Assessing the Predictive Factors for Bleeding in Esophageal Variceal Disease: A Systematic Review

Esophageal varices, dilated submucosal distal esophageal veins, are a common source of upper gastrointestinal bleeding in patients with portal hypertension. This review aims to comprehensively assess predictive factors for both the first occurrence and subsequent risk of esophageal variceal bleeding. A systematic search was conducted in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online) and Cochrane databases. A total of 33 studies were selected using rigorous inclusion and exclusion criteria. The risk of bias was assessed using the Newcastle-Ottawa Scale. Several predictive factors were identified for esophageal variceal bleeding, including the Child-Pugh score, Fibrosis Index, specific endoscopic findings, ultrasound parameters, portal vein diameter, presence and size of collaterals, CT scan findings, ascites, platelet counts, coagulation parameters, albumin levels, Von Willebrand Factor, bilirubin levels, diabetes mellitus, and the use of b-blocking agents in primary prophylaxis. The findings of this systematic review shed light on multiple potential predictive factors for esophageal variceal bleeding. Endoscopic findings were found to be reliable predictors. Additionally, ultrasound parameters showed associations with bleeding risk. This systematic review identifies multiple potential predictive factors for esophageal variceal bleeding in patients with portal hypertension. While certain factors exhibit strong predictive capabilities, further research is needed to refine and validate these findings, considering potential limitations and biases. This study serves as a critical resource for bridging knowledge gaps in this field.


Introduction And Background
Esophageal varices are dilated submucosal distal esophageal veins connecting the portal and systemic circulations [1].The response of the body to the increased venous pressure is the development of collaterals.These portosystemic collaterals divert blood from the portal venous system to the inferior and superior vena cava.At the same time, one important system is the gastroesophageal collaterals that drain into the azygos vein and lead to the development of esophageal varices.When these varices get enlarged, they rupture, causing severe hemorrhage [1].
Variceal hemorrhage represents approximately 70% of all upper gastrointestinal bleeding (UGB) episodes in patients with portal hypertension.In a cross-sectional study conducted in the United States from 2005 to 2014, a total of 348,958 (34,895 per year) patients were hospitalized with esophageal variceal bleeding [2]; furthermore, the mortality rate in patients with acute variceal bleeding is as high as 12-22% [3].
Predicting the occurrence of esophageal variceal bleeding and effectively stratifying individuals susceptible to this condition holds the promise of significantly reducing hospitalizations and mortality rates.Several scoring systems have been developed for the assessment of patients with UGB to predict clinical outcomes.The most frequently used are the Rockfall score, the Glasgow-Blatchford score (GBS), and AIMS65 (albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years) [4].However, these scoring systems are limited to assessing post-bleed risk [5], leaving a critical gap in predicting the initial bleeding episode.This study aims to comprehensively assess predictive factors for both the first occurrence and the subsequent risk of esophageal variceal bleeding.

Search Strategy
Pubmed/MEDLINE (Medical Literature Analysis and Retrieval System Online and Cochrane databases were searched using Medical Subject Headings (MeSH) terms and free-text terms (Tables 1, 2) on September 19, 2023.This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the selection of articles for the systematic review and meta-analysis [6].This rigorous approach resulted in a homogeneous dataset, allowing for more accurate and reliable results.

