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Friebus‐Kardash J, Louzi A, Kribben A, Schmidt HH, Jahn M, Tyczynski B, Rashidi‐Alavijeh J, Schütte A, Zeller A. Comparison of Open Albumin Dialysis (OPAL) With Prometheus Fractionated Plasma Separation and Adsorption (FPSA) and Standard Medical Treatment for Acute-On-Chronic Liver Failure. Artif Organs 2025; 49:997-1011. [PMID: 39995389 PMCID: PMC12120814 DOI: 10.1111/aor.14977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 01/11/2025] [Accepted: 02/11/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is associated with high short-term mortality of up to 40%. Albumin dialysis is a therapeutic option that can be used to bridge patients with ACLF to liver transplantation or recovery. METHODS This retrospective cohort study was conducted to determine the effectiveness and adverse effects of open albumin dialysis (OPAL) by comparing the biochemical and clinical variables of model for end-stage liver disease (MELD)-matched ACLF patients who received one of three treatments: OPAL plus standard medical treatment (SMT; 22 patients), Prometheus dialysis fractionated plasma separation and adsorption (FPSA) plus SMT (41 patients), or hemodialysis plus SMT (24 patients) at the University Hospital Essen. RESULTS OPAL treatment significantly reduced liver function tests such as bilirubin (p = 0.0001) and creatinine levels (p = 0.049). Therefore, OPAL therapy significantly reduced the MELD score (p = 0.001) and the Chronic Liver Failure Consortium (CLIF-C) ACLF (p = 0.0005) score. In both extracorporeal liver support groups, the decrease in MELD score was significantly stronger than that achieved with SMT (OPAL vs. SMT, p = 0.002; Prometheus vs. SMT, p = 0.0001; OPAL vs. Prometheus p = 0.90). In comparison to the SMT group, survival rates after 14 and 30 days were significantly higher in the Prometheus group (p = 0.0008 and 0.03) and tended to be better in the OPAL group, although statistical significance was not reached (p = 0.06 and p = 0.11). CONCLUSIONS Our analysis revealed OPAL is an efficient method of albumin dialysis yielding a reduction of bilirubin and creatinine levels and improving clinical scoring in ACLF patients. OPAL as well as Prometheus were associated with a stronger reduction of relevant biochemical variables of liver function and amelioration in clinical scoring in comparison to SMT. However, it should be considered that patients from the SMT group were older and experienced progressive ACLF with high mortality risks compared to the patients from the OPAL and Prometheus groups. Thus, when interpreting the study results, several limitations including small sample size and heterogeneity of the treatment groups due to the lack of randomization should be taken into account.
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Affiliation(s)
- Justa Friebus‐Kardash
- Department of NephrologyUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Amina Louzi
- Department of NephrologyUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Andreas Kribben
- Department of NephrologyUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Hartmut H. Schmidt
- Department of Gastroenterology, Hepatology and Transplant MedicineUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Michael Jahn
- Department of NephrologyUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Bartosz Tyczynski
- Department of NephrologyUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Jassin Rashidi‐Alavijeh
- Department of Gastroenterology, Hepatology and Transplant MedicineUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Andreas Schütte
- Department of Gastroenterology, Hepatology and Transplant MedicineUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
| | - Amos Zeller
- Department of Gastroenterology, Hepatology and Transplant MedicineUniversity of Duisburg‐Essen, University Hospital EssenEssenGermany
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Wu L, Li J, Zou J, Tang D, Chen R. Vagus nerve modulates acute-on-chronic liver failure progression via CXCL9. Chin Med J (Engl) 2025; 138:1103-1115. [PMID: 38945689 PMCID: PMC12068771 DOI: 10.1097/cm9.0000000000003104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Indexed: 07/02/2024] Open
Abstract
BACKGROUND Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF. METHODS Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology were used for in vivo or in vitro mechanistic studies. RESULTS The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells' accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling. CONCLUSIONS Our novel findings highlighted that the neuroimmune communication of the vagus nerve-macrophage-CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
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Affiliation(s)
- Li Wu
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Jie Li
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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Dai ZS, Zhang M, Deng YY, Zhou N, Tian Y. Efficacy of a novel artificial liver versatile plasma purification system in patients with acute-on-chronic liver failure. World J Gastroenterol 2025; 31:103892. [PMID: 40248372 PMCID: PMC12001202 DOI: 10.3748/wjg.v31.i14.103892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/05/2025] [Accepted: 03/26/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND We have innovatively amalgamated membrane blood purification and centrifugal blood cell separation technologies to address the limitations of current artificial liver support (ALS) models, and develop a versatile plasma purification system (VPPS) through centrifugal plasma separation. AIM To investigate the influence of VPPS on long-term rehospitalization and mortality rates among patients with acute-on-chronic liver failure (ACLF). METHODS This real-world, prospective study recruited inpatients diagnosed with ACLF from the Second Xiangya Hospital of Central South University between October 2021 and March 2024. Patients were categorized into the VPPS and non-VPPS groups based on the distinct ALS models administered to them. Self-administered questionnaires, clinical records, and self-reported data served as the primary methods for data collection. The laboratory results were evaluated at six distinct time points. All patients were subjected to follow-up assessments for > 12 months. Kaplan-Meier survival analyses and Cox proportional hazards models were used to evaluate the risks of hospitalization and mortality during the follow-up period. RESULTS A cohort of 502 patients diagnosed with ACLF was recruited, with 260 assigned to the VPPS group. On comparing baseline characteristics, the VPPS group exhibited a significantly shorter length of stay, higher incidence of spontaneous peritonitis and pulmonary aspergillosis compared to the non-VPPS group (P < 0.05). Age [hazard ratio (HR) = 1.142, 95%CI: 1.01-1.23, P = 0.018), peritonitis (HR = 2.825, 95%CI: 1.07-6.382, P = 0.026), albumin (HR = 0.67, 95%CI: 0.46-0.942, P = 0.023), total bilirubin (HR = 1.26, 95%CI: 1.01-3.25, P = 0.021), international normalized ratio (HR = 1.97, 95%CI: 1.21-2.908, P = 0.014), and VPPS/non-VPPS (HR = 3.24, 95%CI: 2.152-4.76, P < 0.001) were identified as significant independent predictors of mortality in both univariate and multivariate analyses throughout the follow-up period. Kaplan-Meier survival analyses demonstrated significantly higher rehospitalization and mortality rates in the non-VPPS group compared to the VPPS group during follow-up of ≥ 2 years (log-rank test, P < 0.001). CONCLUSION These findings suggest that VPPS is safe and has a positive influence on prognostic outcomes in patients with ACLF.
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Affiliation(s)
- Zhong-Shang Dai
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Min Zhang
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yuan-Ye Deng
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Ning Zhou
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Yi Tian
- Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
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Schulz MS, Angeli P, Trebicka J. Acute and non-acute decompensation of liver cirrhosis (47/130). Liver Int 2025; 45:e15861. [PMID: 38426268 PMCID: PMC11815624 DOI: 10.1111/liv.15861] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 12/18/2023] [Accepted: 01/19/2024] [Indexed: 03/02/2024]
Abstract
In the traditional view, the occurrence of cirrhosis-related complications, such as hepatic encephalopathy, formation of ascites or variceal haemorrhage, marks the transition to the decompensated stage of cirrhosis. Although the dichotomous stratification into a compensated and decompensated state reflects a prognostic water-shed moment and remains to hold its prognostic validity, it represents an oversimplification of clinical realities. A broadening understanding of pathophysiological mechanisms underpinning decompensation have led to the identification of distinct prognostic subgroups, associated with different clinical courses following decompensation. Data provided by the PREDICT study uncovered three distinct sub-phenotypes of acute decompensation (AD). Moreover, acute-on-chronic liver failure (ACLF) has been established as a distinct clinical entity for many years, which is associated with a high short-term mortality. Recently, non-acute decompensation (NAD) has been proposed as a distinct pathway of decompensation, complementing current concepts of the spectrum of decompensation. In contrast to AD, NAD is characterized by a slow and progressive development of complications, which are often presented at first decompensation and/or in patients in an earlier stage of chronic liver disease. Successful treatment of AD or NAD may lead to a clinical stabilization or even the concept of recompensation. This review aims to provide an overview on current concepts of decompensation and to delineate recent advances in our clinical and pathophysiological understanding.
