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Kumar R, Kumar A, Kumar S. Sepsis in liver failure patients: Diagnostic challenges and recent advancements. World J Crit Care Med 2025; 14:101587. [DOI: 10.5492/wjccm.v14.i2.101587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 01/19/2025] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
Acute liver failure (ALF) and acute-on-chronic LF (ACLF) are prevalent hepatic emergencies characterized by an increased susceptibility to bacterial infections (BI), despite significant systemic inflammation. Literature indicates that 30%–80% of ALF patients and 55%–81% of ACLF patients develop BI, attributed to immunological dysregulation. Bacterial sepsis in these patients is associated with adverse clinical outcomes, including prolonged hospitalization and increased mortality. Early detection of bacterial sepsis is critical; however, distinguishing between sterile systemic inflammation and sepsis poses a significant challenge due to the overlapping clinical presentations of LF and sepsis. Conventional sepsis biomarkers, such as procalcitonin and C-reactive protein, have shown limited utility in LF patients due to inconsistent results. In contrast, novel biomarkers like presepsin and sTREM-1 have demonstrated promising discriminatory performance in this population, pending further validation. Moreover, emerging research highlights the potential of machine learning-based approaches to enhance sepsis detection and characterization. Although preliminary findings are encouraging, further studies are necessary to validate these results across diverse patient cohorts, including those with LF. This article provides a comprehensive review of the magnitude, impact, and diagnostic challenges associated with BI in LF patients, focusing on novel advancements in early sepsis detection and characterization.
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Abhishek Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Sudhir Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Dong V, Durkalski V, Lee WM, Karvellas CJ. Outcomes of patients with acute liver failure not listed for liver transplantation: A cohort analysis. Hepatol Commun 2024; 8:e0575. [PMID: 39470433 PMCID: PMC11524736 DOI: 10.1097/hc9.0000000000000575] [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: 07/02/2024] [Accepted: 09/06/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Acute liver failure (ALF) is a rare condition leading to morbidity and mortality. Liver transplantation (LT) is often required, but patients are not always listed for LT. There is a lack of data regarding outcomes in these patients. Our aim is to describe outcomes of patients with ALF not listed for LT and to compare this with those listed for LT. METHODS Retrospective analysis of all nonlisted patients with ALF enrolled in the Acute Liver Failure Study Group (ALFSG) registry between 1998 and 2018. The primary outcome was 21-day mortality. Multivariable logistic regression was done to identify factors associated with 21-day mortality. The comparison was then made with patients with ALF listed for LT. RESULTS A total of 1672 patients with ALF were not listed for LT. The median age was 41 (IQR: 30-54). Three hundred seventy-one (28.9%) patients were too sick to list. The most common etiology was acetaminophen toxicity (54.8%). Five hundred fifty-eight (35.7%) patients died at 21 days. After adjusting for relevant covariates, King's College Criteria (adjusted odds ratio: 3.17, CI 2.23-4.51), mechanical ventilation (adjusted odds ratio: 1.53, CI: 1.01-2.33), and vasopressors (adjusted odds ratio: 2.10, CI: 1.43-3.08) (p < 0.05 for all) were independently associated with 21-day mortality. Compared to listed patients, nonlisted patients had higher mortality (35.7% vs. 24.3%). Patients deemed not sick enough had greater than 95% survival, while those deemed too sick still had >30% survival. CONCLUSIONS Despite no LT, the majority of patients were alive at 21 days. Survival was lower in nonlisted patients. Clinicians are more accurate in deeming patients not sick enough to require LT as opposed to deeming patients too sick to survive.