Inclusion and Exclusion Criteria
The review included studies that satisfied the search terms, were published between 2003 and 2023, and were written in either Spanish or English.A rigorous exclusion criterion was applied to ensure the quality and relevance of the studies included in the analysis.Studies with participants who were not diagnosed with portal hypertension were excluded.In addition, studies that were not available in full text or could not be obtained through interlibrary loans were excluded.The detailed inclusion and exclusion criteria in different categories are detailed below.
Types of studies: Observational studies, cohort studies, and case-control studies were included.Case reports, case series, cross-sectional studies, dissertations, book chapters, protocol articles, reviews, news articles, conference abstracts, letters to the editor, editorials, and comment publications were excluded, as these may not provide the depth of data required for our analysis.Additionally, studies lacking a clear operationalization description, duplicates, and those where necessary data couldn't be obtained or where we didn't receive a response from the original author were also excluded, ensuring the precision and reliability of the studies included in our systematic review.
Types of participants: Studies with adult participants (aged ≥ 18 years) of all genders diagnosed with portal hypertension, regardless of its etiology, were included.Patients with confirmed esophageal varices through relevant diagnostic procedures such as endoscopy, imaging, or clinical assessment.We included patients with or without a history of bleeding secondary to esophageal varices.On the other hand, patients without a diagnosis of portal hypertension, those experiencing UGB unrelated to esophageal varices (including gastric varices, esophageal trauma, gastric mucosal lesions, benign or malignant tumors of the stomach and esophagus, and peptic ulcer disease) were excluded.Studies pertaining to UGB secondary to coagulopathy or anticoagulant therapy and pediatric populations (individuals under 18 years of age) were also excluded.These refined criteria aim to enhance the study's focus and ensure the selection of appropriate participants for investigating predictive factors associated with the risk of bleeding in esophageal variceal disease.
Types of intervention: In this review, there was no specified type of intervention outlined within the methodology.Unlike some research studies that focus on evaluating specific interventions or treatment, the primary aim of the current review was to identify and assess predictive factors associated with the risk of bleeding in esophageal variceal disease like portal hypertension severity, variceal size and location, liver function, coagulation profile, and other relevant parameters.The goal was to comprehensively understand and delineate these factors that could aid in early interventions, better prognosis, and management strategies with a posterior reduction in mortality and number of hospitalizations.This allows for a broad investigation into clinical and diagnostic factors without being confined to a specific intervention or treatment modality.
Outcomes: Studies that focused on identifying predictive factors associated with bleeding risk in esophageal variceal disease were included.Participants should have undergone an assessment of predictive factors for bleeding in esophageal variceal disease; participants with incomplete or missing data on this matter will be excluded.Studies that aimed to establish correlations between these factors and the occurrence of bleeding in esophageal varices were included.

Selection of Studies/Data Extraction
Following an initial screening based on the title and abstract, two reviewers (MMM and JACP) independently selected trials for inclusion in this review using predetermined inclusion and exclusion criteria.This search was performed by using Rayyan [7] to extract relevant data; duplicates were filtered.We resolved any disagreements about the inclusion of studies by consensus and consultation with a third review author (CG).

Data Evaluation/Assessment of Risk of Bias
Data were evaluated using the criteria outlined in Cochrane.To assess the quality of studies included in the systematic review, for case-control and cohort studies, we employed the Newcastle-Ottawa Scale (NOS) [8] to assess the risk of bias.Two independent blinded reviewers (CG and AFM) evaluated the risk of bias in each study, considering the specific criteria and guidelines provided by the respective tools.Any discrepancies between the reviewers were resolved through discussion or by consulting with a third, blinded reviewer as needed (ECM).
The methodological components of the case-control and cohort studies were assessed as having a low, high, or unclear risk of bias in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [9], and the NOS guidelines [8], respectively.Details of any down-or-upgrading of the quality of evidence were presented in the summary of the findings table, providing transparency and explanations for the assessment of bias in each study included.

Study Identification and Selection
Across the database, we were able to narrow the pool of possible articles down to 1740 articles.After a thorough examination, 71 duplicate articles were eliminated along with 1490 other articles.A total of 179 publications were selected for further review after an initial screening of titles and abstracts, and of these, 178 were assessed followed by the retrieval of complete texts.After determining the eligibility and quality of the full-text papers that had been shortlisted, 33 were selected for the review process.The PRISMA flow chart is given in Figure 1.We evaluated the results of the risk of bias following the NOS rules [8] and Cochrane Handbook for Systematic Reviews of Interventions [9].Our results showed that good quality studies predominated, being 51.5% of the total, while the poor and fair quality ones accounted for 33.3% and 15.2%, respectively (Table 3).

Hemodynamics of the
LGV appears to be superior in predicting bleeding.Group II: patients who died <6 weeks of AVH.
Group   The included studies found the following to be predictors for esophageal variceal bleeding: (i) predictive scores, models, and indexes (48.5%); among them, the most frequent were Child-Pugh class B/C (12.1%) and Fib-4 (6.1%); (ii) imaging factors (33.3%) including liver stiffness measurement, spleen size, diameter or stiffness, total area of esophageal varice, hemodynamics of the left gastric vein, hepatic vein, and portal vein, portal vein thrombosis (PVT)/superior mesenteric vein thrombosis, ascites, iodine concentration in the short gastric vein and spleen, and the presence and size of collaterals; (iii) endoscopic factors (24.2%) such as red wale sign, large varices size, higher grade of varices and number of bands after esophageal variceal ligation; (iv) laboratory factors (excluding platelet count) (18.2%) like high bilirubin, high creatinine, high aspartate aminotransferase (AST) levels, coagulation parameters, low albumin and low fibrinogen; and (v) thrombocytopenia (9.1%).Other factors were diabetes mellitus (6.1%), the use of sorafenib in HCC (3%) and prophylactic nonselective beta-blocker (NSBB) in cirrhosis (3%).It is important to state the predictive scores, models and indexes used many parameters including some of the previously mentioned factors and others like: alanine transaminase (ALT), gamma-glutamyl transferase (GGT), RBC, CT features of the liver and spleen, glucagonemia and interventional radiology (IR), age, alcohol and smoking history (Table 4).

