Portal hypertension and variceal bleeding in patients with liver cancer: Evidence gaps for prevention and management.

BACKGROUND AND AIMS: Portal hypertension (PHT) and HCC are 2 major complications of cirrhosis that often coexist in the same patient and impact the prognosis, especially in patients with acute variceal bleeding. In this review, we aim to discuss the best strategy for PHT screening and primary prophylaxis, as well as the management of acute variceal bleeding, to improve the management of PHT in HCC patients. RESULTS: Recent therapeutic advances observed in the management of HCC, notably through the advent of immunotherapy, have led to a clear improvement in the survival of patients. The prevention of complications related to underlying cirrhosis, such as PHT and acute variceal bleeding, is now part of the management of HCC patients. The Baveno VII conference recently redefined screening and prophylaxis in patients with cirrhosis. However, data regarding the applicability of these criteria in patients with HCC have been sparse. From our point of view, the Baveno criteria are not appropriate to exclude high-risk esophageal varices (EV) in HCC patients, and endoscopy should be performed except in HCC patients with a liver stiffness measurement (LSM) ≥25 kPa, who should benefit from nonselective beta-blockers (NSSBs) without performing endoscopy. We are also in favor of using NSBBs as primary prophylaxis in patients with EV regardless of the size and with gastric varices since these patients display clinically significant PHT. CONCLUSIONS: Appropriate evaluation and treatment of PHT remain major issues in improving the outcomes of HCC patients. Many questions remain unanswered, opening the field to many areas of research.

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension.

BACKGROUND: Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis. Although primary prevention drugs, including non-selective ß-blockers, have effectively reduced the incidence of bleeding, their efficacy is limited due to side effects and related contraindications. With recent advances in precision medicine, precise drug treatment provides better treatment efficacy. DATA SOURCES: Literature search was conducted in PubMed, MEDLINE and Web of Science for relevant articles published up to May 2022. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/. RESULTS: The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs. According to the site of action, these drugs could be classified into four classes: intrahepatic, extrahepatic, both intrahepatic and extrahepatic targets and others. All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension. CONCLUSIONS: This review classified and summarized the promising drugs, which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension, demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

Beta-blockers in the era of precision medicine in patients with cirrhosis.

For decades, non-selective beta-blockers (NSBBs) have been the standard of care for the primary and secondary prevention of bleeding from oesophageal varices. However, several questions regarding the best clinical use of NSBBs remain unanswered and new data continue to emerge. Herein, we aim to delineate the therapeutic window of NSBBs in cirrhosis from a more individualised perspective. We address the current controversy of widening the therapeutic window and prescribing NSBBs to all patients with clinically significant portal hypertension. Although transient elastography is useful to rule-in clinically significant portal hypertension, we lack robust data supporting the use of NSBBs in patients without varices. While most data are based on propranolol, accumulating evidence suggests that carvedilol is superior and should be the first-line treatment until the decompensated stage. The clinical risk-to-benefit ratio appears to deteriorate in advanced decompensated stages and the risk of harm is high in patients with refractory ascites, low blood pressure and renal impairment, which clinically define closure of the therapeutic window. We also critically review non-invasive surrogates and biomarkers for predicting the haemodynamic response to NSBBs and confirm that the absence of reliable non-invasive methods is one of the main challenges facing the field.

5-MTHF enhances the portal pressure reduction achieved with propranolol in patients with cirrhosis: A randomized placebo-controlled trial.