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Affiliation(s)
- Victor Dong
- Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of medicine, Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Valerie Durkalski
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - William M. Lee
- Department of medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Constantine J. Karvellas
- Department of Critical Care Medicine, University of Alberta, Edmonton, Alberta, Canada
- Department of medicine, Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Alberta, Canada
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Anand AC, Acharya SK. The Story of Ammonia in Liver Disease: An Unraveling Continuum. J Clin Exp Hepatol 2024; 14:101361. [PMID: 38444405 PMCID: PMC10910335 DOI: 10.1016/j.jceh.2024.101361] [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: 12/10/2023] [Accepted: 02/03/2024] [Indexed: 03/07/2024] Open
Abstract
Hyperammonemia and liver disease are closely linked. Most of the ammonia in our body is produced by transamination and deamination activities involving amino acid, purine, pyrimidines, and biogenic amines, and from the intestine by bacterial splitting of urea. The only way of excretion from the body is by hepatic conversion of ammonia to urea. Hyperammonemia is associated with widespread toxicities such as cerebral edema, hepatic encephalopathy, immune dysfunction, promoting fibrosis, and carcinogenesis. Over the past two decades, it has been increasingly utilized for prognostication of cirrhosis, acute liver failure as well as acute on chronic liver failure. The laboratory assessment of hyperammonemia has certain limitations, despite which its value in the assessment of various forms of liver disease cannot be negated. It may soon become an important tool to make therapeutic decisions about the use of prophylactic and definitive treatment in various forms of liver disease.
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Dong V, Robinson AM, Dionne JC, Cardoso FS, Rewa OG, Karvellas CJ. Continuous renal replacement therapy and survival in acute liver failure: A systematic review and meta-analysis. J Crit Care 2024; 81:154513. [PMID: 38194760 DOI: 10.1016/j.jcrc.2023.154513] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 12/05/2023] [Accepted: 12/26/2023] [Indexed: 01/11/2024]
Abstract
OBJECTIVE Acute liver failure (ALF) is a rare syndrome leading to significant morbidity and mortality. An important cause of mortality is cerebral edema due to hyperammonemia. Different therapies for hyperammonemia have been assessed including continuous renal replacement therapy (CRRT). We conducted a systematic review and meta-analysis to determine the efficacy of CRRT in ALF patients. MATERIALS AND METHODS We searched MEDLINE, EMBASE, Cochrane Library, and Web of Science. Inclusion criteria included adult patients admitted to an ICU with ALF. Intervention was the use of CRRT for one or more indications with the comparator being standard care without the use of CRRT. Outcomes of interest were overall survival, transplant-free survival (TFS), mortality and changes in serum ammonia levels. RESULTS In total, 305 patients underwent CRRT while 1137 patients did not receive CRRT. CRRT was associated with improved overall survival [risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70-0.99, p-value 0.04, I2 = 50%] and improved TFS (RR 0.65, 95% CI 0.49-0.85, p-value 0.002, I2 = 25%). There was a trend towards higher mortality with no CRRT (RR 1.24, 95% CI 0.84-1.81, p-value 0.28, I2 = 37%). Ammonia clearance data was unable to be pooled and was not analyzable. CONCLUSION Use of CRRT in ALF patients is associated with improved overall and transplant-free survival compared to no CRRT.
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Affiliation(s)
- Victor Dong
- Department of Critical Care Medicine, University of Calgary, 3134 Hospital Drive NW, Calgary, Alberta T2N 2T9, Canada.
| | - Andrea M Robinson
- Department of Critical Care Medicine, University of Alberta, 2-124 Clinical Sciences Building, Edmonton, Alberta T6G 2G3, Canada.
| | - Joanna C Dionne
- Department of Medicine, Division of Critical Care, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
| | - Filipe S Cardoso
- Intensive Care Unit and Transplant Unit, Nova University, R. da Beneficência 8, Lisbon 1050-099, Portugal.
| | - Oleksa G Rewa
- Department of Critical Care Medicine, University of Alberta, 2-124 Clinical Sciences Building, Edmonton, Alberta T6G 2G3, Canada.
| | - Constantine J Karvellas
- Department of Critical Care Medicine, University of Alberta, 2-124 Clinical Sciences Building, Edmonton, Alberta T6G 2G3, Canada; Department of Medicine, Division of Gastroenterology, University of Alberta, 8540 112 St NW, Edmonton, Alberta T6G 2P8, Canada.