Discussion
Predictive Factors The Child-Pugh score, evaluated across multiple articles [20,22,24,37], plays a significant role in assessing the risk of bleeding in cirrhotic inpatients.Specifically, rebleeding in cirrhotic inpatients was associated with Child-Pugh grade B [16].The Child-Pugh score is a well-established system used to evaluate the severity of cirrhosis, with Grade B indicating a moderate degree of liver dysfunction.In the context of variceal bleeding risk, this grade signifies a higher risk of rebleeding.
The Fibrosis Index stands out as a genuinely predictive factor, and what's even more reassuring is that the studies investigating it were of high quality.The Fibrosis index with a cut-off value of 3.95 showed a negative predictive value (NPV) of 94.3% and an area under the receiver operating characteristic (ROC) curve (AUROC) of 62.95% for predicting f within one year [32].FIB-4 appears to be the most efficient non-invasive liver fibrosis marker which can be used as an initial screening tool for cirrhotic patients [27].

Ultrasound, Endoscopy, and Other Imaging Values
Predictive factors for rebleeding identified through endoscopy encompassed specific findings, which included the presence of the red wale sign or cherry red spot, esophageal variceal grading, and the number of band ligations performed [14,40,39].These factors were consistently supported across multiple articles, and their reliability was reinforced by their low risk of bias.
Ultrasound analysis revealed significant associations, such as the assessment of left gastric vein hemodynamics.Notably, EVB was more frequently observed in patients with a left gastric vein diameter exceeding 6 mm and a hepatofugal flow velocity surpassing 15 cm/s [11].Moreover, a comprehensive MUI (Model for End-Stage Liver Disease (MELD)-Ultrasound Doppler index), which factored in the assessment of the left gastric vein, emerged as another predictive factor [21].While both articles exhibited a fair quality concerning the risk of bias, the consensus drawn from their findings underscores the strength of these factors as reliable predictors.
High liver stiffness, as determined through ultrasound evaluation, has been established as a reliable predictor of bleeding risk [17].This finding is further corroborated by an additional study indicating that low liver stiffness measurements effectively excluded patients with high-risk varices, particularly in individuals with Child-Pugh A cirrhosis [25].In contrast, spleen stiffness demonstrates a correlation with the presence, severity, and bleeding risk of esophageal varices, as indicated in one study; however, it's worth noting that this study was of suboptimal quality due to a risk of bias [24].
Qingjing Zhu et al. present strong evidence that both spleen and liver stiffness are excellent predictors of liver stiffness measurement and spleen diameter, with the study's quality being good [29].Nevertheless, it's crucial to recognize that these factors are interconnected and not necessarily independent of each other, limiting the findings of the spleen diameter as a predictor.This interrelation suggests that the outcome of one factor might be influenced by another.In summary, liver stiffness is a reliable predictor, while spleen diameter requires further research and exploration to fully understand its predictive capabilities.
Another factor evaluated by ultrasound was the portal vein diameter.Patients with variceal red signs had significantly higher values of portal diameter, cross-sectional area, blood flow volume, and congestion index [13].The high risk of bias in the study limits the interpretation.Hepatic vein pressure gradient is a predictive factor for six-week rebleed episode [23].
Portal vein tumor thrombosis (PVTT) elevates the incidence of high-risk varices and EVB [35].This underscores the clinical significance of PVTT in patients, particularly those with HCC, in terms of the associated risk of these adverse outcomes.Gao et al. further substantiate this by indicating that patients with PVTT exhibit a higher rate of rebleeding, both at the 14-day and six-week intervals [37].This reinforces the idea that PVTT contributes to the risk of variceal bleeding recurrence.
The utilization of CT scans as an imaging tool in assessing esophageal varices and their potential to predict bleeding events have been the subject of recent investigations, notably in high-quality studies: the total area of esophageal varices showed more accuracy (being 7.83±2.76mm in bleeding group) as a potential and novel indicator for bleeding prediction [31].Findings of esophageal varices in multidetector CT (MDCT) analysis were the best predictor of esophageal varices or esophageal variceal hemorrhage, and the presence (and/or size) of specific collaterals showed a significant relationship with both esophageal varices and esophageal variceal hemorrhage: coronary, short gastric, and paraesophageal [34].These particular findings not only provide a novel indicator for predicting bleeding but also underscore the potential of CT scans to offer precise assessments of esophageal varices, enhancing clinical decision-making.Therefore, it is advisable that CT scans be integrated more widely into the clinical management of patients with esophageal varices, particularly in the context of risk assessment and preventive measures.
Another imaging measurement provided by the analysis of a dual-energy CT scan was the iodine concentration in the short gastric vein and in the spleen [38], and although they were found to be independent predictors for EVB risk, usefulness as a predictor of EVB is limited due to a high risk of bias of the study.