BACKGROUND & AIMS: ß-blockers reduce hepatic venous pressure gradient (HVPG) by decreasing portal inflow, with no reduction in intrahepatic vascular resistance. 5-Methyltetrahydrofolate (5-MTHF) can prevent oxidative loss of tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase coupling. It also converts homocysteine (tHcy) into methionine and enables the degradation of asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase. The aim of this study was to evaluate the effects of 5-MTHF in combination with propranolol on HVPG and nitric oxide bioavailability markers in patients with cirrhosis and portal hypertension. METHOD: Sixty patients with cirrhosis and HVPG ≥12 mmHg were randomized 1:1 to receive treatment with 5-MTHF+propranolol or placebo+propranolol for 90 days under double-blind conditions. HVPG and markers of nitric oxide bioavailability (BH4, ADMA and tHcy) were measured again at the end of treatment. RESULTS: Groups were similar in terms of baseline clinical and hemodynamic data and nitric oxide bioavailability markers. HVPG decreased in both groups, but the magnitude of the change was significantly greater in the group treated with 5-MTHF+propranolol compared to placebo+propranolol (percentage decrease, 20 [29-9] vs. 12.5 [22-0], p = 0.028), without differences in hepatic blood flow. At the end of treatment, 5-MTHF+propranolol (vs. placebo+propranolol) was associated with higher BH4 (1,101.4 ± 1,413.3 vs. 517.1 ± 242.8 pg/ml, p <0.001), lower ADMA (109.3 ± 52.7 vs. 139.9 ± 46.7 µmol/L, p = 0.027) and lower tHcy (µmol/L, 11.0 ± 4.6 vs. 15.4 ± 7.2 µmol/L, p = 0.010) plasma levels. CONCLUSION: In patients with cirrhosis and portal hypertension, 5-MTHF administration significantly enhanced the HVPG reduction achieved with propranolol. This effect appears to be mediated by improved nitric oxide bioavailability in the hepatic microcirculation. CLINICAL TRIAL EUDRACT NUMBER: 2014-002018-21. IMPACT AND IMPLICATIONS: Currently, the pharmacological prevention of cirrhosis complications due to portal hypertension, such as esophageal varices rupture, is based on the use of ß-blockers, but some patients still present with acute variceal bleeding, mainly due to an insufficient reduction of portal pressure. In this study, we sought to demonstrate that the addition of folic acid to ß-blockers is more effective in reducing portal pressure than ß-blockers alone. This finding could represent the basis for validation studies in larger cohorts, which could impact the future prophylactic management of variceal bleeding in cirrhosis. Enhancing the benefit of ß-blockers with a safe, accessible, cost-effective drug could improve clinical outcomes in cirrhosis, which in turn could translate into a reduction in the rates and costs of hospitalization, and ultimately into improved survival.

Endoscopic resection of early esophageal tumors in patients with cirrhosis or portal hypertension: a multicenter observational study.

BACKGROUND: Liver cirrhosis and esophageal cancer share several risk factors, such as alcohol intake and excess weight. Endoscopic resection is the gold standard treatment for superficial tumors. Portal hypertension and coagulopathy may increase the bleeding risk in these patients. This study aimed to assess the safety and efficacy of endoscopic resection for early esophageal neoplasia in patients with cirrhosis or portal hypertension. METHODS: This retrospective multicenter international study included consecutive patients with cirrhosis or portal hypertension who underwent endoscopic resection in the esophagus from January 2005 to March 2021. RESULTS: 134 lesions in 112 patients were treated, including by endoscopic submucosal dissection in 101 cases (75 %). Most lesions (128/134, 96 %) were in patients with liver cirrhosis, with esophageal varices in 71 procedures. To prevent bleeding, 7 patients received a transjugular intrahepatic portosystemic shunt, 8 underwent endoscopic band ligation (EBL) before resection, 15 received vasoactive drugs, 8 received platelet transfusion, and 9 underwent EBL during the resection procedure. Rates of complete macroscopic resection, en bloc resection, and curative resection were 92 %, 86 %, and 63 %, respectively. Adverse events included 3 perforations, 8 delayed bleedings, 8 sepsis, 6 cirrhosis decompensations within 30 days, and 22 esophageal strictures; none required surgery. In univariate analysis, cap-assisted endoscopic mucosal resection was associated with delayed bleeding (P = 0.01). CONCLUSIONS: In patients with liver cirrhosis or portal hypertension, endoscopic resection of early esophageal neoplasia appeared to be effective and should be considered in expert centers with choice of resection technique, following European Society of Gastrointestinal Endoscopy guidelines to avoid undertreatment.