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Sehrawat SS, Premkumar M. Critical care management of acute liver failure. Indian J Gastroenterol 2024; 43:361-376. [PMID: 38578565 DOI: 10.1007/s12664-024-01556-8] [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: 12/12/2023] [Accepted: 02/12/2024] [Indexed: 04/06/2024]
Abstract
The management of acute liver failure (ALF) in modern hepatology intensive care units (ICU) has improved patient outcomes. Critical care management of hepatic encephalopathy, cerebral edema, fluid and electrolytes; prevention of infections and organ support are central to improved outcomes of ALF. In particular, the pathogenesis of encephalopathy is multifactorial, with ammonia, elevated intra-cranial pressure and systemic inflammation playing a central role. Although ALF remains associated with high mortality, the availability of supportive care, including organ failure support such as plasma exchange, timely mechanical ventilation or continuous renal replacement therapy, either conservatively manages patients with ALF or offers bridging therapy until liver transplantation. Thus, appropriate critical care management has improved the likelihood of patient recovery in ALF. ICU care interventions such as monitoring of cerebral edema, fluid status assessment and interventions for sepsis prevention, nutritional support and management of electrolytes can salvage a substantial proportion of patients. In this review, we discuss the key aspects of critical care management of ALF.
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Affiliation(s)
- Surender Singh Sehrawat
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
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Biswas S, Kumar R, Shalimar, Acharya SK. Viral hepatitis-induced acute liver failure. Indian J Gastroenterol 2024; 43:312-324. [PMID: 38451383 DOI: 10.1007/s12664-024-01538-w] [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: 01/04/2024] [Accepted: 01/18/2024] [Indexed: 03/08/2024]
Abstract
Viral hepatitis-induced acute liver failure (ALF) is a preventable cause for liver-related mortality worldwide. Viruses are the most common cause for ALF in developing nations in contrast to the west, where acetaminophen is largely responsible. Viruses may be hepatotropic or affect the liver secondary to a systemic infection. In tropical countries, infections such as leptospirosis, scrub typhus and malaria can mimic the symptoms of ALF. Differentiating these ALF mimics is crucial because they require etiology-specific therapy. Treatment of viral hepatitis-induced ALF is two-pronged and directed towards providing supportive care to prevent organ failures and antiviral drugs for some viruses. Liver transplantation (LT) is an effective modality for patients deteriorating despite adequate supportive care. Early referral and correct identification of patients who require a transplant are important. Liver support devices and plasma exchange have evolved into "bridging modalities" for LT. Preventive strategies such as hand hygiene, use of clean and potable water and inclusion of vaccines against viral hepatitis in the national program are simple yet very effective methods focusing on the preventive aspect of this disease.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna, 801 507, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India.
| | - Subrat Kumar Acharya
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 110 029, India
- KIIT University, Bhubaneswar, 751 024, India
- Fortis Escorts Digestive and Liver Institute, Okhla, New Delhi, 110 025, India
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Biswas S, Shalimar. Liver Transplantation for Acute Liver Failure- Indication, Prioritization, Timing, and Referral. J Clin Exp Hepatol 2023; 13:820-834. [PMID: 37693253 PMCID: PMC10483009 DOI: 10.1016/j.jceh.2023.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 01/17/2023] [Indexed: 09/12/2023] Open
Abstract
Acute liver failure (ALF) is a major success story in gastroenterology, with improvements in critical care and liver transplant resulting in significant improvements in patient outcomes in the current era compared to the dismal survival rates in the pretransplant era. However, the ever-increasing list of transplant candidates and limited organ pool makes judicious patient selection and organ use mandatory to achieve good patient outcomes and prevent organ wastage. Several scoring systems exist to facilitate the identification of patients who need a liver transplant and would therefore need an early referral to a specialized liver unit. The timing of the liver transplant is also crucial as transplanting a patient too early would lead to those who would recover spontaneously receiving an organ (wastage), and a late decision might result in the patient becoming unfit for transplant (delisted) or have an advanced disease which would result in poor post-transplant outcomes. The current article reviews the indications and contraindications of liver transplant in ALF patients, the various prognostic scoring systems, etiology-specific outcomes, prioritization and timing of referral.
