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Karvellas CJ, Gustot T, Fernandez J. Management of the acute on chronic liver failure in the intensive care unit. Liver Int 2025; 45:e15659. [PMID: 37365997 DOI: 10.1111/liv.15659] [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: 04/30/2023] [Revised: 06/01/2023] [Accepted: 06/15/2023] [Indexed: 06/28/2023]
Abstract
Acute on chronic liver failure (ACLF) reflects the development of organ failure(s) in a patient with cirrhosis and is associated with high short-term mortality. Given that ACLF has many different 'phenotypes', medical management needs to take into account the relationship between precipitating insult, organ systems involved and underlying physiology of chronic liver disease/cirrhosis. The goals of intensive care management of patients suffering ACLF are to rapidly recognize and treat inciting events (e.g. infection, severe alcoholic hepatitis and bleeding) and to aggressively support failing organ systems to ensure that patients may successfully undergo liver transplantation or recovery. Management of these patients is complex since they are prone to develop new organ failures and infectious or bleeding complications. ICU therapy parallels that applied in the general ICU population in some complications but differs in others. Given that liver transplantation in ACLF is an emerging and evolving field, multidisciplinary teams with expertise in critical care and transplant medicine best accomplish management of the critically ill ACLF patient. The focus of this review is to identify the common complications of ACLF and to describe the proper management in critically ill patients awaiting liver transplantation in our centres, including organ support, prognostic assessment and how to assess when recovery is unlikely.
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Affiliation(s)
- Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada
| | - Thierry Gustot
- Department of Gastroenterology, Hepato-Pancreatology and Digestive Oncology, H.U.B., CUB Hôpital Erasme, Brussels, Belgium
| | - Javier Fernandez
- Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS and CIBERehd, Barcelona, Spain
- EF CLIF, EASL-CLIF Consortium, Barcelona, Spain
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2
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Kalo E, Read S, Baig A, Marshall K, Ma WS, Crowther H, Gofton C, Lynch KD, Sood S, Holmes J, Lubel J, Wigg A, McCaughan G, Roberts SK, Caraceni P, Ahlenstiel G, Majumdar A. Efficacy of albumin use in decompensated cirrhosis and real-world adoption in Australia. JGH Open 2024; 8:e70029. [PMID: 39301299 PMCID: PMC11410680 DOI: 10.1002/jgh3.70029] [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: 05/01/2024] [Revised: 08/26/2024] [Accepted: 09/03/2024] [Indexed: 09/22/2024]
Abstract
The current treatment approach to patients with liver cirrhosis relies on the individual management of complications. Consequently, there is an unmet need for an overall therapeutic strategy for primary and secondary prevention of complications. The clinical potential of long-term albumin infusions supported by recent clinical trials has expanded its indications and holds promise to transform the management and secondary prevention of cirrhosis-related complications. This renewed interest in albumin comes with inherent controversies, compounding challenges and pressing need for rigorous evaluation of its clinical potential to capitalize on its therapeutic breakthroughs. Australia is among a few countries worldwide to adopt outpatient human albumin infusion. Here, we summarize currently available evidence of the potential benefits of human albumin for the management of multiple liver cirrhosis-related complications and discuss key challenges for wide application of long-term albumin administration strategy in Australian clinical practice. Australian Gastroenterological week (AGW), organised by the Gastroenterological Society of Australia (GESA), was held between 9-11 September 2022. A panel of hepatologists, advanced liver nurses and one haematologist, were invited to a roundtable meeting to discuss the use of long-term albumin infusions for liver cirrhosis. management in Australia. In this review, we summarise the proceedings of this meeting in context of the current literature.
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Affiliation(s)
- Eric Kalo
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Scott Read
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Asma Baig
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Kate Marshall
- Royal Prince Alfred Hospital Sydney New South Wales Australia
| | - Wai-See Ma
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Helen Crowther
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
| | - Cameron Gofton
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
- Department of Gastroenterology and Hepatology Royal North Shore Hospital St Leonards New South Wales Australia
| | - Kate D Lynch
- Department of Gastroenterology and Hepatology Royal Adelaide Hospital, Central Adelaide Local Health Network Adelaide South Australia Australia
- Faculty of Health and Medical Sciences University of Adelaide Adelaide South Australia Australia
| | - Siddharth Sood
- Department of Gastroenterology Northern Health Melbourne Victoria Australia
- Department of Medicine The University of Melbourne Parkville Victoria Australia
| | - Jacinta Holmes
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Department of Gastroenterology St Vincent's Hospital Fitzroy Victoria Australia
| | - John Lubel
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Alan Wigg
- Hepatology and Liver Transplant Medicine Unit Southern Adelaide Local Health Network Adelaide South Australia Australia
- Flinders University of South Australia Adelaide South Australia Australia
| | - Geoff McCaughan
- A.W. Morrow Gastroenterology and Liver Centre Centenary Research Institute for Cancer Research and Cell Biology Camperdown New South Wales Australia
- Australian National Liver Transplant Unit Royal Prince Alfred Hospital Sydney New South Wales Australia
- Faculty of Medicine and Health University of Sydney Sydney New South Wales Australia
| | - Stuart K Roberts
- Department of Gastroenterology Alfred Health Melbourne Victoria Australia
- Central Clinical School Monash University Melbourne Victoria Australia
| | - Paolo Caraceni
- Unit of Semeiotics, Liver and Alcohol-Related Diseases IRCCS Azienda-Ospedaliera Universitaria di Bologna, EMR Bologna Italy
- Department of Medical and Surgical Sciences University of Bologna, EMR Bologna Italy
| | - Golo Ahlenstiel
- Blacktown Clinical School and Research Centre, School of Medicine Western Sydney University Blacktown New South Wales Australia
- Blacktown Hospital, Western Sydney Local Health District Blacktown New South Wales Australia
- Storr Liver Centre, The Westmead Institute for Medical Research University of Sydney Westmead New South Wales Australia
| | - Avik Majumdar
- Department of Medicine The University of Melbourne Parkville Victoria Australia
- Victorian Liver transplant Unit Austin Health Heidelberg Victoria Australia
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Abedi F, Zarei B, Elyasi S. Albumin: a comprehensive review and practical guideline for clinical use. Eur J Clin Pharmacol 2024; 80:1151-1169. [PMID: 38607390 DOI: 10.1007/s00228-024-03664-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 03/04/2024] [Indexed: 04/13/2024]
Abstract
PURPOSE Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. METHODS Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. RESULTS A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. CONCLUSION Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.
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Affiliation(s)
- Farshad Abedi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran
| | - Batool Zarei
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran.
| | - Sepideh Elyasi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box, Mashhad, 91775-1365, Iran.
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Callum J, Skubas NJ, Bathla A, Keshavarz H, Clark EG, Rochwerg B, Fergusson D, Arbous S, Bauer SR, China L, Fung M, Jug R, Neill M, Paine C, Pavenski K, Shah PS, Robinson S, Shan H, Szczepiorkowski ZM, Thevenot T, Wu B, Stanworth S, Shehata N. Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines. Chest 2024; 166:321-338. [PMID: 38447639 PMCID: PMC11317816 DOI: 10.1016/j.chest.2024.02.049] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 02/23/2024] [Accepted: 02/27/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. STUDY DESIGN AND METHODS Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. RESULTS The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. INTERPRETATION Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.
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Affiliation(s)
- Jeannie Callum
- Department of Pathology and Molecular Medicine, Queen's University and Kingston Health Sciences Centre, Kingston, ON, Canada.
| | - Nikolaos J Skubas
- Department of Cardiothoracic Anesthesiology, Anesthesiology Institute, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH
| | | | | | - Edward G Clark
- Division of Nephrology, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Bram Rochwerg
- Department of Medicine and Department of Health Research Methods, Evidence and Impact, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Dean Fergusson
- Department of Medicine, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Sesmu Arbous
- Department of Critical Care, Leiden University Medical Center, Leiden, The Netherlands
| | - Seth R Bauer
- Department of Pharmacy, Cleveland Clinic, Cleveland, OH
| | - Louise China
- Department of Hepatology and Institute for Liver and Digestive Health, The Royal Free NHS Trust and University College London, London, England
| | - Mark Fung
- Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT
| | - Rachel Jug
- University of Cincinnati College of Medicine, Cincinnati, OH
| | | | - Cary Paine
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA
| | - Katerina Pavenski
- Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, Toronto, ON, Canada
| | - Prakesh S Shah
- Institute of Health Policy, Management, and Evaluation, Mount Sinai Hospital, Toronto, ON, Canada; Department of Pediatrics, Mount Sinai Hospital, Toronto, ON, Canada
| | - Susan Robinson
- Department of Clinical Haematology, Guy's and St Thomas' NHS Foundation Trust, London, England
| | - Hua Shan
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA
| | | | - Thierry Thevenot
- Service d'Hépatologie, Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France
| | - Bovey Wu
- Department of Internal Medicine, Graduate Medical Education, Loma Linda University, Loma Linda, CA
| | - Simon Stanworth
- NHS Blood and Transplant, Oxford, England; Radcliffe Department of Medicine, University of Oxford, Oxford, England; John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, England
| | - Nadine Shehata
- Department of Medicine, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada; Transfusion Medicine Laboratory, Mount Sinai Hospital, Toronto, ON, Canada
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Karvellas CJ, Bajaj JS, Kamath PS, Napolitano L, O'Leary JG, Solà E, Subramanian R, Wong F, Asrani SK. AASLD Practice Guidance on Acute-on-chronic liver failure and the management of critically ill patients with cirrhosis. Hepatology 2024; 79:1463-1502. [PMID: 37939273 DOI: 10.1097/hep.0000000000000671] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 11/01/2023] [Indexed: 11/10/2023]
Affiliation(s)
- Constantine J Karvellas
- Division of Gastroenterology (Liver Unit), Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
| | - Jasmohan S Bajaj
- Virginia Commonwealth University, Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, Minnesota, USA
| | | | - Jacqueline G O'Leary
- Department of Medicine, Dallas Veterans Medical Center, University of Texas Southwestern Medical Center Dallas, Texas, USA
| | - Elsa Solà
- Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, USA
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Murtaza F, Mathew M, Fagbamila O, Subramani S, Nimal S, Nyshita VN, Priya V, Sany AT, Kumar Y, Cicani L, Ehsan M, Kandel K. Efficacy and safety of albumin for the treatment of hepatic encephalopathy: an updated systematic review and meta-analysis of randomized controlled trials. Ann Med Surg (Lond) 2024; 86:3416-3422. [PMID: 38846811 PMCID: PMC11152777 DOI: 10.1097/ms9.0000000000002039] [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: 10/14/2023] [Accepted: 03/30/2024] [Indexed: 06/09/2024] Open
Abstract
Background Albumin acts as a scavenger of reactive oxygen species and an inhibitor of inflammatory processes that underlie hepatic encephalopathy (HE). However, the role of albumin in hepatic encephalopathy is not well-established. The authors performed this meta-analysis to evaluate the efficacy and safety of albumin in the management of hepatic encephalopathy. Methods The authors carried out an extensive search across multiple databases, including MEDLINE (via PubMed), Embase, CENTRAL, and various trial registries, to identify randomized controlled trials (RCTs) evaluating the impact of albumin administration in HE. The authors used a random-effects model for analyses and presented dichotomous outcomes and continuous outcomes as relative risk and mean difference, along with corresponding 95% CIs, respectively. Heterogeneity was assessed using both the I2 index and χ2 test. Results Our meta-analysis included 4 RCTs involving 306 patients. Our primary outcomes, mortality, and persistence of HE were reported by all four studies. Albumin was found to significantly decrease mortality in patients with HE [risk ratio (RR) 0.52, 95% CI 0.32-0.83; I2 =0%]. Persistence of HE was found to be comparable between the two groups (RR 0.83, 95% CI 0.68-1.00; I2 =24%). There was no significant difference between the albumin and control groups regarding length of hospital stay (MD -1.55, 95% CI -3.5 to 0.14; I2 =41%), adverse events (RR 1.00, 95% CI 0.87-1.16; I2 =0%), and severe adverse events (RR 0.89, 95% CI 0.59-1.35). Conclusion Albumin administration in patients with hepatic encephalopathy decreases mortality but does not significantly impact the persistence of HE. Further high-quality, large-scale randomized controlled trials are needed to provide conclusive evidence.