Transjugular intrahepatic portosystemic shunt for portal hypertension: 30 years experience from China.

Liver diseases are a major cause of illness and death worldwide. In China, liver diseases, primarily viral hepatitis, affect approximately 300 million people, thus having a major impact on the global burden of liver diseases. Portal hypertension is the most severe complication of chronic liver diseases, including ascites, hepatic encephalopathy and bleeding from gastroesophageal varices. Transjugular intrahepatic portosystemic shunt (TIPS) represents a very effective treatment of these complications. Since its introduction 30 years ago in China, the use of TIPS has evolved and has played an increasingly important role in the management of the complications of portal hypertension. This review will focus on the history, current application and management of complications of TIPS in China.

Transjugular Intrahepatic Portosystemic Shunt Creation in Children Weighing <10 kg Using an Unconventional Technique.

Transjugular intrahepatic portosystemic shunt (TIPS) creation is a standard therapeutic procedure for the management of complications of portal hypertension. However, in small children, this procedure is infrequently performed because of technical difficulties owing to their small size and scarce information on outcomes. This article presents the results of treatment of variceal bleeding with TIPS creation in 8 children weighing <10 kg, along with the description of the unconventional techniques and materials required. Technical and clinical success rates were 100%. Although this was a small cohort of patients, the results obtained suggest that this is a safe and technically and clinically effective treatment option for complications of portal hypertension in this age group.

Large left varicocele in a patient with portal hypertension treated via transjugular intrahepatic portosystemic shunt placement and both variceal and varicocele embolization.

BACKGROUND: Scrotal swelling from varicocele is a common complaint in adult men. Varicocele due to portosystemic collaterals is a rare presentation of portal hypertension. Imaging workup and intervention for varicocele in this case is more complex than varicocele due to absent or incompetent valves in the testicular veins and pampiniform plexus. CASE PRESENTATION: We present the case of a 53-year-old man with alcohol-related cirrhosis presented with persistent left scrotal heaviness, pain, and swelling found to have a large left varicocele. Given his history of cirrhosis, a contrast-enhanced CT of the abdomen and pelvis was obtained showing that the varices were supplied by a vessel arising from the splenic vein and draining into the left renal vein as well as gastric varices. Varicocele embolization alone is not sufficient in this case, and we treated with transjugular intrahepatic portosystemic shunt, variceal and varicocele embolization. CONCLUSION: In patients presenting with a varicocele with a history of cirrhosis/portal hypertension, cross sectional imaging of the abdomen and pelvis should be obtained prior to treatment to evaluate for the presence of varices which may be pressured by varicocele embolization. If present, consideration should be given to referral to an interventional radiologist for possible concurrent variceal embolization and TIPS placement.

Outcomes of Transjugular Intrahepatic Portosystemic Shunt and Gastric Coronary Vein Embolization for Variceal Bleeding in Cirrhotic Portal Hypertension.

