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Esophageal Stent in Acute Refractory Variceal Bleeding: A Systematic Review and a Meta-Analysis
Songtanin, B., Kahathuduwa, C., Nugent, K.
Journal of clinical medicine. 2024;13(2)
Abstract
Background: Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. Aim: To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Results: Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, I(2) = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, I(2) = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, I(2) = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, I(2) = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, I(2) = 34). Conclusions: SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.
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Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis
Hassan, M., Merza, N., Nawras, Y., Bahbah, E. I., Al-Hillan, A., Ahmed, Z., ElSheref, Sedm, Dahiya, D. S., Dar, S., Al Azzawi, M., et al
Annals of medicine and surgery (2012). 2023;85(10):5001-5010
Abstract
BACKGROUND Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. METHODS This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. RESULTS Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). CONCLUSION This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.
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Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures
Ding, Z., Wu, H., Zeng, Y., Kuang, M., Yang, W., Meng, Z., Chen, Y., Hao, C., Zou, S., Sun, H., et al
Hepatology International. 2023;17(1):180-189
Abstract
PURPOSE Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 10(9)/L) patients undergoing elective invasive procedures. METHODS In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 10(9)/L that increased to ≥ 20 × 10(9)/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 10(9)/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded. RESULTS The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 10(9)/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups. CONCLUSIONS Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.
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Comparative Efficacy of Early TIPS, Non-Early TIPS, and Standard treatment in patients with cirrhosis and acute variceal bleeding: a network meta-analysis
Huang, Y., Wang, X., Li, X., Sun, S., Xie, Y., Yin, X.
International journal of surgery (London, England). 2023
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Editor's Choice
Abstract
BACKGROUND Cirrhosis is a chronic disease characterized by chronic liver inflammation and diffuse fibrosis. A combination of vasoactive drugs, preventive antibiotics, and endoscopy is the recommended standard treatment for patients with acute variceal bleeding; however, this has been challenged. We compared the effects of early transjugular intrahepatic portosystemic shunt (TIPS), non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. MATERIALS AND METHODS The present network meta-analysis was conducted in accordance with the criteria outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Assessing the methodological quality of systematic reviews guidelines. The review has been registered with the International Prospective Register of Systematic Reviews. The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and World Health Organization-approved trial registry databases were searched for randomized controlled trials (RCTs) evaluating early TIPS, non-early TIPS, and standard treatment in patients with cirrhosis and acute variceal bleeding. RESULTS Twenty-four RCTs (1,894 patients) were included in the review. Compared with standard treatment, early TIPS (odds ratio [OR], 0.53; 95% credible interval [CrI], 0.30-0.94; surface under the cumulative ranking curve [SUCRA], 98.3) had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI, 0.11-0.28; SUCRA, 98.2) and non-early TIPS (OR, 0.30, 95% CrI: 0.23-0.42; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR, 2.78; 95% CrI, 1.89-4.23, SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions. CONCLUSION Based on the moderate-to-high quality evidence presented in this study, early TIPS placement was associated with reduced all-cause mortality [with a median follow-up of 1.9 years (25th-75th percentile range 1.9-2.3 years)] and rebleeding compared to standard treatment and non-early TIPS. Although early TIPS and standard treatment had a comparable incidence of hepatic encephalopathy, early TIPS showed superiority over non-early TIPS in this aspect. Recent studies have also shown promising results in controlling TIPS-related hepatic encephalopathy. However, it is important to consider individual patient characteristics and weigh the potential benefits against the risks associated with early TIPS. Therefore, we recommend that clinicians carefully evaluate the patient's condition, considering factors such as severity of variceal bleeding, underlying liver disease, and overall clinical status, before making a treatment decision. Further well-designed RCTs comparing early TIPS with non-early TIPS are needed to validate these findings and provide more definitive guidance.
PICO Summary
Population
Patients with cirrhosis and acute variceal bleeding (24 randomised controlled trials, n= 1,894).
Intervention
Early transjugular intrahepatic portosystemic shunt (TIPS).