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Affiliation(s)
| | - Midhun Mathew
- Department of Medicine, Pennsylvania Hospital, Philadelphia, PA
| | | | - Sachin Subramani
- Department of Medicine, ESIC Medical College and Hospital, Gulbarga
| | - Simran Nimal
- Department of Medicine, BJ Medical College, Pune
| | | | - Vishnu Priya
- Department of Medicine, Government Kilpauk Medical College, Chennai, India
| | - Abu Talha Sany
- Department of Medicine, Brahmanbaria Medical College & Hospital, Brahmanbaria, Bangladesh
| | - Yamanth Kumar
- Department of Medicine, Government Kilpauk Medical College, Chennai, India
| | - Laura Cicani
- Department of Medicine, International University of Health Sciences, Las Vegas, NV
| | - Muhammad Ehsan
- Department of Medicine, King Edward Medical University, Lahore, Pakistan
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Kulkarni AV, Avadhanam M, Karandikar P, Rakam K, Gupta A, Simhadri V, Premkumar M, Zuberi AA, Gujjarlapudi D, Narendran R, Shaik S, Sharma M, Iyengar S, Alla M, Venishetty S, Reddy DN, Rao PN. Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial. Am J Gastroenterol 2024; 119:864-874. [PMID: 37942950 DOI: 10.14309/ajg.0000000000002575] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 10/10/2023] [Indexed: 11/10/2023]
Abstract
INTRODUCTION Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE). METHODS In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed. RESULTS Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32-70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8-63) in ab + r arm achieved the primary objective ( P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections ( P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2-0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6-1.63]) because of reduced nosocomial infections. DISCUSSION Reversal of overt HE in those on ab was comparable with those on ab + r.
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Affiliation(s)
| | | | | | - Kalyan Rakam
- Department of Critical Care Medicine, AIG Hospitals, Hyderabad, India
| | - Anand Gupta
- Department of Critical Care Medicine, AIG Hospitals, Hyderabad, India
| | - Venu Simhadri
- Department of Basic Sciences, Asian Healthcare Foundation, Hyderabad, India
| | | | | | | | | | - Sameer Shaik
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Sowmya Iyengar
- Department of Hepatology, AIG Hospitals, Hyderabad, India
| | - Manasa Alla
- Department of Hepatology, AIG Hospitals, Hyderabad, India
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8
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Buckholz AP, Brown RS. Future Therapies of Hepatic Encephalopathy. Clin Liver Dis 2024; 28:331-344. [PMID: 38548443 PMCID: PMC10987054 DOI: 10.1016/j.cld.2024.02.002] [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] [Indexed: 04/02/2024]
Abstract
Hepatic encephalopathy, either covert or overt, affects more than half of patients with cirrhosis and has lasting effects even after portal hypertension is corrected. Unfortunately, the current therapeutic options still result in high rates of relapse and progression, in part owing to cost barriers and side effects, leading to poor adherence. This review summarizes emerging treatment options, which could take advantage of alternative disease pathways to improve future care of those with hepatic encephalopathy.
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Affiliation(s)
- Adam P Buckholz
- Division of Gastroenterology and Hepatology, New York/Presbyterian-Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, New York/Presbyterian-Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021, USA.
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9
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Kulkarni AV, Zuberi AA, Chaitanya K, Doolam H, Reddy S, Lakshmi PK, Godbole S, Shantan V, Iyengar S, Alla M, Sharma M, Reddy DN, Rao PN. Human albumin infusion is safe and effective even in patients without acute kidney injury and spontaneous bacterial peritonitis. Indian J Gastroenterol 2024; 43:485-493. [PMID: 38085502 DOI: 10.1007/s12664-023-01475-0] [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: 08/17/2023] [Accepted: 10/21/2023] [Indexed: 05/28/2024]
Abstract
BACKGROUND AND OBJECTIVES Human albumin (HA) solution is currently recommended only for patients with spontaneous bacterial peritonitis (SBP) and acute kidney injury (AKI). However, its use in hospitalized patients is quite frequent. The objective was to compare the outcomes of patients receiving HA in recommended (Gr. A) vs. non-recommended (Gr. B) indications. METHODS In this prospective study, consecutive hospitalized patients who received HA were included. Apart from comparing the proportion of patients achieving resolution of hyponatremia, infection and hepatic encephalopathy among Gr. A and Gr. B, we also compared the in-hospital survival and performed a sub-group analysis of patients with the European Association for the Study of the Liver (EASL) acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC). RESULTS Of the 396 hospitalized patients who received HA, 180 had AKI and/or SBP (Gr. A), and 216 received albumin for non-recommended indications (Gr. B). The mean age, sex and etiology distribution were similar. The total dose of HA was higher (88 ± 61.62 g vs. 71.31 ± 488.17 g; p = 0.003) and the duration longer (4 ± 2.37 vs. 3.4 ± 1.82 days; p = 0.005) in Gr. A than B. The resolution of infection and HE was similar among both groups, while hyponatremia resolution was significantly higher in Gr. B (94.7%) than Gr. A (75.6%; p < 0.001). On Kaplan-Meier analysis, survival was significantly higher in Gr. B (94%) than Gr. A (78.9%; p < 0.001). The incidence of albumin-induced fluid overload was comparable (2.8% vs. 1.4%; p = 0.32). Patients with ACLF were sicker with a higher incidence of microbiologically proven infection, hepatic encephalopathy (HE) and hyponatremia than in the DC group. Resolution of infection and hyponatremia and in-hospital survival was significantly lower in the ACLF group (72.5%) than in the DC group (92.7%; p < 0.001). Eighty-six per cent of patients achieved resolution of ACLF. CONCLUSIONS HA infusion is safe and effective even in patients without AKI and SBP and leads to the resolution of infection, hyponatremia, HE and ACLF.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India.
| | - Asim Ahmed Zuberi
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - K Chaitanya
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - Harshitha Doolam
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - Santhosh Reddy
- Department of Clinical Pharmacy, AIG Hospitals, Hyderabad, 500 032, India
| | - P K Lakshmi
- Department of Pharmacy Practice, G. Pulla Reddy College of Pharmacy, Hyderabad, 500 028, India
| | | | | | - Sowmya Iyengar
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | - Manasa Alla
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | - Mithun Sharma
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
| | | | - P N Rao
- Department of Hepatology, AIG Hospitals, Hyderabad, 500 032, India
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10
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Heybe MA, Mehta KJ. Role of albumin infusion in cirrhosis-associated complications. Clin Exp Med 2024; 24:58. [PMID: 38551716 PMCID: PMC10980629 DOI: 10.1007/s10238-024-01315-1] [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: 01/26/2024] [Accepted: 02/29/2024] [Indexed: 04/01/2024]
Abstract
Cirrhosis is an advanced-stage liver disease that occurs due to persistent physiological insults such as excessive alcohol consumption, infections, or toxicity. It is characterised by scar tissue formation, portal hypertension, and ascites (accumulation of fluid in the abdominal cavity) in decompensated cirrhosis. This review evaluates how albumin infusion ameliorates cirrhosis-associated complications. Since albumin is an oncotic plasma protein, albumin infusion allows movement of water into the intravascular space, aids with fluid resuscitation, and thereby contributes to resolving cirrhosis-induced hypovolemia (loss of extracellular fluid) seen in ascites. Thus, albumin infusion helps prevent paracentesis-induced circulatory dysfunction, a complication that occurs when treating ascites. When cirrhosis advances, other complications such as spontaneous bacterial peritonitis and hepatorenal syndrome can manifest. Infused albumin helps mitigate these by exhibiting plasma expansion, antioxidant, and anti-inflammatory functions. In hepatic encephalopathy, albumin infusion is thought to improve cognitive function by reducing ammonia concentration in blood and thereby tackle cirrhosis-induced hepatocyte malfunction in ammonia clearance. Infused albumin can also exhibit protective effects by binding to the cirrhosis-induced proinflammatory cytokines TNFα and IL6. While albumin administration has shown to prolong overall survival of cirrhotic patients with ascites in the ANSWER trial, the ATTIRE and MACHT trials have shown either no effect or limitations such as development of pulmonary oedema and multiorgan failure. Thus, albumin infusion is not a generic treatment option for all cirrhosis patients. Interestingly, cirrhosis-induced structural alterations in native albumin (which lead to formation of different albumin isoforms) can be used as prognostic biomarkers because specific albumin isoforms indicate certain complications of decompensated cirrhosis.
