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Wang L, Song L, Yang J. Effect of Plasma Exchange on Hepatitis B-Related Acute-On-Chronic Liver Failure: A Cross-Sectional Study. Health Sci Rep 2025; 8:e70729. [PMID: 40264640 PMCID: PMC12011990 DOI: 10.1002/hsr2.70729] [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: 03/19/2024] [Revised: 03/28/2025] [Accepted: 04/03/2025] [Indexed: 04/24/2025] Open
Abstract
Background To evaluate the effect of plasma exchange (PE) on the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods The basic information (gender, age, blood type), the frequency and dosage of PE, the changes of indicators before and after PE, the adverse reactions related to PE and the prognosis of patients with HBV-ACLF who received PE in our hospital from April 2018 to December 2021 were retrospectively analyzed. Results 197 patients with HBV-ACLF who underwent PE were included in the analysis. Multivariate analysis shows that blood ammonia, ALBI, bacterial infection rate, HBV-DNA load, MELD score, etc., are independent risk factors affecting the efficacy of PE treatment in HBV-ACLF patients before and after PE treatment. Conclusion There are many factors influencing the efficacy of plasma exchange in patients with HBV-ACLF. Compared to other factors, high blood ammonia levels and high ALBI are the independent risk factors for poor short-term efficacy of plasma exchange.
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Affiliation(s)
- Lu Wang
- Clinical Laboratory, The People's Hospital of DanyangDanyang Hospital Affiliated to Nantong UniversityDanyangJiangsuChina
| | - Lu Song
- Clinical Laboratory, The People's Hospital of DanyangDanyang Hospital Affiliated to Nantong UniversityDanyangJiangsuChina
| | - Jie Yang
- Clinical Laboratory, The People's Hospital of DanyangDanyang Hospital Affiliated to Nantong UniversityDanyangJiangsuChina
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2
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Ma Y, Xu Y, Du L, Bai L, Tang H. Association between volume of processed plasma and total bilirubin reduction during plasma adsorption for severe liver disease. Eur J Med Res 2025; 30:175. [PMID: 40089798 PMCID: PMC11909836 DOI: 10.1186/s40001-025-02419-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 02/27/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND The double plasma molecular adsorption system (DPMAS) is a crucial therapeutic modality for the management of severe liver disease. Current literature reports considerable variability in the volume of processed plasma (VPP) utilized during DPMAS treatment, and there is currently no consensus on the appropriate VPP. We aimed to investigate the relationship between VPP and changes in total bilirubin levels during DPMAS treatment. METHODS A prospective observational study with a repeated-measures design was conducted in patients with severe liver disease. The generalized estimation equations were used to evaluate the relationship between VPP and changes in total bilirubin levels during DPMAS treatment. The Bonferroni method was used for multiple comparisons. Tests for linear trends were performed by entering the median value of each category as a continuous variable. Total bilirubin level were detected repeatedly at four different times (four different VPP) (at 0.0 h (0 mL); at 2.0 h (3000 mL); at 2.5 h (3750 mL); at 3.0 h (4500 mL)). RESULTS Twenty-nine patients who underwent 75 sessions of DPMAS treatment were enrolled. The baseline total bilirubin levels and model for end-stage liver disease score were 426.1 (356.6-487.3) μmol/L and 21.9 (18.7-24.9). The total bilirubin levels and their reduction ratios in all patients (75 sessions) or patients with total bilirubin <425 μmol/L (39 sessions) or ≥425 μmol/L (36 sessions) decreased gradually and significantly at four different times (four different VPP) (all adjusted P for pairwise comparisons <0.001; adjusted P for trend <0.001). The reduction ratios of total bilirubin in patients with total bilirubin ≥425 μmol/L were similar to those with total bilirubin <425 μmol/L (adjusted OR (95% CI), 1.001 (0.966-1.036)). The positive relationship between the reduction ratios of total bilirubin and VPP was less remarkable in patients with higher height (adjusted P for interaction = 0.027) or lower albumin levels (adjusted P for interaction = 0.017). CONCLUSION The VPP of DPMAS treatment could be more than 4500 mL. Patients with higher height or lower albumin levels might require a higher VPP to achieve sufficient therapeutic efficacy.
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Affiliation(s)
- Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China
| | - Yan Xu
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China.
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China.
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, 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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Ma Y, Du L, Bai L, Tang H. Association between lactate-to-albumin ratio and short-term prognosis of acute-on-chronic liver failure treated with artificial liver support system. Eur J Gastroenterol Hepatol 2025; 37:327-336. [PMID: 39589807 PMCID: PMC11781548 DOI: 10.1097/meg.0000000000002885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024]
Abstract
BACKGROUND The impact of lactate-to-albumin ratio (LAR) on the outcome of acute-on-chronic liver failure (ACLF) is scant. AIMS To investigate the relationship between LAR and short-term prognosis in patients with COSSH (Chinese Group on the Study of Severe Hepatitis B) ACLF. METHODS A retrospective cohort study was conducted in patients with COSSH ACLF treated with an artificial liver support system. Restricted cubic splines, linear regression models, and Cox regression models were used to investigate the relationships of LAR with disease severity and 28-day prognosis. RESULTS The 28-day transplant-free and overall survival rates in the 258 eligible patients were 76.4% and 82.2%, respectively. The LAR in 28-day transplant-free survivors was lower than that in transplant or death patients [0.74 (0.58-0.98) vs. 1.03 (0.79-1.35), P < 0.001]. The LAR was positively associated with disease severity, 28-day transplant-free survival [adjusted hazard ratio (HR) (95% confidence interval (CI)) for transplant or death: 2.18 (1.37-3.46), P = 0.001], and overall survival [adjusted HR (95% CI) for death: 2.14 (1.21-3.80), P = 0.009]. Compared with patients with LAR < 1.01, patients with LAR ≥ 1.01 had poor 28-day prognosis [all adjusted HR (95% CI) > 1, P < 0.05]. Lactate was not a potential modifier of the relationship between LAR and short-term prognosis. CONCLUSION LAR was positively associated with disease severity and poor short-term prognosis in patients with COSSH ACLF.
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Affiliation(s)
- Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
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Ma Y, Du L, Bai L, Tang H. Association between lactate-to-albumin ratio and all-cause mortality in critically ill cirrhotic patients with sepsis: a retrospective analysis of the MIMIC-IV database. BMC Gastroenterol 2025; 25:112. [PMID: 39994557 PMCID: PMC11853895 DOI: 10.1186/s12876-025-03686-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/12/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND The impact of lactate-to-albumin ratio (LAR) on mortality of critically ill cirrhotic patients with sepsis is scant. METHODS Critically ill cirrhotic patients with sepsis were obtained from the MIMIC-IV database (v3.0). Cox regression models alone and in combination with restricted cubic splines, generalized additive models and smoothed curve fitting were used to investigate the relationship between LAR and all-cause mortality. RESULTS A total of 1864 patients were included. The 30-day, 90-day, and 180-day all-cause mortality rates were 38.0%, 46.3%, and 49.5%, respectively. Higher LAR were significantly and nonlinearly associated with higher risks of 30-day, 90-day, and 180-day all-cause mortality (all adjusted HR = 1.17, P < 0.001). L-shaped associations between LAR and 30-day, 90-day, and 180-day all-cause mortality were observed, with an inflection point of 1.05 (P for log-likelihood ratio < 0.01). Compared with patients with LAR < 1.05, patients with LAR ≥ 1.05 had higher risks of 30-day, 90-day, and 180-day all-cause mortality (adjusted HR (95% CI): 1.48 (1.27-1.72), 1.44 (1.25-1.66), and 1.38 (1.21-1.57), respectively). No potential modifiers were found in the relationship between LAR and mortality. CONCLUSIONS LAR was positively and nonlinearly associated with all-cause mortality in critically ill cirrhotic patients with sepsis. Thus, it could be used as a prognostic biomarker.
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Affiliation(s)
- Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Wuhou District, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Wuhou District, Chengdu, 610041, China.
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Wuhou District, Chengdu, 610041, China.
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Wuhou District, Chengdu, 610041, China
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Ma Y, Du L, Bai L, Tang H. Association between neutrophil percentage to albumin ratio and short term prognosis of acute on chronic liver failure treated with artificial liver support system. Sci Rep 2025; 15:5042. [PMID: 39934390 PMCID: PMC11814120 DOI: 10.1038/s41598-025-89832-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 02/07/2025] [Indexed: 02/13/2025] Open
Abstract
The impact of neutrophil percentage-to-albumin ratio (NPAR) on the outcome of acute-on-chronic liver failure (ACLF) is scant. A retrospective cohort study was conducted in patients with ACLF treated with artificial liver support system (ALSS). The ACLF was diagnosed according to the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF) criteria. Disease severity was rated according to the COSSH ACLF score. Restricted cubic splines, linear or Cox regression models were used to investigate the relationships of baseline NPAR with disease severity and 90-day prognosis. The 90-day transplant-free and overall survival rates of 258 eligible patients were 58.5% and 66.3%, respectively. The NPAR in transplant-free survivors was lower than that in transplant or death patients (22.8 ± 4.4 vs. 25.3 ± 3.7, P < 0.001). NPAR was positively associated with COSSH ACLF score (adjusted β (95% CI) > 0, P < 0.001), transplant-free survival (adjusted HR (95% CI) for transplant or death: 1.07 (1.02-1.13), P = 0.007), and overall survival (adjusted HR (95% CI) for death: 1.09 (1.03-1.15), P = 0.003). Patients with NPAR ≥ 22.4 had poor 90-day prognosis compared to the rest (all adjusted HR (95% CI) > 1, P < 0.05). NPAR was positively associated with disease severity and poor short-term prognosis in patients with COSSH ACLF who underwent ALSS treatment. Thus, it could be used as a prognostic biomarker for COSSH ACLF.
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Affiliation(s)
- Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China.
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China.