Comparison
Non-early TIPS. Standard treatment.
Outcome
Compared with standard treatment, early TIPS (odds ratio (OR) 0.53; 95% credible interval (CrI), [0.30, 0.94]; surface under the cumulative ranking curve [SUCRA], 98.3) had a lower risk of all-cause mortality (moderate-to-high-quality evidence), and early TIPS (OR, 0.19; 95% CrI [0.11, 0.28]; SUCRA, 98.2) and non-early TIPS (OR, 0.30; 95% CrI [0.23, 0.42]; SUCRA, 1.8) were associated with a lower risk of rebleeding (moderate-to-high-quality evidence). Early TIPS was not associated with a reduced risk of hepatic encephalopathy, and non-early TIPS (OR 2.78; 95% CrI [1.89, 4.23] SUCRA, 0) was associated with an increased incidence of hepatic encephalopathy (moderate-to-high-quality evidence). There was no difference in the incidence of new or worsening ascites (moderate-to-high-quality evidence) among the three interventions.
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Comparison of clinical effect of octreotide and pituitrin in treatment of upper gastrointestinal hemorrhage in cirrhosis
Zhu Y, Ren Y, Li C, Si Z, Chi N
Indian journal of pharmacology. 2023;55(1):21-26
Abstract
OBJECTIVE The objective of the study was to compare and observe the therapeutic effect of octreotide and pituitrin in upper gastrointestinal hemorrhage caused by cirrhosis. MATERIALS AND METHODS In this prospective, randomized, open, single-blind, controlled, and single-center study, patients with upper gastrointestinal hemorrhage induced by cirrhosis were divided into control group (treated with pituitrin) and experimental group (treated with octreotide). The effective time, hemostasis time, and average bleeding volume of the two groups were observed and recorded, and the incidence of adverse reactions, rebleeding rate, and total effective rate of the two groups were compared. RESULTS One hundred and thirty-two patients with upper gastrointestinal hemorrhage caused by cirrhosis were included from March 2017 to September 2018. By a single-blind method, the patients were randomly divided into control group (n = 66) and experimental group (n = 66). Compared with the control group, the effective time and hemostasis time of the drug were significantly shorter in the experimental group, whereas the average bleeding volume of patients was lower (average P < 0.05). Compare with the control group, the total effective rate was higher in the experimental group, whereas the incidence of adverse reactions was lower (average P < 0.05). During 1-year follow-up, early and late rebleeding rates and hemorrhage-related mortality between the two groups have no difference (average P > 0.05). CONCLUSION In the treatment of upper gastrointestinal hemorrhage in cirrhosis, octreotide is superior to pituitrin, with advantages of quick onset, short hemostasis time, and less adverse reactions, which is helpful to control the rebleeding rate and bleeding-related mortality.
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Systematic Review with Meta-Analysis: Efficacy and Safety of Lusutrombopag for Severe Thrombocytopenia in Patients with Chronic Liver Disease Undergoing Invasive Procedures
Orme, M. E., Bentley, R., Marcella, S., Peck-Radosavljevic, M., Perard, R., Wedemeyer, H., Yoshiji, H., Agarwal, K., Dusheiko, G.