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Affiliation(s)
- Sagnik Biswas
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences New Delhi, India
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Agumava LU, Gulyaev VA, Lutsyk KN, Olisov OD, Akhmetshin RB, Magomedov KM, Kazymov BI, Akhmedov AR, Alekberov KF, Yaremin BI, Novruzbekov MS. Issues of intensive care and liver transplantation tactics in fulminant liver failure. BULLETIN OF THE MEDICAL INSTITUTE "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH) 2023. [DOI: 10.20340/vmi-rvz.2023.1.tx.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Fulminant liver failure is usually characterized as severe acute liver injury with encephalopathy and synthetic dysfunction (international normalized ratio [INR] ≥1.5) in a patient without cirrhosis or previous liver disease. Management of patients with acute liver failure includes ensuring that the patient is cared for appropriately, monitoring for worsening liver failure, managing complications, and providing nutritional support. Patients with acute liver failure should be treated at a liver transplant center whenever possible. Serial laboratory tests are used to monitor the course of a patient's liver failure and to monitor for complications. It is necessary to monitor the level of aminotransferases and bilirubin in serum daily. More frequent monitoring (three to four times a day) of blood coagulation parameters, complete blood count, metabolic panels, and arterial blood gases should be performed. For some causes of acute liver failure, such as acetaminophen intoxication, treatment directed at the underlying cause may prevent the need for liver transplantation and reduce mortality. Lactulose has not been shown to improve overall outcomes, and it can lead to intestinal distention, which can lead to technical difficulties during liver transplantation. Early in acute liver failure, signs and symptoms of cerebral edema may be absent or difficult to detect. Complications of cerebral edema include increased intracranial pressure and herniation of the brain stem. General measures to prevent increased intracranial pressure include minimizing stimulation, maintaining an appropriate fluid balance, and elevating the head of the patient's bed. For patients at high risk of developing cerebral edema, we also offer hypertonic saline prophylaxis (3%) with a target serum sodium level of 145 to 155 mEq/L (level 2C). High-risk patients include patients with grade IV encephalopathy, high ammonia levels (>150 µmol/L), or acute renal failure, and patients requiring vasopressor support. Approximately 40 % of patients with acute liver failure recover spontaneously with supportive care. Predictive models have been developed to help identify patients who are unlikely to recover spontaneously, as the decision to undergo liver transplant depends in part on the likelihood of spontaneous recovery of the liver. However, among those who receive a transplant, the one-year survival rate exceeds 80 %, making this treatment the treatment of choice in this difficult patient population.
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Affiliation(s)
- L. U. Agumava
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - V. A. Gulyaev
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. N. Lutsyk
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - O. D. Olisov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - R. B. Akhmetshin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. M. Magomedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Kazymov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - A. R. Akhmedov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - K. F. Alekberov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center
| | - B. I. Yaremin
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
| | - M. S. Novruzbekov
- Research Institute of Ambulance them. N.V. Sklifosovsky, liver transplant center; Pirogov Russian National Research Medical University, Department of Transplantology and Artificial Organs
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Prognostic Scores in Acute Liver Failure Due to Viral Hepatitis. Diagnostics (Basel) 2023; 13:diagnostics13061035. [PMID: 36980341 PMCID: PMC10047191 DOI: 10.3390/diagnostics13061035] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/02/2023] [Accepted: 03/04/2023] [Indexed: 03/11/2023] Open
Abstract
Viral infections are among the major causes of acute liver failure (ALF) worldwide. While the role of agents such as hepatitis A, B, C, D and E viruses in precipitating ALF are well known, improvements in serological assays have led to the detection of viral agents such as Epstein Barr virus, cytomegalovirus etc. as atypical causes of ALF. Despite the plethora of literature available on viral hepatitis and ALF, there is very limited large-scale epidemiologic data on the prevalence, risk factors of progression and outcomes in ALF of viral causes. This is important as viral infections remain the leading cause of ALF in the East and in developing countries, while the impact of viral ALF in the West has largely been ameliorated by effective vaccination and sanitization programs. This review focuses specifically on the available prognostic scores that aid in the management of ALF of viral etiologies while also briefly reviewing the current literature on newer viral agents known to cause ALF, risk factors of progression, outcomes and how management algorithms can be developed by incorporation of prognostic scoring systems for referral and transplant listing.