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, No.37 GuoXue Xiang, Wuhou District, Chengdu, 610041, China
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Song YQ, Fu XY, Yan SY, Qi RB, Zhou YJ, Liang JW, Zhang JQ, Ye LP, Mao XL, Li SW. Clinical Utility of the Trajectory of Serum Bilirubin and International Normalized Ratio Values in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. Int J Gen Med 2025; 18:643-658. [PMID: 39935709 PMCID: PMC11812449 DOI: 10.2147/ijgm.s490328] [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: 08/07/2024] [Accepted: 01/30/2025] [Indexed: 02/13/2025] Open
Abstract
Background and Aim Acute-on-chronic liver failure (ACLF) is a rapidly progressive and highly fatal condition. Early identification of critically ill patients is crucial. Hepatitis B virus-related ACLF (HBV-ACLF), the main cause of ACLF in China, is characterized by liver failure and coagulation dysfunction. Dynamic changes in total bilirubin (TB) and international normalized ratio (INR) can reflect disease progression. This study aims to investigate the clinical application of dynamic trajectories of TB and INR in HBV-ACLF patients. Methods Retrospective data from 194 patients at Taizhou Hospital, China (Jan 2012 - June 2023), meeting COSSH-ACLF criteria, were analyzed. A latent class mixed model (LCMM) identified three trajectory groups (declining, stable, fluctuating) based on bilirubin and INR changes. Clinical applicability of these groups was investigated. Results The 194 patients were divided into the trajectory groups mentioned above. The declining group had lower predicted scores and a better prognosis. The stable and fluctuating groups had worse prognosis compared to the declining group (P<0.001). Artificial liver support did not improve short-term prognosis for the stable group; instead, it was a risk factor (OR 2.16, 95% CI [0.23-3.79], P=0.007). Subgroup analysis showed no interaction between predictive models and trajectory groups. Additionally, trajectory grouping improved the predictive effectiveness of existing models. Conclusion Based on our trajectory analysis, patients with a continuous declining in bilirubin and INR values showed the best prognosis, highlighting the clinical significance of trajectory grouping in treatment decisions. Trajectory grouping can complement existing scoring models, improving predictive effectiveness.
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Affiliation(s)
- Ya-Qi Song
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang, People's Republic of China
| | - Xin-Yu Fu
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
- Dalian Medical University, Dalian, People's Republic of China
| | - Si-Yan Yan
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Zhejiang University, Linhai, Zhejiang, People's Republic of China
| | - Rong-Bin Qi
- Department of Respiratory Medicine, TaiZhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
| | - Yi-Jing Zhou
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
| | - Jia-Wei Liang
- Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People's Republic of China
| | - Jin-Qiu Zhang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
| | - Li-Ping Ye
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
| | - Xin-Li Mao
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
| | - Shao-Wei Li
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People's Republic of China
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Gan C, Yuan Y, Shen H, Gao J, Kong X, Che Z, Guo Y, Wang H, Dong E, Xiao J. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Ther 2025; 10:33. [PMID: 39904973 PMCID: PMC11794951 DOI: 10.1038/s41392-024-02072-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 10/06/2024] [Accepted: 11/12/2024] [Indexed: 02/06/2025] Open
Abstract
As a highly complex organ with digestive, endocrine, and immune-regulatory functions, the liver is pivotal in maintaining physiological homeostasis through its roles in metabolism, detoxification, and immune response. Various factors including viruses, alcohol, metabolites, toxins, and other pathogenic agents can compromise liver function, leading to acute or chronic injury that may progress to end-stage liver diseases. While sharing common features, liver diseases exhibit distinct pathophysiological, clinical, and therapeutic profiles. Currently, liver diseases contribute to approximately 2 million deaths globally each year, imposing significant economic and social burdens worldwide. However, there is no cure for many kinds of liver diseases, partly due to a lack of thorough understanding of the development of these liver diseases. Therefore, this review provides a comprehensive examination of the epidemiology and characteristics of liver diseases, covering a spectrum from acute and chronic conditions to end-stage manifestations. We also highlight the multifaceted mechanisms underlying the initiation and progression of liver diseases, spanning molecular and cellular levels to organ networks. Additionally, this review offers updates on innovative diagnostic techniques, current treatments, and potential therapeutic targets presently under clinical evaluation. Recent advances in understanding the pathogenesis of liver diseases hold critical implications and translational value for the development of novel therapeutic strategies.
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Affiliation(s)
- Can Gan
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yuan Yuan
- Aier Institute of Ophthalmology, Central South University, Changsha, China
| | - Haiyuan Shen
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China
| | - Jinhang Gao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiangxin Kong
- Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China
| | - Zhaodi Che
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yangkun Guo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Hua Wang
- Department of Oncology, the First Affiliated Hospital; The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
| | - Erdan Dong
- Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital, School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.
| | - Jia Xiao
- Clinical Medicine Research Institute and Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
- Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
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Swanson LA, Tapper EB, Mazumder NR. CON: Is the management of ACLF better in a liver-dedicated ICU? Liver Transpl 2025; 31:247-249. [PMID: 39292726 DOI: 10.1097/lvt.0000000000000491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 09/07/2024] [Indexed: 09/20/2024]
Affiliation(s)
- Linnea A Swanson
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Elliot B Tapper
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
| | - Nikhilesh R Mazumder
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Department of Internal Medicine, Gastroenterology Section, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
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Saliba F. Acute liver failure: Beyond the guidelines, the challenge of liver support therapies. Clin Res Hepatol Gastroenterol 2025; 49:102528. [PMID: 39788200 DOI: 10.1016/j.clinre.2025.102528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025]
Affiliation(s)
- Faouzi Saliba
- Hôpital Paul Brousse, Centre hépato-Biliaire, 12 avenue paul Vaillant Couturier, 94800 Villejuif, France..
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Shi R, Hui X, Tong T, Li J, Zhang L, Yang K. Non-bioartificial artificial liver support system in acute liver failure: A comprehensive systematic review and meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol 2025; 49:102527. [PMID: 39800222 DOI: 10.1016/j.clinre.2025.102527] [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] [Received: 08/20/2024] [Revised: 12/14/2024] [Accepted: 01/06/2025] [Indexed: 01/15/2025]
Abstract
BACKGROUND Acute liver failure (ALF) poses a significant threat to patient health with high mortality rates. While Non-Bioartificial Artificial Liver Support system (NBALSS) has been utilized as a transitional intervention to liver transplant, its efficacy remains uncertain, It is also used as a last-line treatment for patients who are not candidates for liver transplantation. OBJECTIVE The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of NBALSS in treating acute liver failure (ALF). The primary outcome was overall survival (OS), while the secondary outcome focused on inflammatory factor levels. METHODS We conducted a comprehensive search across various databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, Wanfang Database, VIP database, and CNKI database. The search spanned from the inception of the databases to July 2023. Two independent reviewers screened literature, extracted data, assessed bias risk in the selected studies and used GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) to rate the certainty of evidence. Random and fixed effects meta-analyses were used to determine the average effect of the interventions on ALF. The sensitivity analysis was conducted using the leave-one-out test. Additionally, subgroup analyses were carried out based on a singular NBALSS treatment or combined treatment of two NBALSS and follow-up duration. RESULTS Twelve RCTs involving 824 patients were identified. The use of NBALSS was associated with a significantly improved overall survival (OS) [RR = 1.42, 95 %CI (1.26, 1.61), low certainty] and notable reductions in total bilirubin (TBIL) [MD = -57.60, 95 %CI (-79.60, -35.59), moderate certainty], alanine aminotransferase (ALT) [MD = -48.28, 95 %CI (-76.57, -19.98), low certainty], tumor necrosis factor (TNF-α) [MD = -1.49, 95 %CI (-2.24, -0.73), very low certainty], and interleukin 6 (IL-6) [MD = -178.72, 95 %CI (-277.37, -80.06), very low certainty]. However, the effects of NBALSS on interleukin-2 (IL-2) [MD = 1.33, 95 %CI (-0.33, 3.00), very low certainty], interleukin-8 (IL-8) [MD = -44.75, 95 %CI (-163.04, 73.55), very low certainty], and Sequential Organ Failure Score (SOFA) [MD = -4.06, 95 %CI (-8.92, 0.80), very low certainty] remained uncertain. CONCLUSIONS Moderate to very low certainty of evidence indicates that NBALSS may improve OS and biochemical indexes, cytokines in patients with ALF. However, the certainty of evidence is limited by risk of bias, incositency and imprecision. High-quality and larger trials are needed to better determine the effect of NBALSS on patient-important outcomes.
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Affiliation(s)
- Ruizhi Shi
- The First Clinical Medical College of Lanzhou University, 730000, Lanzhou, China; Evidence-Based Medicine Center, School of Basic Medical Science, Lanzhou University, 730000, Lanzhou, China
| | - Xu Hui
- Evidence-Based Medicine Center, School of Basic Medical Science, Lanzhou University, 730000, Lanzhou, China; Centre for Evidence-Based Social Science/Center for Health Technology Assessment, School of Public Health, Lanzhou University, 730000, Lanzhou, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou University, 730000, Lanzhou, China
| | - Ting Tong
- The First Clinical Medical College of Lanzhou University, 730000, Lanzhou, China
| | - Junfeng Li
- The First Clinical Medical College of Lanzhou University, 730000, Lanzhou, China; Department of Hepatology & Infectious Diseases, the First Hospital of Lanzhou University, 730000, Lanzhou, China
| | - Liting Zhang
- The First Clinical Medical College of Lanzhou University, 730000, Lanzhou, China; Department of Hepatology & Infectious Diseases, the First Hospital of Lanzhou University, 730000, Lanzhou, China; Institute of Portal Hypertension, the First Hospital of Lanzhou University, 730000, Lanzhou, China.