Advances in Therapy. 2022;39(9):4169-4188
Abstract
INTRODUCTION Lusutrombopag is an oral thrombopoietin receptor agonist (TPO-RA). Clinical trials have shown lusutrombopag's efficacy in reducing need for preoperative platelet transfusion in patients with chronic liver disease (CLD) and severe thrombocytopenia. This analysis assessed efficacy and safety of lusutrombopag in patients with severe thrombocytopenia and CLD undergoing planned invasive procedures. METHODS An electronic database search (through 1 December 2020) identified three randomised, placebo-controlled, double-blind clinical trials comparing lusutrombopag with placebo in patients with CLD and platelet count below 50 × 10(9)/L scheduled to undergo a procedure with a perioperative bleeding risk. A random-effects meta-analysis examined treatment effect, with Cochrane Collaboration's tool assessing risk of bias. RESULTS The meta-analysis included 343 (lusutrombopag 3 mg, n = 173; placebo, n = 170) patients. More patients met the criteria for treatment response (platelet count at least 50 × 10(9)/L and increase of at least 20 × 10(9)/L from baseline anytime during the study) with lusutrombopag versus placebo (risk ratio [RR] 6.39; 95% confidence interval [CI] 3.69, 11.07; p < 0.0001). The primary efficacy outcome, proportion of patients requiring no platelet transfusion and no rescue therapy for bleeding for at least 7 days post procedure, was achieved by more patients treated with lusutrombopag versus placebo (RR 3.42; 95% CI 1.86, 6.26; p = 0.0001). The risk of any bleeding event was significantly lower with lusutrombopag compared to placebo (RR 0.55; 95% CI 0.32, 0.95; p = 0.03); conversely, thrombosis event rates were similar between lusutrombopag and placebo (RR 0.79; 95% CI 0.19, 3.24; p = 0.74). CONCLUSION This meta-analysis showed that treatment of severe thrombocytopenia with lusutrombopag in patients with CLD prior to a planned invasive procedure was efficacious and safe in increasing platelet counts, avoiding the need for platelet transfusions, and reducing risk of bleeding, thereby enhancing the certainty of evidence supporting the efficacy and safety of lusutrombopag.
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Avatrombopag ethnic sensitivity analysis in chronic liver disease and thrombocytopenia patients: individual-level pooled analysis
Lu J, Jamieson BD, Hui AM
Therapeutic advances in gastroenterology. 2022;15:17562848221105976
Abstract
INTRODUCTION Few data have been published on the ethnic sensitivity of effectiveness, pharmacokinetics (PK), and pharmacodynamics (PD) of avatrombopag for the management of thrombocytopenia in patients with chronic liver disease (CLD). METHODS An ethnic sensitivity analysis was performed based on the results from two phase III studies (ADAPT-1 and ADAPT-2), with a primary endpoint of the proportion of patients without the requirement of platelet transfusion or rescue treatment for bleeding after randomization to 7 days following a scheduled procedure, and three phase I studies in healthy subjects. Cochran-Mantel-Haenszel and Fisher's exact tests were used to compare the differences in effectiveness in different ethnicities and overall population. RESULTS In total, 435 patients (placebo, n = 158; avatrombopag, n = 277) were stratified into various ethnic groups: 121 East Asians, including the subgroup of 27 Chinese, and 259 Caucasians. The proportion of patients who did not receive a platelet transfusion and those with a platelet count ⩾50 × 10(9)/L in the avatrombopag 40 and 60 mg groups were higher than that of placebo for all ethnicities and in the overall population. Statistical significance was obtained in the overall population and for all ethnicities other than Chinese patients, a group with a very small sample size. No significant difference was observed in the proportion of responders in each ethnic group compared to overall population (p > 0.05). The incidence of adverse events in East Asians was similar to that in both Caucasians and the overall population. CONCLUSION Avatrombopag was effective and safe in the management of thrombocytopenia in Chinese patients with CLD. Ethnicity does not appear to influence the efficacy, safety, PK, or PD of avatrombopag.