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Kumar R, Anand U, Priyadarshi RN. Liver transplantation in acute liver failure: Dilemmas and challenges. World J Transplant 2021; 11:187-202. [PMID: 34164294 PMCID: PMC8218344 DOI: 10.5500/wjt.v11.i6.187] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 03/17/2021] [Accepted: 05/24/2021] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure (ALF) refers to a state of severe hepatic injury that leads to altered coagulation and sensorium in the absence of pre-existing liver disease. ALF has different causes, but the clinical characteristics are strikingly similar. In clinical practice, however, inconsistency in the definition of ALF worldwide and confusion regarding the existence of pre-existing liver disease raise diagnostic dilemmas. ALF mortality rates used to be over 80% in the past; however, survival rates on medical treatment have significantly improved in recent years due to a greater understanding of pathophysiology and advances in critical care management. The survival rates in acetaminophen-associated ALF have become close to the post-transplant survival rates. Given that liver transplantation (LT) is an expensive treatment that involves a major surgical operation in critically ill patients and lifelong immunosuppression, it is very important to select accurate patients who may benefit from it. Still, emergency LT remains a lifesaving procedure for many ALF patients. However, there is a lack of consistency in current prognostic models that hampers the selection of transplant candidates in a timely and precise manner. The other problems associated with LT in ALF are the shortage of graft, development of contraindications on the waiting list, vaguely defined delisting criteria, time constraints for pre-transplant evaluation, ethical concerns, and comparatively poor post-transplant outcomes in ALF. Therefore, there is a desperate need to establish accurate prognostic models and explore the roles of evolving adjunctive and alternative therapies, such as liver support systems, plasma exchange, stem cells, auxiliary LT, and so on, to enhance transplant-free survival and to fill the void created by the graft shortage
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Affiliation(s)
- Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Utpal Anand
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Rajeev Nayan Priyadarshi
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Patna 801507, Bihar, India
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Abstract
ABSTRACT Exposure to high doses of ammonia gas can result in lethal injuries to humans. This case series presents 5 fatalities and an injured individual, caused by acute ammonia exposure, which occurred in the rubber industry. One of the fatalities and the survivor were reported in an incident of ammonia gas cylinder explosion, whereas the other 4 fatalities were accidentally exposed to gaseous ammonia, where they had started working at a reopened rubber factory that had been abandoned for a long time. Autopsy, scene investigation, and the toxicological findings of the deceased and the clinical forensic examination of the survivor revealed corrosive burns on the skin and the oropharynx, diffuse alveolar damage, and high level of ammonia in blood and the scene. These cases highlight how the comprehensive death investigation helps the forensic practitioner to conclude ammonia exposure as the cause of death/injury where there is a possibility of gas inhalation.
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Chiriac S, Stanciu C, Cojocariu C, Singeap AM, Sfarti C, Cuciureanu T, Girleanu I, Igna RA, Trifan A. Role of ammonia in predicting the outcome of patients with acute-on-chronic liver failure. World J Clin Cases 2021; 9:552-564. [PMID: 33553393 PMCID: PMC7829715 DOI: 10.12998/wjcc.v9.i3.552] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 12/02/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND High venous ammonia (VA) values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis (LC) as well as acute hepatitis. Moreover, VA has been associated with poor prognosis and high mortality in these clinical settings. However, the role of ammonia in acute-on-chronic liver failure (ACLF) has not yet been clearly established.
AIM To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center.
METHODS We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites, hepatic encephalopathy (HE), upper gastrointestinal bleeding, or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver (APASL) criteria for ACLF. The study was conducted in “St. Spiridon” University Hospital, Iasi, Romania, a tertiary care center, between January 2017 and January 2019. The APASL ACLF Research Consortium (AARC) score was calculated and ACLF grade was established accordingly. West-haven classification was used for HE. Statistical analysis was performed using IBM SPSS version 22.0.
RESULTS Four hundred and forty-six patients were included, aged 59 (50-65) years, 57.4% men. Child-Pugh, model for end-stage liver disease (MELD) and AARC scores were 11 (10-12), 19.13 ± 6.79, and 7 (6-8), respectively. 66.4% had ACLF grade I, 31.2% ACLF grade II, and 2.5% ACLF grade III. HE was diagnosed in 83.9%, 34% grade I, 37.2% grade II, 23.5% grade III, and 5.3% grade IV. Overall mortality was 7.8%. VA was 103 (78-148) μmol/L. Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score [Area under the curve (AUC) = 0.886], MELD score (AUC = 0.816), VA (AUC = 0.812) and a fair accuracy for the Child-Pugh score (AUC = 0.799). Subsequently, a cut-off value for the prediction of mortality was identified for VA (152.5 μmol/L, sensitivity = 0.706, 1-specificity = 0.190). Univariate analysis found acute kidney injury, severe HE (grade III or IV), VA ≥ 152.5 μmol/L, MELD score ≥ 22.5, Child-Pugh score ≥ 12.5, and AARC score ≥ 8.5 to be associated with in-hospital mortality. Multivariate analysis identified AARC score ≥ 8.5 and venous ammonia ≥ 152 μmol/L to be independent predictors of in-hospital mortality.
