Thromboelastography-Guided Therapy Enhances Patient Blood Management in Cirrhotic Patients: A Meta-analysis Based on Randomized Controlled Trials
Seminars in thrombosis and hemostasis. 2022
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.
Patients with cirrhosis (5 studies, n= 302).
Thromboelastography-guided haemostatic management.
Standard coagulation testing (standard practice).
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]).
Systematic review and meta-analysis: incidence of variceal hemorrhage in patients with cirrhosis undergoing transesophageal echocardiography
Alimentary pharmacology & therapeutics. 2022
BACKGROUND The presence of esophageal varices is considered a relative contraindication to transesophageal echocardiography (TEE) by cardiology professional societies, so gastroenterologists are often consulted to perform upper endoscopy prior to TEE in patients with cirrhosis. AIM: To perform a systematic review to quantify the risk of bleeding complications in patients with cirrhosis following TEE. METHODS Two reviewers searched Ovid MEDLINE, MEDLINE In-Process and EMBASE databases from January 1992 to May 2021 for studies reporting bleeding complications from TEE in patients with cirrhosis. We calculated the pooled incidence rate of bleeding events using the metaprop command with a random effect model. RESULTS We identified 21 studies comprising 4050 unique patients with cirrhosis; 9 studies (n = 3015) assessed the risk of intraoperative TEE during liver transplant (LT) and 12 studies (n = 1035) assessed bleeding risk in patients undergoing TEE for other indications. The pooled incidence of bleeding post-TEE was 0.37% (95% CI 0.04-0.94%) across all studies. Bleeding complications were low among patients undergoing TEE during LT as well as those undergoing TEE for other diagnostic reasons (0.97% vs. 0.004%) and among studies with mean MELD >18 compared to those with mean MELD <18 (0.43% vs. 0.08%). Few studies had a comparator arm, and data on patient-level factors impacting bleeding complications (including degree of liver dysfunction and coagulopathy) were limited across studies. CONCLUSIONS The risk of bleeding complications following TEE is low in patients with cirrhosis, suggesting TEE is safe and risk stratification with upper endoscopy may not be necessary.
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
Frontiers in nutrition. 2022;9:1029432
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].
Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review
Frontiers in pharmacology. 2021;12:785790
Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.
Systematic review with meta-analysis: abnormalities in the international normalised ratio do not correlate with periprocedural bleeding events among patients with cirrhosis
Alimentary pharmacology & therapeutics. 2020;52(8):1298-1310
BACKGROUND Cirrhotic coagulopathy is a delicate interplay comprising deficiencies of both procoagulant and anticoagulant factors. AIM: To identify the relationship between international normalised ratio [INR] with periprocedural bleeding risk among patients with cirrhosis. METHODS Following a thorough database search of the primary literature, 29 studies were targeted for analysis, including 13 276 patients with cirrhosis undergoing indicated procedures. RESULTS There was no significant association between periprocedural bleeding events and pre-procedural INR [pooled odds ratio 1.52; 95% CI 0.99, 2.33; P = 0.06]. Furthermore, there was no significant difference in mean INR [pooled mean difference 0.05; 95% CI -0.03, 0.13; P = 0.23] upon comparison of patients who either did or did not experience a periprocedural bleeding event. Significant heterogeneity among some studies was primarily fuelled by significant subgroup effects of both specific procedure types performed. Additionally, there were markedly inconsistent transfusion practices across studies. CONCLUSIONS INR fails to serve as a significant correlate for periprocedural bleeding events among patients with cirrhosis. Ideally, these new findings will help serve as a springboard for future studies, as well as to minimize transfusion of blood products, which command a myriad of adverse effects among patients with cirrhosis.