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Efficacy and safety of roxadustat for the treatment of anemia in non-dialysis chronic kidney disease patients: A systematic review and meta-analysis of randomized double-blind controlled clinical trials
Chen T, Huang J, Dong H, Xu L, Chen C, Tang Y, Huang W
Frontiers in nutrition. 2022;9:1029432
Abstract
OBJECTIVE To evaluate the efficacy and safety of roxadustat in the treatment of anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. MATERIALS AND METHODS For this systematic review and meta-analysis, we searched for randomized controlled trials (RCTs) of anemia in NDD-CKD patients to assess the efficacy and safety of roxadustat. The primary efficacy endpoint was the proportion of patients who achieved a hemoglobin (Hb) response. Secondary efficacy endpoints were hepcidin, serum iron, serum ferritin (SF), total iron-binding capacity (TIBC), transferrin saturation (TAST), and low-density lipoprotein (LDL). In addition, adverse events (AEs) were compared. Meta-analyses were performed using Revman 5.4 software. The quality of the evidence was assessed using the Cochrane risk of bias tool. This study was conducted under a pre-established protocol registered with PROSPERO (registration number: CRD42021252331). RESULTS Seven studies enrolled 4,764 patients, of whom 2,730 received roxadustat and 2,034 received placebo. The results of this meta-analysis showed that roxadustat increased Hb levels [weighted mean difference (WMD) = 1.43, 95% CI: 1.17 to 1.68, P < 0.001, I (2) = 95%], and Hb response [relative ratio (RR) = 8.12, 95% CI: 5.80 to 11.37, P < 0.001, I (2) = 61%]. In addition, roxadustat significantly increased transferrin TAST. During the treatment period in patients with anemia, the AEs of roxadustat compared with placebo was not statistically significant. CONCLUSION Roxadustat can improve anemia in NDD-CKD patients by increasing Hb levels and regulating iron metabolism, but does not increase the incidence of AEs. SYSTEMATIC REVIEW REGISTRATION [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021252331].
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Timing of endoscopic intervention in patients with cirrhosis with acute variceal haemorrhage (TEACH trial): protocol for a randomised clinical trial (RCT)
Yang, Z., Xuan, J., Yang, F., Qi, Y., Yang, M., Xu, H., Jiang, M., Shen, S., Lu, M., Shi, H., et al
BMJ open. 2022;12(9):e060290
Abstract
INTRODUCTION Acute variceal haemorrhage (AVH) in patients with cirrhosis remains a topic of great interest. Although several guidelines recommend endoscopy within 24 hours after AVH, there is no consensus on the most appropriate time to perform this intervention. The purpose of this study is to identify whether urgent endoscopy (within 6 hours after gastroenterological consultation) is superior to non-urgent endoscopy (between 6 hours and 24 hours after gastroenterological consultation) in reducing the rebleeding rate of these patients. METHODS AND ANALYSIS This is a single-centred, prospective, randomised clinical trial. Between March 2021 and December 2023, an estimated 400 patients will be randomised in a 1:1 ratio to receive endoscopic intervention either within 6 hours or between 6 and 24 hours after gastroenterological consultation. Randomisation will be conducted by permuted block randomisation, with stratification by age, systolic blood pressure and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of AVH. The secondary efficacy endpoints mainly include all-cause mortality within 42 days after randomisation, persistent bleeding, length of hospitalisation, etc. ETHICS AND DISSEMINATION The study protocol was approved by the Ethical Committees of Jinling Hospital (authorised ethics no. DZQH-KYLL-21-01). This trial will provide valuable insights into the timing of endoscopic intervention for AVH in patients with cirrhosis. Furthermore, the trial results and conclusions could provide high-quality evidence to guide clinical research and treatment. TRIAL REGISTRATION NUMBER NCT04786743.