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Affiliation(s)
- Martin S. Schulz
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
| | - Paolo Angeli
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
| | - Jonel Trebicka
- Department of Internal Medicine BUniversity of MünsterMünsterGermany
- European Foundation for Study of Chronic Liver FailureBarcelonaSpain
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Sun X, Wang F, Chen Z, Liao J, Yang Y, Bai L, Zhang L. Integrative anticoagulation of nafamostat mesylate in double plasma molecular adsorption system plus sequential half-dose plasmapheresis for patients with liver failure: a randomised controlled trial protocol. BMJ Open 2025; 15:e098898. [PMID: 40000083 DOI: 10.1136/bmjopen-2025-098898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/27/2025] Open
Abstract
INTRODUCTION Nafamostat mesylate (NM) is widely recognised as a premier anticoagulant, especially in Japan and Korea. However, it has not yet been used as an anticoagulant in double plasma molecular adsorption system (DPMAS) plus sequential half-dose plasmapheresis (PE) therapy. This study aims to comprehensively evaluate the safety and efficacy of NM-integrated anticoagulation during DPMAS plus sequential half-dose PE therapy for patients with liver failure. METHODS AND ANALYSIS A two-arm, open-label, parallel, randomised controlled trial involving 132 patients with liver failure will be conducted in China. Eligible participants will be randomly allocated to either the nafamostat mesylate integrative anticoagulation group or the heparin integrative anticoagulation group, employing a central randomisation system at a 1:1 ratio throughout the course of DPMAS plus sequential half-dose PE therapy. The primary outcome includes the number of successfully completed DPMAS plus sequential half-dose PE therapy. The secondary outcomes include liver function indicators, extracorporeal circulation pressures, coagulation function parameters, all-cause mortality rates and survival rates. Clinical safety will be assessed by analysis of the number of bleeding events, the number of clotting events and adverse events. Outcome analyses will be performed on both the intention-to-treat population, which includes all patients randomised, and the per-protocol population, which includes eligible patients who adhere to the planned treatment and follow-ups. ETHICS AND DISSEMINATION The trial protocol was approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (approval number (2022)860). During the protocol revision process, all changes were reexamined and reapproved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University. The results will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER ChiCTR2200064725.
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Affiliation(s)
- Xiankun Sun
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Fang Wang
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Zhiwen Chen
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Juan Liao
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Yingying Yang
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, People's Republic of China
| | - Ling Zhang
- Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, People's Republic of China
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Brown RS, Fisher RA, Subramanian RM, Griesemer A, Fernandes M, Thatcher WH, Stiede K, Curtis M. Artificial Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure: Systematic Review and Meta-Analysis. Crit Care Explor 2025; 7:e1199. [PMID: 39804005 PMCID: PMC11732652 DOI: 10.1097/cce.0000000000001199] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2025] Open
Abstract
OBJECTIVES To systematically review the safety and efficacy of nonbiological (NBAL) or biological artificial liver support systems (BAL) and whole-organ extracorporeal liver perfusion (W-ECLP) systems, in adults with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). DATA SOURCES Eligible NBAL/BAL studies from PubMed/Embase searches were randomized controlled trials (RCTs) in adult patients with ALF/ACLF, greater than or equal to ten patients per group, reporting outcomes related to survival, adverse events, transplantation rate, and hepatic encephalopathy, and published in English from January 2000 to July 2023. Separately, we searched for studies evaluating W-ECLP in adult patients with ALF or ACLF published between January1990 and July 2023. STUDY SELECTION AND DATA EXTRACTION Two researchers independently screened citations for eligibility and, of eligible studies, retrieved data related to study characteristics, patients and interventions, outcomes definition, and intervention effects. The Cochrane Risk of Bias 2 tool and Joanna Briggs Institute checklists were used to assess individual study risk of bias. Meta-analysis of mortality at 28-30 days post-support system initiation and frequency of at least one serious adverse event (SAE) generated pooled risk ratios (RRs), based on random (mortality) or fixed (SAE) effects models. DATA SYNTHESIS Of 17 trials evaluating NBAL/BAL systems, 11 reported 28-30 days mortality and five reported frequency of at least one SAE. Overall, NBAL/BAL was not statistically associated with mortality at 28-30 days (RR, 0.85; 95% CI, 0.67-1.07; p = 0.169) or frequency of at least one SAE (RR, 1.15; 95% CI, 0.99-1.33; p = 0.059), compared with standard medical treatment. Subgroup results on ALF patients suggest possible benefit for mortality (RR, 0.67; 95% CI, 0.44-1.03; p = 0.069). From six reports of W-ECLP (12 patients), more than half (58%) of severe patients were bridged to transplantation and survived without transmission of porcine retroviruses. CONCLUSIONS Despite no significant pooled effects of NBAL/BAL devices, the available evidence calls for further research and development of extracorporeal liver support systems, with larger RCTs and optimization of patient selection, perfusion durability, and treatment protocols.
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Affiliation(s)
- Robert S. Brown
- Center for Liver Disease, Weill Cornell Medicine, New York, NY
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Al Haddad A, Arber A, Cox A, Gallagher A. The Challenges Experienced by ICU Nurses in Kuwait during the COVID-19 Pandemic. INTERNATIONAL JOURNAL OF NURSING STUDIES ADVANCES 2024; 7:100226. [PMID: 39155969 PMCID: PMC11327471 DOI: 10.1016/j.ijnsa.2024.100226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 07/05/2024] [Accepted: 07/13/2024] [Indexed: 08/20/2024] Open
Abstract
Background The coronavirus (COVID-19) pandemic presented unprecedented challenges to healthcare systems worldwide, with intensive care unit (ICU) nurses at the forefront of patient care. To date, there is limited evidence into ICU nurses'experiences of the pandemic in Kuwait. Research question/aims/objectives To elucidate the challenges faced by ICU nurses in Kuwait during the pandemic, by considering two research questions: "What contributed to intensified pressure for the ICU nurses?" and "How were the nurses affected?". Research design This was a qualitative study which utilised semi-structured interviews. Interviews were conducted between January 2021 and June 2022 with ICU nurses who worked during the COVID-19 pandemic. The data were analysed using Charmaz's grounded theory methodology. Participants and research context 25 nurses from three ICUs in Kuwait. Ethical considerations The study was approved by the University Ethics Committee and by the Ministry of Health in Kuwait. Findings/Results The analysis identified two themes (the factors contributing to intensified pressure in the ICU, and the impact on the nurses) and seven sub-themes. The pressure in the ICU intensified due to the rise in the number of patients, staff shortages, and the requirement to adhere to unrealistic new procedures for infection control. Restricted and cancelled leave, as well as impaired autonomy at work, impeded the nurses' ability to recover from stress. The heightened stress also contributed to a worsening in interpersonal relationships between the nurses and their colleagues. The nurses' care was compromised by these challenges, leading to moral distress and a range of mental health symptoms (e.g., stress, anxiety, emotional exhaustion). Conclusions The study accords with other research conducted during the pandemic in revealing a significant mental health toll among healthcare workers during the pandemic. The stressors were similar to those which have been reported in other studies, although there were also context-specific effects relating to the environment of the ICU and the Kuwaiti context.
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Affiliation(s)
| | - Anne Arber
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Anna Cox
- Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Ann Gallagher
- Department of Health Sciences, Brunel University London, London, UK
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Gräfe C, Graf H, Wustrow V, Liebchen U, Conter P, Paal M, Habler K, Scharf C. Correlation of bilirubin and toxic bile acids in critically ill patients with cholestatic liver dysfunction and adsorber application. Sci Rep 2024; 14:21762. [PMID: 39294181 PMCID: PMC11411055 DOI: 10.1038/s41598-024-72676-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 09/10/2024] [Indexed: 09/20/2024] Open
Abstract
Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients' blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration > 10 mg/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12 h). Relative reduction (RR) was calculated using the formula[Formula: see text]. A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (rstart=0.64, p = 0.008; r6h = 0.85, p < 0.001, r12h = 0.72, p = 0.002) was observed. In the first six hours of CS-application, a significant elimination of TBA (median TBA: 30.8→20.1µmol/l, p < 0.001) and bilirubin (median bilirubin: 17.1→11.9 mg/dl, p < 0.001) was observed. The median RR after 6 h was 26.1% and 39.8% for bilirubin and TBA, respectively. No further reduction was observed after 12 h (RRbilirubin: - 0.6%, RRTBA: 1.8%). There was an at least moderate correlation between bilirubin and TBA in patients with cholestatic liver dysfunction. Therefore, bilirubin seems to be a suitable surrogate parameter for TBA elimination during CytoSorb application.
