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Portal hypertension, a common sequela of chronic liver disease, is complicated by variceal hemorrhage, one of its most serious complications. Evidence-based approaches to managing variceal hemorrhage are limited by the scarcity of data related to this rare entity. Multicenter international registries are increasingly utilized to garner critical information about rare diseases. The International Multicenter Pediatric Portal Hypertension Registry (IMPPHR) was developed to acquire pediatric data about the mortality of first variceal hemorrhage and approaches to primary and second prophylaxis of variceal hemorrhage with a goal of improving outcomes in children with portal hypertension. IMPPHR evolved from pediatric portal hypertension symposia at the Baveno V and VI meetings in 2010 and 2015, with a formal executive committee initiating the development of IMPPHR in 2019. The registry opened in 2020, with data closure in 2024, including information from 44 centers and >700 subjects. The complexities and approaches to developing IMPPHR are described., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

To expand on the work of previous meetings, a virtual Baveno VII workshop was organised for October 2021. Among patients with compensated cirrhosis or compensated advanced chronic liver disease (cACLD - defined at the Baveno VI conference), the presence or absence of clinically significant portal hypertension (CSPH) is associated with differing outcomes, including risk of death, and different diagnostic and therapeutic needs. Accordingly, the Baveno VII workshop was entitled "Personalized Care for Portal Hypertension". The main fields of discussion were the relevance and indications for measuring the hepatic venous pressure gradient as a gold standard, the use of non-invasive tools for the diagnosis of cACLD and CSPH, the impact of aetiological and non-aetiological therapies on the course of cirrhosis, the prevention of the first episode of decompensation, the management of an acute bleeding episode, the prevention of further decompensation, as well as the diagnosis and management of splanchnic vein thrombosis and other vascular disorders of the liver. For each of these 9 topics, a thorough review of the medical literature was performed, and a series of consensus statements/recommendations were discussed and agreed upon. A summary of the most important conclusions/recommendations derived from the workshop is reported here. The statements are classified as unchanged, changed, and new in relation to Baveno VI., Competing Interests: Conflict of interest None relating to this manuscript. JB has been a consultant for Zydus, Surrozen and Actelion. TR is a consultant for and/or receives research support from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Philips, Pliant Pharmaceuticals, Roche, and Siemens. RdF, CR and GGT have no disclosures to report. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Approaches to the management of portal hypertension and variceal hemorrhage in pediatrics remain controversial, in large part because they are not well informed by rigorous clinical studies. Fundamental biological and clinical differences preclude automatic application of approaches used for adults to children. On April 11-12, 2015, experts in the field convened at the first Baveno Pediatric Satellite Meeting to discuss and explore current available evidence regarding indications for MesoRex bypass (MRB) in extrahepatic portal vein obstruction and the role of primary prophylaxis of variceal hemorrhage in children. Consensus was reached regarding MRB. The vast majority of children with extrahepatic portal vein obstruction will experience complications that can be prevented by successful MRB surgery. Therefore, children with extrahepatic portal vein obstruction should be offered MRB for primary and secondary prophylaxis of variceal bleeding and other complications, if appropriate surgical expertise is available, if preoperative and intraoperative evaluation demonstrates favorable anatomy, and if appropriate multidisciplinary care is available for postoperative evaluation and management of shunt thrombosis or stenosis. In contrast, consensus was not achieved regarding primary prophylaxis of varices. Although variceal hemorrhage is a concerning complication of portal hypertension in children, the first bleed appears to be only rarely fatal and the associated morbidity has not been well characterized., Conclusion: There are few pediatric data to indicate the efficacy and safety of pharmacologic or endoscopic therapies as primary prophylaxis or that prevention of a sentinel variceal bleed will ultimately improve survival; therefore, no recommendation for primary prophylaxis with endoscopic variceal ligation, sclerotherapy, or nonspecific beta-blockade in children was proposed., (© 2015 by the American Association for the Study of Liver Diseases.)