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Science, Lanzhou University, 730000, Lanzhou, China; Centre for Evidence-Based Social Science/Center for Health Technology Assessment, School of Public Health, Lanzhou University, 730000, Lanzhou, China; Gansu Key Laboratory of Evidence-Based Medicine, Lanzhou University, 730000, Lanzhou, 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: 0] [Impact Index Per Article: 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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13
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Saner FH, Scarlatescu E, Gold A, Abufarhaneh E, Alghamdi SA, Tolba Y, Aljudaibi B, Broering DC, Raptis DA, Bezinover D. Advanced strategies for intensive care management of acute liver failure. Best Pract Res Clin Gastroenterol 2024; 73:101962. [PMID: 39709216 DOI: 10.1016/j.bpg.2024.101962] [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] [Received: 06/26/2024] [Revised: 10/21/2024] [Accepted: 11/21/2024] [Indexed: 12/23/2024]
Abstract
Acute liver failure (ALF) is defined as the loss of hepatic function in conjunction with hepatic encephalopathy and coagulopathy. There is histological evidence of profound hepatocyte damage. If it is not aggressively managed, ALF can be fatal within a few days. It is a rare disease, often occurring in patients without prior liver disease. Despite numerous causes, ALF usually presents as acute liver necrosis with a clinical picture that includes cognitive dysfunction, increased aminotransferases, and severe coagulopathy. It is essential to distinguish between ALF and acute-on-chronic liver failure (ACLF). Causes for ALF include paracetamol Acute liver failure (ALF) is characterized by acute liver dysfunction associated with overdose, right heart failure (ischemic liver injury), viral hepatitis (A, B, D and E), autoimmune hepatitis and drug-induced liver injury (including some herbal and nutritional supplements). In developed countries, the prevalence of ALF is 1:1,000,000. Survival rates have increased due to improved ICU management.
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Affiliation(s)
- Fuat H Saner
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia.
| | - Ecaterina Scarlatescu
- Department of Anesthesia and Intensive Care Medicine III, Fundeni Clinical Institute, Bucharest, Romania; University of Medicine and Pharmacy "Carol Davila", Anesthesia and Intensive Care Department, Bucharest, Romania
| | - Andrew Gold
- Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA
| | - Ehab Abufarhaneh
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia
| | - Saad Ali Alghamdi
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia
| | - Yasser Tolba
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Bandar Aljudaibi
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia
| | - Dieter C Broering
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia
| | - Dimitri A Raptis
- Hospital & Research Center, Organ Transplant Center of Excellence, Riyadh, Saudi Arabia
| | - Dmitri Bezinover
- Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104, USA
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14
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Riva I, Marino A, Valetti TM, Marchesi G, Fabretti F. Extracorporeal liver support techniques: a comparison. J Artif Organs 2024; 27:261-268. [PMID: 37335451 PMCID: PMC11345327 DOI: 10.1007/s10047-023-01409-9] [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: 03/16/2023] [Accepted: 06/06/2023] [Indexed: 06/21/2023]
Abstract
ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.
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Affiliation(s)
- Ivano Riva
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
| | - Antonella Marino
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy.
| | - Tino Martino Valetti
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
| | - Gianmariano Marchesi
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
| | - Fabrizio Fabretti
- General Intensive Care Unit, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Piazza OMS, 1, 24127, Bergamo, Italy
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15
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Li W, Du L, Ma Y, Tang H. Successful recovery from acute-on-chronic liver failure due to acute hepatitis E virus superinfection in chronic hepatitis B: A case report. IDCases 2024; 37:e02069. [PMID: 39281308 PMCID: PMC11401153 DOI: 10.1016/j.idcr.2024.e02069] [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: 04/28/2024] [Revised: 08/16/2024] [Accepted: 08/24/2024] [Indexed: 09/18/2024] Open
Abstract
Introduction Acute hepatitis E virus (HEV) infection is a self-limiting disease, but HEV superinfection in patients with chronic hepatitis B virus (HBV) infection may lead to acute-on-chronic liver failure (ACLF) and significantly increase short-term mortality. Diagnosis and comprehensive management of these patients remain in a dilemma. Case presentation A 32-year-old man with chronic HBV infection for 8 years received entecavir due to abnormal liver function for 4 months. He was admitted for symptomatic hepatitis flare for nearly 2 weeks. Initial investigations did not reveal a cause other than HBV, but repeated tests showed a progressive increase in his anti-HEV IgM. His condition worsened rapidly. Mid-stage ACLF and spontaneous peritonitis were diagnosed. Entecavir and hepatoprotective drugs were continued. Ribavirin, ceftriaxone, and repeated artificial liver support system (ALSS) therapy were administered. His condition gradually improved and his liver function eventually returned to normal. Conclusions Repeated HEV screening is important for patients with chronic liver disease and symptomatic hepatitis flare. Negative anti-HEV IgM for the first time can easily lead clinicians to mistakenly rule out HEV infection. A progressive increase in anti-HEV IgM is one of the diagnostic criteria for HEV infection, which is not rare but deserves attention. Additionally, comprehensive management including ribavirin and ALSS would be effective therapies for patients who superinfect with HEV and develop ACLF.
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Affiliation(s)
- Weixiu Li
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province 610041, PR China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province 610041, PR China
| | - Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province 610041, PR China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan Province 610041, PR China
- Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, Sichuan Province 610041, PR China
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16
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Ahmad S, Novokhodko A, Liou IW, Smith NC, Carithers RL, Reyes J, Bakthavatsalam R, Martin C, Bhattacharya R, Du N, Hao S, Gao D. Development and First Clinical Use of an Extracorporeal Artificial Multiorgan System in Acute-on-Chronic Liver Failure Patients. ASAIO J 2024; 70:690-697. [PMID: 39079087 DOI: 10.1097/mat.0000000000002174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2024] Open
Abstract
Multiple organ failure (MOF) is a common and deadly condition. Patients with liver cirrhosis with acute-on-chronic liver failure (AOCLF) are particularly susceptible. Excess fluid accumulation in tissues makes routine hemodialysis generally ineffective because of cardiovascular instability. Patients with three or more organ failures face a mortality rate of more than 90%. Many cannot survive liver transplantation. Extracorporeal support systems like MARS (Baxter, Deerfield, IL) and Prometheus (Bad Homburg, Germany) have shown promise but fall short in bridging patients to transplantation. A novel Artificial Multi-organ Replacement System (AMOR) was developed at the University of Washington Medical Center. AMOR removes protein-bound toxins through a combination of albumin dialysis, a charcoal sorbent column, and a novel rinsing method to prevent sorbent column saturation. It removes excess fluid through hemodialysis. Ten AOCLF patients with over three organ failures were treated by the AMOR system. All patients showed significant clinical improvement. Fifty percent of the cohort received liver transplants or recovered liver function. AMOR was successful in removing large amounts of excess body fluid, which regular hemodialysis could not. AMOR is cost-effective and user-friendly. It removes excess fluid, supporting the other vital organs such as liver, kidneys, lungs, and heart. This pilot study's results encourage further exploration of AMOR for treating MOF patients.
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Affiliation(s)
- Suhail Ahmad
- From the Department of Medicine, University of Washington, Seattle, Washington
| | - Alexander Novokhodko
- Department of Mechanical Engineering, University of Washington, Seattle, Washington
| | - Iris W Liou
- From the Department of Medicine, University of Washington, Seattle, Washington
| | | | - Robert L Carithers
- From the Department of Medicine, University of Washington, Seattle, Washington
| | - Jorge Reyes
- Department of Surgery, University of Washington, Seattle, Washington
| | | | - Carl Martin
- Department of Clinical Engineering, University of Washington, Seattle, Washington
| | - Renuka Bhattacharya
- From the Department of Medicine, University of Washington, Seattle, Washington
| | - Nanye Du
- Department of Mechanical Engineering, University of Washington, Seattle, Washington
| | - Shaohang Hao
- Department of Mechanical Engineering, University of Washington, Seattle, Washington
| | - Dayong Gao
- Department of Mechanical Engineering, University of Washington, Seattle, Washington
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Orban C, Agapie M, Bratu A, Jafal M, Duțu M, Popescu M. No Significant Beneficial Effects of Intravenous N-Acetylcysteine on Patient Outcome in Non-Paracetamol Acute Liver Failure: A Meta-Analysis of Randomized Controlled Trials. Biomedicines 2024; 12:1462. [PMID: 39062036 PMCID: PMC11274394 DOI: 10.3390/biomedicines12071462] [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: 05/06/2024] [Revised: 06/22/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Acute liver failure is a life-threatening organ dysfunction with systemic organ involvement and is associated with significant mortality and morbidity unless specific management is undertaken. This meta-analysis aimed to assess the effects of intravenous N-acetylcysteine (NAC) on mortality and the length of hospital stay in patients with non-acetaminophen acute liver failure. Two hundred sixty-six studies from four databases were screened, and four randomized control trials were included in the final analysis. Our results could not demonstrate increased overall survival (OR 0.70, 95% CI [0.34, 1.44], p = 0.33) or transplant-free survival (OR 0.90, 95% CI [0.25, 3.28], p = 0.87) in patients treated with intravenous NAC. We observed an increased overall survival in adult patients treated with NAC (OR 0.59, 95% CI [0.35, 0.99], p = 0.05) compared to pediatric patients, but whether this is attributed to the age group or higher intravenous dose administered remains unclear. We did not observe a decreased length of stay in NAC-treated patients (OR -5.70, 95% CI [-12.44, 1.05], p = 0.10). In conclusion, our meta-analysis could not demonstrate any significant benefits on overall and transplant-free patient survival in non-acetaminophen ALF. Future research should also focus on specific etiologies of ALF that may benefit most from the use of NAC.
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Affiliation(s)
- Carmen Orban
- Department of Anesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (C.O.); (M.J.); (M.D.); (M.P.)
- Department of Anesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Mihaela Agapie
- Department of Anesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (C.O.); (M.J.); (M.D.); (M.P.)
- Department of Anesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Angelica Bratu
- Department of Anesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Mugurel Jafal
- Department of Anesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (C.O.); (M.J.); (M.D.); (M.P.)
- Department of Anesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Mădălina Duțu
- Department of Anesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (C.O.); (M.J.); (M.D.); (M.P.)
- Department of Anesthesiology and Intensive Care, “Dr. Carol Davila” University Emergency Central Military Hospital, 134 Calea Plevnei, 010242 Bucharest, Romania
| | - Mihai Popescu
- Department of Anesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (C.O.); (M.J.); (M.D.); (M.P.)
