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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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Efficacy and Safety of Prothrombin Complex Concentrates in Liver Transplantation: Evidence from Observational Studies
Punzo, G., Di Franco, V., Perilli, V., Sacco, T., Sollazzi, L., Aceto, P.
Journal of clinical medicine. 2023;12(11)
Abstract
The risk/benefit ratio of using prothrombin complex concentrates (PCCs) to correct coagulation defects in patients with end-stage liver disease is still unclear. The primary aim of this review was to assess the clinical effectiveness of PCCs in reducing transfusion requirements in patients undergoing liver transplantation (LT). This systematic review of non-randomized clinical trials was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was previously registered (PROSPEROCRD42022357627). The primary outcome was the mean number of transfused units for each blood product, including red blood cells (RBCs), fresh frozen plasma, platelets, and cryoprecipitate. Secondary outcomes included the incidence of arterial thrombosis, acute kidney injury, and haemodialysis, and hospital and intensive care unit length of stay. There were 638 patients from 4 studies considered for meta-analysis. PCC use did not affect blood product transfusions. Sensitivity analysis, including only four-factor PCC, showed a significant reduction of RBC effect size (MD: 2.06; 95%CI: 1.27-2.84) with no true heterogeneity. No significant differences in secondary outcomes were detected. Preliminary evidence indicated a lack of PCC efficacy in reducing blood product transfusions during LT, but further investigation is needed. In particular, future studies should be tailored to establish if LT patients will likely benefit from four-factor PCC therapy.
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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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Prophylactic fresh frozen plasma versus prothrombin complex concentrate for preprocedural management of the coagulopathy of liver disease: A systematic review
Evans CR, Cuker A, Crowther M, Pishko AM
Research and practice in thrombosis and haemostasis. 2022;6(4):e12724
Abstract
BACKGROUND The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known. OBJECTIVES Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease. METHODS We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single-arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion-related complications. RESULTS A total of 95 articles were identified for full-text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single-arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta-analysis was not possible. Our study found no evidence to favor a specific product over another. CONCLUSIONS Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.
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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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The Clinical Efficacy of Double Plasma Molecular Absorption System Combined with Plasma Exchange in the Treatment of Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis
Bai, W., Yao, C., Mao, D., Wu, J., Wang, K., Wei, H., Huang, Z., Shi, Q., Wang, N.
Journal of Healthcare Engineering. 2022;2022:3139929
Abstract
OBJECTIVE This study aims to investigate the clinical efficacy of plasma exchange in treating acute-on-chronic liver failure (ACLF) through meta-analysis. METHOD PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched using a computer for all relevant Chinese and English literature from 2000 to 2021 in each database. At the same time, a large number of related papers and materials were manually consulted. Randomized controlled trials of plasma exchange (PE, control group) and combined double plasma molecular absorption system (DPMAS + PE, observation group) for the treatment of ACLF were collected. Meta-analysis was performed with Stata16.0 software. RESULT A total of 474 articles were retrieved, and 11 papers were finally included for research after screening. Meta-analysis results showed that the effective rate of treatment in the experimental group was significantly higher than that in the control group. At the same time, the observation group's prothrombin activity (PTA) level was better than that of the control group after treatment. After treatment, there was no significant difference in prothrombin time (PT) and international normalized ratio (INR) between the two groups. In addition, after treatment, the alanine aminotransferase (ALT) level of the observation group was significantly lower than that of the control group. However, TBIL levels and albumin (ALB) levels did not change significantly between the two groups. Regarding blood routine indexes, there were no significant changes in creatinine (Cr) levels and platelet counts (PLT) in the two groups after treatment, but hemoglobin (HGB) levels in the observation group were significantly lower than those in the control group. CONCLUSION DPMAS combined with plasma exchange therapy can improve liver function, coagulation function, and blood routine level of ACLF patients and increase the effective rate of treatment. It is an effective treatment for acute-on-chronic liver failure.
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Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials
Hartmann J, Dias JD, Pivalizza EG, Garcia-Tsao G
Seminars in thrombosis and hemostasis. 2022
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Editor's Choice
Abstract
Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.
PICO Summary
Population
Patients with cirrhosis (5 studies, n= 302).
Intervention
Thromboelastography-guided haemostatic management.
Comparison
Standard coagulation testing (standard practice).
Outcome
Platelet use was five times lower with thromboelastography vs. standard practice, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]), but fresh frozen plasma (FFP) use did not differ significantly. Thromboelastography was associated with less blood product, FFP + platelets, and cryoprecipitate use. No differences were reported in bleeding rates or longer-term mortality between groups, with the thromboelastography group having lower mortality at 7 days vs. standard practice (relative risk [95% CI] = 0.52 [0.30-0.91]).
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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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Efficacy of Intravenous Albumin for Spontaneous Bacterial Peritonitis Infection Among Patients With Cirrhosis: A Meta-Analysis of Randomized Control Trials
Batool S, Waheed MD, Vuthaluru K, Jaffar T, Garlapati SKP, Bseiso O, Nousherwani MD, Saleem F
Cureus. 2022;14(12):e33124
Abstract
Albumin is an important component in the standard therapeutic approach to spontaneous bacterial peritonitis (SBP). This meta-analysis aimed to determine the impact of intravenous human albumin in patients with cirrhosis and SBP. This study was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently searched relevant studies using electronic databases including PubMed, Embase and Cochrane Library from the date of database inception to October 2022. The outcomes assessed in the current meta-analysis include 30-day mortality, renal impairment, changes in serum creatinine levels (mg/dl) and resolution of bacterial infection. It was found that the risk of all-cause mortality and renal impairment was significantly lower in patients receiving albumin compared to the control group. However, no significant difference was reported between the two groups in relation to changes in mean creatinine levels and resolution of infection.