CONCLUSION VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF. Patients with both ACLF and VA > 152.5 μmol/L have a high risk for a poor outcome.
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Affiliation(s)
- Stefan Chiriac
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Camelia Cojocariu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Ana-Maria Singeap
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Catalin Sfarti
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Tudor Cuciureanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Irina Girleanu
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
| | - Razvan Alexandru Igna
- Intensive Care, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
| | - Anca Trifan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi 700115, Romania
- Institute of Gastroenterology and Hepatology, "St. Spiridon" Emergency Hospital, Iasi 700111, Romania
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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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Mattke AC, Shikata F, McGill J, Justo R, Venugopal P. Successful management of a neonate with OTC deficiency presenting with hyperammonemia and severe cardiac dysfunction with extracorporeal membrane oxygenation support and continuous renal replacement therapy. JIMD Rep 2020; 55:12-14. [PMID: 32905004 PMCID: PMC7463050 DOI: 10.1002/jmd2.12135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 02/22/2020] [Accepted: 02/24/2020] [Indexed: 11/24/2022] Open
Abstract
Ornithine transcarbamylase (OTC) deficiency is an X-linked urea cycle disorder which-in severe form-results in rapid accumulation of ammonia and glutamine with subsequent irreversible brain injury. We present a case of severe left ventricular dysfunction with hyperammonemic crisis caused by OTC deficiency which was managed with veno-arterial extracorporeal membrane oxygenation support combined with continuous renal replacement therapy. Aggressive treatment led to normalization of ammonia and full left ventricular recovery.
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Affiliation(s)
- Adrian C. Mattke
- Paediatric Intensive Care Unit, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
- Queensland Pediatric Cardiac Service, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
- University of Queensland, Brisbane, School of MedicineSt LuciaQueenslandAustralia
- Paediatric Critical Care Research Group, CCHRUniversity of QueenslandSt LuciaQueenslandAustralia
| | - Fumiaki Shikata
- Queensland Pediatric Cardiac Service, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
| | - James McGill
- Metabolic Medicine, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
| | - Rob Justo
- Queensland Pediatric Cardiac Service, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
- University of Queensland, Brisbane, School of MedicineSt LuciaQueenslandAustralia
| | - Prem Venugopal
- Queensland Pediatric Cardiac Service, Queensland Children's HospitalSouth BrisbaneQueenslandAustralia
- University of Queensland, Brisbane, School of MedicineSt LuciaQueenslandAustralia
- Paediatric Critical Care Research Group, CCHRUniversity of QueenslandSt LuciaQueenslandAustralia
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Anand AC, Nandi B, Acharya SK, Arora A, Babu S, Batra Y, Chawla YK, Chowdhury A, Chaoudhuri A, Eapen EC, Devarbhavi H, Dhiman R, Datta Gupta S, Duseja A, Jothimani D, Kapoor D, Kar P, Khuroo MS, Kumar A, Madan K, Mallick B, Maiwall R, Mohan N, Nagral A, Nath P, Panigrahi SC, Pawar A, Philips CA, Prahraj D, Puri P, Rastogi A, Saraswat VA, Saigal S, Shalimar, Shukla A, Singh SP, Verghese T, Wadhawan M. Indian National Association for the Study of the Liver Consensus Statement on Acute Liver Failure (Part 1): Epidemiology, Pathogenesis, Presentation and Prognosis. J Clin Exp Hepatol 2020; 10:339-376. [PMID: 32655238 PMCID: PMC7335721 DOI: 10.1016/j.jceh.2020.04.012] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/12/2020] [Indexed: 12/12/2022] Open
Abstract
Acute liver failure (ALF) is an infrequent, unpredictable, potentially fatal complication of acute liver injury (ALI) consequent to varied etiologies. Etiologies of ALF as reported in the literature have regional differences, which affects the clinical presentation and natural course. In this part of the consensus article designed to reflect the clinical practices in India, disease burden, epidemiology, clinical presentation, monitoring, and prognostication have been discussed. In India, viral hepatitis is the most frequent cause of ALF, with drug-induced hepatitis due to antituberculosis drugs being the second most frequent cause. The clinical presentation of ALF is characterized by jaundice, coagulopathy, and encephalopathy. It is important to differentiate ALF from other causes of liver failure, including acute on chronic liver failure, subacute liver failure, as well as certain tropical infections which can mimic this presentation. The disease often has a fulminant clinical course with high short-term mortality. Death is usually attributable to cerebral complications, infections, and resultant multiorgan failure. Timely liver transplantation (LT) can change the outcome, and hence, it is vital to provide intensive care to patients until LT can be arranged. It is equally important to assess prognosis to select patients who are suitable for LT. Several prognostic scores have been proposed, and their comparisons show that indigenously developed dynamic scores have an edge over scores described from the Western world. Management of ALF will be described in part 2 of this document.