Ascites
Ascites was determined to be a risk factor for variceal bleeding according to the findings of Krige et al. [15], Yang et al. [22], and Hung et al. [26], two of them being high-quality studies.Goh et al.'s study, which had low risk of bias, determine thrombocytopenia, splenomegaly, or ascites as unreliable predictors of bleeding esophageal varices [12].It is interesting to notice that only 27.5% of patients evaluated in this study had ascites.Only six patients had the three criteria, so we could consider that the sample size was relatively small to conclude that ascites is not related to the risk of bleeding.Wang et al. [16] determined that ascites was negatively correlated to EVB, although this study had a high risk of bias, therefore being less significative than the previous ones stating the opposite.

Platelets
Our comprehensive review of high-quality studies reveals a consistent consensus that questions the utility of thrombocytopenia, splenomegaly, and ascites as reliable predictors of EVB in patients with liver cirrhosis.Goh et al. emphasize the unreliability of thrombocytopenia, splenomegaly, and ascites in predicting EVB [12].This challenges the traditional view that low platelet count indicates EVB risk, highlighting the need for a reevaluation of the factors contributing to EVB.Giannini et al. support the notion that platelet counts are not suitable predictors for post-endoscopic variceal band ligation (EVBL) bleeding [28].These findings suggest the limitations of these commonly considered parameters in assessing EVB risk.

Laboratory Values
Low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients and may be used to stratify patients' risk [28].Another coagulation parameter considered to be a predictor of variceal bleeding is the Von Willebrand Factor (vEF) and the VITRO (vEF antigen/ platelet count) score [30], although our analysis determined this study to have a high risk of bias, therefore being limited in its application in predicting bleeding from esophageal varices.
Albumin was introduced as a variable considered in clinical radiomics nomogram to predict EVB in cirrhotic patients [41].It's important to highlight the study's high risk of bias.PVT and low albumin levels <30 g/l were identified as potential predictors for six-week rebleeding following EVBL [37].However, further analysis revealed that only PVT remained as an independent factor and albumin did not retain its predictive power in this context.The presence of PVT in cirrhotic patients often complicates the clinical picture, and it can be a crucial factor in assessing rebleeding risk.However, the limitations of the high risk of bias in this study should be taken into account, and further investigations are necessary to confirm these results.
The role of high creatinine levels in predicting rebleeding in cirrhotic inpatients has been examined by Wang et al. [16].However, their study's quality does not meet the criteria required for robust predictive factors.As a result, the reliability of high creatinine as an independent predictor for rebleeding remains questionable.
In a study by Luo et al., AST levels were considered part of a clinical radiomics nomogram thar can noninvasively predict whether cirrhotic patients will develop EVB [41].However, it's important to notice the quality of their study was poor and there was simultaneous evaluation of albumin, fibrinogen, PVT, AST, and spleen thickness.Further research is needed to validate the findings and assess the generalizability of the clinical-radiomics model.Future studies should also explore the feasibility of implementing this nomogram in clinical practice.
Bilirubin levels were also considered by two different studies [15,16], and both found that high bilirubin levels are directly correlated to rebleeding of esophageal varices.However, it is important to take into account that one of them has a high risk of bias, needing further investigation on this parameter.