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Primary prevention of variceal bleeding in people with oesophageal varices due to liver cirrhosis: a network meta-analysis
Roccarina D, Best LM, Freeman SC, Roberts D, Cooper NJ, Sutton AJ, Benmassaoud A, Plaz Torres MC, Iogna Prat L, Csenar M, et al
The Cochrane database of systematic reviews. 2021;4:Cd013121
Abstract
BACKGROUND Approximately 40% to 95% of people with cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed in about one to three years. There are several different treatments to prevent bleeding, including: beta-blockers, endoscopic sclerotherapy, and variceal band ligation. However, there is uncertainty surrounding their individual and relative benefits and harms. OBJECTIVES To compare the benefits and harms of different treatments for prevention of first variceal bleeding from oesophageal varices in adults with liver cirrhosis through a network meta-analysis and to generate rankings of the different treatments for prevention of first variceal bleeding from oesophageal varices according to their safety and efficacy. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to December 2019 to identify randomised clinical trials in people with cirrhosis and oesophageal varices with no history of bleeding. SELECTION CRITERIA We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and oesophageal varices with no history of bleeding. We excluded randomised clinical trials in which participants had previous bleeding from oesophageal varices and those who had previously undergone liver transplantation or previously received prophylactic treatment for oesophageal varices. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the differences in treatments using hazard ratios (HR), odds ratios (OR), and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute for Health and Care Excellence Decision Support Unit guidance. We performed the direct comparisons from randomised clinical trials using the same codes and the same technical details. MAIN RESULTS We included 66 randomised clinical trials (6653 participants) in the review. Sixty trials (6212 participants) provided data for one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those at high risk of bleeding from oesophageal varices. The follow-up in the trials that reported outcomes ranged from 6 months to 60 months. All but one of the trials were at high risk of bias. The interventions compared included beta-blockers, no active intervention, variceal band ligation, sclerotherapy, beta-blockers plus variceal band ligation, beta-blockers plus nitrates, nitrates, beta-blockers plus sclerotherapy, and portocaval shunt. Overall, 21.2% of participants who received non-selective beta-blockers ('beta-blockers') - the reference treatment (chosen because this was the most common treatment compared in the trials) - died during 8-month to 60-month follow-up. Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates all had lower mortality versus no active intervention (beta-blockers: HR 0.49, 95% CrI 0.36 to 0.67; direct comparison HR: 0.59, 95% CrI 0.42 to 0.83; 10 trials, 1200 participants; variceal band ligation: HR 0.51, 95% CrI 0.35 to 0.74; direct comparison HR 0.49, 95% CrI 0.12 to 2.14; 3 trials, 355 participants; sclerotherapy: HR 0.66, 95% CrI 0.51 to 0.85; direct comparison HR 0.61, 95% CrI 0.41 to 0.90; 18 trials, 1666 participants; beta-blockers plus nitrates: HR 0.41, 95% CrI 0.20 to 0.85; no direct comparison). No trials reported health-related quality of life. Based on low-certainty evidence, variceal band ligation had a higher number of serious adverse events (number of events) than beta-blockers (rate ratio 10.49, 95% CrI 2.83 to 60.64; 1 trial, 168 participants). Based on low-certainty evidence, beta-blockers plus nitrates had a higher number of 'any adverse events (number of participants)' than beta-blockers alone (OR 3.41, 95% CrI 1.11 to 11.28; 1 trial, 57 participants). Based on low-certainty evidence, adverse events (number of events) were higher in sclerotherapy than in beta-blockers (rate ratio 2.49, 95% CrI 1.53 to 4.22; direct comparison rate ratio 2.47, 95% CrI 1.27 to 5.06; 2 trials, 90 participants), and in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison rate ratio 1.72, 95% CrI 1.08 to 2.76; 1 trial, 140 participants). Based on low-certainty evidence, any variceal bleed was lower in beta-blockers plus variceal band ligation than in beta-blockers (direct comparison HR 0.21, 95% CrI 0.04 to 0.71; 1 trial, 173 participants). Based on low-certainty evidence, any variceal bleed was higher in nitrates than beta-blockers (direct comparison HR 6.40, 95% CrI 1.58 to 47.42; 1 trial, 52 participants). The evidence indicates considerable uncertainty about the effect of the interventions in the remaining comparisons. AUTHORS' CONCLUSIONS Based on low-certainty evidence, beta-blockers, variceal band ligation, sclerotherapy, and beta-blockers plus nitrates may decrease mortality compared to no intervention in people with high-risk oesophageal varices in people with cirrhosis and no previous history of bleeding. Based on low-certainty evidence, variceal band ligation may result in a higher number of serious adverse events than beta-blockers. The evidence indicates considerable uncertainty about the effect of beta-blockers versus variceal band ligation on variceal bleeding. The evidence also indicates considerable uncertainty about the effect of the interventions in most of the remaining comparisons.