- Department of Anesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
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18
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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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Ma Y, Xu Y, Du L, Bai L, Tang H. Outcome of patients with different stages of acute-on-chronic liver failure treated with artificial liver support system. Front Med (Lausanne) 2024; 11:1381386. [PMID: 38835796 PMCID: PMC11149554 DOI: 10.3389/fmed.2024.1381386] [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: 02/03/2024] [Accepted: 04/26/2024] [Indexed: 06/06/2024] Open
Abstract
Background Elevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail. Methods A previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR < 1.5 (Pre-stage), 1.5 ≤ PT-INR < 2.0 (Early-stage), 2.0 ≤ PT-INR < 2.5 (Mid-stage), and PT-INR ≥ 2.5 (End-stage). The Cox proportional hazards models were used to estimate the association between stages of ACLF or sessions of ALSS treatment and 90 day mortality. Results A total of 301 ACLF patients were enrolled. The 90 day mortality risk of Early-stage ACLF patients (adjusted hazard ratio (aHR) (95% confidence interval (CI)), 3.20 (1.15-8.89), p = 0.026), Mid-stage ACLF patients (3.68 (1.34-10.12), p = 0.011), and End-stage ACLF patients (12.74 (4.52-35.91), p < 0.001) were higher than that of Pre-stage ACLF patients, respectively. The 90 day mortality risk of Mid-stage ACLF patients was similar to that of Early-stage ACLF patients (1.15 (0.69-1.94), p = 0.591). The sessions of ALSS treatment was an independent protective factor (aHR (95% CI), 0.81 (0.73-0.90), p < 0.001). The 90 day mortality risk in ACLF patients received 3-5 sessions of ALSS treatment was lower than that of patients received 1-2 sessions (aHR (95% CI), 0.34 (0.20-0.60), p < 0.001), whereas the risk in patients received ≥6 sessions of ALSS treatment was similar to that of patients received 3-5 sessions (0.69 (0.43-1.11), p = 0.128). Conclusion ACLF patients in Pre-, Early-, and Mid-stages might be more eligible for ALSS treatment. Application of 3-5 sessions of ALSS treatment might be reasonable.
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Affiliation(s)
- Yuanji Ma
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Yan Xu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Lingyao Du
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Lang Bai
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, China
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Xie K, Jing H, Guan S, Kong X, Ji W, Du C, Jia M, Wang H. Extracorporeal membrane oxygenation technology for adults: an evidence mapping based on systematic reviews. Eur J Med Res 2024; 29:247. [PMID: 38650017 PMCID: PMC11036703 DOI: 10.1186/s40001-024-01837-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 04/10/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Extracorporeal membrane oxygenation (ECMO) is a cutting-edge life-support measure for patients with severe cardiac and pulmonary illnesses. Although there are several systematic reviews (SRs) about ECMO, it remains to be seen how quality they are and how efficacy and safe the information about ECMO they describe is in these SRs. Therefore, performing an overview of available SRs concerning ECMO is crucial. METHODS We searched four electronic databases from inception to January 2023 to identify SRs with or without meta-analyses. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were used to assess the methodological quality, and evidence quality for SRs, respectively. A bubble plot was used to visually display clinical topics, literature size, number of SRs, evidence quality, and an overall estimate of efficacy. RESULTS A total of 17 SRs met eligibility criteria, which were combined into 9 different clinical topics. The methodological quality of the included SRs in this mapping was "Critically low" to "Moderate". One of the SRs was high-quality evidence, three on moderate, three on low, and two on very low-quality evidence. The most prevalent study used to evaluate ECMO technology was observational or cohort study with frequently small sample sizes. ECMO has been proven beneficial for severe ARDS and ALI due to the H1N1 influenza infection. For ARDS, ALF or ACLF, and cardiac arrest were concluded to be probably beneficial. For dependent ARDS, ARF, ARF due to the H1N1 influenza pandemic, and cardiac arrest of cardiac origin came to an inconclusive conclusion. There was no evidence for a harmful association between ECMO and the range of clinical topics. CONCLUSIONS There is limited available evidence for ECMO that large sample, multi-center, and multinational RCTs are needed. Most clinical topics are reported as beneficial or probably beneficial of SRs for ECMO. Evidence mapping is a valuable and reliable methodology to identify and present the existing evidence about therapeutic interventions.
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Affiliation(s)
- Kai Xie
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Hui Jing
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Shengnan Guan
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Xinxin Kong
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Wenshuai Ji
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Chen Du
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Mingyan Jia
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China
| | - Haifeng Wang
- Department of Respiratory Medicine, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China.
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, China.
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Deep A, Tissieres P. Editorial: Acute liver failure in children. Front Pediatr 2024; 12:1402119. [PMID: 38633329 PMCID: PMC11021655 DOI: 10.3389/fped.2024.1402119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 03/19/2024] [Indexed: 04/19/2024] Open
Affiliation(s)
- Akash Deep
- Paediatric Intensive Care Unit, King’s College Hospital NHS Foundation Trust, London, United Kingdom
- Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Pierre Tissieres
- Pediatric Intensive Care and Neonatal Medicine, Bicêtre Hospital, AP-HP Paris Saclay University, Le Kremlin-Bicêtre, Paris, France
- Institute of Integrative Biology of the Cell, CNRS, CEA, Paris Saclay University, Gif-sur-Yvette, France
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Popescu M, Bratu A, Agapie M, Borjog T, Jafal M, Sima RM, Orban C. The Use and Potential Benefits of N-Acetylcysteine in Non-Acetaminophen Acute Liver Failure: An Etiology-Based Review. Biomedicines 2024; 12:676. [PMID: 38540289 PMCID: PMC10967777 DOI: 10.3390/biomedicines12030676] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2024] [Revised: 03/04/2024] [Accepted: 03/15/2024] [Indexed: 08/13/2024] Open
Abstract
Acute liver failure represents a life-threatening organ dysfunction with high mortality rates and an urgent need for liver transplantation. The etiology of the disease varies widely depending on various socio-economic factors and is represented mainly by paracetamol overdose and other drug-induced forms of liver dysfunction in the developed world and by viral hepatitis and mushroom poisoning in less developed countries. Current medical care constitutes either specific antidotes or supportive measures to ensure spontaneous recovery. Although it has been proven to have beneficial effects in paracetamol-induced liver failure, N-acetylcysteine is widely used for all forms of acute liver failure. Despite this, few well-designed studies have been conducted on the assessment of the potential benefits, dose regimens, or route of administration of N-acetylcysteine in non-acetaminophen liver failure. This review aims to summarize the current evidence behind the use of this drug in different forms of liver failure.
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Affiliation(s)
- Mihai Popescu
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (M.A.); (T.B.); (M.J.); (C.O.)
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Angelica Bratu
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Mihaela Agapie
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (M.A.); (T.B.); (M.J.); (C.O.)
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Tudor Borjog
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (M.A.); (T.B.); (M.J.); (C.O.)
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Mugurel Jafal
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (M.A.); (T.B.); (M.J.); (C.O.)
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
| | - Romina-Marina Sima
- Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania;
| | - Carmen Orban
- Department of Anaesthesia and Intensive Care, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021 Bucharest, Romania; (M.A.); (T.B.); (M.J.); (C.O.)
- Department of Anaesthesia and Intensive Care, Bucharest University Emergency Hospital, 169 Independentei Street, 050098 Bucharest, Romania;
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Li WY, Wang LW, Dong J, Wang Y. Evaluation of G3BP1 in the prognosis of acute and acute-on-chronic liver failure after the treatment of artificial liver support system. World J Hepatol 2024; 16:251-263. [PMID: 38495274 PMCID: PMC10941744 DOI: 10.4254/wjh.v16.i2.251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/24/2023] [Accepted: 01/15/2024] [Indexed: 02/27/2024] Open
Abstract
BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure. AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) after the treatment of artificial liver support system (ALSS). METHODS A total of 244 patients with ALF and ACLF were enrolled in this study. The levels of G3BP1 on admission and at discharge were detected. The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis. RESULTS This study was shown that lactate dehydrogenase (LDH), alpha-fetoprotein (AFP) and prothrombin time were closely related to the prognosis of patients. After the ALSS treatment, the patient' amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission (difG3BP1) < 0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index. The subgroup analysis showed that the difG3BP1 < 0 group had a higher risk of progression, regardless of model for end-stage liver disease high-risk or low-risk group. At the same time, compared with the inflammatory marks [tumor necrosis factor-α, interleukin (IL)-1β and IL-18], G3BP1 had higher discrimination and was more stable in the model analysis and validation set. When combined with AFP and LDH, concordance index was respectively 0.84 and 0.8 in training and validation cohorts. CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS. The combination of G3BP1, AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
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Affiliation(s)
- Wen-Yuan Li
- Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Lu-Wen Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jin Dong
- Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Yao Wang
- Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China.
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Beran A, Mohamed MFH, Shaear M, Nayfeh T, Mhanna M, Srour O, Nawras M, Mentrose JA, Assaly R, Kubal CA, Ghabril MS, Hernaez R, Patidar KR. Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis. Liver Transpl 2024; 30:127-141. [PMID: 37530812 DOI: 10.1097/lvt.0000000000000231] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 07/20/2023] [Indexed: 08/03/2023]
Abstract
Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared with standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients ≥ 18 years of age with ALF and ACLF. Pooled risk ratios (RR) with corresponding 95% CIs were calculated by the Mantel-Haenszel method within a random-effect model. The primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared with SMT, PE was significantly associated with higher 30-day (RR 1.41, 95% CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95% CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95% CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95% CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials, results remained unchanged in ALF, but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates or as a bridge to LT in otherwise eligible patients. Further randomized controlled trials are needed to confirm the survival benefit of PE in ACLF.
