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The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Esophageal varices (EV) are the most fatal complication of chronic hepatitis B (CHB) related cirrhosis. The prognosis is poor, especially after the first upper gastrointestinal hemorrhage., Aim: To construct nomograms to predict the risk and severity of EV in patients with CHB related cirrhosis., Methods: Between 2016 and 2018, the patients with CHB related cirrhosis were recruited and divided into a training or validation cohort at The First Affiliated Hospital of Wenzhou Medical University. Clinical and ultrasonic parameters that were closely related to EV risk and severity were screened out by univariate and multivariate logistic regression analyses, and integrated into two nomograms, respectively. Both nomograms were internally and externally validated by calibration, concordance index (C-index), receiver operating characteristic curve, and decision curve analyses (DCA)., Results: A total of 307 patients with CHB related cirrhosis were recruited. The independent risk factors for EV included Child-Pugh class [odds ratio (OR) = 7.705, 95% confidence interval (CI) = 2.169-27.370, P = 0.002], platelet count (OR = 0.992, 95%CI = 0.984-1.000, P = 0.044), splenic portal index (SPI) (OR = 3.895, 95%CI = 1.630-9.308, P = 0.002), and liver fibrosis index (LFI) (OR = 3.603, 95%CI = 1.336-9.719, P = 0.011); those of EV severity included Child-Pugh class (OR = 5.436, 95%CI = 2.112-13.990, P < 0.001), mean portal vein velocity (OR = 1.479, 95%CI = 1.043-2.098, P = 0.028), portal vein diameter (OR = 1.397, 95%CI = 1.021-1.912, P = 0.037), SPI (OR = 1.463, 95%CI = 1.030-2.079, P = 0.034), and LFI (OR = 3.089, 95%CI = 1.442-6.617, P = 0.004). Two nomograms (predicting EV risk and severity, respectively) were well-calibrated and had a favorable discriminative ability, with C-indexes of 0.916 and 0.846 in the training cohort, respectively, higher than those of other predictive indexes, like LFI (C-indexes = 0.781 and 0.738), SPI (C-indexes = 0.805 and 0.714), ratio of platelet count to spleen diameter (PSR) (C-indexes = 0.822 and 0.726), King's score (C-indexes = 0.694 and 0.609), and Lok index (C-indexes = 0.788 and 0.700). The areas under the curves (AUCs) of the two nomograms were 0.916 and 0.846 in the training cohort, respectively, higher than those of LFI (AUCs = 0.781 and 0.738), SPI (AUCs = 0.805 and 0.714), PSR (AUCs = 0.822 and 0.726), King's score (AUCs = 0.694 and 0.609), and Lok index (AUCs = 0.788 and 0.700). Better net benefits were shown in the DCA. The results were validated in the validation cohort., Conclusion: Nomograms incorporating clinical and ultrasonic variables are efficient in noninvasively predicting the risk and severity of EV., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: There are two types of esophageal varices (EVs): high-risk EVs (HEVs) and low-risk EVs, and HEVs pose a greater threat to patient life than low-risk EVs. The diagnosis of EVs is mainly conducted by gastroscopy, which can cause discomfort to patients, or by non-invasive prediction models. A number of non-invasive models for predicting EVs have been reported; however, those that are based on the formula for calculation of liver and spleen volume in HEVs have not been reported., Aim: To establish a non-invasive prediction model based on the formula for liver and spleen volume for predicting HEVs in patients with viral cirrhosis., Methods: Data from 86 EV patients with viral cirrhosis were collected. Actual liver and spleen volumes of the patients were determined by computed tomography, and their calculated liver and spleen volumes were calculated by standard formulas. Other imaging and biochemical data were determined. The impact of each parameter on HEVs was analyzed by univariate and multivariate analyses, the data from which were employed to establish a non-invasive prediction model. Then the established prediction model was compared with other previous prediction models. Finally, the discriminating ability, calibration ability, and clinical efficacy of the new model was verified in both the modeling group and the external validation group., Results: Data from univariate and multivariate analyses indicated that the liver-spleen volume ratio, spleen volume change rate, and aspartate aminotransferase were correlated with HEVs. These indexes were successfully used to establish the non-invasive prediction model. The comparison of the models showed that the established model could better predict HEVs compared with previous models. The discriminating ability, calibration ability, and clinical efficacy of the new model were affirmed., Conclusion: The non-invasive prediction model for predicting HEVs in patients with viral cirrhosis was successfully established. The new model is reliable for predicting HEVs and has clinical applicability., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Spontaneous porto-systemic shunts (SPSS) are frequent in liver cirrhosis and their prevalence increases as liver function deteriorates, probably as a consequence of worsening portal hypertension, but without achieving an effective protection against cirrhosis' complications. Several types of SPSS have been described in the literature, each one associated with different clinical manifestations. In particular, recurrent or persistent hepatic encephalopathy is more frequent in patients with splenorenal shunt, while the presence of gastric varices and consequently the incidence of variceal bleeding is more common in gastrorenal shunt. In the advanced stage, the presence of large SPSS can lead to the so called "portosystemic shunt syndrome", characterized by a progressive deterioration of hepatic function, hepatic encephalopathy and, sometimes, portal vein thrombosis. The detection of SPSS in patients with liver cirrhosis is recommended in order to prevent or treat recurrent hepatic encephalopathy or variceal bleeding., Competing Interests: Conflict-of-interest statement: All authors have nothing to disclose and no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is currently used for the treatment of complications of portal hypertension. The incidence of hepatic encephalopathy (HE) remains a problem in TIPS placement. It has been reported that the right branch mainly receives superior mesenteric venous blood while the left branch mainly receives blood from the splenic vein. We hypothesized that targeted puncture of the left portal vein would divert the non-nutritive blood from the splenic vein into the TIPS shunt; therefore, targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE., Aim: To evaluate the influence of targeted puncture of left branch of portal vein in TIPS on HE., Methods: A retrospective analysis of 1244 patients with portal-hypertension-related complications of refractory ascites or variceal bleeding who underwent TIPS from January 2000 to January 2013 was performed. Patients were divided into group A (targeting left branch of portal vein, n = 937) and group B (targeting right branch of portal vein, n = 307). TIPS-related HE and clinical outcomes were analyzed., Results: The symptoms of ascites and variceal bleeding disappeared within a short time. By the endpoint of follow-up, recurrent bleeding and ascites did not differ significantly between groups A and B ( P = 0.278, P = 0.561, respectively). Incidence of HE differed significantly between groups A and B at 1 mo (14.94% vs 36.80%, χ 2 = 4.839, P = 0.028), 3 mo (12.48% vs 34.20%, χ 2 = 5.054, P = 0.025), 6 mo (10.03% vs 32.24%, χ 2 = 6.560, P = 0.010), 9 mo (9.17% vs 31.27%, χ 2 = 5.357, P = 0.021), and 12 mo (8.21% vs 28.01, χ 2 = 3.848, P = 0.051). There were no significant differences between groups A and B at 3 years (6.61% vs 7.16%, χ 2 = 1.204, P = 0.272) and 5 years (5.01% vs 6.18%, χ 2 = 0.072, P = 0.562). The total survival rate did not differ between groups A and B ( χ 2 = 0.226, P = 0.634, log-rank test)., Conclusion: Targeted puncture of the left branch of the intrahepatic portal vein during TIPS may reduce the risk of HE but has no direct influence on prognosis of portal-hypertension-related complications., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.