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Affiliation(s)
- Mohamed A Heybe
- GKT School of Medical Education, Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Kosha J Mehta
- Centre for Education, Faculty of Life Sciences and Medicine, King's College London, London, UK.
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11
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Pun CK, Huang HC, Chang CC, Hsu SJ, Huang YH, Hou MC, Lee FY. Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments. J Chin Med Assoc 2024; 87:245-251. [PMID: 38109364 DOI: 10.1097/jcma.0000000000001041] [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: 12/20/2023] Open
Abstract
Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE.
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Affiliation(s)
- Chon Kit Pun
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hui-Chun Huang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ching-Chih Chang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Shao-Jung Hsu
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Hsiang Huang
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Ming-Chih Hou
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Fa-Yauh Lee
- Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Therapeutic and Research Center of Liver Cirrhosis and Portal Hypertension, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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12
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Devisetty JV, Mallick B, Praharaj D, Tiwari A, Kumar R, Nath P, Panigrahi SC, Anand AC, Acharya SK, Chawla YK. A Study of Impact of Fixed-Dose Albumin Infusion on Outcome in Patients With Cirrhosis and Infection: A Randomized Open-label Clinical Trial. J Clin Exp Hepatol 2024; 14:101270. [PMID: 38076352 PMCID: PMC10709162 DOI: 10.1016/j.jceh.2023.08.006] [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] [Received: 05/03/2022] [Accepted: 08/14/2023] [Indexed: 01/05/2025] Open
Abstract
Background and aim Antibiotics and albumin infusion constitute the standard of treatment in patients with decompensated cirrhosis who have spontaneous bacterial peritonitis (SBP). Recent studies have also shown that the use of albumin in patients with advanced liver disease who have infections other than SBP leads to the resolution of acute and chronic liver failure and prevents the development of nosocomial infections. The recommended dose of albumin for these patients is out of reach for many in resource-limited settings like India. The evidence for this recommendation is also scarce. This study aimed to assess the efficacy of a lower dose of albumin infusion in addition to antibiotics on short-term mortality and morbidity in patients with cirrhosis and infections. Patients and methods A prospective, open-label, randomized control study was performed. Consecutive patients with cirrhosis and infections were randomized in a 2:1 ratio into two groups: group A (116) and group B (58) patients. In addition to antibiotics and standard medical therapy, group A was given albumin in a dose of 20 g/day for five days, and group B was given the recommended dose (1.5 g/kg/body weight and 1 g/kg body weight on days one and three, respectively). The primary outcome was in-hospital mortality. Secondary outcomes were improvements in clinical and laboratory parameters. Results Except for etiology, all the baseline clinical and laboratory variables in both groups were comparable. The in-hospital mortality in groups A and B was (11 [10.67%] vs. 6 [10.09%], (P = 0.965). The duration of hospitalization, 30-day mortality, improvement in shock and sensorium, and absolute improvements in serum creatinine, international normalized ratio (INR), and serum bilirubin were also comparable in both groups. Conclusion Low-dose albumin infusion in patients with cirrhosis and infections can have the same results as standard-dose albumin and can be used in resource-limited situations. Clinical trial registration number CTRI/2020/03/023794.
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Affiliation(s)
- Jayadeep V. Devisetty
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Bipadabhanjan Mallick
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Dibyaloahan Praharaj
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Anirudh Tiwari
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Raj Kumar
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Preetam Nath
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Sarat C. Panigrahi
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Anil C. Anand
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
| | - Yogesh K. Chawla
- Department of Gastroenterology and Hepatology, Kalinga Institute of Medical Sciences, Bhubaneswar, India
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Guo H, Wang G, Huang W, Li L, Bai Y, Wang H, Gao L. The Mechanism of Hepatic Encephalopathy Induced by Thioacetamide Based on Metabolomics and Proteomics: A Preliminary Study. Int J Mol Sci 2023; 25:284. [PMID: 38203455 PMCID: PMC10779174 DOI: 10.3390/ijms25010284] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 12/15/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
Hepatic encephalopathy (HE) is a central nervous system dysfunction syndrome caused by acute and chronic liver failure or various portal systemic shunt disorders. HE arises from metabolic disorder and excludes other known types of encephalopathy. HE is a major cause of death in people with liver disease. Early diagnosis and timely treatment are key to improving HE prognosis. Herein, we established a model of HE and performed metabolomics to identify 50 significantly differential metabolites between the HE group and control group. The main metabolic pathways associated with these differential metabolites were the purine metabolism, pyrimidine metabolism, aminoacyl tRNA biosynthesis, and glucose metabolism. Through proteomics analysis, we identified 226 significantly differential proteins (52 up-regulated and 174 down-regulated). The main (Kyoto Encyclopedia of Genes and Genomes) enrichment pathways were the Staphylococcus aureus infection, vitamin digestion and absorption, and complement and coagulation cascades. Through the conjoint analysis of proteomics and metabolomics, the differentially present proteins and metabolites were found to be involved in vitamin digestion and absorption, and ferroptosis pathways. In HE, malondialdehyde was significantly elevated, but glutathione was significantly diminished, and the redox balance was destroyed, thus leading to changes in proteins' levels associated with the ferroptosis pathway. In conclusion, this study preliminarily explored the molecular and metabolic mechanisms underlying HE.
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Affiliation(s)
- Honghui Guo
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
| | - Guang Wang
- Department of Laboratory Animal Science, China Medical University, Shenyang 110122, China;
| | - Wei Huang
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
| | - Lingrui Li
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
| | - Yang Bai
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
| | - Haifeng Wang
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
| | - Lina Gao
- Liaoning Province Key Laboratory of Forensic Bio-Evidence Sciences, Shenyang 110122, China; (H.G.); (W.H.)
- China Medical University Center of Forensic Investigation, Shenyang 110122, China
- Department of Forensic Analytical Toxicology, China Medical University, Shenyang 110122, China
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14
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Cai YJ, Dong JJ, Chen RC, Xiao QQ, Li XM, Chen DY, Cai C, Lin XL, Shi KQ, Lu MQ. Serum ammonia variation predicts mortality in patients with hepatitis B virus-related acute-on-chronic liver failure. Front Microbiol 2023; 14:1282106. [PMID: 38111648 PMCID: PMC10725913 DOI: 10.3389/fmicb.2023.1282106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Accepted: 11/15/2023] [Indexed: 12/20/2023] Open
Abstract
Background Hyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients. Methods A total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality. Results The 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1-3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia. Conclusion Serum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.
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Affiliation(s)
- Yi-Jing Cai
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
- Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jia-Jia Dong
- Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Rui-Cong Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qian-Qian Xiao
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xu-Mei Li
- Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - De-Yuan Chen
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chao Cai
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiu-Li Lin
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ke-Qing Shi
- Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ming-Qin Lu
- Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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15
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Gagliardi R, Zeni N, Piano S. Intravenous albumin in cirrhosis: Updated clinical uses and novel perspectives. Ann Hepatol 2023; 28:101150. [PMID: 37659473 DOI: 10.1016/j.aohep.2023.101150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 08/08/2023] [Indexed: 09/04/2023]
Affiliation(s)
- Roberta Gagliardi
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University and Hospital of Padova, Italy
| | - Nicola Zeni
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University and Hospital of Padova, Italy
| | - Salvatore Piano
- Department of Medicine (DIMED), Unit of Internal Medicine and Hepatology (UIMH), University and Hospital of Padova, Italy.
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16
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Bai Z, Méndez-Sánchez N, Romeiro FG, Mancuso A, Philips CA, Tacke F, Basaranoglu M, Primignani M, Ibrahim M, Wong YJ, Nery FG, Teschke R, Ferreira CN, Muñoz AE, Pinyopornpanish K, Thevenot T, Singh SP, Mohanty A, Satapathy SK, Ridola L, Maruyama H, Cholongitas E, Levi Sandri GB, Yang L, Shalimar, Yang Y, Villa E, Krag A, Wong F, Jalan R, O’Brien A, Bernardi M, Qi X. Use of albumin infusion for cirrhosis-related complications: An international position statement. JHEP Rep 2023; 5:100785. [PMID: 37456673 PMCID: PMC10339261 DOI: 10.1016/j.jhepr.2023.100785] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 04/06/2023] [Accepted: 04/18/2023] [Indexed: 07/18/2023] Open
Abstract
Background & Aims Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion.
