Canadian Journal of Gastroenterology and Hepatology
Volume 2018 (2018), Article ID 3541365, 14 pages
https://doi.org/10.1155/2018/3541365

Clinical Study

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

Yingying Li,1,2 Bing Han,1,2 Hongyu Li,¹ Tingxue Song,1,3 Wenchun Bao,1,3 Ran Wang,¹ Zhaohui Bai,1,4 Kexin Zheng,1,2 Qianqian Li,1,5 Xiaozhong Guo,¹ and Xingshun Qi¹

¹Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, 110840, China
²Postgraduate College, Jinzhou Medical University, Jinzhou 121001, China
³Postgraduate College, Liaoning University of Traditional Chinese Medicine, Shenyang, 110840, China
⁴Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110840, China
⁵Postgraduate College, Dalian Medical University, Dalian 116044, China

Correspondence should be addressed to Hongyu Li; 13309887041@163.com, Xiaozhong Guo; guo_xiao_zhong@126.com, and Xingshun Qi; xingshunqi@126.com

Received 1 August 2018; Revised 29 October 2018; Accepted 7 November 2018; Published 29 November 2018

Guest Editor: Eduardo Garcia Vilela

Copyright © 2018 Yingying Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

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 ×    + 3.78 ×   + 11.2 ×    + 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 ×   [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 Table 1. 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 (Table 1). 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 Table 2).

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 Table 2. 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 (Table 2). 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 Table 3). 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 Table 3. 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) (Table 3).

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 Table 4. 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 (Table 4). 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.

Abbreviations

AUGIB: | Acute upper gastrointestinal bleeding
UGIB: | Upper gastrointestinal bleeding
INR: | International normalized ratio
PPIs: | Proton pump inhibitors
MELD: | Model for end-stage liver disease
ALBI: | Albumin-bilirubin.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Disclosure

Yingying Li and Bing Han are co-first authors.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Yingying Li reviewed and searched the literature, wrote the protocol, collected the data, performed the statistical analysis, interpreted the data, and drafted the manuscript. Bing Han and Tingxue Song performed the statistical analysis and critical revision of the manuscript for important intellectual content. Wenchun Bao, Ran Wang, Zhaohui Bai, Kexin Zheng, and Qianqian Li collected the data and revised the manuscript. Hongyu Li and Xiaozhong Guo checked the data and gave critical comments. Xingshun Qi conceived the work, wrote the protocol, performed the statistical analysis, interpreted the data, and revised the manuscript. All authors have made an intellectual contribution to the manuscript and approved the submission. This work was partially presented at the 18th Congress of Gastroenterology China that was held in Dalian, China on September 2018.

Acknowledgments

This study was partially supported by the grant from the Fourth Batch of Science and Technology Planning Projects of Liaoning Province in 2015 (no. 2015225019) for Professor Xiaozhong Guo.

Supplementary Materials

Supplementary Table 1. Treatment of cirrhotic patients with AUGIB at different departments from our hospital in test cohort. Supplementary Table 2. Subgroup analyses of patients with liver cirrhosis and AUGIB based on the origin of bleeding in test cohort. Supplementary Table 3. AUGIB patients with endoscopically confirmed varices after propensity matching analysis in test cohort. (Supplementary Materials)

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