Aim: To examine the medical status of children with biliary atresia (BA) surviving with native livers., Methods: In this cross-sectional review, data collected included complications of chronic liver disease (CLD) (cholangitis in the preceding 12 mo, portal hypertension, variceal bleeding, fractures, hepatopulmonary syndrome, portopulmonary hypertension) and laboratory indices (white cell and platelet counts, total bilirubin, albumin, international normalized ratio, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase). Ideal medical outcome was defined as absence of clinical evidence of CLD or abnormal laboratory indices., Results: Fifty-two children [females = 32, 62%; median age 7.4 years, n = 35 (67%) older than 5 years] with BA (median age at surgery 60 d, range of 30 to 148 d) survived with native liver. Common complications of CLD noted were portal hypertension (40%, n = 21; 2 younger than 5 years), cholangitis (36%) and bleeding varices (25%, n = 13; 1 younger than 5 years). Fifteen (29%) had no clinical complications of CLD and three (6%) had normal laboratory indices. Ideal medical outcome was only seen in 1 patient (2%)., Conclusion: Clinical or laboratory evidence of CLD are present in 98% of children with BA living with native livers after hepatoportoenterostomy. Portal hypertension and variceal bleeding may be seen in children younger than 5 years of age, underscoring the importance of medical surveillance for complications of BA starting at a young age., Competing Interests: Conflict-of-interest statement: None of the authors has any potential conflict of interest to declare.