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Affiliation(s)
- Azizullah Beran
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
| | - Mouhand F H Mohamed
- Department of Internal Medicine, Warren Alpert Medical School Brown University, Providence, Rhode Island, USA
| | - Mohammad Shaear
- Department of General Surgery, College of Medicine, Central Michigan University, Saginaw, Michigan, USA
| | - Tarek Nayfeh
- Evidence-based practice research program, Mayo Clinic, Rochester, USA
| | - Mohammed Mhanna
- Department of Cardiology, University of Iowa, Iowa City, Iowa, USA
| | - Omar Srour
- Department of Critical Care and Pulmonary Medicine, Henry Ford Health System, Detroit, Michigan, USA
| | - Mohamad Nawras
- College of Medicine and Life Sciences, University of Toledo, Toledo, Ohio, USA
| | - Jonathan A Mentrose
- Department of Internal Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Ragheb Assaly
- Divison of Critical Care and Pulmonary Medicine, University of Toledo, Toledo, Ohio, USA
| | - Chandrashekhar A Kubal
- Division of Transplantation, Department of Surgery, Indiana University, Indianapolis, Indiana, USA
| | - Marwan S Ghabril
- Division of Gastroenterology and Hepatology, Indiana University, Indianapolis, Indiana, USA
| | - Ruben Hernaez
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Kavish R Patidar
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
- Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
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Jin D, Kang K, Yan BZ, Zhang JN, Zheng JB, Wang ZH, Wu D, Tang YJ, Wang XT, Lai QQ, Cao Y, Wang HL, Gao Y. Combined Age with Mean Decrease Rates of Total Bilirubin and MELD Score as a Novel and Simple Clinical Predictor on 90-Day Transplant-Free Mortality in Adult Patients with Acute Liver Failure Undergoing Plasma Exchange: A Single-Center Retrospective Study. Can J Gastroenterol Hepatol 2023; 2023:6115499. [PMID: 38021269 PMCID: PMC10645502 DOI: 10.1155/2023/6115499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/13/2023] [Accepted: 10/27/2023] [Indexed: 12/01/2023] Open
Abstract
Background Acute liver failure (ALF), previously known as fulminant hepatic failure, has become a common, rapidly progressive, and life-threatening catastrophic hepatic disease in intensive care unit (ICU) due to the continuous increase in drug abuse, viral infection, metabolic insult, and auto-immune cause. At present, plasma exchange (PE) is the main effective alternative treatment for ALF in ICU clinical practice, and high-volume plasma exchange (HVP) has been listed as a grade I recommendation for ALF management in the American Society for Apheresis (ASFA) guidelines. However, no existing models can provide a satisfactory performance for clinical prediction on 90-day transplant-free mortality in adult patients with ALF undergoing PE. Our study aims to identify a novel and simple clinical predictor of 90-day transplant-free mortality in adult patients with ALF undergoing PE. Methods This retrospective study contained adult patients with ALF undergoing PE from the Medical ICU (MICU) in the Second Affiliated Hospital of Harbin Medical University between January 2017 and December 2020. Baseline and clinical data were collected and calculated on admission to ICU before PE, including gender, age, height, weight, body mass index (BMI), etiology, total bilirubin, direct bilirubin, indirect bilirubin, prothrombin activity, model for end-stage liver disease (MELD) score, and sequential organ failure assessment (SOFA) score. Enrolled adult patients with ALF undergoing PE were divided into a survival group and a death group at discharge and 90 days on account of medical records and telephone follow-up. After each PE, decreased rates of total bilirubin and MELD score and increased rates of prothrombin activity were calculated according to the clinical parameters. In clinical practice, different patients underwent different times of PE, and thus, mean decrease rates of total bilirubin and MELD score and mean increase rate of prothrombin activity were obtained for further statistical analysis. Results A total of 73 adult patients with ALF undergoing 204 PE were included in our retrospective study, and their transplant-free mortality at discharge and 90 days was 6.85% (5/73) and 31.51% (23/73), respectively. All deaths could be attributed to ALF-induced severe and life-threatening complications or even multiple organ dysfunction syndrome (MODS). Most of the enrolled adult patients with ALF were men (76.71%, 56/73), with a median age of 48.77 years. Various hepatitis virus infections, unknown etiology, auto-immune liver disease, drug-induced liver injury, and acute pancreatitis (AP) accounted for 75.34%, 12.33%, 6.85%, 4.11%, and 1.37% of the etiologies in adult patients with ALF, respectively. Univariate analysis showed a significant difference in age, mean decrease rates of total bilirubin and MELD score mean increase rate of prothrombin activity, decrease rates of total bilirubin and MELD score, and increase rate of prothrombin activity after the first PE between the death group and survival group. Multivariate analysis showed that age and mean decrease rates of total bilirubin and MELD score were closely associated with 90-day transplant-free mortality in adult patients with ALF undergoing PE. The 90-day transplant-free mortality was 1.081, 0.908, and 0.893 times of the original value with each one-unit increase in age and mean decrease rates of total bilirubin and MELD score, respectively. The areas under the receiver operatingcharacteristic (ROC) curve of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 0.689, 0.225, 0.123, and 0.912, respectively. The cut-off values of age, mean decrease rates of total bilirubin and MELD score, and the three combined were 61.50, 3.12, 1.21, and 0.33, respectively. The specificity and sensitivity of combined age with mean decrease rates of total bilirubin and MELD score for predicting 90-day transplant-free mortality in adult patients with ALF undergoing PE were 87% and 14%. Conclusion Combined age with mean decrease rates of total bilirubin and MELD score as a novel and simple clinical predictor can accurately predict 90-day transplant-free mortality in adult patients with ALF undergoing PE, which is worthy of application and promotion in clinical practice, especially in the identification of potential transplant candidates.
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Affiliation(s)
- Di Jin
- Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Kai Kang
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Bing-zhu Yan
- Department of Infectious Diseases, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Jian-nan Zhang
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Jun-bo Zheng
- Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Zhi-hui Wang
- Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin 150027, Heilongjiang Province, China
| | - Di Wu
- Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin 150027, Heilongjiang Province, China
| | - Yu-jia Tang
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Xin-tong Wang
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Qi-qi Lai
- Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China
| | - Yang Cao
- Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Hong-liang Wang
- Department of Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang Province, China
| | - Yang Gao
- Department of Critical Care Medicine, The Sixth Affiliated Hospital of Harbin Medical University, Harbin 150027, Heilongjiang Province, China
- Institute of Critical Care Medicine, The Sino Russian Medical Research Center of Harbin Medical University, Harbin 150081, Heilongjiang Province, China
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Baker DR, Mac H, Steinman B, Soshnick SH, Frager SZ, Goilav B, Kogan-Liberman D, Ovchinsky N, Shlomovich M. Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program. Crit Care Explor 2023; 5:e1002. [PMID: 37954902 PMCID: PMC10635609 DOI: 10.1097/cce.0000000000001002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023] Open
Abstract
IMPORTANCE Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent. OBJECTIVES We sought to report our experiences and patient outcomes from the first 2 years of operation of a new ELS program, within an established pediatric liver transplantation center. DESIGN SETTING AND PARTICIPANTS Retrospective review of outcomes in pediatric and adult patients treated with MARS therapy for ALF, from 2021 to 2022. MAIN OUTCOMES AND MEASURES Outcomes included reduction in HE and biochemical markers of ALF after MARS therapy, survival, and transplant-free survival. Comparisons were made via Wilcoxon signed-rank test. RESULTS Five pediatric and two adult patients underwent MARS for ALF. Ages ranged from 2 to 29 years. Overall, 21 MARS runs were performed (median 3 runs per patient, 12.4 hr per run [interquartile range, IQR 10.1-17]). Overall survival was 85.7%, and transplant-free survival was 71.4%. There was a statistically significant reduction in HE score with MARS therapy (median 3 [IQR 3-4] to 1 [IQR 0-1], p = 0.03), and in ALF biomarkers including ammonia (256 µL/dL [195-265] to 75 µL/dL [58-101], p = 0.02), aspartate aminotransferase (6,362 U/L [920-8,305] to 212 U/L [72-431], p = 0.02), alanine aminotransferase (8,362 U/L [3,866-9,189] to 953 U/L [437-1,351], p = 0.02), and international normalized ratio (4.5 [3.3-6.7] to 1.3 [1.2-1.4], p = 0.02). CONCLUSIONS AND RELEVANCE MARS therapy for ALF was well tolerated by both pediatric and adult patients, and resulted in significant improvement in clinical and biochemical parameters. We demonstrated encouraging overall and transplant-free survival, suggesting that early initiation of MARS with relatively long and frequent cycle times may be of significant benefit to ALF patients, and is worthy of additional study in larger cohorts.
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Affiliation(s)
- David R Baker
- Division of Pediatric Critical Care, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Helen Mac
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Benjamin Steinman
- Division of Pediatric Nephrology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Sara H Soshnick
- Division of Pediatric Critical Care, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Shalom Z Frager
- Division of Hepatology, Department of Medicine, Montefiore Medical Center, Bronx, NY
| | - Beatrice Goilav
- Division of Pediatric Nephrology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
| | - Debora Kogan-Liberman
- Division of Pediatric Gastroenterology and Hepatology, Hassenfeld Children's Hospital, NYU Grossman School of Medicine, New York, NY
| | - Nadia Ovchinsky
- Division of Pediatric Gastroenterology and Hepatology, Hassenfeld Children's Hospital, NYU Grossman School of Medicine, New York, NY
| | - Mark Shlomovich
- Division of Pediatric Critical Care, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY
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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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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: 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: 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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Nanchal R, Subramanian R, Alhazzani W, Dionne JC, Peppard WJ, Singbartl K, Truwit J, Al-Khafaji AH, Killian AJ, Alquraini M, Alshammari K, Alshamsi F, Belley-Cote E, Cartin-Ceba R, Hollenberg SM, Galusca DM, Huang DT, Hyzy RC, Junek M, Kandiah P, Kumar G, Morgan RL, Morris PE, Olson JC, Sieracki R, Steadman R, Taylor B, Karvellas CJ. Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations. Crit Care Med 2023; 51:657-676. [PMID: 37052436 DOI: 10.1097/ccm.0000000000005824] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2023]
Abstract
OBJECTIVES To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.