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Affiliation(s)
- Caroline Gräfe
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany.
| | - Helen Graf
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Vassilissa Wustrow
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Uwe Liebchen
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Philippe Conter
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Michael Paal
- Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Katharina Habler
- Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Christina Scharf
- Department of Anesthesiology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany
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Artru F, Trovato F, Morrison M, Bernal W, McPhail M. Liver transplantation for acute-on-chronic liver failure. Lancet Gastroenterol Hepatol 2024; 9:564-576. [PMID: 38309288 DOI: 10.1016/s2468-1253(23)00363-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Revised: 10/02/2023] [Accepted: 10/13/2023] [Indexed: 02/05/2024]
Abstract
Acute-on-chronic liver failure (ACLF) occurs in the context of advanced liver disease and is associated with hepatic and extrahepatic organ failure, eventually leading to a major risk of short-term mortality. To date, there are very few effective therapeutic options for ACLF. In many cases, liver transplantation is the only life-saving treatment that has acceptable outcomes in carefully selected recipients. This Review addresses key aspects of the use of liver transplantation for patients with ACLF, providing an in-depth discussion of existing evidence regarding candidate selection, the optimal window for transplantation, potential prioritisation of liver grafts for this indication, and the global management of ACLF to bridge patients to liver transplantation.
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Affiliation(s)
- Florent Artru
- Liver Intensive Care Unit, Institute of Liver Studies, King's College Hospital, London, UK; Department of Inflammation Biology, School of Infection and Microbial Sciences, King's College London, London, UK; Liver Disease Unit, Rennes University Hospital, Rennes, France; Inerm 1241 NuMeCan, University of Rennes, Rennes, France
| | - Francesca Trovato
- Liver Intensive Care Unit, Institute of Liver Studies, King's College Hospital, London, UK; Department of Inflammation Biology, School of Infection and Microbial Sciences, King's College London, London, UK
| | - Maura Morrison
- Liver Intensive Care Unit, Institute of Liver Studies, King's College Hospital, London, UK
| | - William Bernal
- Liver Intensive Care Unit, Institute of Liver Studies, King's College Hospital, London, UK.
| | - Mark McPhail
- Liver Intensive Care Unit, Institute of Liver Studies, King's College Hospital, London, UK; Department of Inflammation Biology, School of Infection and Microbial Sciences, King's College London, London, UK
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Kosuta I, Premkumar M, Reddy KR. Review article: Evaluation and care of the critically ill patient with cirrhosis. Aliment Pharmacol Ther 2024; 59:1489-1509. [PMID: 38693712 DOI: 10.1111/apt.18016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/21/2024] [Accepted: 04/12/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND The increase in prevalence of liver disease globally will lead to a substantial incremental burden on intensive care requirements. While liver transplantation offers a potential life-saving intervention, not all patients are eligible due to limitations such as organ availability, resource constraints, ongoing sepsis or multiple organ failures. Consequently, the focus of critical care of patients with advanced and decompensated cirrhosis turns to liver-centric intensive care protocols, to mitigate the high mortality in such patients. AIM Provide an updated and comprehensive understanding of cirrhosis management in critical care, and which includes emergency care, secondary organ failure management (mechanical ventilation, renal replacement therapy, haemodynamic support and intensive care nutrition), use of innovative liver support systems, infection control, liver transplantation and palliative and end-of life care. METHODS We conducted a structured bibliographic search on PubMed, sourcing articles published up to 31 March 2024, to cover topics addressed. We considered data from observational studies, recommendations of society guidelines, systematic reviews, and meta-analyses, randomised controlled trials, and incorporated our clinical expertise in liver critical care. RESULTS Critical care management of the patient with cirrhosis has evolved over time while mortality remains high despite aggressive management with liver transplantation serving as a crucial but not universally available resource. CONCLUSIONS Implementation of organ support therapies, intensive care protocols, nutrition, palliative care and end-of-life discussions and decisions are an integral part of critical care of the patient with cirrhosis. A multi-disciplinary approach towards critical care management is likely to yield better outcomes.
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Affiliation(s)
- Iva Kosuta
- Department of Intensive Care Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Madhumita Premkumar
- Department of Hepatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Haselwanter P, Scheiner B, Balcar L, Semmler G, Riedl-Wewalka M, Schmid M, Reiberger T, Zauner C, Schneeweiss-Gleixner M. Use of the CytoSorb adsorber in patients with acute-on-chronic liver failure. Sci Rep 2024; 14:11309. [PMID: 38760460 PMCID: PMC11101465 DOI: 10.1038/s41598-024-61658-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 05/08/2024] [Indexed: 05/19/2024] Open
Abstract
CytoSorb is a hemoadsorptive column used to remove high concentrations of proinflammatory cytokines in septic shock. Data on CytoSorb application in acute-on-chronic liver failure (ACLF) is lacking. This retrospective observational study analyzed 21 ACLF patients admitted to ICUs at the Vienna General Hospital who received CytoSorb adsorber therapy between 2017 and 2023. Median ICU length of stay was 8 days (IQR: 3-13), the ICU survival rate was 23.8% (n = 5). Significant decreases in bilirubin (median peak: 20.7 mg/dL to median post-treatment: 10.8 mg/dL; - 47.8%; p < 0.001), procalcitonin (1.34 to 0.74 pg/mL; - 44.6%; p < 0.001), interleukin-6 (385 to 131 ng/mL; - 66.0%; p = 0.0182)-but also of platelets (72 to 31 G/L; - 56.9%; p = 0.0014) and fibrinogen (230 to 154 mg/dL; - 33.0%; p = 0.0297) were detected. ICU survivors had a trend towards a stronger relative decrease in bilirubin (- 76.1% vs. - 48.2%), procalcitonin (- 90.6% vs. - 23.5%), and IL-6 (- 54.6% vs. - 17.8%) upon CytoSorb treatment. Moreover, no serious CytoSorb-attributed complications were detected. In conclusion, use of CytoSorb adsorber in ACLF patients results in a significant decrease in bilirubin and proinflammatory cytokines, while platelets and fibrinogen were also lowered. Prospective trials are warranted to investigate the impact of CytoSorb on clinical outcomes of ACLF patients with high proinflammatory cytokine levels.
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Affiliation(s)
- Patrick Haselwanter
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Bernhard Scheiner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Lorenz Balcar
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Georg Semmler
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Marlene Riedl-Wewalka
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Monika Schmid
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Thomas Reiberger
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Christian Zauner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - Mathias Schneeweiss-Gleixner
- Intensive Care Unit 13H1, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
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12
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Lam AH, King JD. Toxin-Induced Liver Injury and Extracorporeal Treatment of Liver Failure. ADVANCES IN KIDNEY DISEASE AND HEALTH 2024; 31:157-165. [PMID: 38649220 DOI: 10.1053/j.akdh.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Revised: 03/05/2024] [Accepted: 03/05/2024] [Indexed: 04/25/2024]
Abstract
Poisoning with a large variety of drugs and naturally occurring toxins may result in acute liver injury and failure. Drug-induced liver injury is a major cause of liver failure nationwide, and it is likely that nephrologists will be involved in treating patients with these conditions. A number of xenobiotics resulting in liver toxicity may cause acute kidney injury or other organ injury as well. Most agents causing drug- or toxin-induced liver failure lack specific therapies, although a few xenobiotics such as acetaminophen have effective antidotal therapies if administered prior to development of hepatotoxicity. The nephrologist should be aware that extracorporeal treatment of liver failure associated with drugs and toxins may be indicated, including therapies conventionally performed by nephrologists (hemodialysis, continuous kidney replacement therapy), therapies occasionally performed by nephrologists and other specialists (plasma exchange, albumin dialysis, hemadsorption), and therapies performed by other specialists (extracorporeal membrane oxygenation). An overview of the role of these therapies in liver failure is provided, as well as a review of their limitations and potential complications.
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Affiliation(s)
- Angela H Lam
- Maryland Poison Center, Baltimore, MD; Providence St. Joseph Health, Everett, WA; Virginia Mason Franciscan Health, Seattle, WA
| | - Joshua D King
- Maryland Poison Center, Baltimore, MD; Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; University of Maryland School of Pharmacy, Baltimore, MD.
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13
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García-Villegas R, Arni S. Hemoadsorption in Organ Preservation and Transplantation: A Narrative Review. Life (Basel) 2023; 14:65. [PMID: 38255680 PMCID: PMC10817660 DOI: 10.3390/life14010065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 12/19/2023] [Accepted: 12/27/2023] [Indexed: 01/24/2024] Open
Abstract
Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such as cytokine storm activation and blood ABO and immune incompatibilities. Cytokine adsorption is also performed for the treatment of various life-threatening conditions, such as endotoxic septic shock, acute respiratory distress syndrome, and cardiogenic shock, all potentially leading to adverse clinical outcomes during transplantation. After surgery, dysmetabolism and stress response limit successful graft survival and can lead to primary or secondary graft dysfunction. In this clinical context, and given that a major problem in transplant medicine is that the demand for organs far exceeds the supply, a technological innovation such as a hemoadsorption system could greatly contribute to increasing the number of usable organ donors. The objectives of this review are to describe the specific advantages and disadvantages of the application of cytokine adsorption in the context of transplantation and examine, before and/or after organ transplantation, the benefits of the addition of a cytokine adsorption therapy protocol.