Purpose: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with gastric coronary vein embolization (GCVE) for cirrhotic portal hypertensive variceal bleeding and compare outcomes of first-line with second-line treatment, coil with glue, and single-covered with double stents.Methods: Fifteen patients received TIPS plus GCVE as the first-line treatment for secondary prophylaxis of variceal bleeding, and 45 received it as second-line treatment. Preoperative and postoperative quantitative variables were compared using a paired t test. The incidence of survival rate, re-bleeding, hepatic encephalopathy, and shunt dysfunction were analyzed using the Kaplan-Meier method.Results: The portal venous pressure was significantly decreased from 39.0 ± 5.0 mm Hg to 22.5 ± 4.4 mm Hg (P≤0.001) after TIPS treatment. After 1, 3, 6, 12, 18, and 24 months re-bleeding rates were 1.6%, 3.3%, 6.6%, 13.3%, 0%, and 0%, respectively. Shunt dysfunction rates were 5%, 0%, 10%, 16.6%, 1.6%, and 5%, respectively. Hepatic encephalopathy rates were 3.3%, 1.6%, 3.3%, 6.6%, 0%, and 0%, respectively. And survival rates were 100%, 100%, 100%, 96.6%, 93.3%, and 88.3% respectively. In comparative analysis, statistically significant differences were seen in re-bleeding between the first-line and second-line treatment groups (26.6% vs 24.4%, log-rank P=0.012), and survival rates between single-covered and double stent (3.7% vs 16.1%, log-rang (P=0.043).Conclusion: The results suggest that TIPS combined with GCVE is effective and safer in the treatment of cirrhotic portal hypertensive variceal bleeding. The use of TIP plus GCVE as first-line treatment, may be preferable for high-risk re-bleeding, and more than 25 mm Hg portal venous pressure with repeated variceal bleeding. However, the sample size was small. Therefore, large, randomized, controlled, multidisciplinary center studies are needed for further evaluation.

Prevention of post-tips hepatic encephalopathy: The search of the ideal candidate.

Transjugular intrahepatic portosystemic shunt (TIPS) has been used since more than 25 years to treat some of the complications of portal hypertension, especially variceal bleeding and ascites refractory to conventional therapy. TIPS establishes a communication between the portal and hepatic veins, inducing the blood to shift from the splanchnic circulation into the systemic vascular bed with the aim of decompressing the portal venous system, and avoids the major complications of portal hypertension. However, the shunt of the portal blood into the systemic circulation is the cause of one of the major complications of the procedure: the post-TIPS hepatic encephalopathy (HE). To date, few pharmacological treatment has been proven effective to prevent this complication and thus, the identification of patients at high risk of post-TIPS hepatic encephalopathy and the patients' carefully selection is the only way to prevent this frequent complication.

Portal hypertension hemorrhage secondary to a stomal varicose vein in a patient with two consecutive thrombosis of a transjugular intrahepatic portosystemic shunt (TIPS).

Less than 5% of patients with liver cirrhosis (LC) with portal hypertension (PH) develop atypical shunt (in regions other than the esophagus or the stomach). Within this group are varices associated with a stoma, for example the ones associated with an uretero-ileostomy which are infrequent. They are a diagnostic and therapeutic challenge, as they can cause hemorrhages due to PH. We present a clinical case about stoma varicose bleeding as the latest guidelines for the management of PH do not mention them or their treatment due to their low incidence.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Portosystemic shunt is an effective treatment for complications of portal hypertension in hepatic myeloid metaplasia and improves nutritional status.

In patients affected by myelofibrosis with hepatic myeloid metaplasia (HMM), portal hypertension (PHT) complications may develop. In this case series, we analysed the efficacy and safety of transjugular portosystemic shunt (TIPS) in the treatment of PHT-related complications and its effects on the nutritional status. Six patients were evaluated and the average follow-up period after TIPS was 33 (IQR 5) months. None of the patients developed hepatic failure, nor any recurrence of variceal bleeding was recorded. No additional paracentesis or endoscopic prophylactic treatment for PHT-related complications were required. In all subjects, the average dose of diuretics was almost halved three months after TIPS. Three patients died during the follow-up, but none for liver-related causes. All patients showed an improvement in the global nutritional status. In conclusion, TIPS represent an effective and safe treatment option for patients affected by complications of PHT secondary to HMM and drives to an improvement of the nutritional status.

Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertensive biliopathy with cavernous transformation of the portal vein: a case report.