Aim: Evaluate the association between phase angle and the development of hepatic encephalopathy in the long-term follow-up of cirrhotic patients., Methods: This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. Mann-Whitney's U and χ 2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy., Results: Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy (18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. Kaplan-Meier curves showed a higher proportion of HE in the group with low phase angle (39%) compared to the normal phase angle group (13%) ( P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80 (1.07-3.03)]., Conclusion: In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Aim: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt (TIPS) in 15 years., Methods: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality., Results: Overall, 12.3% of patients died during hospitalization with downward trend in-hospital mortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients (OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients (OR = 1.347 vs non-transferred, P < 0.001), emergency admissions (OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region (OR = 1.449 vs West, P < 0.001) had significantly higher odds of in-hospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death (OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure (OR = 8.246), acute kidney failure (OR = 4.359), hepatic encephalopathy (OR = 2.217) and esophageal variceal bleeding (OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites (OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders (OR = 2.823), coagulopathy (OR = 2.016), and lymphoma (OR = 1.842)., Conclusion: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

Aim: To examine hospitalization rates for variceal hemorrhage and relation to cause of cirrhosis during an era of increased cirrhosis prevalence., Methods: We performed a retrospective review of patients with cirrhosis and gastroesophageal variceal hemorrhage who were admitted to a tertiary care referral center from 1998 to 2009. Subjects were classified according to the etiology of their liver disease: alcoholic cirrhosis and non-alcoholic cirrhosis. Rates of hospitalization for variceal bleeding were determined. Data were also collected on total hospital admissions per year and cirrhosis-related admissions per year over the same time period. These data were then compared and analyzed for trends in admission rates., Results: Hospitalizations for cirrhosis significantly increased from 611 per 100000 admissions in 1998-2001 to 1232 per 100000 admissions in 2006-9 (P value for trend < 0.0001). This increase was seen in admissions for both alcoholic and non-alcoholic cirrhosis (P values for trend < 0.001 and < 0.0001 respectively). During the same time period, there were 243 admissions for gastroesophageal variceal bleeding (68% male, mean age 54.3 years, 62% alcoholic cirrhosis). Hospitalizations for gastroesophageal variceal bleeding significantly decreased from 96.6 per 100000 admissions for the time period 1998-2001 to 70.6 per 100000 admissions for the time period 2006-2009 (P value for trend = 0.01). There were significant reductions in variceal hemorrhage from non-alcoholic cirrhosis (41.6 per 100000 admissions in 1998-2001 to 19.7 per 100000 admissions in 2006-2009, P value for trend = 0.007)., Conclusion: Hospitalizations for variceal hemorrhage have decreased, most notably in patients with non-alcoholic cirrhosis, and this may reflect broader use of strategies to prevent bleeding.

Aim: To determine the clinical effects and complications of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension due to cirrhosis., Methods: Two hundred and eighty patients with portal hypertension due to cirrhosis who underwent TIPS were retrospectively evaluated. Portal trunk pressure was measured before and after surgery. The changes in hemodynamics and the condition of the stent were assessed by ultrasound and the esophageal and fundic veins observed endoscopically., Results: The success rate of TIPS was 99.3%. The portal trunk pressure was 26.8 ± 3.6 cmH2O after surgery and 46.5 ± 3.4 cmH2O before surgery (P < 0.01). The velocity of blood flow in the portal vein increased. The internal diameters of the portal and splenic veins were reduced. The short-term hemostasis rate was 100%. Esophageal varices disappeared completely in 68% of patients and were obviously reduced in 32%. Varices of the stomach fundus disappeared completely in 80% and were obviously reduced in 20% of patients. Ascites disappeared in 62%, were markedly reduced in 24%, but were still apparent in 14% of patients. The total effective rate of ascites reduction was 86%. Hydrothorax completely disappeared in 100% of patients. The incidence of post-operative stent stenosis was 24% at 12 mo and 34% at 24 mo. The incidence of post-operative hepatic encephalopathy was 12% at 3 mo, 17% at 6 mo and 19% at 12 mo. The incidence of post-operative recurrent hemorrhage was 9% at 12 mo, 19% at 24 mo and 35% at 36 mo. The cumulative survival rate was 86% at 12 mo, 81% at 24 mo, 75% at 36 mo, 57% at 48 mo and 45% at 60 mo., Conclusion: TIPS can effectively lower portal hypertension due to cirrhosis. It is significantly effective for hemorrhage of the digestive tract due to rupture of esophageal and fundic veins and for ascites and hydrothorax caused by portal hypertension.