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Affiliation(s)
- Refugio García-Villegas
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, D.F., Mexico City 07360, Mexico;
| | - Stephan Arni
- Department of Thoracic Surgery, University Hospital Zürich, 8091 Zürich, Switzerland
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14
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Turan C, Szigetváry CE, Kói T, Engh MA, Atakan I, Zubek L, Terebessy T, Hegyi P, Molnár Z. Hemoadsorption Therapy for Critically Ill Patients with Acute Liver Dysfunction: A Meta-Analysis and Systematic Review. Biomedicines 2023; 12:67. [PMID: 38255174 PMCID: PMC10813081 DOI: 10.3390/biomedicines12010067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/15/2023] [Accepted: 12/24/2023] [Indexed: 01/24/2024] Open
Abstract
Critically ill patients are at risk of developing acute liver dysfunction as part of multiorgan failure sequelae. Clearing the blood from toxic liver-related metabolites and cytokines could prevent further organ damage. Despite the increasing use of hemoadsorption for this purpose, evidence of its efficacy is lacking. Therefore, we conducted this systematic review and meta-analysis to assess the evidence on clinical outcomes following hemoadsorption therapy. A systematic search conducted in six electronic databases (PROSPERO registration: CRD42022286213) yielded 30 eligible publications between 2011 and 2023, reporting the use of hemoadsorption for a total of 335 patients presenting with liver dysfunction related to acute critical illness. Of those, 26 are case presentations (n = 84), 3 are observational studies (n = 142), and 1 is a registry analysis (n = 109). Analysis of data from individual cases showed a significant reduction in levels of aspartate transaminase (p = 0.03) and vasopressor need (p = 0.03) and a tendency to lower levels of total bilirubin, alanine transaminase, C-reactive protein, and creatinine. Pooled data showed a significant reduction in total bilirubin (mean difference of -4.79 mg/dL (95% CI: -6.25; -3.33), p = 0.002). The use of hemoadsorption for critically ill patients with acute liver dysfunction or failure seems to be safe and yields a trend towards improved liver function after therapy, but more high-quality evidence is crucially needed.
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Affiliation(s)
- Caner Turan
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary; (C.T.); (C.E.S.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
| | - Csenge Erzsébet Szigetváry
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary; (C.T.); (C.E.S.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
| | - Tamás Kói
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
- Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics, 1111 Budapest, Hungary
| | - Marie Anne Engh
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
| | - Işıl Atakan
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
| | - László Zubek
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
| | - Tamás Terebessy
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
- Department of Orthopaedics, Semmelweis University, 1085 Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
- Institute of Pancreatic Diseases, Semmelweis University, 1085 Budapest, Hungary
- Institute for Translational Medicine, Medical School, University of Pécs, 7623 Pécs, Hungary
| | - Zsolt Molnár
- Department of Anesthesiology and Intensive Therapy, Semmelweis University, 1085 Budapest, Hungary; (C.T.); (C.E.S.)
- Centre for Translational Medicine, Semmelweis University, 1085 Budapest, Hungary; (T.K.); (I.A.); (L.Z.); (T.T.); (P.H.)
- Department of Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, 60-806 Poznan, Poland
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15
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Torre A, Cisneros-Garza LE, Castillo-Barradas M, Navarro-Alvarez N, Sandoval-Salas R, González-Huezo MS, Pérez-Hernández JL, Méndez-Guerrero O, Ruiz-Manríquez JA, Trejo-Estrada R, Chavez-Tapia NC, Solís-Gasca LC, Moctezuma-Velázquez C, Aguirre-Valádez J, Flores-Calderón J, Higuera-de-la-Tijera F, García-Juárez I, Canedo-Castillo NA, Malé-Velázquez R, Montalvo-Gordon I, Vilatobá M, Márquez-Guillén E, Córdova-Gallardo J, Flores-García NC, Miranda-Zazueta G, Martínez-Saldívar BI, Páez-Zayas VM, Muñoz-Espinosa LE, Solís-Galindo FA. Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology. Ann Hepatol 2023; 28:101140. [PMID: 37482299 DOI: 10.1016/j.aohep.2023.101140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/26/2023] [Accepted: 05/31/2023] [Indexed: 07/25/2023]
Abstract
Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.
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Affiliation(s)
- Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
| | - Laura Esthela Cisneros-Garza
- Gastroenterology and Hepatology Department, Hospital Christus Muguerza Alta Especialidad, Monterrey, Nuevo León, Mexico
| | | | - Nalu Navarro-Alvarez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Osvely Méndez-Guerrero
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | | | - Luis Carlos Solís-Gasca
- Gastroenterology Department, Hospital General de Zona #12 Benito Juárez del Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Department of Medicine - Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
| | | | - Judith Flores-Calderón
- Pediatrics Department, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Iaarah Montalvo-Gordon
- Clinic of Gastrointestinal and Hepatic Specialties, Hospital Faro del Mayab, Mérida, Yucatán, Mexico
| | - Mario Vilatobá
- Transplant Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Ernesto Márquez-Guillén
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Ángeles del Pedregal, Mexico City, Mexico
| | - Jacqueline Córdova-Gallardo
- Hepatology Department - General Surgery Service, Hospital General Dr. Manuel Gea González, Mexico City, Mexico
| | - Nayeli Cointa Flores-García
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Linda Elsa Muñoz-Espinosa
- Universidad Autónoma de Nuevo León. Liver Unit, Department of Internal Medicine, University Hospital 'Dr. José E. González', Monterrey, Nuevo León, Mexico
| | - Francisco Alfonso Solís-Galindo
- Gastroenterology Department, Unidad Médica de Alta Especialidad # 71 Instituto Mexicano del Seguro Social, Torreón, Coahuila, Mexico
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16
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Nelson VL, Stumbras AR, Palumbo RN, Riesgraf SA, Balboa MS, Hannah ZA, Bergstrom IJ, Fecteau CJ, Lake JR, Barry JJ, Ross JJ. Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure. Bioengineering (Basel) 2023; 10:1201. [PMID: 37892931 PMCID: PMC10604724 DOI: 10.3390/bioengineering10101201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Revised: 09/29/2023] [Accepted: 10/10/2023] [Indexed: 10/29/2023] Open
Abstract
Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF.
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Affiliation(s)
- Victoria L. Nelson
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Aron R. Stumbras
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - R. Noelle Palumbo
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Shawn A. Riesgraf
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Marie S. Balboa
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Zachary A. Hannah
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Isaac J. Bergstrom
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Christopher J. Fecteau
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - John R. Lake
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN 55455, USA
| | - John J. Barry
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
| | - Jeff J. Ross
- Miromatrix Medical Inc., Eden Prairie, MN 55344, USA; (A.R.S.); (R.N.P.); (S.A.R.); (M.S.B.); (Z.A.H.); (C.J.F.); (J.R.L.); (J.J.R.)
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17
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Gräfe C, Paal M, Winkels M, Irlbeck M, Liebchen U, Scharf C. Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia. Blood Purif 2023; 52:849-856. [PMID: 37820591 DOI: 10.1159/000532059] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 07/12/2023] [Indexed: 10/13/2023]
Abstract
INTRODUCTION Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients' outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb® (CS) reduces mortality in patients with hyperbilirubinemia. METHODS Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. RESULTS Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. CONCLUSION The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.
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Affiliation(s)
- Caroline Gräfe
- Department of Anesthesiology, LMU Hospital, Munich, Germany
| | - Michael Paal
- Institute of Laboratory Medicine, LMU Hospital, Munich, Germany
| | - Martin Winkels
- Institute of Laboratory Medicine, LMU Hospital, Munich, Germany
| | | | - Uwe Liebchen
- Department of Anesthesiology, LMU Hospital, Munich, Germany
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18
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Butt MF, Jalan R. Review article: Emerging and current management of acute-on-chronic liver failure. Aliment Pharmacol Ther 2023; 58:774-794. [PMID: 37589507 DOI: 10.1111/apt.17659] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/02/2023] [Accepted: 07/24/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is a clinically and pathophysiologically distinct condition from acutely decompensated cirrhosis and is characterised by systemic inflammation, extrahepatic organ failure, and high short-term mortality. AIMS To provide a narrative review of the diagnostic criteria, prognosis, epidemiology, and general management principles of ACLF. Four specific interventions that are explored in detail are intravenous albumin, extracorporeal liver assist devices, granulocyte-colony stimulating factor, and liver transplantation. METHODS We searched PubMed and Cochrane databases for articles published up to July 2023. RESULTS Approximately 35% of hospital inpatients with decompensated cirrhosis have ACLF. There is significant heterogeneity in the criteria used to diagnose ACLF; different definitions identify different phenotypes with varying mortality. Criteria established by the European Association for the Study of the Liver were developed in prospective patient cohorts and are, to-date, the most well validated internationally. Systemic haemodynamic instability, renal dysfunction, coagulopathy, neurological dysfunction, and respiratory failure are key considerations when managing ACLF in the intensive care unit. Apart from liver transplantation, there are no accepted evidence-based treatments for ACLF, but several different approaches are under investigation. CONCLUSION The recognition of ACLF as a distinct entity from acutely decompensated cirrhosis has allowed for better patient stratification in clinical settings, facilitating earlier engagement with the intensive care unit and liver transplantation teams. Research priorities over the next decade should focus on exploring novel treatment strategies with a particular focus on which, when, and how patients with ACLF should be treated.