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Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Andrea Mancuso
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
| | - Cyriac Abby Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Metin Basaranoglu
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Massimo Primignani
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Mostafa Ibrahim
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
| | - Yu Jun Wong
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Filipe Gaio Nery
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Rolf Teschke
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
| | - Carlos Noronha Ferreira
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
| | - Alberto E. Muñoz
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
| | - Kanokwan Pinyopornpanish
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Thierry Thevenot
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
| | | | - Arpan Mohanty
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
| | - Sanjaya K. Satapathy
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Li Yang
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Yongping Yang
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Erica Villa
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Florence Wong
- Department of Medicine, University of Toronto, Toronto, ON, Canada
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
| | | | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - the Liver Cirrhosis-related Complications (LCC)-International Special Interest Group
- Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
- Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
- Liver Research Unit, Medica Sur Clinic and Foundation, National Autonomous University of Mexico, Mexico City, Mexico
- Internal Medicine Department, Botucatu Medical School, São Paulo, Brazil
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Palermo, Italy
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, India
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
- Division of Gastroenterology, Department of Internal Medicine, Bezmialem Vakif University, Istanbul, Turkey
- Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
- Serviço de Cuidados Intensivos, Unidade de Cuidados Intermédios Médico-Cirúrgica, Centro Hospitalar Universitário do Porto, Porto, Portugal
- Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Germany
- Serviço de Gastrenterologia e Hepatologia, Hospital de Santa Maria-Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal
- Sección Hepatología, Hospital Dr. Carlos B. Udaondo. Ciudad Autónoma de Buenos Aires, Argentina
- Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Centre Hospitalier Universitaire de Besançon, Hôpital Jean Minjoz, Service d’Hépatologie et de Soins Intensifs Digestifs, Besançon, France
- Kalinga Gastroenterology Foundation, Odisha, India
- Section of Gastroenterology, Boston Medical Center, Boston, MA, USA
- Department of Internal Medicine, Division of Hepatology, Sandra Atlas Bass Center for Liver Diseases & Transplantation, Donald and Barbara Zucker School of Medicine for Hofstra/Northwell Health, Manhasset, New York, USA
- Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy
- Department of Gastroenterology, Juntendo University, Hongo, Bunkyo-ku, Tokyo, Japan
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy
- Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
- Senior Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Department of Gastroenterology, University of Modena & Reggio Emilia and Azienda Ospedaliero-Universitaria di Modena, Italy
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
- Department of Medicine, University of Toronto, Toronto, ON, Canada
- Liver Failure Group, UCL Institute for Liver and Digestive Health, The Royal Free Hospital, University College London, London, UK
- Division of Medicine, Royal Free Campus, London, UK
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
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17
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Nardelli S, Gioia S, Faccioli J, Riggio O, Ridola L. Hepatic encephalopathy - recent advances in treatment and diagnosis. Expert Rev Gastroenterol Hepatol 2023; 17:225-235. [PMID: 36843291 DOI: 10.1080/17474124.2023.2183386] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2023]
Abstract
INTRODUCTION Hepatic encephalopathy (HE) is a peculiar kind of brain dysfunction typical of liver cirrhosis characterized by nonspecific neurological and psychiatric manifestations. HE ranges from minimal hepatic encephalopathy (MHE) to the most severe form characterized by alteration of consciousness or coma (overt HE, OHE). Once the diagnosis of OHE is made, every effort to identify and correct the precipitating cause is essential for the resolution of symptoms. Clinical studies that assessed the prevalence and incidence of any type of HE (MHE and OHE) in patients affected by cirrhosis were included in this review. No language, publication date, or publication status restrictions were imposed. The studies were identified by searching electronic databases (PubMed and SCOPUS). AREAS COVERED The most widely empirical pharmacological approach consists of non-absorbable antibiotics (rifaximin) and non-absorbable disaccharides (lactulose, lactitol per os and per enemas). Other agents (including branched-chain amino acids, probiotics, other antibiotics, or intravenous L-ornithine L-aspartate) are available, but the evidence supporting their efficacy remains under debate. EXPERT OPINION Gray areas and future needs remain the therapeutic approach to MHE and issues in the design of therapeutic studies for HE which have been extensively discussed in this review.
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Affiliation(s)
- Silvia Nardelli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Lorenzo Ridola
- Department of Translational and Precision Medicine, "Sapienza" University of Rome, Rome, Italy
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Fagan A, Gavis EA, Gallagher ML, Mousel T, Davis B, Puri P, Sterling RK, Luketic VA, Lee H, Matherly SC, Sanyal AJ, Stravitz RT, Patel V, Siddiqui MS, Asgharpour A, Fuchs M, Thacker L, Bajaj JS. A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL study. J Hepatol 2023; 78:312-321. [PMID: 36152764 DOI: 10.1016/j.jhep.2022.09.009] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 08/26/2022] [Accepted: 09/13/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND & AIMS Even after recovery from overt hepatic encephalopathy (HE), minimal HE (MHE), which impairs quality of life (QoL), can persist. A double-blind, placebo-controlled randomized clinical trial was performed to determine the impact of albumin vs. saline on MHE and QoL in individuals with prior HE already on standard of care. METHODS Outpatients with cirrhosis and prior HE, MHE and hypoalbuminemia already on treatment for HE were included. Patients on regular IV albumin infusions were excluded. Participants were randomized 1:1 to receive either weekly infusions of 25% IV albumin 1.5 g/kg or saline over 5 weeks. MHE was defined using either psychometric hepatic encephalopathy score (PHES), Stroop or critical clicker frequency. MHE, QoL (based on sickness impact profile [SIP] total, physical, psychosocial domain) and serum markers (inflammation, endothelial dysfunction, and ischemia-modified albumin) were compared between baseline, the final infusion visit (end-of-drug [EOD]) and 1-week post final infusion (end-of-study [EOS]). RESULTS Forty-eight (24/group) participants were randomized and balanced (including by HE medication use) at baseline. Adverse events were similar, with MELD and ammonia remaining stable between/within groups. Albumin levels increased and ischemia-modified albumin decreased only in the albumin group at EOD and EOS vs. baseline. PHES and Stroop MHE reversal and improvement were greater in the albumin group at EOD and persisted at EOS. SIP total and psychosocial, but not physical, domain improved only in the albumin group at EOD and EOS vs. baseline. A significant reduction in IL-1β and endothelial dysfunction markers was also observed in the albumin group. CONCLUSION In a double-blind, placebo-controlled trial of outpatients with cirrhosis, prior HE and current MHE, albumin infusions were associated with improved cognitive function and psychosocial QoL, likely due to amelioration of endothelial dysfunction. CLINICAL TRIALS REGISTRATION www. CLINICALTRIALS gov NCT03585257. IMPACT AND IMPLICATIONS Even after recovery from overt hepatic encephalopathy (HE), minimal HE (MHE), which impairs quality of life, can persist. We found that intravenous albumin infusions were associated with improved cognitive function and psychosocial quality of life, likely owing to amelioration of endothelial dysfunction, compared to placebo in outpatients with prior HE and current MHE. In patients who continue to demonstrate cognitive dysfunction and impaired quality of life despite standard of care therapy for HE, albumin infusions could be considered if these results are validated.
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Affiliation(s)
- Andrew Fagan
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Edith A Gavis
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | | | - Travis Mousel
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Brian Davis
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Puneet Puri
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Richard K Sterling
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Velimir A Luketic
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Hannah Lee
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Scott C Matherly
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Arun J Sanyal
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - R Todd Stravitz
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Vaishali Patel
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Mohammad S Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Amon Asgharpour
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Michael Fuchs
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA
| | - Leroy Thacker
- Department of Biostatistics, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Richmond, Virginia, USA.
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Abstract
Hepatic encephalopathy (HE) is brain dysfunction secondary to liver insufficiency or portosystemic shunting. HE is a major burden on patients and caregivers, impairs quality of life and is associated with higher mortality. Overt HE is a clinical diagnosis while Covert HE, needs specialized diagnostic strategies. Mainstay of treatment of HE is nonabsorbable disaccharides such as lactulose as well as rifaximin; however, investigational therapies are discussed in this review. Better tools are needed to prognosticate which patients will go on to develop HE but microbiome and metabolomic-driven strategies are promising. Here we review methods to prevent the HE development and admissions.
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20
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Bai Z, Wang L, Wang R, Zou M, Méndez-Sánchez N, Romeiro FG, Cheng G, Qi X. Use of human albumin infusion in cirrhotic patients: a systematic review and meta-analysis of randomized controlled trials. Hepatol Int 2022; 16:1468-1483. [PMID: 36048318 DOI: 10.1007/s12072-022-10374-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/04/2022] [Indexed: 11/04/2022]
Abstract
BACKGROUND Human albumin infusion is effective for controlling systemic inflammation, thereby probably managing some liver cirrhosis-related complications, such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and hepatorenal syndrome. However, its clinical benefits remain controversial. METHODS EMBASE, PubMed, and Cochrane Library databases were searched. Randomized controlled trials (RCTs) regarding use of human albumin infusion in cirrhotic patients were eligible. Mortality and incidence of liver cirrhosis-related complications were pooled. Effect of human albumin infusion on mortality was also evaluated by subgroup analyses primarily according to target population and duration of human albumin infusion treatment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS Forty-two RCTs were finally included. Meta-analysis showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients (OR = 0.81, 95% CI = 0.67-0.98, p = 0.03). Subgroup analyses showed that human albumin infusion could significantly decrease the mortality of cirrhotic patients with SBP (OR = 0.36, 95% CI = 0.20-0.64, p = 0.0005) and HE (OR = 0.43, 95% CI = 0.22-0.85, p = 0.02), but not those with ascites or non-SBP infections or undergoing large-volume paracentesis. Short-term human albumin infusion treatment could significantly decrease short-term mortality (OR = 0.67, 95% CI = 0.50-0.89, p = 0.005), but not long-term mortality. Long-term human albumin infusion treatment could not significantly decrease long-term mortality (OR = 0.72, 95% CI = 0.48-1.08, p = 0.11). In addition, human albumin infusion could significantly decrease the incidence of renal impairment (OR = 0.63, 95% CI = 0.45-0.88, p = 0.007) and ascites (OR = 0.45, 95% CI = 0.25-0.81, p = 0.007), but not infections or gastrointestinal bleeding. CONCLUSIONS Human albumin infusion may improve the outcomes of cirrhotic patients. However, its indications for different complications and infusion strategy in liver cirrhosis should be further explored.
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Affiliation(s)
- Zhaohui Bai
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
- Postgraduate College, China Medical University, Shenyang, Liaoning, China
| | - Ran Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China
| | - Meijuan Zou
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Nahum Méndez-Sánchez
- Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | | | - Gang Cheng
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
- NMPA Key Laboratory for Research and Evaluation of Drug Regulatory Technology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
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21
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Vidal-Cevallos P, Chávez-Tapia NC, Uribe M. Current approaches to hepatic encephalopathy. Ann Hepatol 2022; 27:100757. [PMID: 36115576 DOI: 10.1016/j.aohep.2022.100757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 09/07/2022] [Indexed: 02/04/2023]
Abstract
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.
