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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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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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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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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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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.
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Treatment for bleeding oesophageal varices in people with decompensated liver cirrhosis: a network meta-analysis
Roberts D, Best LM, Freeman SC, Sutton AJ, Cooper NJ, Arunan S, Begum T, Williams NR, Walshaw D, Milne EJ, et al
The Cochrane database of systematic reviews. 2021;4:Cd013155
Abstract
BACKGROUND Approximately 40% to 95% of people with liver cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed within about one to three years after diagnosis. Several different treatments are available, including, among others, endoscopic sclerotherapy, variceal band ligation, somatostatin analogues, vasopressin analogues, and balloon tamponade. However, there is uncertainty surrounding the individual and relative benefits and harms of these treatments. OBJECTIVES To compare the benefits and harms of different initial treatments for variceal bleeding from oesophageal varices in adults with decompensated liver cirrhosis, through a network meta-analysis; and to generate rankings of the different treatments for acute bleeding oesophageal varices, according to their benefits and harms. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until 17 December 2019, to identify randomised clinical trials (RCTs) in people with cirrhosis and acute bleeding from oesophageal varices. SELECTION CRITERIA We included only RCTs (irrespective of language, blinding, or status) in adults with cirrhosis and acutely bleeding oesophageal varices. We excluded RCTs in which participants had bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those in whom initial haemostasis was achieved before inclusion into the trial, and those who had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS software, using Bayesian methods, and calculated the differences in treatments using odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We performed also the direct comparisons from RCTs using the same codes and the same technical details. MAIN RESULTS We included a total of 52 RCTs (4580 participants) in the review. Forty-eight trials (4042 participants) were included in one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those with and without a previous history of bleeding. We included outcomes assessed up to six weeks. All trials were at high risk of bias. A total of 19 interventions were compared in the trials (sclerotherapy, somatostatin analogues, vasopressin analogues, sclerotherapy plus somatostatin analogues, variceal band ligation, balloon tamponade, somatostatin analogues plus variceal band ligation, nitrates plus vasopressin analogues, no active intervention, sclerotherapy plus variceal band ligation, balloon tamponade plus sclerotherapy, balloon tamponade plus somatostatin analogues, balloon tamponade plus vasopressin analogues, variceal band ligation plus vasopressin analogues, balloon tamponade plus nitrates plus vasopressin analogues, balloon tamponade plus variceal band ligation, portocaval shunt, sclerotherapy plus transjugular intrahepatic portosystemic shunt (TIPS), and sclerotherapy plus vasopressin analogues). We have reported the effect estimates for the primary and secondary outcomes when there was evidence of differences between the interventions against the reference treatment of sclerotherapy, but reported the other results of the primary and secondary outcomes versus the reference treatment of sclerotherapy without the effect estimates when there was no evidence of differences in order to provide a concise summary of the results. Overall, 15.8% of the trial participants who received the reference treatment of sclerotherapy (chosen because this was the commonest treatment compared in the trials) died during the follow-up periods, which ranged from three days to six weeks. Based on moderate-certainty evidence, somatostatin analogues alone had higher mortality than sclerotherapy (OR 1.57, 95% CrI 1.04 to 2.41; network estimate; direct comparison: 4 trials; 353 participants) and vasopressin analogues alone had higher mortality than sclerotherapy (OR 1.70, 95% CrI 1.13 to 2.62; network estimate; direct comparison: 2 trials; 438 participants). None of the trials reported health-related quality of life. Based on low-certainty evidence, a higher proportion of people receiving balloon tamponade plus sclerotherapy had more serious adverse events than those receiving only sclerotherapy (OR 4.23, 95% CrI 1.22 to 17.80; direct estimate; 1 RCT; 60 participants). Based on moderate-certainty evidence, people receiving vasopressin analogues alone and those receiving variceal band ligation had fewer adverse events than those receiving only sclerotherapy (rate ratio 0.59, 95% CrI 0.35 to 0.96; network estimate; direct comparison: 1 RCT; 219 participants; and rate ratio 0.40, 95% CrI 0.21 to 0.74; network estimate; direct comparison: 1 RCT; 77 participants; respectively). Based on low-certainty evidence, the proportion of people who developed symptomatic rebleed was smaller in people who received sclerotherapy plus somatostatin analogues than those receiving only sclerotherapy (OR 0.21, 95% CrI 0.03 to 0.94; direct estimate; 1 RCT; 105 participants). The evidence suggests considerable uncertainty about the effect of the interventions in the remaining comparisons where sclerotherapy was the control intervention. AUTHORS' CONCLUSIONS Based on moderate-certainty evidence, somatostatin analogues alone and vasopressin analogues alone (with supportive therapy) probably result in increased mortality, compared to endoscopic sclerotherapy. Based on moderate-certainty evidence, vasopressin analogues alone and band ligation alone probably result in fewer adverse events compared to endoscopic sclerotherapy. Based on low-certainty evidence, balloon tamponade plus sclerotherapy may result in large increases in serious adverse events compared to sclerotherapy. Based on low-certainty evidence, sclerotherapy plus somatostatin analogues may result in large decreases in symptomatic rebleed compared to sclerotherapy. In the remaining comparisons, the evidence indicates considerable uncertainty about the effects of the interventions, compared to sclerotherapy.
