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Safety and efficacy of double plasma molecular adsorption system with sequential low-volume plasma exchange in intermediate-stage hepatitis B virus-related acute-on-chronic liver failure
Xu W, Zhu S, Yang L, Li Z, Wu L, Zhang Y, Chen J, Deng Z, Luo Q, Peng L
Journal of medical virology. 2023
Abstract
BACKGROUND Current evidence suggests that the mortality rate of intermediate-stage hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) remains high. We aimed to investigate the safety and efficacy of double plasma molecular adsorption system (DPMAS) with sequential low-volume plasma exchange (LPE) treatment in intermediate-stage HBV-related ACLF. METHODS This prospective study recruited intermediate-stage HBV-related ACLF patients and was registered on ClinicalTrials.gov (NCT04597164). Eligible patients were randomly divided into a trial group and a control group. Patients in both groups received comprehensive medical treatment. Patients in the trial group further received DPMAS with sequential LPE. Data were recorded from baseline to week 12. RESULTS 50 patients with intermediate-stage HBV-related ACLF were included in this study. The incidence of bleeding events and allergic reactions in the trial group was 12% and 4%, respectively, with no other treatment-related adverse events. The levels of TBIL and PT-INR, and MELD scores after each session of DPMAS with sequential LPE were significantly lower than those before treatment (all p<0.05). The 12-week cumulative liver transplantation-free survival rates in the trial and control groups were 52% and 24%, respectively (p=0.041). The 12-week cumulative overall survival rates in the trial and control groups were 64% and 36%, respectively (p=0.048). The Kaplan-Meier survival analysis revealed significant differences in liver transplantation-free survival (p=0.047) and overall survival (p=0.038) between the trial and control groups. COX regression analysis indicated that BUN (p=0.038), DPMAS with sequential LPE (p=0.048) and COSSH-ACLF II score (p<0.001) were significant risk factors for mortality. CONCLUSION DPMAS with sequential LPE treatment is safe and effective for patients with intermediate-stage HBV-related ACLF. This article is protected by copyright. All rights reserved.
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Plasma exchange for acute and acute on chronic liver failure: A systematic review and Meta-Analysis
Beran, A., Mohamed, M. F. H., Shaear, M., Nayfeh, T., Mhanna, M., Srour, O., Nawras, M., Mentrose, J., Assaly, R., Kubal, C. A., et al
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2023
Abstract
Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared to standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients > 18 years of age with ALF and ACLF. Pooled risk-ratios (RR) with corresponding 95% confidence intervals (CIs) were calculated by Mantel-Haenszel method within a random-effect model. Primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared to SMT, PE was significantly associated with higher 30-day (RR 1.41, 95%CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95%CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95%CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95%CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials (RCT), results remained unchanged in ALF but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates, or as a bridge to LT in otherwise eligible patients. Further RCTs are needed to confirm the survival benefit of PE in ACLF.
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3.
Comparable Triglyceride Reduction With Plasma Exchange and Insulin in Acute Pancreatitis - A Randomized Trial
Gubensek J, Andonova M, Jerman A, Persic V, Vajdic-Trampuz B, Zupunski-Cede A, Sever N, Plut S
Frontiers in medicine. 2022;9:870067
Abstract
BACKGROUND AND AIMS Both insulin and plasma exchange (PE) are used in hypertriglyceridemic acute pancreatitis (HTG-AP). Our aim was to compare the efficacy of both treatments. METHODS A randomized, parallel group study performed in a tertiary hospital in 22 HTG-AP patients with non-severe prognosis and triglycerides between 15 and 40 mmol/L. Patients were randomized to daily PE or insulin infusion until triglycerides were <10 mmol/L. Primary outcome was % reduction in triglycerides within 24 h. Secondary outcomes were days needed to lower triglycerides <10 mmol/L, highest CRP and percentage of patients with a severe course of pancreatitis. RESULTS There was a trend toward a greater decrease in triglycerides within the first 24 h in the PE group (67 ± 17% vs. 53 ± 17%, p = 0.07), but the absolute difference was modest [mean difference of 6 mmol/L (14% of initial value)]. Triglycerides fell below 10 mmol/L in a median (IQR) of 1 (1-2) and 2 (1-2) days, respectively (p = 0.25). Secondary outcomes related to disease severity were also comparable: highest CRP 229 vs. 211 mg/L (p = 0.69) and severe course of pancreatitis in 2/11 cases in both groups (p = 1.0). Regarding treatment complications, there was one mild hypoglycemia and one allergic reaction during PE. Survival was 100% in both groups. CONCLUSION There was no significant difference, but only a trend toward a greater decrease in triglycerides with PE, and the clinical course was also comparable. These results do not support universal use of PE in patients with HTG-AP. CLINICAL TRIAL REGISTRATION [ClinicalTrials.gov], identifier [NCT02622854].
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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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Standard-Volume Plasma Exchange Improves Outcomes in Patients With Acute Liver Failure: A Randomized Controlled Trial
Maiwall R, Bajpai M, Singh A, Agarwal T, Kumar G, Bharadwaj A, Nautiyal N, Tevethia H, Jagdish RK, Vijayaraghavan R, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022;20(4):e831-e854
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Editor's Choice
Abstract
BACKGROUND High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL gov (identifier: NCT02718079).