BACKGROUND: Portal hypertensive biliopathy (PHB) was caused by anatomical and functional abnormalities in the intrahepatic and extrahepatic bile ducts secondary to portal hypertension. Currently, there is no consensus regarding to the optimal treatment for PHB. Transjugular intrahepatic portosystemic shunt (TIPS) is the treatment choice for the management of symptomatic PHB, however, it could be very difficult in patients with PHB and cavernous transformation of portal vein. CASE PRESENTATION: We report a case of PHB, successfully managed with TIPS. A 23-year-old man with liver cirrhosis presented with jaundice. Magnetic resonance cholangiopancreatography (MRCP) showed multiple tortuous hepatopetal collateral vessels compressing the common bile duct (CBD) and leading to the dilated proximal bile duct. He was diagnosed with PHB and treated with TIPS. A guidewire was inserted into the appropriate collateral vessel through transsplenic approach to guide intrahepatic puncture and TIPS was performed successfully. After the operation, portal vein pressure decreased and the symptoms of biliary obstruction were relieved significantly. In addition, the patient showed no jaundice at a follow-up of one year. CONCLUSIONS: For PHB patients presenting for cavernous transformation of the portal vein, which precludes the technical feasibility of TIPS, a combined transjugular/transsplenic approach could be an alternative option.

Efficacy and Safety of Endoscopic Primary Prophylaxis of Bleeding in Children With High-Risk Gastroesophageal Varices.

OBJECTIVES: Primary prophylaxis of bleeding is debated in children with gastroesophageal varices; one of the reasons is the limited number of studies concerning its efficacy and safety. We report our experience with endoscopic primary prophylaxis. METHODS: From 2006 to 2019, 145 children (median age, 3.5 years; cirrhosis, n = 116) with high-risk gastroesophageal varices underwent primary prophylaxis (banding, n = 114; sclerotherapy n = 31, primarily in smaller children). RESULTS: We observed the eradication of varices in 93% of children after a mean of 6 months, at least one recurrence of varices in 45% after eradication, and gastrointestinal bleeding in 17% of children. Irrespective of the cause of portal hypertension, grade 3 esophageal varices, presence of gastric varices along the cardia and a lower composite score of endoscopic severity were associated with a worse probability of eradication, a longer time to eradication and a lower risk of a first recurrence and of bleeding following the procedure, respectively. Ten-year probabilities of overall survival and of bleeding-free survival were 95% and 75%, respectively. CONCLUSIONS: Endoscopic primary prophylaxis of variceal bleeding is reasonably effective and safe in children with high-risk gastroesophageal varices. Worse results are observed in children with more advanced endoscopic features. This pleads for endoscopic screening in children with portal hypertension and early detection of varices warranting primary prophylaxis.

National Consensus on Portal Hypertension Management in Indonesia.

Portal hypertension is a clinical syndrome that consists of hypersplenism, ascites, gastroesophageal varices, and encephalopathy. This condition is marked by increased portal pressure gradient and may occur with or without liver cirrhosis. To date, portal hypertension remains as the leading cause of severe complications and death of a patient with chronic liver disease, especially liver cirrhosis. Therefore, thorough understanding about management of portal hypertension is strongly required, especially considering that many complications of portal hypertension require early diagnosis and treatment to improve the prognosis of the patients. Additionally, although hepatic venous pressure gradient (HVPG) measurement has become a gold standard procedure for measuring portal pressure in the last twenty years, utilization of this method in Indonesia has been hindered by reluctance of the patients due to its invasiveness, high cost, and limited availability. This consensus is developed with evidence-based medicine principles to provide a guideline for portal hypertension management for general practitioners, specialists, and consultants, to achieve better clinical outcomes of portal hypertension in Indonesia.  Keywords: portal hypertension, liver cirrhosis, chronic liver disease.

[Emphasis on the prevention and treatment of hepatic vascular diseases].

Portal hypertension, as a common and complex hepatic vascular disease, is a key pathophysiological link in many events of acute cirrhosis decompensation and the progression of multiple organ failure. The most effective measure to reduce portal hypertension is a transjugular intrahepatic portosystemic shunt (TIPS). Maintaining liver function, reducing complications, and improving patients' quality of life and survival time are positively impacted by early TIPS insertion. Patients with cirrhosis have a risk of portal vein thrombosis (PVT) that is 1 000 times higher than that of the normal population. Hepatic sinusoidal obstruction syndrome has a severe clinical course and a high mortality risk. The primary treatment approaches for PVT and HSOS are anticoagulation and TIPS. The innovative magnetic anastomosis vascular technique significantly shortens the anhepatic time and restores normal liver function in patients following liver transplantation.

[Effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors].

Objective: To investigate the effects of primary preventive treatment under endoscope for esophageal and gastric varices on bleeding rate and its relevant factors. Methods: 127 cases with liver cirrhosis accompanied with esophageal and gastric varices without bleeding history were included in the endoscopic and non-endoscopic treatment group, respectively. Informed consent was obtained from both groups. Gastric varices (Lgf) and esophageal varices (Leg) were diagnosed according to LDRf classification criteria, and the corresponding treatment scheme was selected according to the recommended principle of this method.The incidence rate of bleeding from ruptured esophageal varices were observed at 3, 6 months, and 1, and 2 years in the treated and the untreated group, and the patients with different Child-Pugh scores were followed-up for 2 years. Gender, age, etiology, varicose degree, Child-Pugh grade, platelet count, prothrombin activity, portal vein thrombosis, collateral circulation, portal vein width and other factors affecting the bleeding rate were assessed. Measurement data were described as mean ± standard deviation (x¯±s), and qualitative data of categorical variables were expressed as percentage (%), and χ2 test was used. Results: 127 cases were followed up for 2 years. There were 55 cases in the endoscopic treatment group (18 cases underwent band ligation, 2 cases underwent band ligation combined with tissue adhesive embolization, 28 cases underwent sclerotherapy, and 7 cases underwent sclerotherapy combined with tissue adhesive embolization). Recurrent bleeding and hemorrhage was occurred in 5 (9.1%) and 28 cases (38.9%), respectively (P<0.05). In addition, there were 72 cases in the untreated group (P<0.05). Severe varicose veins proportions in treated and untreated group were 91.1% and 85.1%, respectively (P>0.05). There was no statistically significant difference in liver cirrhosis-related medication and ß-blocker therapy between the treated and untreated group (P>0.05). There was no statistically significant difference in the bleeding rate between the different treated groups (P>0.05). The bleeding rates at 3, 6 months, 1, and 2 years in endoscopic treated and untreated group were 2.00% vs. 2.59% (P>0.05), 2.30% vs. 5.88% (P>0.05), 3.10% vs. 7.55% (P>0.05) and 4.00% vs. 21.62% (P<0.05), respectively. All patients with Child-Pugh grade A, B and C in the treated and the untreated group were followed-up for 2 years, and the bleeding rates were 1.8% vs. 8.1% (P<0.05), 1.1% vs. 9.4% (P<0.05) and 9.1% vs. 10.1% (P>0.05), respectively. There were statistically significant differences in the rupture and bleeding of esophageal and gastric varices, varices degree, Child-Pugh grade and presence or absence of thrombosis formation in portal vein (P<0.05); however, no statistically significant differences in gender, age, etiology, platelet count, prothrombin activity, collateral circulation and portal vein width (P>0.05). There was no intraoperative bleeding and postoperative related serious complications in the treated group. Conclusion: The risk of initial episodes of bleeding from esophageal and gastric varices is significantly correlated with the varices degree, Child-Pugh grade, and portal vein thrombosis. Primary preventive treatment under endoscope is safe and effective for reducing the long-term variceal bleeding risk from esophageal and gastric varices.

[Meta-analysis of ß-blockers for the primary prevention of liver cirrhosis with clinically significant portal hypertension with no or small esophageal varices].