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Affiliation(s)
- Rahul Nanchal
- Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI
| | | | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Joanna C Dionne
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | | | | | | | | | | | | | | | | | | | | | | | | | - David T Huang
- University of Pittsburgh Medical Center, Pittsburgh, PA
| | | | - Mats Junek
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | | | - Gagan Kumar
- Northeast Georgia Medical Center, Gainesville, GA
| | - Rebecca L Morgan
- Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Peter E Morris
- University of Kentucky College of Medicine, Lexington, KY
| | - Jody C Olson
- Kansas University Medical Center, Kansas City, KS
| | | | - Randolph Steadman
- University of California Los Angeles Medical Center, Los Angeles, CA
| | | | - Constantine J Karvellas
- Department of Critical Care Medicine and Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, AB, Canada
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Ma L, Liu S, Xing H, Jin Z. Research progress on short-term prognosis of acute-on-chronic liver failure. Expert Rev Gastroenterol Hepatol 2023; 17:45-57. [PMID: 36597928 DOI: 10.1080/17474124.2023.2165063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
INTRODUCTION Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized as a severe condition with rapid progression, poor therapeutic response and poor prognosis. Early and timely evaluation of the prognosis is helpful for providing appropriate clinical intervention and prolonging patient survival. AREAS COVERED Currently, there are no specific dynamic and comprehensive approaches to assess the prognosis of patients with ACLF. This article reviews the progress in evaluating the short-term prognosis of ACLF to provide future directions for more dynamic prospective large-scale multicenter studies and a basis for individualized and precise treatment for ACLF patients. We searched PubMed and Web of Science with the term 'acute on chronic liver failure' and 'prognosis.' There was no date or language restriction, and our final search was on 26 October 2022. EXPERT OPINION ACLF is a dynamic process, and the best prognostic marker is the clinical evolution of organ failure over time. New prognostic markers are developing not only in the fields of genetics and histology but also toward diversification combined with imaging. Determining which patients will benefit from continued advanced life support is a formidable challenge, and accurate short-term prognostic assessments of ACLF are a good approach to addressing this issue.
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Affiliation(s)
- Luyao Ma
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun City, Jilin Province, China
| | - Siqi Liu
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun City, Jilin Province, China
| | - Hao Xing
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun City, Jilin Province, China
| | - Zhenjing Jin
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun City, Jilin Province, China
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Liu J, Shi X, Xu H, Tian Y, Ren C, Li J, Shan S, Liu S. A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure. Front Cell Infect Microbiol 2023; 13:1107351. [PMID: 37026054 PMCID: PMC10072158 DOI: 10.3389/fcimb.2023.1107351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 02/27/2023] [Indexed: 04/08/2023] Open
Abstract
Background Postoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients' clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability. Methods We enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome. Results We built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models. Conclusions The multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS.
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Affiliation(s)
- Jie Liu
- Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Xinrong Shi
- Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Hongmin Xu
- Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Yaqiong Tian
- Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
| | - Chaoyi Ren
- Hepatobiliary Surgery Department, The Third Central Hospital of Tianjin, Tianjin, China
| | - Jianbiao Li
- Hepatobiliary Surgery Department, The Third Central Hospital of Tianjin, Tianjin, China
| | - Shigang Shan
- Hepatobiliary Surgery Department, The Third Central Hospital of Tianjin, Tianjin, China
| | - Shuye Liu
- Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- Artificial Cell Engineering Technology Research Center, Tianjin, China
- Tianjin Institute of Hepatobiliary Disease, Tianjin, China
- *Correspondence: Shuye Liu,
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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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Deep A, Alexander EC, Bulut Y, Fitzpatrick E, Grazioli S, Heaton N, Dhawan A. Advances in medical management of acute liver failure in children: promoting native liver survival. THE LANCET. CHILD & ADOLESCENT HEALTH 2022; 6:725-737. [PMID: 35931098 DOI: 10.1016/s2352-4642(22)00190-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/12/2022] [Accepted: 06/13/2022] [Indexed: 06/15/2023]
Abstract
Paediatric acute liver failure (PALF) is defined as a biochemical evidence of acute liver injury in a child with no previous history of chronic liver disease characterised by an international normalised ratio (INR) of 1·5 or more unresponsive to vitamin K with encephalopathy, or INR of 2·0 or more with or without encephalopathy. PALF can rapidly progress to multiorgan dysfunction or failure. Although the transplant era has substantially changed the outlook for these patients, transplantation itself is not without risks, including those associated with life-long immunosuppression. Consequently, there has been an increased focus on improving medical management to prioritise bridging of patients to native liver survival, which is possible due to improved understanding of the underlying pathophysiology of multiorgan involvement in PALF. In this Review, we discuss recent advances in the medical management of PALF with an aim of reducing the need for liver transplantation. The Review will focus on the non-specific immune-mediated inflammatory response, extracorporeal support devices, neuromonitoring and neuroprotection, and emerging cellular and novel future therapeutic options.
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Affiliation(s)
- Akash Deep
- Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, London, UK; Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
| | - Emma C Alexander
- Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, London, UK
| | - Yonca Bulut
- Department of Pediatrics, Division of Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Emer Fitzpatrick
- Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, London, UK; Department of Paediatric Gastroenterology and Hepatology, Children's Health Ireland at Crumlin, Dublin, Ireland
| | - Serge Grazioli
- Division of Neonatal and Pediatric Intensive Care, Department of Pediatrics, Gynecology, and Obstetrics, Children's Hospital, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Nigel Heaton
- Liver Transplant Surgery, Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital NHS Foundation Trust, London, UK
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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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35
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Hui WF, Cheung WL, Chung FS, Leung KKY, Ku SW. The successful application of hemoadsorption for extracorporeal liver support in a child with acute liver failure. Int J Artif Organs 2022; 45:878-882. [PMID: 35918853 DOI: 10.1177/03913988221116135] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
A 6-year-old boy developed acute liver failure with hepatic coma due to drug rash with eosinophilia and systemic symptoms (DRESS) after multiple antibiotics exposure. He had hyperbilirubinemia, elevated serum bile acids and hyperammonemia with peak serum levels of total bilirubin, direct bilirubin, bile acids and ammonia measuring 418, 328, 174, and 172 μmol/L respectively. In addition to the use of systemic steroid and other supportive therapy, he also received three sessions of hemoadsorption using the Cytosorb® column incorporated into the continuous renal replacement therapy circuit as extracorporeal liver support for a total duration of 75 h, which brought down his serum levels of total bilirubin to 119 μmol/L, bile acids to 58 μmol/L, and ammonia to 55 μmol/L. His conscious level gradually regained coupling an improvement of liver function. Except for mild thrombocytopenia and electrolyte disturbances, the therapy was well tolerated with no major complication encountered. Our case demonstrated that hemoadsorption can be safely employed as an adjunctive extracorporeal liver support modality in children with acute liver failure. The potential role and technical concerns of applying such technique in pediatric patients requires further evaluation in future studies.
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Affiliation(s)
- Wun Fung Hui
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
| | - Wing Lum Cheung
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
| | - Fung Shan Chung
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
| | - Karen Ka Yan Leung
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
| | - Shu Wing Ku
- Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Kowloon, Hong Kong
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Martí-Carvajal AJ, Gluud C, Gluud LL, Pavlov CS, Mauro E, Monge Martín D, Liu JP, Nicola S, Comunián-Carrasco G, Martí-Amarista CE. Liver support systems for adults with acute liver failure. Hippokratia 2022. [DOI: 10.1002/14651858.cd015059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Arturo J Martí-Carvajal
- Facultad de Ciencias de la Salud Eugenio Espejo; Universidad UTE (Cochrane Ecuador); Quito Ecuador
- Facultad de Medicina, Universidad Francisco de Vitoria (Cochrane Madrid); Madrid Spain
- Cátedra Rectoral de Medicina Basada en la Evidencia; Universidad de Carabobo; Valencia Venezuela
| | - Christian Gluud
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research; The Capital Region, Copenhagen University Hospital - Rigshospitalet; Copenhagen Denmark
- Department of Regional Health Research; The Faculty of Health Sciences, University of Southern Denmark; Odense Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division; Copenhagen University Hospital Hvidovre; Hvidovre Denmark
| | - Chavdar S Pavlov
- Cochrane Hepato-Biliary Group; Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital - Rigshospitalet; Copenhagen Denmark
- Department of Therapy ; IM Sechenov First Moscow State Medical University; Moscow Russian Federation
- Department of Gastroenterology; Botkin Hospital; Moscow Russian Federation
| | - Ezequiel Mauro
- Liver Unit & Liver Transplant Unit; Hospital Italiano de Buenos Aires; Buenos Aires Argentina
| | - Diana Monge Martín
- Facultad de Medicina; Universidad Francisco de Vitoria (Cochrane Madrid); Madrid Spain
| | - Jian Ping Liu
- Centre for Evidence-Based Chinese Medicine; Beijing University of Chinese Medicine; Beijing China
| | - Susana Nicola
- Centro Asociado Cochrane Ecuador, Centro de Investigación en Salud Pública y Epidemiología Clínica (CISPEC); Universidad UTE; Quito Ecuador
| | - Gabriella Comunián-Carrasco
- Cátedra Rectoral de Medicina Basada en la Evidencia; Universidad de Carabobo; Valencia Venezuela
- Departamento de Obstetricia y Ginecología; Universidad de Carabobo; Valencia Venezuela
| | - Cristina Elena Martí-Amarista
- Division of General, Geriatric and Hospital Medicine; Stony Brook University, Renaissance School of Medicine HSC, Level 2, Rm 155; Stony Brook, 11794-8228 New York USA
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Abstract
PURPOSE OF REVIEW Present an outline of acute liver failure, from its definition to its management in critical care, updated with findings of selected newer research. RECENT FINDINGS Survival of patients with acute liver failure has progressively improved. Intracranial hypertension complicating hepatic encephalopathy is now much less frequent than in the past and invasive ICP monitoring is now rarely used. Early renal replacement therapy and possibly therapeutic plasma exchange have consolidated their role in the treatment. Further evidence confirms the low incidence of bleeding in these patients despite striking abnormalities in standard tests of coagulation and new findings of abnormalities on thromboelastographic testing. Specific coagulopathy profiles including an abnormal vWF/ADAMTS13 ratio may be associated with poor outcome and increased bleeding risk. Use of N-acetylcysteine in nonparacetamol-related cases remains unsupported by robust clinical evidence. New microRNA-based prognostic markers to select patients for transplantation are described but are still far from widespread clinical applicability; imaging-based prognostication tools are also promising. The use of extracorporeal artificial liver devices in clinical practice is yet to be supported by evidence. SUMMARY Medical treatment of patients with acute liver failure is now associated with significantly improved survival. Better prognostication and selection for emergency liver transplant may further improve care for these patients.