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8.
Vasoactive Agents for the Management of Acute Variceal Bleeding: A Systematic Review and Meta-analysis
Huaringa-Marcelo J, Huaman MR, Brañez-Condorena A, Villacorta-Landeo P, Pinto-Ruiz DF, Urday-Ipanaqué D, García-Gomero D, Montes-Teves P, Lozano Miranda A
Journal of gastrointestinal and liver diseases : JGLD. 2021;30(1):110-121
Abstract
BACKGROUND AND AIMS Vasoactive agents with endoscopic therapy are used to treat acute variceal bleeding (AVB). There are two main groups of vasoactive agents: terlipressin and vasopressin (T-V), and octreotide and somatostatin (O-S). However, the benefit/harm balance is unclear. Our aim was to assess the efficacy and safety of T-V versus O-S for the management of AVB. METHODS We performed a systematic search for randomized controlled trials (RCTs) in PubMed, Scopus, and CENTRAL. Our main outcomes were mortality and adverse events. Secondary outcomes were bleeding control, rebleeding, blood transfusion, hospital stay. We evaluated the certainty of evidence using GRADE methodology. RESULTS We included 21 RCTs. The risk of mortality (RR: 1.01; 95%CI: 0.83-1.22), bleeding control (RR: 0.96; 95%CI: 0.91-1.02; I 2 =53%), early rebleeding (RR: 0.91; 95%CI: 0.66-1.24: I 2 =0%), late rebleeding (RR: 0.94; 95 CI: 0.56-1.60; I 2 =0%), blood transfusion (MD: 0.04; 95%CI: -0.31-0.39; I 2 =68%) and hospital stay (MD: -1.06; 95%CI: -2.80-0.69; I 2 =0%) were similar between T-V and O-S groups. Only 15 studies reported adverse events, which were significantly higher in the T-V compared to the O-S group (RR 2.39; 95%CI: 1.58-3.63; I 2 =57%). The certainty of evidence was moderate for the main outcomes, and low or very low for others. CONCLUSIONS In cirrhotic patients with AVB, those treated with T-V had similar mortality risk compared to O-S. However, the use of T-V showed an increased risk of adverse events compared to O-S.
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9.
The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis
Lindquist I, Olson SR, Li A, Al-Samkari H, Jou JH, McCarty OJT, Shatzel JJ
Platelets. 2021;:1-7
Abstract
Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 10(9)/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.
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10.
Terlipressin effect on hepatorenal syndrome: Updated meta-analysis of randomized controlled trials
Mohamed MMG, Rauf A, Adam A, Kheiri B, Lacasse A, El-Halawany H
JGH open : an open access journal of gastroenterology and hepatology. 2021;5(8):896-901
Abstract
BACKGROUND AND AIM Hepatorenal syndrome (HRS) is a fatal complication of liver cirrhosis with a limited pharmacological option. Terlipressin is a vasoconstrictor that is approved in many countries but not yet in the United States. This is a meta-analysis of randomized controlled trials (RCTs) to review terlipressin effect on HRS and the safety profile. METHODS We searched electronic databases for RCTs comparing terlipressin versus placebo in addition to albumin in patients with type 1 or 2 HRS. Primary outcome was HRS reversal. Secondary outcomes were change in serum creatinine (Cr), requirement for renal replacement therapy (RRT) at 30 days of randomization, and 90-day survival. Risk ratios (RRs) and mean differences (MD) were calculated with 95% confidence intervals (CIs) using a random-effects model. RESULTS We identified eight RCTs with a total of 974 patients, and median follow up of 100 days. Mean age was 55 ± 10 years, 61% were males. Alcoholic liver disease represented 56%. Compared with placebo, terlipressin was associated with a significantly higher likelihood of HRS reversal (RR 2.08; 95% CI [1.51, 2.86], P < 0.001), significantly lower serum Cr (MD -0.64; 95% CI (-1.02, -0.27), P < 0.001], and a trend toward less RRT requirements (RR 0.61; 95% CI [0.36, 1.02], P = 0.06). There was no difference in survival at 90 days between groups (RR 1.09; 95% CI (0.84, 1.43), P = 0.52). Major adverse effects (AEs) were gastrointestinal cramps, discomfort, and respiratory distress. CONCLUSION In patients with liver cirrhosis complicated by HRS, terlipressin was associated with significant HRS reversal and decrease in serum Cr. No survival benefit was detected at 90 days.