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Affiliation(s)
- Paulina Vidal-Cevallos
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Norberto C Chávez-Tapia
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico
| | - Misael Uribe
- Obesity and Digestive Disease Unit, Medica Sur Clinic and Foundation, Puente de Piedra 150, col. Toriello Guerra, C.P. 14050, Mexico City, Mexico.
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22
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Mallet M, Desplats V, Bouzbib C, Sultanik P, Alioua I, Marika Rudler MS, Weiss N, Thabut D. Blood ammonia in patients with chronic liver diseases: A better defined role in clinical practice. Anal Biochem 2022; 657:114873. [PMID: 36108794 DOI: 10.1016/j.ab.2022.114873] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 07/26/2022] [Accepted: 08/18/2022] [Indexed: 11/28/2022]
Abstract
Ammonia is one of the main players in the pathogenesis of hepatic encephalopathy (HE) in patients with chronic liver diseases. The usefulness of measuring ammonemia has been debated since many years. New data reveal that besides helping in the differential diagnosis of HE, ammonemia could be a prognostic marker not only in patients with HE, but also in patients without any neurological symptoms, suggesting a potential toxic role of ammonia beyond the brain. Finally, targeting ammonemia while monitoring therapeutic response could be a way to improve outcomes in patients with HE.
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Affiliation(s)
- Maxime Mallet
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Victor Desplats
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Charlotte Bouzbib
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Philippe Sultanik
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Imen Alioua
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (MTS), MetaboHUB, F-91191, Gif sur Yvette, France
| | - M S Marika Rudler
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Nicolas Weiss
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à orientation Neurologique, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France & Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Université, France
| | - Dominique Thabut
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D'hépato-gastroentérologie, Unité de soins intensifs D'hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et fibro-inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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23
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de Mattos ÂZ, Simonetto DA, Terra C, Farias AQ, Bittencourt PL, Pase THS, Toazza MR, de Mattos AA. Albumin administration in patients with cirrhosis: Current role and novel perspectives. World J Gastroenterol 2022; 28:4773-4786. [PMID: 36156923 PMCID: PMC9476855 DOI: 10.3748/wjg.v28.i33.4773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 06/05/2022] [Accepted: 07/06/2022] [Indexed: 02/06/2023] Open
Abstract
Mortality in cirrhosis is mostly associated with the development of clinical decompensation, characterized by ascites, hepatic encephalopathy, variceal bleeding, or jaundice. Therefore, it is important to prevent and manage such complications. Traditionally, the pathophysiology of decompensated cirrhosis was explained by the peripheral arterial vasodilation hypothesis, but it is currently understood that decompensation might also be driven by a systemic inflammatory state (the systemic inflammation hypothesis). Considering its oncotic and nononcotic properties, albumin has been thoroughly evaluated in the prevention and management of several of these decompensating events. There are formal evidence-based recommendations from international medical societies proposing that albumin be administered in individuals with cirrhosis undergoing large-volume paracentesis, patients with spontaneous bacterial peritonitis, those with acute kidney injury (even before the etiological diagnosis), and those with hepatorenal syndrome. Moreover, there are a few randomized controlled trials and meta-analyses suggesting a possible role for albumin infusion in patients with cirrhosis and ascites (long-term albumin administration), individuals with hepatic encephalopathy, and those with acute-on-chronic liver failure undergoing modest-volume paracentesis. Further studies are necessary to elucidate whether albumin administration also benefits patients with cirrhosis and other complications, such as individuals with extraperitoneal infections, those hospitalized with decompensated cirrhosis and hypoalbuminemia, and patients with hyponatremia.
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Affiliation(s)
- Ângelo Zambam de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
| | - Douglas Alano Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55902, United States
| | - Carlos Terra
- Department of Gastroenterology, State University of Rio de Janeiro, Rio de Janeiro 20550-170, Brazil
| | | | | | - Tales Henrique Soares Pase
- Internal Medicine Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Marlon Rubini Toazza
- Gastroenterology and Hepatology Unit, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Brazil
| | - Angelo Alves de Mattos
- Graduate Program in Medicine: Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil
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Castro-Narro G, Moctezuma-Velázquez C, Male-Velázquez R, Trejo-Estrada R, Bosques FJ, Moreno-Alcántar R, Rodríguez-Hernández H, Bautista-Santos A, Córtez-Hernández C, Cerda-Reyes E, Pérez-Escobar J, Aldana-Ledesma JM, Aguirre-Valadez J, Ruiz-Velasco JAV, Contreras-Omaña R, Miranda-Zazueta G, Reyes-Bastidas MDR, Meza-Cardona JM, Chávez-Tapia N, Fernández-Pérez NJ, García-Jiménez ES, Torre A. Position statement on the use of albumin in liver cirrhosis. Ann Hepatol 2022; 27:100708. [PMID: 35550187 DOI: 10.1016/j.aohep.2022.100708] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 02/15/2022] [Indexed: 02/04/2023]
Abstract
Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.
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Affiliation(s)
- Graciela Castro-Narro
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico; Gastroenterology Unit, Hospital Médica Sur, Mexico City, Mexico
| | - Carlos Moctezuma-Velázquez
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | - Rene Male-Velázquez
- Instituto de la Salud Digestiva y Hepática [Institute of Gastrointestinal and Liver Health], Guadalajara, Jalisco, Mexico
| | | | | | - Rosalba Moreno-Alcántar
- Centro Médico de Alta Especialidad Siglo XXI [21st Century High Speciality Medical Centre], Mexico City, Mexico
| | | | - Aleida Bautista-Santos
- Gastroenterology Department, Centro Médico Nacional 20 de Noviembre ["20 November" National Medical Centre], Mexico City, Mexico
| | | | - Eira Cerda-Reyes
- Hospital Central Militar, Mexico City, Mexico; Escuela Militar de Graduados de Sanidad, Mexico City, Mexico
| | - Juanita Pérez-Escobar
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | | | | | | | - Raúl Contreras-Omaña
- Centro de Estudio e Investigación en Enfermedades Hepáticas y Toxicológicas (CEIHET) [Centre for Study and Research in Hepatic and Toxicological Diseases], Pachuca de Soto, Hidalgo, Mexico
| | - Godolfino Miranda-Zazueta
- Gastroenterology Department, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico
| | | | | | | | | | | | - Aldo Torre
- Metabolic Unit, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" ["Salvador Zubirán" National Institute of Medical Sciences and Nutrition], Mexico City, Mexico.
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25
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Rajpurohit S, Musunuri B, Shailesh, Basthi Mohan P, Shetty S. Novel Drugs for the Management of Hepatic Encephalopathy: Still a Long Journey to Travel. J Clin Exp Hepatol 2022; 12:1200-1214. [PMID: 35814520 PMCID: PMC9257922 DOI: 10.1016/j.jceh.2022.01.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatic encephalopathy (HE) is one of the reversible complications of chronic liver disease, associated with a higher mortality rate. In current clinical practice, treatment with rifaximin and lactulose/lactitol is the first line of treatment in HE. With the advance in pathophysiology, a new class of ammonia lowering drugs has been revealed to overcome the hurdle and disease burden. The mechanism of the novel agents differs significantly and includes the alteration in intestinal microbiota, intestinal endothelial integrity, oxidative stress, inflammatory markers, and modulation of neurotoxins. Most of the trials have reported promising results in the treatment and prevention of HE with fecal microbiota transplantation, albumin, probiotics, flumazenil, polyethylene glycol, AST-120, glycerol phenylbutyrate, nitazoxanide, branched-chain amino acid, naloxone, and acetyl-l-carnitine. However, their clinical use is limited due to the presence of major drawbacks in their study design, sample size, safety profile, bias, and heterogenicity. This study will discuss the novel therapeutic targets for HE in liver cirrhosis patients with supporting clinical trial data.
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Key Words
- ALC, acetyl-L-carnitine
- BCAA, branched-chain amino acid
- BD, twice a day
- BDI, Beck Depression Inventory
- BUN, blood urea nitrogen
- CHESS, Clinical Hepatic Encephalopathy Staging Scale
- CLDQ, Chronic Liver Disease Questionnaire
- ECT, estimated completion time
- EEG, electroencephalogram
- FMT, fecal microbiota transplantation
- GPB, glycerol phenylbutyrate
- HESA, Hepatic Encephalopathy Scoring Algorithm
- HRQOL, health-related quality of life
- IV, intravenous
- MED, Modified Encephalopathy Scale
- MELD, Model for End-stage Liver Disease
- MMSE, Mini-Mental State Examination
- NTZ, nitazoxanide
- Nal, naloxone
- OD, once a day
- ORT, object recognition test
- PEG, polyethylene glycol
- QID, four times a day
- QOL, quality of life
- RBNS, Repeatable Battery for the Assessment of Neuropsychological Status
- RCT, randomized control trial
- RT-qPCR, real-time quantitative polymerase chain reaction
- TID, three times a day
- VSL#3, high concentration probiotic preparations
- hepatic encephalopathy
- liver cirrhosis
- novel drugs
- treatment outcome
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Affiliation(s)
- Siddheesh Rajpurohit
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Balaji Musunuri
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shailesh
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Pooja Basthi Mohan
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
| | - Shiran Shetty
- Department of Gastroenterology and Hepatology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka, India
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26
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Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers 2022; 8:43. [PMID: 35739133 DOI: 10.1038/s41572-022-00366-6] [Citation(s) in RCA: 98] [Impact Index Per Article: 32.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/12/2022] [Indexed: 01/18/2023]
Abstract
Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging.