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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: 23] [Impact Index Per Article: 7.7] [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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Yoo SW, Ki MJ, Kim D, Kim SK, Park S, Han HJ, Lee HB. Bleeding complications associated with the molecular adsorbent recirculating system: a retrospective study. Acute Crit Care 2022; 36:322-331. [PMID: 35263827 PMCID: PMC8907459 DOI: 10.4266/acc.2021.00276] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 08/25/2021] [Indexed: 01/15/2023] Open
Abstract
Background The molecular adsorbent recirculating system (MARS) is a hepatic replacement system that supports excretory liver function in patients with liver failure. However, since MARS has been employed in our hospital, bleeding complications have occurred in many patients during or after MARS. The objective of this study was to determine how MARS affects coagulopathy and identify specific factors associated with bleeding complications. Methods We retrospectively analyzed data from 17 patients undergoing a total of 41 MARS sessions. Complete blood count, coagulation profiles, and blood chemistry values were compared before and after MARS. To identify pre-MARS factors associated with increased bleeding after MARS, we divided patients into bleeder and non-bleeder groups and compared their pre-MARS laboratory values. Results MARS significantly reduced bilirubin and creatinine levels. MARS also increased prothrombin time and reduced platelet and fibrinogen, thus negatively impacting coagulation. Pre-MARS hemoglobin was significantly lower in the bleeder group than in the non-bleeder group (P=0.015). When comparing the upper and lower 33% of MARS sessions based on the hemoglobin reduction rate, hemoglobin reduction was significantly greater in MARS sessions involving patients with low pre-MARS international normalized ratio of prothrombin time (PT-INR) and factor V (P=0.038 and P=0.023, respectively). Conclusions MARS could appears to alter coagulation-related factors such as factor V and increase the risk of bleeding complications particularly in patient with low hemoglobin. However, individual differences among patients were large, and various factors, such as low hemoglobin, PT-INR, and factor V levels, appear to be involved.
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Affiliation(s)
- Seon Woo Yoo
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Min-Jong Ki
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
| | - Dal Kim
- Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Seul Ki Kim
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - SeungYong Park
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Hyo Jin Han
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Heung Bum Lee
- Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.,Humidifier Disinfectant Health Center, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea.,Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Research Center for Pulmonary Disorders, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
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Zellos A, Debray D, Indolfi G, Czubkowski P, Samyn M, Hadzic N, Gupte G, Fischler B, Smets F, de Cléty SC, Grenda R, Mozer Y, Mancell S, Jahnel J, Auzinger G, Worth A, Lisman T, Staufner C, Baumann U, Dhawan A, Alonso E, Squires RH, Verkade HJ. Proceedings of ESPGHAN Monothematic Conference 2020: "Acute Liver Failure in Children": Diagnosis and Initial Management. J Pediatr Gastroenterol Nutr 2022; 74:e45-e56. [PMID: 35226643 DOI: 10.1097/mpg.0000000000003341] [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] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. METHODS The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. RESULTS In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. CONCLUSIONS The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.
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Affiliation(s)
- Aglaia Zellos
- First Department of Pediatrics, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dominique Debray
- Pediatric Hepatology Unit, Hôpital Necker-Enfants Malades, Reference Center for Rare Pediatric Liver Diseases, ERN Rare Liver and Transplant Child, Paris, France
| | - Giuseppe Indolfi
- Department Neurofarba University of Florence, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology and Nutritional Disorders and Pediatrics. The Children's Memorial Health Institute, Warsaw, Poland
| | - Marianne Samyn
- Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital
| | | | - Girish Gupte
- Birmingham Children's Hospital NHS Trust, Birmingham, UK
| | - Björn Fischler
- Department of Pediatrics, CLINTEC Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Françoise Smets
- Pediatrics, Cliniques universitaires Saint-Luc, Université Catholique de Louvain
| | - Stéphan Clément de Cléty
- Paediatric intensive care, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Ryszard Grenda
- Department of Nephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, Warsaw, Poland
| | - Yael Mozer
- Schneider Children's Medical Center, Israel
| | | | | | - Georg Auzinger
- King's College Hospital, Department Chair, Critical Care Cleveland Clinic
| | - Austen Worth
- Great Ormond Street Hospital for Children, London, UK
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Christian Staufner
- Division of Neuropediatrics and Pediatric Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Anil Dhawan
- Variety Children Hospital, Director Paediatric Liver GI and Nutrition and Mowat Labs, King's College Hospital, London, UK
| | - Estelle Alonso
- Siragusa Transplant Center, Ann and Robert H. Lurie Children' Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Robert H Squires
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Henkjan J Verkade
- Department of Paediatrics, University of Groningen, Beatrix Children's Hospital, University Medical Center, Groningen, The Netherlands
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Acharya M, Berger R, Popov AF. The role of the ADVanced Organ Support (ADVOS) system in critically ill patients with multiple organ failure. Artif Organs 2022; 46:735-746. [PMID: 35128695 PMCID: PMC9306712 DOI: 10.1111/aor.14188] [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: 11/11/2021] [Revised: 01/03/2022] [Accepted: 01/19/2022] [Indexed: 11/30/2022]
Abstract
Background Multi‐organ failure characterized by acute kidney injury, liver dysfunction, and respiratory failure is a complex condition associated with high mortality, for which multiple individual support devices may be simultaneously required. This review aims to appraise the current evidence for the ADVanced Organ Support (ADVOS) system, a novel device integrating liver, lung, and kidney support with blood detoxification. Methods We performed a literature review of the PubMed database to identify human and animal studies evaluating the ADVOS system. Results In porcine models of acute liver injury and small clinical studies in humans, ADVOS significantly enhanced the elimination of water‐soluble and protein‐bound toxins and metabolites, including creatinine, ammonia, blood urea nitrogen, and lactate. Cardiovascular parameters (mean arterial pressure, cerebral perfusion pressure, and cardiac index) and renal function were improved. ADVOS clears carbon dioxide (CO2) effectively with rapid correction of pH abnormalities, achieving normalization of CO2, and bicarbonate levels. In patients with COVID‐19 infection, ADVOS enables rapid correction of acid–base disturbance and respiratory acidosis. ADVOS therapy reduces mortality in multi‐organ failure and has been shown to be safe with minimal adverse events. Conclusions From the small observational studies analyzed, ADVOS demonstrates excellent detoxification of water‐soluble and protein‐bound substances. In particular, ADVOS permits the correction of metabolic and respiratory acidosis through the fluid‐based direct removal of acid and CO2. ADVOS is associated with significant improvements in hemodynamic and biochemical parameters, a trend toward improved survival in multi‐organ failure, and is well‐tolerated. Larger randomized trials are now necessary to further validate these encouraging results.
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Affiliation(s)
- Metesh Acharya
- Department of Cardiac Surgery, Glenfield Hospital, Leicester, UK
| | - Rafal Berger
- Department of Thoracic and Cardiovascular Surgery, University Hospital of Tübingen, Tübingen, Germany
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Single-pass albumin dialysis and hemoadsorption for bilirubin and bile acids removal for a child with hyperbilirubinemia after ventricular assist device implantation. J Artif Organs 2022; 25:270-273. [PMID: 35038050 DOI: 10.1007/s10047-022-01309-4] [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: 10/24/2021] [Accepted: 01/04/2022] [Indexed: 10/19/2022]
Abstract
We report the successful management of hyperbilirubinemia using two different modalities of extracorporeal bilirubin removal therapy for a pediatric patient. A 13-year-old boy with dilated cardiomyopathy requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) developed acute kidney injury and was dependent on continuous renal replacement therapy. He developed hyperbilirubinemia with a peak total bilirubin level of 786 μmol/L after implantation of biventricular assist device (BiVAD). Extracorporeal bilirubin and bile acids removal using single-pass albumin dialysis (SPAD) with 4% albumin as dialysate brought down the bilirubin level to 672 μmol/L after 21 h of therapy. Subsequently, he was started on two sessions of hemoadsorption using the Cytosorb® column which further lowered the total bilirubin level to 306 μmol/ in 24 h and 173 μmol/ after the treatment. No complication was encountered. Our case illustrated that both SPAD and hemoadsorption can effectively and safely reduce the serum bilirubin and bile acid levels in pediatric patients with BiVAD implantation. The ease of set-up, faster rate of bilirubin decline and capability of cytokine removal make hemoadsorption a favorable alternative to albumin dialysis.
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43
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Azasevac T, Knezevic V, Celic D, Ljubicic B, Lakic T, Mitic I. The use of a single pass albumin dialysis for the management of liver failure. VOJNOSANIT PREGL 2022. [DOI: 10.2298/vsp201116027a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Introduction. A single pass albumin dialysis (SPAD) is a form of extracorporeal liver support system for removing albumin-bound toxins and water-soluble substances that accumulate in liver failure (LF). Case report. We presented three patients hospitalized for LF and treated using the SPAD at the University Clinical Center of Vojvodina, Serbia, from 2018 to 2019. Two of the patients presented with acute LF and one with acute-on-chronic LF. A total of 6 SPAD sessions were performed on each patient, resulting in decreased serum bilirubin and bile acid levels and hepatic encephalopathy grade. On discharge from the hospital, the liver function was improved in all the patients. Conclusion. SPAD removes the hepatotoxic substances without improvement of synthetic liver function. It represents a supportive treatment for LF patients who do not respond to the standard of care, offering a longer time for bridging to organ transplantation or spontaneous recovery of the liver function.