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Affiliation(s)
- Mohsin F Butt
- Centre for Neuroscience, Trauma and Surgery, Wingate Institute of Neurogastroenterology, The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, University of Nottingham, Nottinghamshire, UK
| | - Rajiv Jalan
- Liver Failure Group, University College London Medical School, Royal Free Hospital Campus, London, UK
- European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain
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19
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Perricone G, Artzner T, De Martin E, Jalan R, Wendon J, Carbone M. Intensive care management of acute-on-chronic liver failure. Intensive Care Med 2023; 49:903-921. [PMID: 37552333 DOI: 10.1007/s00134-023-07149-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 06/21/2023] [Indexed: 08/09/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a clinical syndrome defined by an acute deterioration of the liver function associated with extrahepatic organ failures requiring intensive care support and associated with a high short-term mortality. ACLF has emerged as a major cause of mortality in patients with cirrhosis and chronic liver disease. ACLF has a unique pathophysiology in which systemic inflammation plays a key role; this provides the basis of novel therapies, several of which are now in clinical trials. Intensive care unit (ICU) therapy parallels that applied in the general ICU population in some organ failures but has peculiar differential characteristics in others. Critical care management strategies and the option of liver transplantation (LT) should be balanced with futility considerations in those with a poor prognosis. Nowadays, LT is the only life-saving treatment that can radically improve the long-term prognosis of patients with ACLF. This narrative review will provide insights on the current understanding of ACLF with emphasis on intensive care management.
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Affiliation(s)
- Giovanni Perricone
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy.
| | - Thierry Artzner
- Hôpitaux Universitaires de Strasbourg, 67000, Strasbourg, France
| | - Eleonora De Martin
- AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, Inserm UMR-S 1193, Université Paris-Saclay, Villejuif, France
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, UK
- European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Julia Wendon
- Liver Intensive Therapy Unit, Division of Inflammation Biology, King's College London, London, UK
| | - Marco Carbone
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
- European Reference Network On Hepatological Diseases (ERN RARE-LIVER), Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
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20
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Moreau R, Tonon M, Krag A, Angeli P, Berenguer M, Berzigotti A, Fernandez J, Francoz C, Gustot T, Jalan R, Papp M, Trebicka J. EASL Clinical Practice Guidelines on acute-on-chronic liver failure. J Hepatol 2023; 79:461-491. [PMID: 37364789 DOI: 10.1016/j.jhep.2023.04.021] [Citation(s) in RCA: 122] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 04/19/2023] [Indexed: 06/28/2023]
Abstract
Acute-on-chronic liver failure (ACLF), which was described relatively recently (2013), is a severe form of acutely decompensated cirrhosis characterised by the existence of organ system failure(s) and a high risk of short-term mortality. ACLF is caused by an excessive systemic inflammatory response triggered by precipitants that are clinically apparent (e.g., proven microbial infection with sepsis, severe alcohol-related hepatitis) or not. Since the description of ACLF, some important studies have suggested that patients with ACLF may benefit from liver transplantation and because of this, should be urgently stabilised for transplantation by receiving appropriate treatment of identified precipitants, and full general management, including support of organ systems in the intensive care unit (ICU). The objective of the present Clinical Practice Guidelines is to provide recommendations to help clinicians recognise ACLF, make triage decisions (ICU vs. no ICU), identify and manage acute precipitants, identify organ systems that require support or replacement, define potential criteria for futility of intensive care, and identify potential indications for liver transplantation. Based on an in-depth review of the relevant literature, we provide recommendations to navigate clinical dilemmas followed by supporting text. The recommendations are graded according to the Oxford Centre for Evidence-Based Medicine system and categorised as 'weak' or 'strong'. We aim to provide the best available evidence to aid the clinical decision-making process in the management of patients with ACLF.
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21
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Göth D, Mahler CF, Kälble F, Speer C, Benning L, Schmitt FCF, Dietrich M, Krautkrämer E, Zeier M, Merle U, Morath C, Fiedler MO, Weigand MA, Nusshag C. Liver-Support Therapies in Critical Illness-A Comparative Analysis of Procedural Characteristics and Safety. J Clin Med 2023; 12:4669. [PMID: 37510784 PMCID: PMC10380554 DOI: 10.3390/jcm12144669] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 07/09/2023] [Accepted: 07/11/2023] [Indexed: 07/30/2023] Open
Abstract
Extracorporeal liver-support therapies remain controversial in critically ill patients, as most studies have failed to show an improvement in outcomes. However, heterogeneous timing and inclusion criteria, an insufficient number of treatments, and the lack of a situation-dependent selection of available liver-support modalities may have contributed to negative study results. We retrospectively investigated the procedural characteristics and safety of the three liver-support therapies CytoSorb, Molecular Adsorbent Recirculating System (MARS) and therapeutic plasma exchange (TPE). Whereas TPE had its strengths in a shorter treatment duration, in clearing larger molecules, affecting platelet numbers less, and improving systemic coagulation and hemodynamics, CytoSorb and MARS were associated with a superior reduction in particularly small protein-bound and water-soluble substances. The clearance magnitude was concentration-dependent for all three therapies, but additionally related to the molecular weight for CytoSorb and MARS therapy. Severe complications did not appear. In conclusion, a better characterization of disease-driving as well as beneficial molecules in critically ill patients with acute liver dysfunction is crucial to improve the use of liver-support therapy in critically ill patients. TPE may be beneficial in patients at high risk for bleeding complications and impaired liver synthesis and hemodynamics, while CytoSorb and MARS may be considered for patients in whom the elimination of smaller toxic compounds is a primary objective.
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Affiliation(s)
- Daniel Göth
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Christoph F Mahler
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Florian Kälble
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Claudius Speer
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Louise Benning
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Felix C F Schmitt
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Maximilian Dietrich
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Ellen Krautkrämer
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Martin Zeier
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Uta Merle
- Department of Gastroenterology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Christian Morath
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Mascha O Fiedler
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Markus A Weigand
- Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany
| | - Christian Nusshag
- Department of Nephrology, Heidelberg University Hospital, 69120 Heidelberg, Germany
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22
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Kimmann M, Trebicka J. Acute-On-Chronic Liver Failure: Current Interventional Treatment Options and Future Challenges. J Pers Med 2023; 13:1052. [PMID: 37511665 PMCID: PMC10381861 DOI: 10.3390/jpm13071052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/20/2023] [Accepted: 06/25/2023] [Indexed: 07/30/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is a frequent complication in patients with liver cirrhosis that has high short-term mortality. It is characterized by acute decompensation (AD) of liver cirrhosis, intra- and extrahepatic organ failure, and severe systemic inflammation (SI). In the recent past, several studies have investigated the management of this group of patients. Identification and treatment of precipitants of decompensation and ACLF play an important role, and management of the respective intra- and extrahepatic organ failures is essential. However, no specific treatment for ACLF has been established to date, and the only curative treatment option currently available for these patients is liver transplantation (LT). It has been shown that ACLF patients are at severe risk of waitlist mortality, and post-LT survival rates are high, making ACLF patients suitable candidates for LT. However, only a limited number of patients are eligible for LT due to related contraindications such as uncontrolled infections. In this case, bridging strategies (e.g., extracorporeal organ support systems) are required. Further therapeutic approaches have recently been developed and evaluated. Thus, this review focuses on current management and potential future treatment options.
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Affiliation(s)
- Markus Kimmann
- Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
| | - Jonel Trebicka
- Department of Internal Medicine B, University of Münster, 48149 Münster, Germany
- European Foundation for the Study of Chronic liver Failure, EFCLIF, 08021 Barcelona, Spain
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23
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Papamichalis P, Oikonomou KG, Valsamaki A, Xanthoudaki M, Katsiafylloudis P, Papapostolou E, Skoura AL, Papamichalis M, Karvouniaris M, Koutras A, Vaitsi E, Sarchosi S, Papadogoulas A, Papadopoulos D. Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions. World J Clin Cases 2023; 11:3932-3948. [PMID: 37388799 PMCID: PMC10303607 DOI: 10.12998/wjcc.v11.i17.3932] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023] Open
Abstract
Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.