Assessing the presence of clinically significant portal hypertension and esophageal varices is clinically important in cirrhosis. The reference standard techniques to assess the presence of portal hypertension and varices are the measurement of the hepatic vein pressure gradient and esophagogastroduodenoscopy, respectively. Some newer methods have shown a good performance, but none has been proven precise enough to replace hepatic vein pressure gradient measurement or esophagogastroduodenoscopy for the diagnosis of portal hypertension or the presence and grade of esophageal varices., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Influence of portal vein thrombosis on efficacy of endoscopic variceal banding in patients with cirrhosis or extrahepatic portal vein obstruction has never been evaluated. Aim of the study was to assess influence of thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal vein obstruction undergoing banding, compared to cirrhotic patients without thrombosis., Methods: Retrospective analysis of 235 consecutive patients (192 with cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic portal vein obstruction) who underwent banding. Banding was performed every 2-3 weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months, then annually., Results: Eradication was achieved in 233 patients. Median time to eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic patients without thrombosis was 50.9 days (12-440) vs. 43.4 days (13-489.4); log-rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic patients without thrombosis 63.9 days (31-321.6) vs. 43.4 days (13.0-489.4); log-rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to eradication., Conclusions: Portal vein thrombosis per se appears to be the cause of a longer time to achieve eradication of varices but, once eradication is achieved, it does not influence their recurrence., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Complications of portal hypertension in children lead to significant morbidity and are a leading indication for consideration of liver transplantation. Approaches to the management of sequelae of portal hypertension are well described for adults and evidence-based approaches have been summarized in numerous meta-analyses and conferences. In contrast, there is a paucity of data to guide the management of complications of portal hypertension in children. An international panel of experts was convened on April 8, 2011 at The Children's Hospital of Pittsburgh of UPMC to review and adapt the recent report of the Baveno V Consensus Workshop on the Methodology of Diagnosis and Therapy in Portal Hypertension to the care of children. The opinions of that expert panel are reported., (© 2012 John Wiley & Sons A/S.)

Since the introduction of small bowel capsule endoscopy, and more recently of esophageal capsule endoscopy, these diagnostic tools have become available for the evaluation of the consequences of portal hypertension in the esophagus, stomach, and small intestine. The main advantage of the esophageal and the small bowel capsule is the relatively less invasiveness that could potentially increase patients' adherence to endoscopic screening/surveillance programs. When esophageal capsule endoscopy was compared with traditional gastroscopy, it showed good sensitivity and specificity in recognizing the presence and the size of esophageal varices. However, the results are not consistent among studies, and more data are needed., (2010 Elsevier Inc. All rights reserved.)

Unlabelled: Bleeding from esophageal varices (EV) is a serious consequence of portal hypertension. Current guidelines recommend screening patients with cirrhosis with esophagogastroduodenoscopy (EGD) to detect varices. However, the unpleasantness and need for sedation of EGD may limit adherence to screening programs. Pilot studies have shown good performance of esophageal capsule endoscopy in detecting varices. This multicenter trial was designed to assess the diagnostic performance of capsule endoscopy in comparison with EGD. Patients undergoing EGD for screening or surveillance of EV underwent a capsule study previously. The study was designed as an equivalence study, assuming that a difference of

Currently, oesophago-gastroduodenoscopy is the standard method to diagnose the presence of oesophago-gastric varices and to estimate the risk of bleeding. It is recommended that all patients undergo endoscopic screening for varices at the time when cirrhosis is diagnosed. After screening endoscopy, patients with medium or large varices should be treated to prevent bleeding, while all other patients should undergo periodic surveillance endoscopy. However, at a given point in time a variable proportion of patients will not have varices, since the prevalence of varices is variable. Thus, screening all cirrhotic patients with endoscopy to detect the presence of varices implies a number of unnecessary endoscopies. In recent years a wealth of new methods have been proposed as alternatives to conventional oesophago-gastroduodenoscopy for the non-invasive or minimally invasive diagnosis of oesophageal varices. Three of these methods (the platelet count/spleen diameter ratio, Fibrotest and Fibroscan) are truly non-invasive. Of these, the former is promising and needs a proper validation, Fibrotest appears to be insufficiently precise, while Fibroscan needs further evaluation. Multidetector CT oesophagography and capsule endoscopy are not entirely "non-invasive", since the first requires air insufflation into the oesophagus via an orally passed tube, and the latter requires swallowing the capsule. Multidetector CT oesophagography is promising, but needs further evaluation; capsule endoscopy is safe and reliable and might be proposed as an alternative to oesophago-gastroduodenoscopy in patients unable or unwilling to undergo oesophago-gastroduodenoscopy.