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Affiliation(s)
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Radha K Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (Uttar Pradesh), India
| | - Vicente Felipo
- Laboratory of Neurobiology, Centro de Investigación Principe Felipe, Valencia, Spain
| | - Boris Görg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Rajiv Jalan
- Liver Failure Group ILDH, Division of Medicine, UCL Medical School, Royal Free Campus, London, UK.,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain
| | - Gerald Kircheis
- Department of Gastroenterology, Diabetology and Hepatology, University Hospital Brandenburg an der Havel, Brandenburg Medical School, Brandenburg an der Havel, Germany
| | - Manuela Merli
- Department of Translational and Precision Medicine, Universita' degli Studi di Roma - Sapienza, Roma, Italy
| | | | - Manuel Romero-Gomez
- UCM Digestive Diseases, Virgen del Rocío University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, UK
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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27
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Wong YJ, Loo JH. Albumin therapy for hepatic encephalopathy: current evidence and controversies. Metab Brain Dis 2022; 38:1759-1763. [PMID: 35616800 DOI: 10.1007/s11011-022-01002-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 05/07/2022] [Indexed: 12/01/2022]
Abstract
Hepatic encephalopathy (HE) is a common complication that occurs in 16-21% of end-stage cirrhosis patients. Emerging evidence suggests that systemic inflammation and oxidative stress may play a role in the development of HE. Recent understanding on the anti-inflammatory properties of human albumin has led to growing interest of using human albumin for the treatment and prevention of HE among decompensated patients. In this review, we aim to discuss the current evidence and controversies of using human albumin for the treatment and prevention of HE in advanced cirrhosis patients.
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Affiliation(s)
- Yu Jun Wong
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore, Singapore.
- Duke-NUS Medicine Academic Clinical Program, SingHealth, Singapore, Singapore.
| | - Jing Hong Loo
- Yong Loo Lin School of Medicine, National University of Singapore, Queenstown, Singapore
- Department of Gastroenterology & Hepatology, Changi General Hospital, Singapore, Singapore
- Duke-NUS Medicine Academic Clinical Program, SingHealth, Singapore, Singapore
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28
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Jain A, Sharma BC, Mahajan B, Srivastava S, Kumar A, Sachdeva S, Sonika U, Dalal A. L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial. Hepatology 2022; 75:1194-1203. [PMID: 34822189 DOI: 10.1002/hep.32255] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 11/13/2021] [Accepted: 11/18/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. APPROACH AND RESULTS In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n = 70) or placebo, lactulose, and rifaximin (n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. CONCLUSIONS Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.
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Affiliation(s)
- Arpan Jain
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | | | - Bhawna Mahajan
- Department of BiochemistryGB Pant HospitalNew DelhiIndia
| | | | - Ajay Kumar
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | | | - Ujjwal Sonika
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
| | - Ashok Dalal
- Department of GastroenterologyGB Pant HospitalNew DelhiIndia
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29
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Bai Z, Zou M, Zhang X, Cheng G. Human Serum Albumin Infusion in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:113-125. [DOI: 10.1007/978-981-19-2615-0_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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30
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Faccioli J, Gioia S, Nardelli S, Riggio O, Ridola L. Lactulose in Liver Cirrhosis. PHARMACOTHERAPY FOR LIVER CIRRHOSIS AND ITS COMPLICATIONS 2022:223-240. [DOI: 10.1007/978-981-19-2615-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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31
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Hasan LZ, Wu GY. Novel Agents in the Management of Hepatic Encephalopathy: A Review. J Clin Transl Hepatol 2021; 9:749-759. [PMID: 34722190 PMCID: PMC8516841 DOI: 10.14218/jcth.2021.00102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/28/2021] [Accepted: 06/01/2021] [Indexed: 12/15/2022] Open
Abstract
Hepatic encephalopathy is an often devastating complication of chronic liver disease, associated with high mortality and increased burden on patients and healthcare systems. Current agents (such as nonabsorbable disaccharides and oral antibiotics) are often only partially effective and associated with unpleasant side effects. With our improved understanding of the pathophysiology of hepatic encephalopathy, multiple treatment modalities have emerged with promising results when used alone or as an adjunct to standard medications. The mechanisms of these agents vary greatly, and include the manipulation of gut microbial composition, reduction of oxidative stress, inhibition of inflammatory mediators, protection of endothelial integrity, modulation of neurotransmitter release and function, and other novel methods to reduce blood ammonia and neurotoxins. Despite their promising results, the studies assessing these treatment modalities are often limited by study design, sample size, outcome assessment heterogeneity, and paucity of data regarding their safety profiles. In this article, we discuss these novel agents in depth and provide the best evidence supporting their use, along with a critical look at their limitations and future directions.
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Affiliation(s)
- Leen Z. Hasan
- Correspondence to: Leen Z. Hasan, Department of Medicine, Internal Medicine Residency Program, UConn Health, 263 Farmington Avenue, Farmington, CT 06030-1235, USA. ORCID: https://orcid.org/0000-0003-3852-8591. Tel: +1-617-283-6633, Fax: +1-860-679-4613, E-mail: ,
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32
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Wong YJ, Kumar R, Chua YJJ, Ang TL. Long-term albumin infusion in decompensated cirrhosis: A review of current literature. World J Hepatol 2021; 13:421-432. [PMID: 33959225 PMCID: PMC8080546 DOI: 10.4254/wjh.v13.i4.421] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/22/2021] [Accepted: 04/13/2021] [Indexed: 02/06/2023] Open
Abstract
Decompensated cirrhosis is characterized by chronic inflammation and severe portal hypertension leading to systemic circulatory dysfunction. Albumin infusion has been widely used in decompensated cirrhosis in patients with spontaneous bacterial peritonitis, large-volume paracentesis and hepatorenal syndrome. Emerging data suggest long-term albumin infusion has both oncotic and non-oncotic properties which may improve the clinical outcomes in decompensated cirrhosis patients. We review the current literature on both the established and potential role of albumin, and specifically address the controversies of long-term albumin infusion in decompensated cirrhosis patients.
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Affiliation(s)
- Yu Jun Wong
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Rahul Kumar
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
| | - Yu Jing Jonathan Chua
- Department of Internal Medicine, Yong Loo Lin School of Medicine, Singapore 117597, Singapore
| | - Tiing Leong Ang
- Department ofGastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
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33
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Hiramine Y, Uto H, Mawatari S, Kanmura S, Imamura Y, Hiwaki T, Saishoji A, Kakihara A, Maenohara S, Tokushige K, Ido A. Efficacy of rifaximin, a poorly absorbed rifamycin antimicrobial agent, for hepatic encephalopathy in Japanese patients. Hepatol Res 2021; 51:445-460. [PMID: 33533150 DOI: 10.1111/hepr.13622] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 12/27/2020] [Accepted: 01/15/2021] [Indexed: 12/21/2022]
Abstract
AIM Rifaximin is recommended as treatment for hepatic encephalopathy (HE) that targets intestinal bacterial flora. Although combined use with synthetic disaccharides is the standard of care worldwide, the therapeutic effects of rifaximin for overt encephalopathy (OHE) in Japanese patients have not been examined sufficiently. We examined the therapeutic effects of rifaximin for OHE in Japanese patients. METHODS A total of 76 patients who developed OHE of West Haven grade II or higher at least once within the 12 months before starting rifaximin were included. Blood ammonia levels and the incidence of OHE during the 12 months before and after starting rifaximin therapy were compared in a before-and-after study. Rifaximin efficacy and predictors of efficacy were also examined. RESULTS Post-treatment blood ammonia levels were significantly lower than pretreatment levels. The mean annual number of OHE incidents and intravenous branched-chain amino acid preparations used per patient were significantly lower after starting rifaximin therapy (2.51 vs. 0.76 times/year, p < 0.001; and 71.9 vs. 20.7 preparations/year, p = 0.003, respectively). The cumulative incidence of hospitalizations associated with HE significantly decreased after rifaximin therapy (hazard ratio 0.187; p < 0.001). The efficacy rate, defined as the proportion of patients without OHE during the administration of rifaximin for 1 year after starting rifaximin therapy, was 65.8%. Serum albumin ≥2.7 g/dl was an independent predictor of efficacy. CONCLUSION Rifaximin was associated with decreased blood ammonia levels, lower incidence of OHE, and fewer hospitalizations in Japanese patients with HE. In addition, serum albumin level was an important predictor on efficacy of rifaximin.
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Affiliation(s)
- Yasunari Hiramine
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Hirofumi Uto
- Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, Miyazaki, Japan.,Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Seiichi Mawatari
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shuji Kanmura
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yasushi Imamura
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Takuya Hiwaki
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akiko Saishoji
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan.,Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Atsuko Kakihara
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan.,Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Shigeho Maenohara
- Department of Surgery, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Koichi Tokushige
- Department of Internal Medicine, Kagoshima Kouseiren Hospital, Kagoshima, Japan
| | - Akio Ido
- Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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34
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Akahane T, Yoshiji H. Role of serum albumin in hepatic encephalopathy. Hepatol Res 2021; 51:353-354. [PMID: 33797845 DOI: 10.1111/hepr.13632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Takemi Akahane
- Department of Gastroenterology, Nara Medical University, Kashihara, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Nara Medical University, Kashihara, Japan
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35
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Kimer N, Gluud LL, Pedersen JS, Tavenier J, Møller S, Bendtsen F. The Psychometric Hepatic Encephalopathy Syndrome score does not correlate with blood ammonia, endotoxins or markers of inflammation in patients with cirrhosis. Transl Gastroenterol Hepatol 2021; 6:8. [PMID: 33409402 DOI: 10.21037/tgh.2020.02.14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 02/10/2020] [Indexed: 12/18/2022] Open
Abstract
Background The pathogenesis of hepatic encephalopathy (HE) remains unclear but impaired clearance of gut-derived neurotoxins and increased systemic inflammation are thought to play key roles. The diagnosis is based on detection of neurophysiological and neuropsychometric abnormalities. The Psychometric Hepatic Encephalopathy Score (PHES) have been found to correlate with markers of systematic inflammation including interleukin 6, C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α). This study explores the associations between the PHES score and systemic inflammation, endotoxins and disease severity using baseline data from a trial involving patients with cirrhosis and minimal or no HE (NCT01769040). Methods Arterial blood was obtained during hepatic vein catheterization, from 54 patients [median age 55 (range, 33-70) years; 83% men] with decompensated but stable cirrhosis. None had clinical evidence of HE but 34 (55.6%) had an abnormal PHES score indicating the presence of minimal HE. Relationships were sought between the PHES score and markers of systemic inflammation, high sensitivity-CRP, cytokines (SDF-1α, TGF-b1, IP-10, IL-6, 10 and 18, and TNF-α; lipopolysaccharide (LPS), the lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14); and the blood ammonia. Results No significant relationships were found between the PHES score and any of the variables tested with the single exception of the correlation with serum IL-6 (r=-0.29, 95% confidence interval, -0.53 to -0.02, P=0.031). No independent predictors of the PHES score were identified in regression analyses. Conclusions No predictive associations were identified between the PHES scores and circulating blood ammonia, endotoxins, or markers of systemic inflammation in this patient population.