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Affiliation(s)
| | - Katerina G Oikonomou
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Asimina Valsamaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Maria Xanthoudaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | | | | | - Apostolia-Lemonia Skoura
- Department of Transfusion Medicine, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
| | - Michail Papamichalis
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
| | | | - Antonios Koutras
- 1st Department of Obstetrics and Gynecology, General Hospital of Athens “ALEXANDRA”, National and Kapodistrian University of Athens, Athens 11528, Greece
| | - Eleni Vaitsi
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Smaragdi Sarchosi
- Department of Anesthesiology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
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24
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Popescu M, David C, Marcu A, Olita MR, Mihaila M, Tomescu D. Artificial Liver Support with CytoSorb and MARS in Liver Failure: A Retrospective Propensity Matched Analysis. J Clin Med 2023; 12:jcm12062258. [PMID: 36983259 PMCID: PMC10058971 DOI: 10.3390/jcm12062258] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/06/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Background: Liver failure represents a life-threatening organ dysfunction with liver transplantation as the only proven curable therapy to date. Liver assist devices have been extensively researched to either bridge such patients to transplantation or promote spontaneous recovery. The aim of our study was to compare two such devices, the Molecular Adsorbent Recirculating System (MARS) and CytoSorb, in patients with liver failure. Methods: We retrospectively included 15 patients who underwent MARS during their intensive care unit stay and matched them to 15 patients who underwent hemoadsorption using CytoSorb. Clinical and paraclinical data obtained after each individual session, after the course of treatment, as well as at the end of the intensive care unit stay were compared between the two groups. Results: Single sessions of CytoSorb and MARS were both associated with a significant decrease in bilirubin (p = 0.04 and p = 0.04, respectively) and ammonia levels (p = 0.04 and p = 0.04, respectively), but only CytoSorb therapy was associated with a decrease in lactate dehydrogenase levels (p = 0.04) and in platelet count (p = 0.04). After the course of treatment, only CytoSorb was associated with a significant decrease in lactate (p = 0.01), bilirubin (p = 0.01), ammonia (p = 0.02), and lactate dehydrogenase levels (p = 0.01), while patients treated with MARS did not show any improvement in paraclinical liver tests. In addition, only CytoSorb treatment was associated with a significant improvement in the Model for End-Stage Liver Disease Score (p = 0.04). Conclusion: In conclusion, our results show a potential benefit of CytoSorb in rebalancing liver functional tests in patients with liver failure compared to MARS but the exact effects on patient outcome, including hospital length of stay and survival, should be further investigated in randomized control trials.
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Affiliation(s)
- Mihai Popescu
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 022328 Bucharest, Romania
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Correspondence: ; Tel.: +40-75-107-5995
| | - Corina David
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Alexandra Marcu
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Mihaela Roxana Olita
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 022328 Bucharest, Romania
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Mariana Mihaila
- Department of Internal Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Dana Tomescu
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 022328 Bucharest, Romania
- Department of Anaesthesia and Intensive Care, Fundeni Clinical Institute, 022328 Bucharest, Romania
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25
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Wilde B, Canbay A, Katsounas A. Clinical and pathophysiological understanding of the hepatorenal syndrome: Still wrong or still not exactly right? World J Clin Cases 2023; 11:1261-1266. [PMID: 36926126 PMCID: PMC10013104 DOI: 10.12998/wjcc.v11.i6.1261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 12/15/2022] [Accepted: 02/03/2023] [Indexed: 02/23/2023] Open
Abstract
The hepatorenal syndrome (HRS) is one major extrahepatic complication of end-stage liver diseases. While circulatory dysregulation is considered as primary etiology for HRS, cirrhosis-related (systemic) inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development. Exclusion of other causes of acute kidney injury (AKI) is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites. However, the pathophysiology of HRS is not understood completely and there are still limited therapeutic options. Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function. The interplay between systemic inflammation and the onset of kidney-related hypometabolism may have a key role and needs to be studied in depth. This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.
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Affiliation(s)
- Benjamin Wilde
- Department of Nephrology, University of Duisburg-Essen, University Hospital Essen, Essen 45147, Germany
| | - Ali Canbay
- Department of Medicine, Ruhr University Bochum, Bochum 44892, Germany
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26
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Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of liver support systems for adults with acute‐on‐chronic liver failure.
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27
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Delgado-Coello B, Navarro-Alvarez N, Mas-Oliva J. The Influence of Interdisciplinary Work towards Advancing Knowledge on Human Liver Physiology. Cells 2022; 11:3696. [PMID: 36429123 PMCID: PMC9688355 DOI: 10.3390/cells11223696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 11/11/2022] [Accepted: 11/13/2022] [Indexed: 11/23/2022] Open
Abstract
The knowledge accumulated throughout the years about liver regeneration has allowed a better understanding of normal liver physiology, by reconstructing the sequence of steps that this organ follows when it must rebuild itself after being injured. The scientific community has used several interdisciplinary approaches searching to improve liver regeneration and, therefore, human health. Here, we provide a brief history of the milestones that have advanced liver surgery, and review some of the new insights offered by the interdisciplinary work using animals, in vitro models, tissue engineering, or mathematical models to help advance the knowledge on liver regeneration. We also present several of the main approaches currently available aiming at providing liver support and overcoming organ shortage and we conclude with some of the challenges found in clinical practice and the ethical issues that have concomitantly emerged with the use of those approaches.
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Affiliation(s)
- Blanca Delgado-Coello
- Department of Structural Biology and Biochemistry, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
| | - Nalu Navarro-Alvarez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico
- Departament of Molecular Biology, Universidad Panamericana School of Medicine, Mexico City 03920, Mexico
- Department of Surgery, University of Colorado Anschutz Medical Campus, Denver, CO 80045, USA
| | - Jaime Mas-Oliva
- Department of Structural Biology and Biochemistry, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
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28
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Saliba F, Bañares R, Larsen FS, Wilmer A, Parés A, Mitzner S, Stange J, Fuhrmann V, Gilg S, Hassanein T, Samuel D, Torner J, Jaber S. Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts. Intensive Care Med 2022; 48:1352-1367. [PMID: 36066598 DOI: 10.1007/s00134-022-06802-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 06/24/2022] [Indexed: 02/04/2023]
Abstract
The present narrative review on albumin dialysis provides evidence-based and expert opinion guidelines for clinicians caring for adult patients with different types of liver failure. The review was prepared by an expert panel of 13 members with liver and ntensive care expertise in extracorporeal liver support therapies for the management of patients with liver failure. The coordinating committee developed the questions according to their importance in the management of patients with liver failure. For each indication, experts conducted a comprehensive review of the literature aiming to identify the best available evidence and assessed the quality of evidence based on the literature and their experience. Summary statements and expert's recommendations covered all indications of albumin dialysis therapy in patients with liver failure, timing and intensity of treatment, efficacy, technical issues related to the device and safety. The panel supports the data from the literature that albumin dialysis showed a beneficial effect on hepatic encephalopathy, refractory pruritus, renal function, reduction of cholestasis and jaundice. However, the trials lacked to show a clear beneficial effect on overall survival. A short-term survival benefit at 15 and 21 days respectively in acute and acute-on-chronic liver failure has been reported in recent studies. The technique should be limited to patients with a transplant project, to centers experienced in the management of advanced liver disease. The use of extracorporeal albumin dialysis could be beneficial in selected patients with advanced liver diseases listed for transplant or with a transplant project. Waiting future large randomized controlled trials, this panel experts' statements may help careful patient selection and better treatment modalities.
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Affiliation(s)
- Faouzi Saliba
- AP-HP Hôpital Paul Brousse, Hepato-Biliary Center and Liver Transplant ICU, University Paris Saclay, INSERM Unit N°1193, Villejuif, France
| | - Rafael Bañares
- Gastroenterology and Hepatology Department, Hospital General Universitario Gregorio Marañón, IISGM, Madrid, Spain.,Facultad de Medicina, Universidad Complutense, Madrid, Spain.,CIBERehd, Madrid, Spain
| | - Fin Stolze Larsen
- Department of Hepatology and Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Alexander Wilmer
- Medical Intensive Care Unit, Department of General Internal Medicine, KU Leuven University Hospitals Leuven, Leuven, Belgium
| | - Albert Parés
- Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain
| | - Steffen Mitzner
- Division of Nephrology and Fraunhofer Institute for Cell Therapy and Immunology, Department of Medicine, University Hospital Rostock, Rostock, Germany
| | - Jan Stange
- Center for Extracorporeal Organ Support, Nephrology, Internal Medicine, Rostock University Medical Center, Rostock, Germany.,Albutec GmbH, Rostock, Germany
| | - Valentin Fuhrmann
- Klinik für Innere Medizin, Heilig Geist-Krankenhaus, Cologne, Germany.,Klinik für Intensivmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Gilg
- Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Solna, Sweden.,Department of HPB Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - Tarek Hassanein
- Southern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA, 92118, USA
| | - Didier Samuel
- AP-HP Hôpital Paul Brousse, Hepato-Biliary Center and Liver Transplant ICU, University Paris Saclay, INSERM Unit N°1193, Villejuif, France
| | | | - Samir Jaber
- Department of Anesthesia and Intensive Care Unit, Regional University Hospital of Montpellier, St-Eloi Hospital, University of Montpellier, PhyMedExp, INSERM U1046, CNRS UMR, 9214, Montpellier Cedex 5, France. .,Département d'Anesthésie Réanimation B (DAR B), 80 Avenue Augustin Fliche, 34295, Montpellier, France.
