Upper gastrointestinal bleeding in patients with liver cirrhosis, Is the difference of clinical outcomes depend on the source?

Acute upper gastrointestinal bleeding (UGIB) is the most common gastroenterological emergency in patients with cirrhosis; It increases the hospital length of stay (LOS), and Chance of 30-day hospital readmission. It has not been clarified if there is a difference in the prognosis of UGIB in cirrhosis depending on the source of bleeding. We aimed to investigate clinical outcomes in patients with cirrhosis with either acute variceal bleeding (AVB) or non-variceal bleeding (NVB) and risk factors for prolonged hospital LOS in both groups.


Background and Study Aims
Acute upper gastrointestinal bleeding (UGIB) is the most common gastroenterological emergency in patients with cirrhosis; It increases the hospital length of stay (LOS), and Chance of 30-day hospital readmission. It has not been clarified if there is a difference in the prognosis of UGIB in cirrhosis depending on the source of bleeding. We aimed to investigate clinical outcomes in patients with cirrhosis with either acute variceal bleeding (AVB) or non-variceal bleeding (NVB) and risk factors for prolonged hospital LOS in both groups.

Patients and Methods
From July 2016 to January 2017, all adult eligible patients hospitalized with cirrhosis and UGIB were enrolled in the retrospective study, we assessed clinical outcomes in both groups and factors associated with prolonged hospital LOS.

Results
Of the 608 patients included in the study, 416 had variceal and 192 non-variceal bleeding. Mortality was higher in AVB group compared to NVB (12.5% vs. 8.3%, P= 0.023). There was a trend towards increased the length of hospital stay for those who had an AVB compared to NVB (5.84±2.16 vs. 4.33±1.18, p=0.001). Rate of hospital Readmission was also higher in the AVB group. Risk factors for prolonged hospital LOS were in hospital rebleeding, presence of Hepatic encephalopathy or ascites, higher MELD score and Patients with child score B, C.

Conclusion
Patients with cirrhosis and AVB have higher mortality rate, longer hospital LOS and re-hospitalization rate than those with NVB.

Background
Acute upper gastrointestinal bleeding (UGIB) is the most common gastroenterological emergency in patients with cirrhosis and correlated with significant morbidity and mortality [1,2]. Acute variceal bleeding (AVB) is the leading cause of UGIB in cirrhosis and account for up to 70% of all cases [3,4], while non variceal bleeding (NVB) is a considerable cause of UGIB and responsible for the remaining cases, with the most frequent being peptic ulcer disease (PUD) [5]. In recent years significant amelioration in the therapeutic management of UGIB and improvement of hemostatic therapies resulted in a reduction of mortality and improvement of prognosis whether the cause is variceal [6,7] or non-variceal [7,8] Observational studies have demonstrated the higher mortality rate among patients with a bleeding Peptic ulcer with cirrhosis than in those without liver disease [9,10]. Risk factors that may be implicated in the higher mortality from UGIB in cirrhosis were the severity of liver disease, the alternation in the coagulation process, severity of the bleeding attack and the associated comorbidities [7,10,11].
Furthermore, UGIB in cirrhosis increases the hospital length of stay (LOS), Chance of 30-day hospital readmission [12], spending on healthcare. However, it has not been clarified if there is a difference in the prognosis of UGIB in cirrhosis depending on the source of bleeding. Therefore in this study, we aimed to investigate clinical outcomes in patients with cirrhosis with either AVB or NVB and risk factors for prolonged hospital LOS in both groups.

Methods
This study was a retrospective cohort study that included all adults (age ≥ 18 years) cirrhotic patients admitted with upper GI bleeding to Internal medicine gastroenterology unit at Zagazig University Hospital from July 2016 to January 2017; Cirrhosis was diagnosed by clinical, biochemical and imaging studies or by previous liver biopsy.
Patients were excluded if they had one or more of the following criteria: death before endoscopy due to severe bleeding, those who receive supportive therapy only or discharged before endoscopy, and patients with incomplete medical records.

Study Design
Emergency upper GI endoscopy was done for all patients included in the study after stabilization, Clinical outcomes were compared between the acute variceal bleeding group and non-variceal bleeding by a retrospective analysis of records of clinical, laboratory and endoscopic data of the patients Clinical outcomes assessed included the length of hospital stay, packed RBCs transfusion rate, inhospital Re-bleeding, the need for repeating endoscopy during admission, the re-hospitalization rate within 30 days from admission and in-hospital mortality.
The data included from the medical records were: (a) baseline characteristics of patients -age, sex, smoking history, medication history (NSAID, PPI, Beta Blocker……) and co-morbidities. (d) Investigations details -CBC, serum albumin, total bilirubin, international normalized ratio (INR), creatinine, blood urea nitrogen, sodium and endoscopy details: the presence of varices, grades, gastric or duodenal ulcers, other sources of UGIB. (F) Re-hospitalization rate within 30 days was also recorded Furthermore, we calculated for all included patients FIB4 score as an indicator for liver fibrosis state [13] and scores reflecting liver function state including MELD [14] and child score [15,16].