Primary prevention of bleeding from esophageal varices in patients with liver cirrhosis: An update and review of the literature
Journal of evidence-based medicine. 2020
All patients with liver cirrhosis and portal hypertension should be stratified by risk groups to individualize different therapeutic strategies to increase the effectiveness of treatment. In this regard, the development of primary prophylaxis of variceal bleeding and its management according to the severity of portal hypertension may be promising. This paper is to describe the modern principles of primary prophylaxis of esophageal variceal bleeding in patients with liver cirrhosis. The PubMed and EMbase databases, Web of Science, Google Scholar, and the Cochrane Database of Systematic Reviews were used to search for relevant publications from 1999 to 2019. The results suggested that depending on the severity of portal hypertension, patients with cirrhosis should be divided into those who need preprimary prophylaxis, which aims to prevent the formation of esophageal varices, and those who require measures that aim to prevent esophageal variceal bleeding. In subclinical portal hypertension, therapy should be etiological and pathogenetic. Cirrhosis with clinically significant portal hypertension should receive nonselective β-blockers if they have small esophageal varices and risk factors for variceal bleeding. Nonselective β-blockers are the first-line drugs for the primary prevention of bleeding from medium to large-sized esophageal varices. Endoscopic band ligation is indicated for the patients who are intolerant to nonselective β-blockers or in the case of contraindications to pharmacological therapy. In summary, the stratification of cirrhotic patients by the severity of portal hypertension and an individual approach to the choice of treatment may increase the effectiveness of therapy as well as improve survival rate of these patients.
The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: A systematic review
BACKGROUND Mostly published as case reports or series, the role of apheresis in hypertriglyceridemia (HTG)-related acute pancreatitis (AP) remains unclear. We performed a systematic review of available literature on this topic with specific focus on disease severity. METHODS A search of electronic databases (PubMed, EMBASE, Cochrane) and gray literature yielded 5020 articles of which 74 met criteria for inclusion (301 unique patients). Relevant data were abstracted from full manuscripts and analyzed. RESULTS Most patients were young (mean age 37.9 +/- 10.4 years) and male (71.5%). About two-thirds (69.7%) received apheresis within 48 h and most required only 1 or 2 sessions (84.4%). Apheresis resulted in an average reduction of serum TG by 85.4% (p < 0.001). There was high variability in reporting the presence of and criteria to define severe AP (reported 221/301, 73.4%; present 85/221, 38.5%) or organ failure (reported 104/301, 34.6%; present 52/104, 50.0%). Improvement was reported in the majority of patients (reported 144/301, 47.8%, present 136/144, 94.4%) mainly by clinical symptoms or laboratory tests. Overall mortality was 7.1% (21/294) which increased to 11.8% (10/85) with severe AP and 19.2% (10/52) with organ failure. CONCLUSIONS Apheresis effectively reduces serum TG levels. However, due to uncontrolled data, reporting bias and lack of a comparison group, definitive conclusions on the efficacy of apheresis in reducing AP severity cannot be made. We propose which patients may be best suitable for apheresis, type of studies needed and outcome measures to be studied in order to provide empiric data on the role of apheresis in HTG-related AP.Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Treatment of anaemia with erythropoiesis-stimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis
Background/Aims: Interpretation of the results of earlier meta-analyses in chronic kidney disease (CKD) patients on the impact of anaemia treatment with erythropoiesis-stimulating agents (ESAs) on clinical outcomes has been hampered by the inclusion of small trials and trials of short duration. We re-evaluated the benefits and harms of treating anaemia, including only relevant clinical trials. Methods: We conducted a systematic review and meta-analysis of randomised controlled trials performed in adults with CKD which allocated patients to different doses of ESAs, and we compared the effect of these interventions on vascular access thrombosis, stroke, risk of end-stage renal disease (ESRD) and all-cause mortality. Additional inclusion criteria were studies with a duration of at least 1 year and enrolling more than 500 participants. Results: Five trials (7,902 participants) met the inclusion criteria and were included in the meta-analysis. The number of patients enrolled in each trial ranged from 596 to 4,038. The mean/median duration of follow-up ranged from 14 to 36 months. A higher haemoglobin target was associated with increased risk of vascular access thrombosis (RR 1.343; 95% CI 1.162-1.554; p = 0.0005) and stroke (RR 1.735; 95% CI 1.323-2.275; p = 0.0005), and no effect on risk of ESRD (RR 1.089; 95% CI 0.986-1.203; p = 0.094) or all-cause mortality (RR 1.148; 95% CI 0.977-1.350; p = 0.093). Conclusion: In CKD patients, treatment of anaemia with ESAs targeting a higher haemoglobin value does not lower mortality or reduce the risk of ESRD, and may increase cardiovascular risk. Copyright 2012 S. Karger AG, Basel.