Portal hypertension leads to a wide variety of complications, which lead to significant morbidity and mortality and are some of the leading reasons for liver transplantation in children with chronic liver disease. Evidence-based approaches to the management of adults with portal hypertension exist and have been comprehensively reviewed in a series of international meetings, including the Baveno meetings. Similar evidence-based approaches for the management of portal hypertension in children do not exist and as such international meetings on portal hypertension have not focused on this problem in children. On October 7, 2005 at The Mount Sinai School of Medicine, a panel of pediatric experts reviewed the most recent Baveno statement and crafted a statement modified with their opinions vis a vis approaches to the management of portal hypertension in children.

The available data on the use of VCE in patients who have cirrhosis and portal hypertension are inadequate to reach a firm conclusion about the usefulness of this diagnostic tool in this patient population. In fact, only retrospective case series exist, in which the characteristics of the patients are heterogeneous in terms of severity of liver disease and of portal hypertension, etiology of cirrhosis, and indication for VCE. In addition, the controls included in the studies are heterogeneous or poorly described. In spite of this, it appears that in patients with portal hypertension, the small bowel frequently shows mucosal abnormalities. Such abnormalities appear to be particularly frequent in patients who have severe portal hypertension and in those with low hemoglobin levels. The clinical significance of these findings remains undefined, however, especially in view of the fact that small bowel lesions also have been found in about 10% of patients with arthritis not taking nonsteroidal anti-inflammatory drugs and in 13.8% of healthy subjects [41,42]. Therefore,large prospective studies are needed to evaluate the prevalence and clinical significance of small bowel mucosal changes in patients who have cirrhosis. Such studies should compare patients who have cirrhosis with healthy subjects. A comparison between cirrhotic patients with a history of intestinal bleeding and bleeding patients without cirrhosis also would be interesting.

Prevention of the first variceal haemorrhage should start when the patients have developed medium-sized to large varices. Non-selective beta-blockers and band ligation are equally effective in preventing the first bleeding episode. Rubber band ligation is the first choice for patients with contraindications or intolerance to beta-blockers. Treatment of acute bleeding should aim at controlling bleeding and preventing early rebleeding and complications, especially infections. Combined endoscopic (band ligation or sclerotherapy) and pharmacological treatment with vasoactive drugs can control bleeding in up to 90% of patients. Antibiotic prophylaxis is an integral part of the treatment of acute variceal haemorrhage, and must be started as soon as possible. Emergency transjugular intrahepatic portosystemic stent shunt (TIPS) is the standard rescue therapy for patients failing combined endoscopic and pharmacological treatment. All patients who survive a variceal bleed should be treated with beta-blockers or band ligation to prevent rebleeding. All patients in whom bleeding cannot be controlled or who continue to rebleed can be treated with salvage TIPS or, in selected cases, with surgical shunts. Liver transplantation should be considered for patients with severe liver insufficiency in which first-line treatments fail.

Prevention of the first variceal haemorrhage should start when the patients have developed medium sized to large varices. Non-selective beta-blockers are the first-line treatment; band ligation is roughly equivalent to beta-blockers and is the first choice for patients with contraindications or intolerance to beta-blockers. Treatment of acute bleeding should aim at controlling bleeding and preventing early rebleeding and complications, especially infections. Combined endoscopic and pharmacological treatment with vasoactive drugs can control bleeding in up to 90% of patients. All patients who survive a variceal bleed should be treated with beta-blockers or band ligation to prevent rebleeding. All patients in whom bleeding cannot be controlled or who continue to rebleed can be treated with salvage TIPS or, in selected cases, with surgical shunts. Liver transplantation should be considered for patients with severe liver insufficiency in which first-line treatments fail.