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Affiliation(s)
- Nina Kimer
- Gastrounit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark.,Centre of Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University Hospital Hvidovre, Hvidovre, Denmark
| | - Lise Lotte Gluud
- Gastrounit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
| | | | - Juliette Tavenier
- Clinical Research Centre, University Hospital Hvidovre, Hvidovre, Denmark
| | - Søren Møller
- Centre of Diagnostic Imaging and Research, Department of Clinical Physiology and Nuclear Medicine, University Hospital Hvidovre, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark
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36
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Rose CF, Amodio P, Bajaj JS, Dhiman RK, Montagnese S, Taylor-Robinson SD, Vilstrup H, Jalan R. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol 2020; 73:1526-1547. [PMID: 33097308 DOI: 10.1016/j.jhep.2020.07.013] [Citation(s) in RCA: 244] [Impact Index Per Article: 48.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 07/01/2020] [Accepted: 07/03/2020] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it contributes greatly to impaired quality of life, morbidity and mortality. This review will critically discuss the latest classification of HE, as well as the pathogenesis and pathophysiological pathways underlying the neurological decline in patients with end-stage liver disease. In addition, management strategies, diagnostic approaches, currently available therapeutic options and novel treatment strategies are discussed.
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Affiliation(s)
- Christopher F Rose
- Hepato-Neuro Laboratory, CRCHUM, Université de Montréal, Montreal, Canada.
| | - Piero Amodio
- Department of Medicine, University of Padova, Padova, Italy
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - Radha Krishan Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Simon D Taylor-Robinson
- Department of Surgery and Cancer, St. Mary's Hospital Campus, Imperial College London, London, United Kingdom
| | - Hendrik Vilstrup
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark
| | - Rajiv Jalan
- Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus, London, United Kingdom; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain.
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37
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Søreide JA, Deshpande R. Post hepatectomy liver failure (PHLF) - Recent advances in prevention and clinical management. Eur J Surg Oncol 2020; 47:216-224. [PMID: 32943278 DOI: 10.1016/j.ejso.2020.09.001] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 08/26/2020] [Accepted: 09/01/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Posthepatectomy liver failure (PHLF) is a relatively rare but feared complication following liver surgery, and associated with high morbidity, mortality and cost implications. Significant advances have been made in detailed preoperative assessment, particularly of the liver function in an attempt to predict and mitigate this complication. METHODS A detailed search of PubMed and Medline was performed using keywords "liver failure", "liver insufficiency", "liver resection", "postoperative", and "post-hepatectomy". Only full texts published in English were considered. Particular emphasis was placed on literature published after 2015. A formal systematic review was not found feasible hence a pragmatic review was performed. RESULTS The reported incidence of PHLF varies widely in reported literature due to a historical absence of a universal definition. Incorporation of the now accepted definition and grading of PHLF would suggest the incidence to be between 8 and 12%. Major risk factors include background liver disease, extent of resection and intraoperative course. The vast majority of mortality associated with PHLF is related to sepsis, organ failure and cerebral events. Despite multiple attempts, there has been little progress in the definitive and specific management of liver failure. This review article discusses recent advances made in detailed preoperative evaluation of liver function and evidence-based targeted approach to managing PHLF. CONCLUSION PHLF remains a major cause of mortality following liver resection. In absence of a specific remedy, the best approach is mitigating the risk of it happening by detailed assessment of liver function, patient selection and general care of a critically ill patient.
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Affiliation(s)
- Jon Arne Søreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
| | - Rahul Deshpande
- Department of HPB Surgery, Manchester Royal Infirmary, Manchester, UK
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38
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Lee EW, Lee AE, Saab S, Kee ST. Retrograde Transvenous Obliteration (RTO): A New Treatment Option for Hepatic Encephalopathy. Dig Dis Sci 2020; 65:2483-2491. [PMID: 32002756 DOI: 10.1007/s10620-020-06050-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 01/06/2020] [Indexed: 12/31/2022]
Abstract
Hepatic Encephalopathy (HE) is a complication of liver disease, consisting of brain dysfunction often due to portosystemic shunting of blood flow in the liver. HE can range from minimal HE, presenting with normal neurological function, to overt HE, with neurological and neuropsychiatric abnormalities. Various clinical grading systems are used to differentiate HE to provide the appropriate treatments. Traditional treatment of HE aims to identify and resolve precipitating factors through targeting hyperammonemia and administering antibiotics or probiotics. While retrograde transvenous obliteration (RTO), including balloon-occluded retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration or plug-assisted retrograde tranvenous obliteration, is an established procedure to manage gastric varices, little is known about its potential to treat HE. RTO is a procedure to occlude a spontaneous portosystemic shunt, minimizing shunting of portal blood to systemic circulation. Though there is not a large study with HE patients who have undergone RTO; the results appear promising in reducing HE. Side effects, however, should be considered in the treatment of HE such as the transient worsening of portal hypertension and the formation of additional shunts. While additional studies are needed to assess the long-term success, RTO appears to be an effective alternative method to alleviate clinical symptoms of HE when pharmacological therapies and other conservative medical managements have failed.
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Affiliation(s)
- Edward Wolfgang Lee
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, Ronald Reagan Medical Center at UCLA, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095-743730, USA. .,Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA Medical Center, Ronald Reagan Medical Center at UCLA, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095-743730, USA.
| | - Audrey E Lee
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, Ronald Reagan Medical Center at UCLA, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095-743730, USA
| | - Sammy Saab
- Division of Liver and Pancreas Transplantation, Department of Surgery, UCLA Medical Center, Ronald Reagan Medical Center at UCLA, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095-743730, USA.,Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA, USA
| | - Stephen T Kee
- Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, Ronald Reagan Medical Center at UCLA, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Los Angeles, CA, 90095-743730, USA
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39
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Bajaj JS, Lauridsen M, Tapper EB, Duarte-Rojo A, Rahimi RS, Tandon P, Shawcross DL, Thabut D, Dhiman RK, Romero-Gomez M, Sharma BC, Montagnese S. Important Unresolved Questions in the Management of Hepatic Encephalopathy: An ISHEN Consensus. Am J Gastroenterol 2020; 115:989-1002. [PMID: 32618647 DOI: 10.14309/ajg.0000000000000603] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Management of hepatic encephalopathy (HE) remains challenging from a medical and psychosocial perspective. Members of the International Society for Hepatic Encephalopathy and Nitrogen Metabolism recognized 5 key unresolved questions in HE management focused on (i) driving, (ii) ammonia levels in clinical practice, (iii) testing strategies for covert or minimal HE, (iv) therapeutic options, and (v) nutrition and patient-reported outcomes. The consensus document addresses these topical issues with a succinct review of the literature and statements that critically evaluate the current science and practice, laying the groundwork for future investigations.
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Affiliation(s)
- Jasmohan S Bajaj
- Virginia Commonwealth University, McGuire VA Medical Center, Richmond, Virginia, USA
| | | | | | | | | | | | | | - Dominique Thabut
- Paris Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France
| | - Radha K Dhiman
- Postgraduate Institute of Medical Education & Research, Chandigarh, India
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Bohra A, Worland T, Hui S, Terbah R, Farrell A, Robertson M. Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care. World J Gastroenterol 2020; 26:2221-2231. [PMID: 32476788 PMCID: PMC7235207 DOI: 10.3748/wjg.v26.i18.2221] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/27/2020] [Accepted: 04/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis.
AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care.
METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012–2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin.
RESULTS 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality.
CONCLUSION Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.
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Affiliation(s)
- Anuj Bohra
- Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
| | - Thomas Worland
- Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
- Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Samuel Hui
- Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
| | - Ryma Terbah
- Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Ann Farrell
- Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
| | - Marcus Robertson
- Department of Gastroenterology, Monash Health, Clayton 3168, Victoria, Australia
- Department of Gastroenterology, Austin Health, Heidelberg 3084, Victoria, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton 3168, Victoria, Australia
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41
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Abstract
Despite widespread use of lactulose and rifaximin for the treatment of hepatic encephalopathy, this complication of advanced liver disease remains a major burden on the health care system in the United States and continues to predispose to high morbidity and mortality. Several agents have surfaced over recent years with promise to treat hepatic encephalopathy and mitigate the cognitive impairment associated with this disease process. The purpose of this article is to highlight the leading emerging therapies in hepatic encephalopathy as well as their therapeutic targets.
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42
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KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol 2020; 26:83-127. [PMID: 31918536 PMCID: PMC7160350 DOI: 10.3350/cmh.2019.0010n] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 10/23/2019] [Indexed: 02/06/2023] Open
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Tufoni M, Zaccherini G, Caraceni P, Bernardi M. Albumin: Indications in chronic liver disease. United European Gastroenterol J 2020; 8:528-535. [PMID: 32213034 DOI: 10.1177/2050640620910339] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Albumin is currently employed as a plasma expander to prevent and treat specific complications of cirrhosis with ascites, such as the prevention of paracentesis-induced circulatory dysfunction and renal dysfunction induced by spontaneous bacterial peritonitis, as well as the diagnosis and treatment of acute kidney injury and hepatorenal syndrome. Recently, evidence has shown that long-term albumin administration in patients with decompensated cirrhosis reduces mortality and incidence of complications, eases the management of ascites, is cost effective, and has a good safety profile.