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29
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Wang L, Zhu S, Liu Y, Zheng L, Xu W, Luo Q, Zhang Y, Deng H, Li X, Xie C, Peng L. Prognostic value of decline in model for end-stage liver disease score and hepatic encephalopathy in hepatitis B-related acute-on-chronic liver failure patients treated with plasma exchange. Scand J Gastroenterol 2022; 57:1089-1096. [PMID: 35435091 DOI: 10.1080/00365521.2022.2063032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 03/25/2022] [Accepted: 04/01/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the prognostic value of Model for End-Stage Liver Disease (MELD) score and Hepatic Encephalopathy (HE) for short-term prognosis of Hepatitis B virus-related Acute-on-Chronic Liver Failure (HBV-ACLF) patients treated with plasma exchange (PE). METHODS A total of 108 patients with HBV-ACLF treated with PE were retrospectively enrolled between January 2014 to December 2020. Based on survival at 28 days, patients were divided into survival (N = 87) and death groups (N = 21). Clinical data and laboratory indicators were analyzed. RESULTS Compared with the survival group, the death group was associated with higher ACLF grade and incidence of HE. The levels of total bilirubin, prothrombin time, creatinine, blood urea nitrogen, MELD score, and Chinese Group on the Study of Severe Hepatitis B-ACLF II (COSSH II) score were significantly higher in the death group than in the survival group (p < .05). Grade 1 ACLF and the MELD score after PE treatment at one week were independent risk factors for 28-day liver transplantation-free mortality (OR = 0.062, 95%CI: 0.005-0.768; OR = 1.328, 95%CI: 1.153-1.531). A MELD score at one week of at least 25.5 was associated with a poor short-term prognosis. Of note, HE was a strong independent risk factor for a decline in MELD score at one week. (OR = 11.815, 95%CI: 3.187-43.796, p < 0.001). CONCLUSION We found patients with HE at admission and MELD score of at least 25.5 at one week after PE treatment had a poor short-term prognosis and should prompt preparation for liver transplantation. Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04231565). Registered 13 May 2020.
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Affiliation(s)
- Lu Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shu Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ying Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Lihua Zheng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Qiumin Luo
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yeqiong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Hong Deng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xinhua Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China
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Mukit AA, Mahtab MA, Rahim MA, Noor-E-Alam SM, Das DC, Moben AL, Khondaker FA, Alam MA, Begum R, Haque ME, Islam MA, Mamun AA, Akbar SMF. Plasma Exchange in Patients of Acute on Chronic Liver Failure: An Observational Study in Bangladesh. Euroasian J Hepatogastroenterol 2022; 12:1-5. [PMID: 35990863 PMCID: PMC9357523 DOI: 10.5005/jp-journals-10018-1354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Therapeutic plasma exchange (PLEX) removes toxins and different mediators from plasma in patients with acute-on-chronic liver failure (ACLF). Aim To observe the safety and outcome of PLEX in ACLF patients in Bangladesh. Materials and methods Twenty-eight patients with ACLF attending Bangabandhu Sheikh Mujib Medical University from September 2020 to May 2021 were enrolled in the study. The patients were given different treatment modalities and followed up for 3 months or up to death. The patients were divided into two groups, each containing 14 patients of ACLF. One group of 14 patients received standard medical therapy (SMT) for ACLF and the second group of 14 patients received SMT plus PLEX. Results At 90 days, a total of 13 patients (46.43%) survived, of them 8 (57.1%) belonged to PLEX group and 5 (35.7%) were from SMT group. Serum bilirubin and ALT declined significantly after 7 and 30 days but not after 90 days in PLEX group in comparison to SMT group (p <0.05) but other biochemical parameters were not significantly different (p >0.05) between these two groups. Significant (p <0.05) improvement of MELD, MELD-Na, and AARC scores was observed in each group from baseline to subsequent first, second, and third follow-up but no significant (p >0.05) difference was observed in between two groups. Binary logistic regression analysis found that bilirubin, MELD score, MELD-Na score, and AARC score were predictors of mortality. Conclusion The study presented here has shown that PLEX is safe in Bangladeshi in ACLF patients, but its efficacy remains to be checked in large-scale randomized trial or in combination therapy with other procedures in ACLF patients. How to cite this article Al Mukit A, Al Mahtab M, Rahim MA, et al. Plasma Exchange in Patients of Acute on Chronic Liver Failure: An Observational Study in Bangladesh. Euroasian J Hepato-Gastroenterol 2022;12(1):1–5.
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Affiliation(s)
- Abdullah Al Mukit
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md. Abdur Rahim
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Dulal Chandra Das
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | | | - Md. Ashraful Alam
- Department of Hepatology, Shaheed Tajuddin Ahmad Medical College, Gazipur, Bangladesh
| | - Rokshana Begum
- Department of Hepatology, Shaheed Suhrawardi Medical College, Dhaka, Bangladesh
| | - Mohammad Ekramul Haque
- Department of Anaesthesia, Sheikh Hasina National Institute of Burn and Plastic Surgery, Dhaka, Bangladesh
| | - Md. Atikul Islam
- Department of Hepatology, Sheikh Russel Gastro liver Institute and Hospital, Dhaka, Bangladesh
| | - Ayub Al Mamun
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sheikh Mohammad Fazle Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
- Sheikh Mohammad Fazle Akbar, Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan, e-mail:
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Sun X, Guo S. Effectiveness of cell- and colony stimulating factor-based therapy for liver cirrhosis: a network meta-analysis of randomized controlled trials. Cytotherapy 2022; 24:516-525. [PMID: 35227600 DOI: 10.1016/j.jcyt.2021.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 11/01/2021] [Accepted: 11/15/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND AIMS Cirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis. METHODS A literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels. RESULTS Twenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49-3.79, P < 0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00-2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators. CONCLUSIONS Cell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.
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Affiliation(s)
- Xiaojun Sun
- Inpatients Department, Nanjing Qi-xia Xi-gang Community Health Service Centers, Nanjing, China
| | - Shilei Guo
- Research and Development Department, Nanjing Regenerative Medicine Engineering and Technology Research Center, Nanjing, China.
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Schulz MS, Gu W, Schnitzbauer AA, Trebicka J. Liver Transplantation as a Cornerstone Treatment for Acute-On-Chronic Liver Failure. Transpl Int 2022; 35:10108. [PMID: 35572467 PMCID: PMC9099355 DOI: 10.3389/ti.2022.10108] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 01/27/2022] [Indexed: 11/13/2022]
Abstract
Acute-on-chronic liver failure (ACLF) is a distinct clinical syndrome, characterized by acute decompensation (AD) of liver cirrhosis, severe systemic inflammation, intra- and extrahepatic organ failures, and a high short-term mortality. Liver transplantation (LT) is a potentially life-saving treatment for patients with decompensated liver cirrhosis and, due to the high mortality rates, particularly for ACLF patients. In the last decade, a plethora of studies has produced compelling evidence in favor of LT in ACLF, demonstrating high post-LT survival rates and excessive waitlist mortality. The importance of LT in these patients is underscored by the fact that no specific therapy for ACLF is available yet, rendering expeditious life-saving LT to be the only feasible treatment option for some ACLF patients. This review aims to provide an overview on pathophysiology, clinical trajectory, and clinical management of ACLF and to delineate the current literature regarding perspectives and limitations of LT as a life-saving treatment option for ACLF patients.