Objective: To explore whether NSBB is suitable for the primary prevention of liver cirrhosis accompanied by CSPH with no or small esophageal varices. Methods: Relevant literatures were retrieved from Cochrane library, PubMed, EMBASE, SinoMed, CNKI and Wanfang databases until December 12, 2020. All randomized controlled trials (RCTs) on NSBB use for primary prevention of cirrhosis accompanied by CSPH with no or small esophageal varices were collected. The literature was strictly screened according to the established inclusion and exclusion criteria, odds ratio (OR), and 95% confidence interval (CI) combined effect size. The development of esophageal varices and the initial upper gastrointestinal bleeding were the primary outcome measures. Death (with a maximum average follow-up of about five years) and adverse events (adverse drug reactions, etc.) were the secondary outcome measures. Results: A total of 9 RCTs with 1396 cases were included. Meta-analysis results showed that, compared with placebo, NSBB significantly reduced the incidence of liver cirrhosis accompanied by CSPH with no or small esophageal varices to large esophageal varices progression (OR=0.51, 95%CI: 0.29-0.89, P=0.02), and mortality (with maximum average follow-up of about five years) (OR=0.64, 95%CI: 0.44-0.92, P=0.02); however, there was no statistically significant difference in the initial upper gastrointestinal bleeding rate between the two groups (OR=0.82, 95%CI: 0.44-1.52, P=0.53). Adverse event incidence was greater in the NSBB than the placebo group (OR=1.74, 95%CI: 1.27-2.37, P=0.0005). Conclusions: NSBB use cannot reduce the initial upper gastrointestinal bleeding rate or adverse event incidence in patients with liver cirrhosis accompanied by CSPH with no or small esophageal varices, but it can delay the progression of gastroesophageal varices and reduce patient mortality.

Beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis.

BACKGROUND: Portal hypertension commonly accompanies advanced liver disease and often gives rise to life-threatening complications, including haemorrhage from oesophageal and gastrointestinal varices. Variceal haemorrhage commonly occurs in children with chronic liver disease or portal vein thrombosis. Therefore, prevention is important. Band ligation, beta-blockers, and sclerotherapy have been proposed as alternatives for primary prophylaxis of oesophageal variceal bleeding in children. However, primary prophylaxis is not the current standard of care in paediatric patients because it is unknown whether those treatments are of benefit or harm when used for primary prophylaxis in children and adolescents. OBJECTIVES: To determine the benefits and harms of beta-blockers compared with placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, PubMed, Embase, LILACS, and Science Citation Index Expanded (April 2020). We screened the reference lists of the retrieved publications and manually searched the main paediatric gastroenterology and hepatology conference (NASPGHAN and ESPGHAN) abstract books from 2008 to December 2019. We searched clinicaltrials.gov, the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO) for ongoing clinical trials. We imposed no language or document type restrictions on our search. SELECTION CRITERIA: We planned to include randomised clinical trials, irrespective of blinding, language, or publication status to assess benefits and harms. We included observational studies, retrieved with the searches for randomised clinical trials, for a narrative report of harm. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials by standard Cochrane methodologies. We planned to asses risk of bias and use GRADE to assess the certainty of evidence. Our primary outcomes were all-cause mortality, serious adverse events and liver-related morbidity, and health-related quality of life. Our secondary outcomes were oesophageal variceal bleeding and adverse events not considered serious. We planned to use intention-to-treat principle. We planned to analyse data with RevMan Analysis. MAIN RESULTS: We found no randomised clinical trials that assessed beta-blockers compared with sham or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis. We found four observational studies that reported on harms. As a systematic search for observational studies was not planned, we only listed the reported harms in a table. AUTHORS' CONCLUSIONS: Randomised clinical trials assessing the benefits or harms of beta-blockers versus placebo or no intervention for primary prophylaxis of oesophageal variceal bleeding in children with chronic liver disease or portal vein thrombosis are lacking. Therefore, trials with adequate power and proper design, assessing the benefits and harms of beta-blockers versus placebo on patient-relevant clinical outcomes, such as mortality, quality of life, failure to control variceal bleeding, and adverse events are needed. Unless such trials are conducted and the results become published, we cannot make any conclusions regarding the benefits or harms of the two interventions.