PICO Summary
Population
Patients with acute liver failure (n= 40).
Intervention
Standard medical treatment with standard volume plasma exchange (SVPE), (n= 20).
Comparison
Standard medical treatment (n= 20).
Outcome
Compared to standard medical treatment alone, at day five SVPE resulted in higher lactate clearance, amelioration of systemic inflammatory response syndrome (84% vs. 26%), reduction in ammonia levels [(221.5 ± 96.9) vs. (439 ± 385.6) μg/dl] and sequential organ failure assessment scores [9.9(±3.3) vs. 14.6(±4.8)]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival (75% vs. 45%). A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and damage-associated molecular patterns was seen with SVPE.
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[Meta-analysis of the therapeutic value of plasma exchange simple or combined with dual plasma molecular adsorption system for liver failure]
Zhang, R. X., Liu, L. X.
Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. 2022;30(10):1107-1114
Abstract
Objective: To systematically analyze the serological parameters, effective rate and survival rate of patients with liver failure after simple plasma exchange treatment and half-dose plasma exchange combined with dual plasma molecular adsorption system. Methods: Randomized controlled trials published in the full-text articles of Pubmed, Embase, Web of Science, The Cochrane Library, Wanfang, Weipu, CNKI, and other journals from June 2020 were retrieved. Revman 5.3 software was used to conduct the meta-analysis after the literature quality evaluation. Results: A total of 10 studies involving 884 cases were selected. Among them, 425 and 459 were treated with combination and simple plasma exchange therapy. The levels of TBIL (MD=-28.58, 95% CI: -37.42～-19.75, P<0.000 01) and ALB (MD=-2.00, 95%CI:-2.61～-1.39, P<0.000 01) were lower in the combined treatment group than those in the simple treatment group, and the difference was statistically significant. HGB (MD=5.96, 95%CI: 1.52-10.40, P=0.009), effective rate (OR=1.92, 95%CI: 1.29-2.85, P=0.001), and survival rate (OR=1.63, 95%CI: 1.13-2.36, P=0.009) were higher in the combined treatment group than those in the simple treatment group, and the difference was statistically significant.The two treatment methods had good curative effects for the improvement of ALT, AST, DBIL, PTA, INR, and PLT levels (P＜0.05), and there was no statistically significant difference between them (P＞0.05). Conclusion: Half-dose plasma exchange combined with dual plasma molecular adsorption system therapy not only effectively improves hyperbilirubinemia, efficacy, and survival rate while significantly reducing plasma dosage, but it also has fewer adverse effects on hemoglobin depletion in patients with liver failure than simple plasma exchange therapy.
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A prognostic score for patients with acute-on-chronic liver failure treated with plasma exchange-centered artificial liver support system
Du L, Ma Y, Zhou S, Chen F, Xu Y, Wang M, Lei X, Feng P, Tang H, Bai L
Scientific reports. 2021;11(1):1469
Abstract
Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng' score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R(2) = 0.970, p = 0.000). PALS score of 0-2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6-9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3-5 who received 3-5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1-2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6-9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471 .
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Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review
Benić MS, Nežić L, Vujić-Aleksić V, Mititelu-Tartau L
Frontiers in pharmacology. 2021;12:785790
Abstract
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.
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Effects of dual plasma molecular adsorption system on liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis
Chen G, Wu M, Wu B, Liu F, Liu J, Liu L
Journal of clinical laboratory analysis. 2019;:e22926
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Abstract
BACKGROUND To investigate the effects of dual plasma molecular adsorption system (DPMAS) on the liver function, electrolytes, inflammation, and immunity in patients with chronic severe hepatitis (CSH). METHODS Total of 162 patients with CSH treated in our hospital from March 2016 to December 2018 were enrolled and equally randomly divided into control group (n = 81) and observation group (n = 81). The patients in control group were treated with plasma exchange, while those in observation group were additionally treated with DPMAS based on the treatment in control group. The liver function, electrolytes, inflammation, and immunity were evaluated and compared between the two groups. RESULTS After treatment, the liver function indexes in observation group were significantly favorable compared with those in control group, with the reduction in TBIL, DBIL, ALT, and rise of CHE levels (P < 0.05). The levels of K(+) , Na(+) , Cl(-) , and Ca(2+) in both groups were significantly improved after treatment (P < 0.05), although there were no significant differences between the two groups (P > 0.05). The levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in both groups declined after treatment compared with those before treatment, and those levels in observation group were higher than that in control group (P < 0.05). After treatment, the levels of cluster of differentiation 3(+) (CD3(+) ), CD4(+) , and CD4(+) /CD8(+) were higher in observation group than those in control group, with decreasing level of CD8(+) (P < 0.05). CONCLUSION Dual plasma molecular adsorption system can effectively improve the liver function, effectively correct the electrolyte disorders, reduce the inflammatory response, and adjust the immunity in patients with CSH.
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Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure
Yuan S, Qian Y, Tan D, Mo D, Li X
Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2018;57((2):):253-258
Abstract
OBJECTIVE To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P>0.05). CONCLUSION Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.