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Affiliation(s)
- Martin S. Schulz
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Wenyi Gu
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
| | - Andreas A. Schnitzbauer
- Department of General and Visceral Surgery, University Hospital, Goethe University, Frankfurt, Germany
| | - Jonel Trebicka
- Department of Internal Medicine I, Goethe University, Frankfurt, Germany
- European Foundation for Study of Chronic Liver Failure (EF-Clif), Barcelona, Spain
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Kumar SE, Goel A, Zachariah U, Nair SC, David VG, Varughese S, Gandhi PB, Barpha A, Sharma A, Vijayalekshmi B, Balasubramanian KA, Elias E, Eapen CE. Low Volume Plasma Exchange and Low Dose Steroid Improve Survival in Patients With Alcohol-Related Acute on Chronic Liver Failure and Severe Alcoholic Hepatitis - Preliminary Experience. J Clin Exp Hepatol 2022; 12:372-378. [PMID: 35535077 PMCID: PMC9077153 DOI: 10.1016/j.jceh.2021.07.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Accepted: 07/14/2021] [Indexed: 12/12/2022] Open
Abstract
Background Alcohol-related acute on chronic liver failure (A-ACLF) patients have high short-term mortality and are poor candidates for steroid therapy. Plasma exchange (PLEX) improves survival in ACLF patients. We analyzed our experience with low volume PLEX (50% of plasma volume exchanged per session) and low dose steroids to treat A-ACLF patients. Methods We retrospectively compared the efficacy of low volume PLEX and low-dose steroids with standard medical treatment (SMT) in A-ACLF patients treated at our center between November 2017 to June 2019. The primary study outcome was one-year survival. Results Twenty-one A-ACLF patients in PLEX group [age 40 (29-56) years, median (range); MELD score 31 (29-46)] and 29 A-ACLF patients in SMT group [age 41.5 (28-63) years, MELD score 37 (21-48)] were studied. All 50 study patients had severe alcoholic hepatitis [mDF 84.7 (50-389)]. PLEX group patients had 3 (1-7) PLEX sessions with 1.5 (1.4-1.6) liters of plasma exchanged per session and oral Prednisolone 20 mg daily, tapered over 1 month. Kaplan Meier analysis showed better survival over 1 year in the PLEX group compared to the SMT group (P = 0.03). There was renal dysfunction in 10 patients in the PLEX group, which normalized in six patients after PLEX. Conclusion In this preliminary report, compared to SMT, low volume PLEX and low dose steroid improved survival over one year in A-ACLF patients with severe alcoholic hepatitis. In patients with renal dysfunction, 60% showed improvement in renal function with PLEX. Studies with a larger number of patients are needed to validate these results.
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Key Words
- A-ACLF, Alcohol-related acute on chronic liver failure
- AARC score, APASL ACLF Research Consortium score
- ADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13
- APASL, Asia pacific association for the study of the liver
- INR, International normalized ratio
- MELD, Model for end-stage liver disease
- PLEX, Plasma exchange
- SMT, standard medical treatment
- VWF, von Willebrand factor
- acute on chronic liver failure
- alcohol
- mDF, modified discriminant function
- plasma exchange
- steroid
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Affiliation(s)
- Santhosh E. Kumar
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Ashish Goel
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Uday Zachariah
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Sukesh C. Nair
- Transfusion Medicine and Immunohematology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Vinoi G. David
- Nephrology, Christian Medical College, Vellore, Tamil Nadu, India
| | | | - Prashanth B. Gandhi
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Amit Barpha
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | - Anand Sharma
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
| | | | | | - Elwyn Elias
- Departments of Hepatology, Christian Medical College, Vellore, Tamil Nadu, India
- Liver Unit, University Hospitals Birmingham, Birmingham, UK
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Chen YY, Li H, Xu BY, Zheng X, Li BL, Wang XB, Huang Y, Gao YH, Qian ZP, Liu F, Lu XB, Shang J, Li H, Wang SY, Zhang YH, Meng ZJ. Plasma Exchange-Based Non-bioartificial Liver Support System Improves the Short-Term Outcomes of Patients With Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure: A Multicenter Prospective Cohort Study. Front Med (Lausanne) 2021; 8:779744. [PMID: 34869500 PMCID: PMC8635207 DOI: 10.3389/fmed.2021.779744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 10/13/2021] [Indexed: 11/13/2022] Open
Abstract
Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated. Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier). Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30-40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018). Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.
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Affiliation(s)
- Yuan-yuan Chen
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Hai Li
- Key Laboratory of Gastroenterology and Hepatology, Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University, Chinese Ministry of Health (Shanghai Jiao Tong University), Shanghai, China
| | - Bao-yan Xu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xin Zheng
- Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bei-ling Li
- Hepatology Unit, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xian-bo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yan Huang
- Hunan Key Laboratory of Viral Hepatitis, Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, China
| | - Yan-hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Zhi-ping Qian
- Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China
| | - Feng Liu
- Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China
| | - Xiao-bo Lu
- Liver Disease Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Hai Li
- Infectious Disease Center, Affiliated Hospital of Logistics University of People's Armed Police Force, Tianjin, China
| | - Shao-yang Wang
- Department of Infectious Diseases, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China
| | - Yin-hua Zhang
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
| | - Zhong-ji Meng
- Department of Infectious Diseases, Hubei Clinical Research Center for Precise Diagnosis and Therapy of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, China
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Hemoadsorption in 'Liver Indication'-Analysis of 109 Patients' Data from the CytoSorb International Registry. J Clin Med 2021; 10:jcm10215182. [PMID: 34768702 PMCID: PMC8584981 DOI: 10.3390/jcm10215182] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 11/01/2021] [Accepted: 11/03/2021] [Indexed: 12/26/2022] Open
Abstract
Background: Our aim is to report the results of the ‘liver indication’ subset of patients in the CytoSorb International Registry. Methods: Structured data were recorded. Treatment characteristics and changes from T1 (start of hemoadsorption) to T2 (termination) were evaluated with a special focus on bilirubin, C-reactive protein, procalcitonin, interleukin-6, platelet levels, SOFA scores, mortality, and subjective assessment by the attending physicians. Results: Until January 2021, from the total 1434 patients, 109 (age: 49.2 ± 17.1 years, 57.8% males) received treatment for hyperbilirubinemia. APACHE II-predicted mortality was 49.6 ± 26.8%. In the study, 91% of patients were alive at the termination of hemoadsorption and improvement was observed by the physicians in 75 cases. Overall, 65 (59.6%) patients died in the hospital, and 60 (55.0%) died in the ICU. Patients received a median of two treatments for a median of 43 h (interquartile range: 24–72 h) in total. Serum bilirubin levels reduced significantly to −4.6 (95% CI: −6.329 to −2.8) mg/dL. Thrombocytopenia was reported in four patients as an adverse event. Conclusions: We report the largest case series on hemoadsorption for ‘liver indication’ from the CytoSorb International Registry. The finding of significant bilirubin removal observed in our study could have substantial impact in designing and executing further studies on the effects of hemoadsorption in liver dysfunction, which are certainly warranted.
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Steurer LM, Schlager G, Sadeghi K, Golej J, Wiedemann D, Hermon M. Hemadsorption as rescue therapy for patients with multisystem organ failure in pediatric intensive care-Two case reports and review of the literature. Artif Organs 2021; 45:1582-1593. [PMID: 34331775 PMCID: PMC9291205 DOI: 10.1111/aor.14047] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 07/04/2021] [Accepted: 07/14/2021] [Indexed: 12/13/2022]
Abstract
Hemadsorption via the cytokine‐adsorber CytoSorb (CytoSorbents Europe, Berlin, Germany) has successfully been used as an adjunctive method in adults, mainly for the purpose of immunomodulation under acute inflammatory conditions such as sepsis and cardiac surgery. In recent years, there has been growing interest in its use in pediatric intensive care to improve outcomes in patients with multiple organ failure following an inflammatory illness. Literature on the application of CytoSorb in neonatal and pediatric patients is scarce, though the implication is that it could be an effective last‐resort treatment option in critically ill pediatric patients. Herein we present the clinical cases of two pediatric patients successfully treated with a combination of the CytoSorb hemadsorber, continuous renal replacement therapy, and extracorporeal membrane oxygenation due to multiple organ failure following different underlying medical conditions. Patient 1 was a 7‐month‐old male child with Down's syndrome admitted to the Pediatric Intensive Care Unit (PICU) after congenital heart surgery, who developed antimicrobial‐resistant septic shock and severe acute respiratory distress syndrome. Patient 2 was a 2‐year‐old male child admitted to the PICU with influenza A‐associated acute liver failure resulting in hyperammonemia, lactate acidosis, hemodynamic instability, and acute kidney failure. In both patients, hemadsorption with CytoSorb was initiated as an adjunctive rescue therapy to treat refractory multisystem organ failure. Improvement of laboratory and clinical parameters was observed within hours of treatment initiation. The application of the hemadsorber—developed for use in adults—proved simple and safe for use in both of our low‐weight pediatric patients.
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Affiliation(s)
- Lisa-Maria Steurer
- Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Gerald Schlager
- Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Kambis Sadeghi
- Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Johann Golej
- Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
| | - Dominik Wiedemann
- Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
| | - Michael Hermon
- Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatric and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
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