The goals of the Baveno workshops were to develop consensus definitions of key events related to portal hypertension and variceal bleeding, and to produce guidelines to facilitate the conduct and reporting of clinical trials. The consensus definitions concern the diagnosis of active bleeding, failure to control bleeding, the criteria to distinguish continuing bleeding from rebleeding, and the means of assessing failure to prevent rebleeding. The guidelines concern the timing of diagnostic endoscopy, the policy for blood volume restitution, the measures to prevent infection and encephalopathy, and the treatment options for acute bleeding, as well as primary and secondary prophylaxis. The intention of the experts who developed the guidelines was that, as feedback from their practical application develops, they should be adapted to better fit the practical needs. The applicability of the Baveno definitions has been evaluated in a study where the definitions of clinically significant bleeding, failure to control bleeding, the time frame for the acute bleeding episode and the definition of rebleeding were tested. The main criticism raised in this study was that tachycardia, one of the criteria that define failure to control bleeding, was misleading in 15% of patients who had the symptom but were not bleeding.

Portal hypertensive gastropathy (PHG) is characterized by changes in the endoscopic appearance of the gastric mucosa, specific for portal hypertension. The identification of the elementary lesions of PHG allowed the development of a reproducible classification, defining mild and severe pictures, and the execution of a natural history study. This study showed a 80% overall prevalence of PHG in patient with cirrhosis of the liver and a correlation between duration of the disease and development of PHG. PHG has often been shown to be a fluctuating condition, thus suggesting that its pathophysiology is not only related to portal hypertension, but also to other, yet unknown, factors. Bleeding from PHG did not occur in patients with a recent diagnosis of liver cirrhosis. Acute and chronic bleeding occurred in 2.5% and 12% of patients, respectively. The death rate from acute PHG bleeding was lower (12.5%) than the death rate of variceal bleeding (39.1%). Vasoactive drugs can be used in the treatment of acute PHG bleeding. For chronic bleeding, non selective 13-blockers and, if needed, iron, are the treatment of choice. TIPS or surgical portosystemic shunt may be considered for acute or chronic PHG bleeding, if medical treatment fails. Clinical controlled trials are needed to evaluate the efficacy of these or other treatments.

All patients with cirrhosis will eventually develop portal hypertension and esophagogastric varices. Bleeding from ruptured esophagogastric varices is the most severe complication of cirrhosis and is the cause of death in about one third of patients. The rate of development and growth of esophageal varices is poorly defined but in general seem to be related to the degree of liver dysfunction. Once varices have formed, they tend to increase in size and eventually to bleed. In unselected patients, the incidence of variceal bleeding is about 20% to 30% at 2 years. Variceal size is the single most important predictor of a first variceal bleeding episode. Several prognostic indexes based on endoscopic and clinical parameters have been developed to predict the risk of bleeding; however, their degree of accuracy is unsatisfactory. Death caused by uncontrolled bleeding occurs in about 6% to 8% of patients; the 6-week mortality rate after a variceal hemorrhage is 25% to 30%. There are no good prognostic indicators of death caused by uncontrolled bleeding or death within 6 weeks. Untreated patients surviving a variceal hemorrhage have a 1- to 2-year risk of rebleeding of about 60% and a risk of death of about 40% to 50%. The risk of bleeding is greatest in the first days after a bleeding episode and slowly declines thereafter. All patients surviving a variceal hemorrhage must be treated to prevent rebleeding. Varices can also be found in the stomach of cirrhotic patients, alone or in association with esophageal varices. Gastric varices bleed less frequently but more severely than esophageal varices. Portal hypertensive gastropathy is a common feature of cirrhosis, and its prevalence parallels the severity of portal hypertension and liver dysfunction. Portal hypertensive gastropathy can progress from mild to severe and vice-versa or even disappear completely. Acute bleeding from portal hypertensive gastropathy seems to be relatively uncommon, and less severe than bleeding from varices.