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Affiliation(s)
- Manuel Tufoni
- Department of Medical and Surgical Sciences, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Giacomo Zaccherini
- Department of Medical and Surgical Sciences, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Paolo Caraceni
- Department of Medical and Surgical Sciences, S Orsola-Malpighi University Hospital, Bologna, Italy
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, S Orsola-Malpighi University Hospital, Bologna, Italy
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Ridola L, Riggio O, Gioia S, Faccioli J, Nardelli S. Clinical management of type C hepatic encephalopathy. United European Gastroenterol J 2020; 8:536-543. [PMID: 32213035 DOI: 10.1177/2050640620909675] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Type-C hepatic encephalopathy is a complex neurological syndrome, characteristic of patients with liver disease, causing a wide and complex spectrum of nonspecific neurological and psychiatric manifestations, ranging from a subclinical entity, minimal hepatic encephalopathy, to a deep form in which a complete alteration of consciousness can be observed: overt hepatic encephalopathy. Overt hepatic encephalopathy occurs in 30-40% of patients. According to the time course, hepatic encephalopathy is subdivided into episodic, recurrent and persistent. Diagnostic strategies range from simple clinical scales to more complex psychometric and neurophysiological tools. Therapeutic options may vary between episodic hepatic encephalopathy, in which it is important to define and treat the precipitating factor and hepatic encephalopathy and secondary prophylaxis, where the standard of care is non-absorbable disaccharides and rifaximin. Grey areas and future needs remain the therapeutic approach to minimal hepatic encephalopathy and issues in the design of therapeutic studies for hepatic encephalopathy.
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Affiliation(s)
- Lorenzo Ridola
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Oliviero Riggio
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Stefania Gioia
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Jessica Faccioli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Silvia Nardelli
- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
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The Efficacy of Lactulose for the Treatment of Hyperammonemic Encephalopathy Due to Severe Heart Failure. Diagnostics (Basel) 2020; 10:diagnostics10020070. [PMID: 32012742 PMCID: PMC7168910 DOI: 10.3390/diagnostics10020070] [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: 11/29/2019] [Revised: 01/23/2020] [Accepted: 01/26/2020] [Indexed: 11/29/2022] Open
Abstract
Hyperammonemic encephalopathy secondary to heart failure is rare and there had been little reports about effective treatment. Organ hypoperfusion or congestion by heart failure may lead to various organ dysfunctions, and liver and intestinal circulatory impairment might cause ammonia metabolic failure. Here, we report on the case of a patient with hyperammonemic encephalopathy that was secondary to heart failure, which was effectively treated by lactulose.
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Bai Z, Bernardi M, Yoshida EM, Li H, Guo X, Méndez-Sánchez N, Li Y, Wang R, Deng J, Qi X. Albumin infusion may decrease the incidence and severity of overt hepatic encephalopathy in liver cirrhosis. Aging (Albany NY) 2019; 11:8502-8525. [PMID: 31596729 PMCID: PMC6814610 DOI: 10.18632/aging.102335] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 09/22/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The role of human albumin infusion for the prevention and treatment of overt hepatic encephalopathy (HE) in liver cirrhosis remains unclear. RESULTS Among the 708 patients without pre-existing overt HE, albumin infusion significantly decreased the incidence of overt HE (4.20% versus 12.70%, P<0.001) and in-hospital mortality (1.70% versus 5.40%, P=0.008). Among the 182 patients with overt HE at admission or during hospitalization, albumin infusion significantly improved overt HE (84.60% versus 68.10%, P=0.009) and decreased in-hospital mortality (7.70% versus 19.80%, P=0.018). Meta-analysis of 6 studies found that albumin infusion might decrease the risk of overt HE (OR=1.63, P=0.07), but the difference was not statistically significant. Meta-analysis of 3 studies found that albumin infusion significantly improved overt HE (OR=2.40, P=0.04). CONCLUSIONS Based on the results of our retrospective study and meta-analysis, albumin infusion might prevent from the occurrence of overt HE and improve the severity of overt HE in cirrhosis. Our retrospective study also suggested that albumin infusion improved the outcomes of cirrhotic patients regardless of overt HE. METHODS Cirrhotic patients consecutively admitted between January 2010 and June 2014 were considered in a retrospective study. A 1:1 propensity score matching analysis was performed. Additionally, publications regarding albumin infusion for the management of overt HE were systematically searched. Meta-analyses were performed by random-effect model. Odds ratio (OR) was calculated.
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Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
- Postgraduate College, Shenyang Pharmaceutical University, Shenyang, P.R. China
| | - Mauro Bernardi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Eric M. Yoshida
- Division of Gastroenterology, Vancouver General Hospital, Vancouver, British Columbia, Canada
| | - Hongyu Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic and Foundation and Faculty of Medicine, National Autonomous University of Mexico, Mexico
| | - Yingying Li
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Ran Wang
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Jiao Deng
- Department of Pharmacology, General Hospital of Northern Theater Command, (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, P.R. China
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Abstract
Patients with end-stage liver disease (ESLD) who require intensive care unit admission have high rates of mortality. This article reviews the pathophysiology and emergency department assessment and management of the most frequent conditions and complications encountered in critically ill ESLD patients including hepatic encephalopathy, gastrointestinal bleeding, sepsis and bacterial peritonitis, hepatorenal syndrome, severe coagulopathy, and hepatic hydrothorax.
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Affiliation(s)
- Sara Crager
- Department of Emergency Medicine, 924 Westwood Boulevard, Suite 300, Los Angeles, CA 90049, USA; Division of Critical Care, Department of Anesthesia, University of California Los Angeles-David Geffen School of Medicine, Los Angeles, CA, USA.
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48
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Bai Z, Guo X, Tacke F, Li Y, Li H, Qi X. Association of serum albumin level with incidence and mortality of overt hepatic encephalopathy in cirrhosis during hospitalization. Therap Adv Gastroenterol 2019; 12:1756284819881302. [PMID: 31636711 PMCID: PMC6783662 DOI: 10.1177/1756284819881302] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Accepted: 09/18/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatic encephalopathy (HE) is a serious complication of cirrhosis. Decreased serum albumin (ALB) level may facilitate the development of HE and accelerate the death of cirrhotic patients with HE. Recent evidence also suggests that human albumin infusion may reduce the incidence of HE and improve the outcomes of cirrhotic patients. This study aimed to explore the association of serum ALB level with the development of overt HE and HE-associated mortality during hospitalization. METHODS Cirrhotic patients admitted to our hospital between January 2010 and February 2019 were screened. Independent predictors for HE were identified by logistic regression analyses. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated. Area under curve (AUC) was calculated by receiver operator characteristic curve analyses. RESULTS Of the 2376 included patients with cirrhosis but without HE at admission, 113 (4.8%) developed overt HE during hospitalizations. ALB level (OR = 0.878, 95% CI = 0.834-0.924) was an independent risk factor for development of overt HE. AUC of ALB level for predicting the development of overt HE was 0.770 (95% CI = 0.752-0.787, p < 0.0001), and the best cut-off value was ⩽31.6 g/l. Of the 183 included patients with cirrhosis and overt HE at admission, 20 (10.9%) died during hospitalizations. ALB level (OR = 0.864, 95% CI = 0.771-0.967) was an independent risk factor for death from overt HE. The AUC of ALB level for predicting death from overt HE was 0.737 (95% CI = 0.667-0.799, p = 0.0001), and the best cut-off value was ⩽22.8 g/l. CONCLUSIONS Decreased serum ALB level may be associated with higher risk of overt HE and HE-associated mortality during hospitalizations in cirrhosis.
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Affiliation(s)
- Zhaohui Bai
- Department of Gastroenterology, General Hospital
of Northern Theater Command (General Hospital of Shenyang Military Area),
Shenyang, PR China
- Postgraduate College, Shenyang Pharmaceutical
University, Shenyang, PR China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital
of Northern Theater Command (General Hospital of Shenyang Military Area),
Shenyang, PR China
| | - Frank Tacke
- Department of Gastroenterology and Hepatology,
Charité University Medical Center, Berlin, Germany
| | - Yingying Li
- Department of Gastroenterology, General Hospital
of Northern Theater Command (General Hospital of Shenyang Military Area),
Shenyang, PR China
- Postgraduate College, Jinzhou Medical
University, Jinzhou, PR China
| | - Hongyu Li
- Department of Gastroenterology, General Hospital
of Northern Theater Command (formerly called General Hospital of Shenyang
Military Area), Shenyang, PR China
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Ridola L, Nardelli S, Gioia S, Riggio O. How to Design a Multicenter Clinical Trial in Hepatic Encephalopathy. J Clin Exp Hepatol 2019; 9:137-145. [PMID: 30765947 PMCID: PMC6363957 DOI: 10.1016/j.jceh.2018.02.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 02/20/2018] [Indexed: 12/12/2022] Open
Abstract
The design of clinical trials on Hepatic Encephalopathy (HE) is not an easy task, in fact there are several issues related to the performance of clinical trials in HE that have impeded progress in the field, mainly because most of the studies on HE therapy were performed before the era of rigorous Randomized Controlled Trials (RCTs). In this review we discuss the major problems affecting previously published trials on HE treatments aiming to provide evidences, suggestions and indications to prepare well designed RCTs in three different settings: (1) management of hospitalized patients with episodic HE; (2) secondary prophylaxis in patients following an episode of HE; and (3) management of minimal/covert HE.
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Affiliation(s)
- Lorenzo Ridola
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy
- Address for correspondence: Lorenzo Ridola, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica, 04110 Latina, Italy.
| | - Silvia Nardelli
- Department of Clinical Medicine, Sapienza University of Rome, Italy
| | - Stefania Gioia
- Department of Clinical Medicine, Sapienza University of Rome, Italy
| | - Oliviero Riggio
- Department of Clinical Medicine, Sapienza University of Rome, Italy
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Affiliation(s)
- Chathur Acharya
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA
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