Aim: To evaluate the outcome of non-malignant and non-cirrhotic patients with portal cavernoma and to determine the predictors for survival., Methods: Between July 2002 and June 2010, we retrospectively enrolled all consecutive patients admitted to our department with a diagnosis of portal cavernoma without abdominal malignancy or liver cirrhosis. The primary endpoint of this observational study was death and cause of death. Independent predictors of survival were identified using the Cox regression model., Results: A total of 64 patients were enrolled in the study. During a mean follow-up period of 18 ± 2.41 mo, 7 patients died. Causes of death were pulmonary embolism (n = 1), acute leukemia (n = 1), massive esophageal variceal hemorrhage (n = 1), progressive liver failure (n = 2), severe systemic infection secondary to multiple liver abscesses (n = 1) and accident (n = 1). The cumulative 6-, 12- and 36-mo survival rates were 94.9%, 86% and 86%, respectively. Multivariate Cox regression analysis demonstrated that the presence of ascites (HR = 10.729, 95%CI: 1.209-95.183, P = 0.033) and elevated white blood cell count (HR = 1.072, 95%CI: 1.014-1.133, P = 0.015) were independent prognostic factors of non-malignant and non-cirrhotic patients with portal cavernoma. The cumulative 6-, 12- and 36-mo survival rates were significantly different between patients with and without ascites (90%, 61.5% and 61.5% vs 97.3%, 97.3% and 97.3%, respectively, P = 0.0008)., Conclusion: The presence of ascites and elevated white blood cell count were significantly associated with poor prognosis in non-malignant and non-cirrhotic patients with portal cavernoma.

Aim: To investigate in a prospective study whether a simplified clinical score prior to endoscopy in upper gastrointestinal bleeding (UGIB) patients was able to predict endoscopic findings at urgent endoscopy., Methods: All consecutive UGIB patients referred to a single endoscopic center during a 16 mo period were enrolled. Before endoscopy patients were stratified according to a simple clinical score (T-score), including T1 (high-risk), T2 (intermediate-risk) and T3 (low-risk). Endoscopy was performed in all cases within 2 h, and high-risk stigmata were considered for further analysis., Results: Out of the 436 patients included into the study, 126 (29%) resulted to be T1, 135 (31%) T2, and 175 (40%) T3. Overall, stigmata of recent haemorrhage (SRH) were detected in 118 cases (27%). SRH occurred more frequently in T1 patients than in T2/T3 cases (85% vs 3.2%; c2 = 304.5309, P < 0.001). Older age (t = 3.311; P < 0.01) and presence of comorbidities (c2 = 14.7458; P < 0.01) were more frequently detected in T1 than in T2/T3 patients., Conclusion: Our simplified clinical score appeared to be associated with the detection of endoscopic findings which may deserve urgent endoscopy. A further, randomised study is needed to assess its accuracy in safely scheduling endoscopy in UGIB patients.

Aim: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV)., Methods: We analyzed case records of 1436 patients with portal hypertension, who underwent endoscopy during the past five years for variceal screening or upper gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters were primary hemostasis (bleeding control within the first 48 h), recurrent bleeding (after 48 h of esophago-gastro-duodenoscopy) and in-hospital mortality were analyzed., Results: The prevalence of GV in patients with portal hypertension was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the 50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%), gastro-oesophageal varices (GOV) on lesser curvature (GOV-I) in 16 (32%), and GOV on greater curvature (GOV-II) in 15 (30%). IGV-I was seen in 44% (22/50) patients who had bleeding as compared to 23% (39/170) who did not have bleeding (P < 0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three patients died after repeat sclerotherapy, one during transjugular intrahepatic portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled bleeding. Treatment failure-related mortality rate was 6% (3/50)., Conclusion: GV can be seen in 15% of patients with portal hypertension and the incidence of bleeding is 22.7%. NBC is highly effective in controlling GV bleeding. In hospital mortality of patients with bleeding GV is 6%.

Aim: To investigate potential roles of per rectal portal scintigraphy in diagnosis of esophageal varices and predicting the risk of bleeding., Methods: Fifteen normal subjects and fifty cirrhotic patients with endoscopically confirmed esophageal varices were included. Patients were categorized into bleeder and non-bleeder groups according to history of variceal bleeding. All had completed per rectal portal scintigraphy using (99m)Technetium pertechnetate. The shunt index was calculated from the ratio of (99m)Technetium pertechnetate in the heart and the liver. Data were analyzed using Student's t-test and receiver operating characteristics., Results: Cirrhotic patients showed a higher shunt index than normal subjects (63.80 +/- 25.21 vs 13.54 +/- 6.46, P < 0.01). Patients with variceal bleeding showed a higher shunt index than those without bleeding (78.45 +/- 9.40 vs 49.35 +/- 27.72, P < 0.01). A shunt index of over 20% indicated the presence of varices and that of over 60% indicated the risk of variceal bleeding., Conclusion: In cirrhotic patients, per rectal portal scintigraphy is a clinically useful test for identifying esophageal varices and risk of variceal bleeding.