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Affiliation(s)
- Tijana Azasevac
- University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
| | - Violeta Knezevic
- University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
| | - Dejan Celic
- University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
| | - Bojana Ljubicic
- University Clinical Center of Vojvodina, Department of Emergency Internal Medicine, Emergency Center, Novi Sad, Serbia
| | - Tanja Lakic
- University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia + University Clinical Center of Vojvodina, Department of Pathology and Histology, Novi Sad, Serbia
| | - Igor Mitic
- University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia + University of Novi Sad, Faculty of Medicine, Novi Sad, Serbia
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Tampe D, Korsten P, Bremer SCB, Winkler MS, Tampe B. Kinetics of Bilirubin and Ammonia Elimination during Hemadsorption Therapy in Secondary Sclerosing Cholangitis Following ECMO Therapy and Severe COVID-19. Biomedicines 2021; 9:biomedicines9121841. [PMID: 34944657 PMCID: PMC8698542 DOI: 10.3390/biomedicines9121841] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/03/2021] [Accepted: 12/04/2021] [Indexed: 12/14/2022] Open
Abstract
In critically ill patients, liver dysfunction often results in coagulopathy and encephalopathy and is associated with high mortality. Extracorporeal clearance of hepatotoxic metabolites, including bilirubin and ammonia, aims to attenuate further hepatocyte damage and liver injury, resulting in decreased mortality. The efficacy of hemadsorption combined with conventional hemodialysis to eliminate bilirubin and ammonia to support the liver's excretory function in acute liver injury has been described previously. However, the optimal use of liver support systems in chronic liver dysfunction due to secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has not been defined yet. We herein describe the kinetics of successful bilirubin and ammonia elimination by hemadsorption in a patient with SSC-CIP after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory distress syndrome (ARDS) in a patient with coronavirus disease 2019 (COVID-19). During the course of the disease, the patient developed laboratory signs of liver injury during ECMO therapy before clinically detectable jaundice or elevated bilirubin levels. A diagnosis of SSC-CIP was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) based on intraductal filling defects in the intrahepatic bile ducts due to biliary casts. The patient showed stable elevations of bilirubin and ammonia levels thereafter, but presented with progressive nausea, vomiting, weakness, and exhaustion. Based on these laboratory findings, hemadsorption was combined with hemodialysis treatment and successfully eliminated bilirubin and ammonia. Moreover, direct comparison revealed that ammonia is more efficiently eliminated by hemadsorption than bilirubin levels. Clinical symptoms of nausea, vomiting, weakness, and exhaustion improved. In summary, bilirubin and ammonia were successfully eliminated by hemadsorption combined with hemodialysis treatment in SSC-CIP following ECMO therapy and severe COVID-19. This observation is particularly relevant since it has been reported that a considerable subset of critically ill patients with COVID-19 suffer from liver dysfunction associated with high mortality.
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Affiliation(s)
- Désirée Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, 37075 Göttingen, Germany; (D.T.); (P.K.)
| | - Peter Korsten
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, 37075 Göttingen, Germany; (D.T.); (P.K.)
| | - Sebastian C. B. Bremer
- Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology, University Medical Center Göttingen, 37075 Göttingen, Germany;
| | - Martin S. Winkler
- Department of Anesthesiology, Emergency and Intensive Care Medicine, University Medical Center Göttingen, 37075 Göttingen, Germany;
| | - Björn Tampe
- Department of Nephrology and Rheumatology, University Medical Center Göttingen, 37075 Göttingen, Germany; (D.T.); (P.K.)
- Correspondence: ; Tel.: +49-551-39-10575
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Wang J, Ren H, Liu Y, Sun L, Zhang Z, Zhao Y, Shi X. Bioinspired Artificial Liver System with hiPSC-Derived Hepatocytes for Acute Liver Failure Treatment. Adv Healthc Mater 2021; 10:e2101580. [PMID: 34599859 DOI: 10.1002/adhm.202101580] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/17/2021] [Indexed: 12/21/2022]
Abstract
Bioartificial liver (BAL) system has become a promising alternative to traditional liver transplantation in rescuing acute liver failure (ALF) patients. Herein, inspired by natural microstructure of hepatic lobules, a novel biomimetic bioartificial liver system (BBALS) is developed by integrating human induced pluripotent stem cell-derived hepatocytes (hiPSC-Heps) -laden microparticles and semipermeable microtubes into a microfluidic platform. As the working units are hepatic lobules-like semipermeable microtubes surrounding with serum-free suspension differentiated hiPSC-Heps microcarriers, the BBALS is endowed with functional cell aggregates and effective circulation system. Thus, the BBALS possesses high cell viability, favorable function regeneration, and effective substances exchange. Based on these features, a 3D liver chip with multiple parallel BBALS units is created for filtering the plasma of ALF rabbits, which validates the research significance and application potential of the proposed BBALS. Moreover, the novel integrated BBALS is applied to treat ALF rabbits and shows great advantages in increasing survival, generating serum proteins, and decreasing inflammation. These properties point to the broad prospects of BBALS in treating related diseases and improving traditional clinical methods.
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Affiliation(s)
- Jinglin Wang
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
| | - Haozhen Ren
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
| | - Yuxiao Liu
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Lingyu Sun
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Zhuohao Zhang
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Yuanjin Zhao
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Xiaolei Shi
- Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Hepatobiliary Institute of Nanjing University, Nanjing, 210008, China
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46
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Deep A, Nagakawa S, Tissieres P. Non-transplant options in paediatric acute liver failure-what is new? Intensive Care Med 2021; 48:114-117. [PMID: 34762137 DOI: 10.1007/s00134-021-06576-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Akash Deep
- Paediatric Intensive Care Unit, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, UK. .,Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
| | - Satoshi Nagakawa
- Critical Care Medicine, National Center for Child Health and Development, Tokyo, Japan
| | - Pierre Tissieres
- Paediatric Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France.,Institute of Integrative Biology of the Cell, CNRS, CEA, Paris Saclay University, Gif-sur-Yvette, France.,FHU Sepsis, AP-HP, Paris Saclay University, Inserm, Le Kremlin-Bicêtre, France
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Abstract
Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.
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48
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Matar AJ, Subramanian R. Extracorporeal Liver Support: A Bridge to Somewhere. Clin Liver Dis (Hoboken) 2021; 18:274-279. [PMID: 34976371 PMCID: PMC8688900 DOI: 10.1002/cld.1140] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 05/13/2021] [Accepted: 05/18/2021] [Indexed: 02/04/2023] Open
Abstract
Content available: Audio Recording.
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Affiliation(s)
- Abraham J. Matar
- Department of SurgeryDivision of SurgeryEmory UniversityAtlantaGA
| | - Ram Subramanian
- Department of MedicineDivision of HepatologyEmory UniversityAtlantaGA,Department of MedicineDivision of Critical Care MedicineEmory UniversityAtlantaGA
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49
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Caraceni P, Abraldes JG, Ginès P, Newsome PN, Sarin SK. The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery. J Hepatol 2021; 75 Suppl 1:S118-S134. [PMID: 34039483 DOI: 10.1016/j.jhep.2021.01.024] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 01/14/2021] [Accepted: 01/15/2021] [Indexed: 02/06/2023]
Abstract
Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing.
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Affiliation(s)
- Paolo Caraceni
- Division of Medical Semeiotics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences and Center for Biomedical Applied Research, Alma Mater Studiorum University of Bologna, Italy.
| | - Juan G Abraldes
- Liver Unit, Division of Gastroenterology, University of Alberta, Canada
| | - Pere Ginès
- Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS, CIBEReHD, Barcelona, Catalonia, Spain
| | - Phil N Newsome
- National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, UK; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, UK; Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shiv K Sarin
- Hepatology, Institute of Liver and Biliary Sciences (ILBS), New Delhi, India
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50
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Weng J, Han X, Zeng F, Zhang Y, Feng L, Cai L, Liang K, Liu S, Li S, Fu G, Zeng M, Gao Y. Fiber scaffold bioartificial liver therapy relieves acute liver failure and extrahepatic organ injury in pigs. Theranostics 2021; 11:7620-7639. [PMID: 34335954 PMCID: PMC8315066 DOI: 10.7150/thno.58515] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
Rationale: Acute liver failure (ALF) causes severe liver injury and a systemic inflammatory response, leading to multiorgan failure with a high short-term mortality. Bioartificial liver (BAL) therapy is a promising approach that is hampered by the lack of appropriate bioreactors and carriers to retain hepatic cell function and poor understanding of BAL treatment mechanisms in ALF and extrahepatic organ injury. Recently, we used a fiber scaffold bioreactor (FSB) for the high-density, three-dimensional (3D) culture of primary porcine hepatocytes (PPHs) combined with an absorption component to construct a BAL and verified its function in a D-galactosamine (D-gal)-induced ALF porcine model to evaluate its protective effects on the liver and extrahepatic organs. Methods: Male pigs were randomized into standard/supportive therapy (ST), ST+no-cell BAL (ST+Sham BAL) and ST+BAL groups and received treatment 48 h after receiving a D-gal injection. Changes in blood chemistry and clinical symptoms were monitored for 120 h. Tissues and plasma were collected for analysis by pathological examination, immunoblotting, quantitative PCR and immunoassays. Results: PPHs cultured in the FSB obtained sufficient aeration and nutrition for high-density, 3D culture and maintained superior viability and functionality (biosynthesis and detoxification) compared with those cultured in flasks. All the animals developed ALF, acute kidney injury (AKI) and hepatic encephalopathy (HE) 48 h after D-gal infusion and received corresponding therapies. Animals in the BAL group showed markedly improved survival (4/5; 80%) compared with those in the ST+Sham BAL (0/5; p < 0.001) and ST (0/5; p < 0.001) groups. The levels of blood ammonia and biochemical and inflammatory indices were alleviated after BAL treatment. Increased liver regeneration and attenuations in the occurrence and severity of ALF, AKI and HE were observed in the ST+BAL group compared with the ST (p = 0.0009; p = 0.038) and ST+Sham BAL (p = 0.011; p = 0.031) groups. Gut leakage, the plasma endotoxin level, bacterial translocation, and peripheral and neuroinflammation were alleviated in the ST+BAL group compared with those in the other groups. Conclusions: BAL treatment enhanced liver regeneration and alleviated the systemic inflammatory response and extrahepatic organ injury to prolong survival in the ALF model and has potential as a therapeutic approach for ALF patients.
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Affiliation(s)
- Jun Weng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Xu Han
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Fanhong Zeng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Yue Zhang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Lei Feng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Lei Cai
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Kangyan Liang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Shusong Liu
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Shao Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
| | - Gongbo Fu
- Department of Medical Oncology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing 210000, China
| | - Min Zeng
- Guangdong Qianhui Biotechnology Co., Ltd., Guangzhou 510285, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510515, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510515, China
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