Statistical analysis
All data were statistically analyzed using SPSS version 20 for Windows (SPSS Inc., Chicago, USA).
Quantitative data were expressed as the mean ± SD. Qualitative data were expressed as absolute frequencies (number) & (percentage). Tests of normality as Levene's test, Shapiro Wilk's test and inspection of their histograms and box plots were performed.
Sensitivity/specificity and positive/negative predictive values for the non-invasive diagnosis of fibrosis were assessed considering liver stiffness as the reference.
All variables with P<0.05 were considered statistically significant.

Results
Seven hundred and thirty-four patients with cirrhosis were presented to the hospital with upper GI bleeding during the study period. From them, 608 patients with cirrhosis were enrolled in the study as shown in Fig. 1  Scoring parameters reflecting Liver function status at the time of admission revealed that 38.4%of patients with AVB were child C in contrast to 16.7% of the non-variceal bleeding group (P = 0.001 ), the severity of liver fibrosis checked by FIB4 score revealed that patients with AVB have significantly higher FIB 4 than NVB group. We have also found that AVB cohorts have significantly higher MELD score, Glasgow-Blatchford Score, AIMS65 Score and rockall score.
The differences between clinical outcomes of the two groups are summarized in  The risk factors associated with prolonged hospital length of stay were evaluated in the two groups of patients (Table 4). Patients presented by hepatic encephalopathy or developed it during hospital admission had significantly prolonged Hospital LOS in Both AVB and NVB groups. The presence of ascites or the re-bleeding during hospital admission were also significant risk factors that influenced the hospital LOS. Other parameters that associated with prolonged hospital LOS were higher MELD score or Child score class B and C.

Discussion
Liver cirrhosis is a major public health problem in Egypt because of the high HCV seroprevalence which was estimated to be 14.7% among the 15-59 years age group [22]. Acute UGIT bleeding is common in patients with liver cirrhosis and is associated with significant morbidity and mortality.
Early detection of the source of UGIT bleeding help to ameliorate management and clinical outcomes [23]. In the present study, we found that the mortality of patients with cirrhosis and AVB is higher than those with NVB. The risk of prolonged hospital LOS and the re-hospitalization rate within 30 days were significantly higher in patients AVB than those with NVB.
The higher mortality rate in patients with AVB than NVB is in agreement with previous studies suggested that patients with cirrhosis and AVB showed a high mortality rate [24,25]. The high mortality in AVB may be related to the severity of presentation, rate of in-hospital re-bleeding, and the different parameters reflecting the more derangement of liver function in patients AVB and cirrhosis than NVB group such as MELD and Child-Pugh scores.
Although in our study the patients with AVB are younger than those with NVB they are more likely to have a history of bleeding episodes, higher Glasgow-Blatchford Score, AIMS65 Score and advanced hepatic cirrhosis. All these factors help to clarify our observation of longer hospital LOS in patients with AVB than those with NVB. This is consistent with other studies which have documented the shorter hospital LOS in cirrhotic patients if the source of upper GIT bleeding is not variceal [3,23].
In this study, certain factors were associated with increased Hospital LOS in the AVB group and NVB Early differentiation of the source of upper GI bleeding whether variceal or non-variceal help for rapid accurate etiology-guided management and prediction of patients prognosis and clinical outcomes. In our study noninvasive predictor tests which correlates with hospital LOS, risk of re-bleeding and mortality, such as AIMS65 Score and glasgow-blatchford score (GBS) were higher in the AVB group than NVB group. Furthermore when we assess the risk of mortality by complete rockall rcore was also significantly higher in AVB cohort. This observation is consistent with preliminary findings of our study that AVB patients have poorer clinical outcomes and higher mortality than NVB patients Although our study is a single-center study, the inclusion of all eligible patients admitted to our tertiary hospital during the study period and the relatively large number of included patients represent the strength of our study Conclusion and re-hospitalization rate than those with NVB. In-hospital bleeding and the severity of liver decompensation were associated with prolonged hospital LOS in both groups.

Ethics approval and consent to participate
The study approved from faculty of medicine Zagazig university ethical committee

Consent for publication
Not applicable

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request Figure 1 Flow chart for patients included in the study