Other Predictive Factors
Diabetes mellitus: Diabetes mellitus has been considered a potential predictive factor for bleeding, especially in those with Child-Pugh Class A cirrhosis, as indicated in a study by Yang et al. [22], with a fair quality in terms of potential bias.Notably, it's intriguing to observe that a higher percentage of patients with diabetes were in Child-Pugh Class B/C, experiencing renal insufficiency, and having a history of gastroesophageal variceal bleeding.However, it's essential to acknowledge that the the outcomes of Yang et al.'s study might have been influenced by the specific characteristics of the population under investigation.Furthermore, the study was constrained by a relatively small number of patients.Diabetes was also a subject of evaluation in a separate study, which also examined age, ascites, and alcohol-related disorders as potential factors, and this study was of good quality [25].However, the need for further research in this area remains, given the complex interplay of factors and potential limitations in the existing studies.
Beta-blockers: According to Kim et al., patients who had their first episode of variceal bleeding while on primary prophylaxis with a b-blocking agent have an increased risk of further bleeding [17].However, their study had a poor quality and there is no support from other studies.

Protective Factor
High albumin levels were stated to serve as a protective factor by Gao et al. [37], but the high risk of bias of their study subjects this factor to further evaluation in the future.No further studies found protective factors for EVB.

Limitations
It is essential to recognize that existing research has limitations, including varied treatment protocols and potential biases.The review adhered to its inclusion criteria for patients with hepatic cirrhosis of all etiologies; however, some studied patients were exposed to cirrhosis of infectious causes, primarily hepatitis B or C, and of HCC in a compensated state.These characteristics could potentially have influenced our findings.It is noteworthy that our research was limited to a specific number of academic databases, focused on articles published in English and Spanish, and was based on a specific time frame.As a result, we understand that there may be a potential bias due to these limitations that defined our search methodology.Therefore, there is a risk of omission of older studies and relevant research in different languages.The possibility that literature that is under review or in the editing process for publication may have been missed is also something to consider.Despite our dedicated search methodology and efforts to include worldwide studies, Asian regions predominated, which could influence our conclusion.It is possible that other publications may have escaped our attention and analysis.It is important to highlight that this is an exceptional systematic review on this topic, for which there were no previous peers, providing essential information that could bridge potential gaps in knowledge.

Conclusions
This comprehensive systematic review has explored a wide range of factors associated with the risk of EVB in patients with portal hypertension.It has shed light on various predictors, both clinical and laboratory, that have been identified in the literature, providing valuable insights into this critical medical issue.The primary findings suggest that the Child-Pugh score, Fibrosis Index, specific endoscopic findings, ultrasound parameters, portal vein diameter, presence and size of collaterals, CT scan findings, ascites, platelet counts, coagulation parameters, albumin levels, Von Willebrand factor, bilirubin levels, diabetes mellitus, and the use of beta-blocking agents in primary prophylaxis are potential predictive factors for EVB.These findings provide a comprehensive overview of the various aspects that can influence the risk of bleeding in patients with portal hypertension.
However, it is important to note that some of the identified factors exhibit varying degrees of reliability and may be subject to limitations and biases, as highlighted in the discussion.The quality of the studies and the potential for bias in some cases warrant caution in interpreting these findings.Further research is needed to refine and validate these predictive factors, taking into consideration the potential limitations of the existing studies.In addition, it is essential to acknowledge that the complex interplay of factors and the diversity of patient populations may influence the predictive capabilities of these factors.Therefore, a more tailored and individualized approach to risk assessment for EVB is necessary, accounting for specific patient characteristics and clinical context.

FIGURE 1 :
FIGURE 1: PRISMA flow diagram PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow velocity of the LGVs were higher for EVBs.Variceal bleeding was more frequent in patients with a diameter of LGV >6 mm. and with a hepatofugal flow velocity >15 cm/s"

3 Goh
27.5% had ascites.Six patients had all three criteria.12 patients with bleeding varices did not have any of the criteria.Patients with variceal red signs had significantly higher values of portal diameter, cross-sectional area, blood flow volume and congestion index, while the perfusion pressure gradient and the platelet/spleen ratio were lower.IV esophageal varices, presence of cherry-red spots and fundal varices were significant risk factors for index bleed and rebleed.blood transfused, the presence of ascites, and a bilirubin level >51 mmol/l were the best set of significant predictor covariates.In the multivariate logistic regression analysis model, bilirubin levels greater than 51 mmol/l and >6 units of blood transfused during the initial hospital admission were significant predictors of Bilirubin levels >51 mmol/l and transfusion of >6 units of blood were predictors of variceal rebleeding.2023 Guinazu et al.Cureus 15(11): e48954.DOI 10.7759/cureus.analysisshowed positively correlations with rebleeding: Child-Pugh grade B, Tbil, creatinine and the cumulative volume of blood transfusion.The presence of ascites and prophylactic antibiotics were negatively correlated of bleeding while on NSBBs had further bleeding, compared with controls.Primary prophylaxis with NSBBs was an independent predictor.patients who survived >6 weeks after endoscopic management and did not rebleed.

