score Matching

After a 1:1 propensity score matching analysis, 20 patients were matched on each group (Table4). No significant difference in demographics, etiology of liver disease, laboratory tests, Child-Pugh score, MELD score, recalibrated MELD score, ALBI score, and treatment options was observed between the two groups (P>0.05, in all comparisons). As for the outcomes, 5-day rebleeding rate, in-hospital mortality, length of stay, and total payment were not significantly different between the two groups (P=0.633, P=0.311, P=0.441, and P=0.829, respectively).


## 4. Discussion

Traditionally, a worse outcome in patients with UGIB during the weekend was potentially attributed to lower staffing levels and relatively younger and inexperienced staff [11]. Indeed, both overall analyses and subgroup analyses of patients with endoscopically confirmed varices in the test cohort demonstrated a significantly higher 5-day rebleeding rate and a larger amount of payment in patients admitted on off-hours. This might be primarily due to worse liver dysfunction in patients admitted on off-hours, such as lower albumin and higher prothrombin time, INR, Child-Pugh score, and ALBI score. As the Child-Pugh score was matched, the propensity score matching analyses of both test and validation cohorts showed no significant effect of admission time on the rebleeding rate, in-hospital mortality, length of stay, and total payment of cirrhotic patients with AUGIB. These findings suggested that the weekend effect might not be an independent risk factor for worse outcomes of cirrhotic patients with AUGIB.A meta-analysis [16] found that off-hours admission was not associated with a higher risk of rebleeding rate (OR=1.06, 95%CI=0.83-1.35, and P=0.66) and longer length of stay (WMD 0.06 day, 95%CI=-0.30 - -0.42, P=0.747). These previous findings were consistent with our results regarding 5-day rebleeding rate and length of stay. Notably, our study focused on the 5-day rebleeding rate after treatment during hospitalization. However, the interval of rebleeding was not specified in the meta-analysis. As we have known, the length of stay was usually associated with the severity of illness [24]. In addition, as well known, liver dysfunction as estimated by Child-Pugh score and MELD score were risk factors for mortality of cirrhotic patients with AUGIB [25–27].Two of the published meta-analyses [16, 17] demonstrated a significant weekend effect on the mortality in patients with nonvariceal UGIB, but not those with variceal bleeding. This finding seemed to be consistent with our results regarding mortality. Notably, our study focused on the outcomes during hospitalization, but not those after discharge. The fact is readily understood that admission time mainly influenced the in-hospitalization outcomes but marginally influenced the outcomes after discharge. Indeed, a meta-analysis also suggested that off-hours admission negatively influenced in-hospital mortality (P=0.009), rather than 30-day mortality (P=0.116).Our study has the following advantages. First, we refined the definitions of off-hours admission. Second, we included a test cohort and a validation cohort which can reduce the sampling bias to some extent. Third, we employed a propensity score matching analysis. Thus, the patient characteristics, especially Child-Pugh and MELD scores which are significantly associated with prognosis of liver cirrhosis, are comparable between the two groups. Our results become more stable. However, the major drawback of our study should be that not all patients undergo endoscopy to evaluate the source of bleeding. Additionally, the sample size is not adequate in the validation cohort. Finally, a potential selection bias could not be neglected due to the retrospective nature of this study.In conclusion, off-hours admission might not be associated with outcomes in patients with liver cirrhosis and AUGIB. However, the geographical difference should not be neglected to extrapolate our findings.



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*Source: 3541365-2018-11-29.xml*