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Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity
Banares R, Ibanez-Samaniego L, Torner JM, Pavesi M, Olmedo C, Catalina MV, Albillos A, Larsen FS, Nevens F, Hassanein T, et al
Therapeutic advances in gastroenterology. 2019;12:1756284819879565
Abstract
Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis (n = 285, ACLF patients = 165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p = 0.001; 30-day survival: 73.9% versus 64.3%, p = 0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p = 0.001; 30-day survival: 73.3% versus 58.5%, p = 0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials.
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Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis
Fernandez J, Angeli P, Trebicka J, Merli M, Gustot T, Alessandria C, Aagaard NK, de Gottardi A, Welzel TM, Gerbes A, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019
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Abstract
BACKGROUND & AIMS We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP). METHODS We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n=61) or antibiotics alone (control group; n=57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course. RESULTS There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P=.02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P=.66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P=.03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P=.007). CONCLUSIONS In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.
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Stratifying risk in the prevention of recurrent variceal hemorrhage: results of an individual patient meta-analysis
Albillos A, Zamora J, Martinez J, Arroyo D, Ahmad I, De-la-Pena J, Garcia-Pagan JC, Lo GH, Sarin S, Sharma B, et al
Hepatology (Baltimore, Md.). 2017;66((4):):1219-1231
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Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant and, in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A vs. B/C) by means of individual time-to-event patient data meta-analysis (IPD) from randomized controlled trials. The study was IPD of 389 patients from 3 trials comparing EVL plus BB vs. BB and 416 patients from 4 trials comparing EVL plus BB vs. EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95%CI 0.18-0.89; p=0.025), but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (p for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95%CI 0.25-0.85; p=0.013). CONCLUSION Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity. In patients with preserved liver function (Child A), combination therapy is recommended since it is more effective in preventing rebleeding, without modifying survival. In patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death as compared with combination therapy, underlining that BB is the key element of combination therapy. This article is protected by copyright. All rights reserved.
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Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: A randomized, controlled trial
Bosch J, Thabut D, Albillos A, Carbonell N, Spicak J, Massard J, D'Amico G, Lebrec D, de Franchis R, Fabricius S, et al
Hepatology (Baltimore, Md.). 2008;47((5):):1604-14.
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A beneficial effect of recombinant activated factor VII (rFVIIa) in Child-Pugh class B and C patients with cirrhosis who have variceal bleeding has been suggested. This randomized controlled trial assessed the efficacy and safety of rFVIIa in patients with advanced cirrhosis and active variceal bleeding. At 31 hospitals in an emergency setting, 256 patients (Child-Pugh > 8; Child-Pugh B = 26%, C = 74%) were randomized equally to: placebo; 600 microg/kg rFVIIa (200 + 4x 100 microg/kg); or 300 microg/kg rFVIIa (200 + 100 microg/kg). Dosing was intravenous at 0, 2, 8, 14, and 20 hours after endoscopy, in addition to standard vasoactive, prophylactic antibiotic, and endoscopic treatment. The primary composite endpoint consisted of failure to control 24-hour bleeding, or failure to prevent rebleeding or death at day 5. Secondary endpoints included adverse events and 42-day mortality. Baseline characteristics were comparable between groups. Administration of rFVIIa had no significant effect on the composite endpoint compared with placebo (P = 0. 37). There was no significant difference in 5-day mortality between groups; however, 42-day mortality was significantly lower with 600 microg/kg rFVIIa compared with placebo (odds ratio 0. 31, 95% confidence interval = 0. 13-0. 74), and bleeding-related deaths were reduced from 12% (placebo) to 2% (600 microg/kg). A marked heterogeneity in the failure rate in all treatment groups was observed across participating centers. Adverse events, including overall thromboembolic events, were comparable between groups. CONCLUSION Treatment with rFVIIa had no significant effect on the primary composite endpoint compared with placebo. Therefore, decision on the use of this hemostatic agent in acute variceal bleeding should be carefully considered, because results of this study do not support the routine use of rFVIIa in this setting. Adverse events were comparable across groups.