GEV
analysis, DM correlated with GEVB in patients with Child-Pugh Class A but not in Class B/multi-variable analyses high-risk stigmata of variceal bleeding, the obliteration range of PTVE, and an HVPG ≥ 20 mmHg were significantly associated with the risk of rebleeding High-risk stigmata, PTVE with trunk obliteration, higher in patients with varices than in those without varices.A tendency toward increasing SS levels was observed with increasing severity of varices and variceal hemorrhage.model based on LSM and PC was more accurate for excluding the presence of high-risk GOV than either alone, with the combination of LSM ≤25 kPa and Pl ≥100 having an NPV of 100% in both the training and validation cohorts.The combination of LSM ≤25 kPa and Pl ≥100 can be used in clinical practice to exclude the presence of high-risk that the HR of EVB history was 4.42 for EVB occurrence.Other predictors for EVB occurrence included hepatocellular carcinoma, young age, ascites, alcohol-related disorders, peptic ulcer bleeding and off value of 3.23 for FIB-4 was a significant predictor of esophageal varices, with a sensitivity of 72%, a specificity of 58% and a proportion of AUC counts were not predictors of post-EVBL bleeding.A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding.varices grade was highly correlated with LSM and the LSPS in cirrhosis.Meanwhile, LSM and spleen 2023 Guinazu et al.Cureus 15(11): e48954.DOI 10.7759/cureus.ofthe vEF antigen and the VITRO score were higher in patients with variceal bleeding.Levels of vEF were correlated positively with esophageal varices grade..76mm in bleeding group, and 6.57±3.42mm in non-bleeding group.The number of venous vessels was 4.5±2 in bleeding group, whereas being 4±2 in non-bleeding group.The blood vessel area was 1.73±1.15cm2 in bleeding group, and 1cut-off value of 3.95 showed an NPV of 94.3% and an AUROC of 62.95% for predicting subsequent EVB within 1 year.Findings of esophageal varices in MDCT analysis were the best predictor of esophageal varices or EVH, and presence (and/or size) of specific collaterals showed a significant relationship with both esophageal varices and EVH: coronary, short gastric and paraesophageal., lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to highrisk varices.Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of accuracy of ML-based model to predict future VB was 98.7%, 93.7 %, and 85.7 % in derivation, internal validation, and external validation cohorts, respectively, which was better than endoscopic classification [58.9%] alone.Application of ML model improved the performance of endoscopic stratification to predict VB in patients with cACLD with EVs.2023 Guinazu et al.Cureus 15(11): e48954.DOI 10.7759/cureus.hada higher rate of 14-day and 6-week rebleeding.The Child-Pugh class, PVT, albumin<30 g/L, and number of bands were identified as the predictors for 14-day rebleeding; multivariate analysis revealed only the number of bands as independent factor.PVT and albumin<30 g/L were identified as predictors for 6-week rebleeding; only PVT was found to be the independent factor in multivariate analysis.Further analysis showed that SMV thrombosis is the only risk factor predicting six-week rebleeding in patients associated with grade of varices, presence of red sign on upper GI endoscopy, site of varices, splenic size and coagulopathy.factors to re-bleeding were the severity of cirrhosis, grades and columns of EVs, number of bands ligation and findings of red wale sign.Increasing age and duration of cirrhosis were contributing predictors of increased re-, PVT, AST, and spleen thickness were selected as independent clinical predictors of EGVB.RadScore, constructed with five CT features of the liver region and three of the spleen regions, performed well.There was excellent predictive performance for the clinical-radiomics model, comparing with the existing noninvasive models such as AST/PC ratio and Fib-4 scores, the combined model had better predictive accuracy.12 independent risk factors, including gender, drinking and smoking history, decompensation, ascites, location and size of varices, ALT, GGT, HCT and NLR levels as well as RBC count were evaluated and used to establish the ANN model, which estimated the 1-year EGVB risk.The ANN model had an AUC of 0