Background & Aims: The clinical importance of portal hypertensive gastropathy (PHG) as a source of gastrointestinal bleeding in patients with cirrhosis is poorly defined. We investigated the natural history of this condition in a large series of patients., Methods: All patients with cirrhosis seen at 7 hospitals during June and July 1992 were followed up with clinical and endoscopic examinations every 6 months for up to 3 years. Gastropathy was classified according to the classification of the New Italian Endoscopic Club., Results: The prevalence of gastropathy was 80% and was correlated with the duration of disease, presence and size of esophagogastric varices, and a previous history of endoscopic variceal sclerotherapy. During 18+/-8 months of follow-up, gastropathy was stable in 29% of patients, deteriorated in 23%, improved in 23%, and fluctuated with time in 25%. The evolution of gastropathy with time was identical in patients with and without previous or current sclerotherapy. Acute bleeding from gastropathy occurred in 8 of 315 patients (2.5%). The bleeding-related mortality rate was 12.5%. Chronic bleeding occurred in 34 patients (10.8%)., Conclusions: PHG is common in patients with cirrhosis, and its prevalence parallels the severity of portal hypertension. Gastropathy can progress from mild to severe and vice versa or even disappear completely. Bleeding from this lesion is relatively uncommon and rarely severe. Sclerotherapy of esophageal varices does not seem to influence the natural history of this condition.

Endoscopic treatments for bleeding gastroesophageal varices include injection sclerotherapy, variceal obturation with tissue adhesives, and variceal rubber band ligation. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from esophageal varices. Although few trials have been published so far, some evidence suggests that the early administration of vasoactive drugs (somatostatin, octreotide, or terlipressin) is safe and may increase the efficacy of endoscopic treatments. Banding ligation is the optimal endoscopic treatment for the prevention of rebleeding from esophageal varices. The use of tissue adhesives and thrombin as injectates to treat bleeding fundal gastric varices and esophageal varices not responding to vasoactive drugs or sclerotherapy is promising but needs further assessment by means of randomized controlled trials. As of today, endoscopic treatments are not recommended for the primary prophylaxis of variceal bleeding.

Objective: To classify elementary endoscopic lesions of portal hypertensive gastropathy, assess their reproducibility, prevalences, sensitivity and specificity in the diagnosis of cirrhosis of the liver., Methods: 1) A classification of portal hypertensive gastropathy elementary lesions was defined. 2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3) Fifteen centres enrolled consecutive patients with or without cirrhosis of the liver and recorded portal hypertensive gastropathy pattern according to its location., Results: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal hypertensive gastropathy prevalence was higher in patients with cirrhosis of the liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was 0.83. Portal hypertensive gastropathy was tentatively classified as mild or severe when mosaic-like pattern alone or red marks of any kind were present, respectively; this classification led to a further improvement in reproducibility., Conclusions: Our results suggest that a sufficient degree of agreement can be achieved in recording portal hypertensive gastropathy. Therefore, the New Italian Endoscopic Club classification should be used to evaluate the natural history of this condition.

Endoscopic treatments for bleeding gastro-oesophageal varices include injection sclerotherapy, variceal obturation with tissue adhesives and variceal rubber band ligation. Today, endoscopic treatments are not recommended for the primary prophylaxis of variceal bleeding. Acute injection sclerotherapy remains a quick and simple technique for the control of active bleeding from oesophageal varices. Its efficacy may be improved by the early administration of vasoactive drugs. Banding ligation is the optimal endoscopic treatment for the prevention of rebleeding from oesophageal varices. The use of tissue adhesives and thrombin as injectates to treat bleeding fundal gastric varices and oesophageal varices not responding to vasoactive drugs or sclerotherapy is promising but needs further assessment by means of randomized controlled trials.