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Key Words
- ACLF, acute on chronic liver failure
- AFLP, acute fatty liver of pregnancy
- AKI, Acute kidney injury
- ALF, Acute liver failure
- ALFED, Acute Liver Failure Early Dynamic
- ALT, alanine transaminase
- ANA, antinuclear antibody
- AP, Alkaline phosphatase
- APTT, activated partial thromboplastin time
- ASM, alternative system of medicine
- ASMA, antismooth muscle antibody
- AST, aspartate transaminase
- ATN, Acute tubular necrosis
- ATP, adenosine triphosphate
- ATT, anti-TB therapy
- AUROC, Area under the receiver operating characteristics curve
- BCS, Budd-Chiari syndrome
- BMI, body mass index
- CBF, cerebral blood flow
- CBFV, cerebral blood flow volume
- CE, cerebral edema
- CHBV, chronic HBV
- CLD, chronic liver disease
- CNS, central nervous system
- CPI, clinical prognostic indicator
- CSF, cerebrospinal fluid
- DAMPs, Damage-associated molecular patterns
- DILI, drug-induced liver injury
- EBV, Epstein-Barr virus
- ETCO2, End tidal CO2
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- HAV, hepatitis A virus
- HBV, Hepatitis B virus
- HELLP, hemolysis
- HEV, hepatitis E virus
- HLH, Hemophagocytic lymphohistiocytosis
- HSV, herpes simplex virus
- HV, hepatic vein
- HVOTO, hepatic venous outflow tract obstruction
- IAHG, International Autoimmune Hepatitis Group
- ICH, intracerebral hypertension
- ICP, intracerebral pressure
- ICU, intensive care unit
- IFN, interferon
- IL, interleukin
- IND-ALF, ALF of indeterminate etiology
- INDILI, Indian Network for DILI
- KCC, King's College Criteria
- LC, liver cirrhosis
- LDLT, living donor liver transplantation
- LT, liver transplantation
- MAP, mean arterial pressure
- MHN, massive hepatic necrosis
- MPT, mitochondrial permeability transition
- MUAC, mid-upper arm circumference
- NAPQI, n-acetyl-p-benzo-quinone-imine
- NPV, negative predictive value
- NWI, New Wilson's Index
- ONSD, optic nerve sheath diameter
- PAMPs, pathogen-associated molecular patterns
- PCR, polymerase chain reaction
- PELD, Pediatric End-Stage Liver Disease
- PPV, positive predictive value
- PT, prothrombin time
- RAAS, renin–angiotensin–aldosterone system
- SHF, subacute hepatic failure
- SIRS, systemic inflammatory response syndrome
- SNS, sympathetic nervous system
- TB, tuberculosis
- TCD, transcranial Doppler
- TGF, tumor growth factor
- TJLB, transjugular liver biopsy
- TLR, toll-like receptor
- TNF, tumor necrosis factor
- TSFT, triceps skin fold thickness
- US, ultrasound
- USALF, US Acute Liver Failure
- VZV, varicella-zoster virus
- WD, Wilson disease
- Wilson disease (WD)
- YP, yellow phosphorus
- acute liver failure
- autoimmune hepatitis (AIH)
- drug-induced liver injury
- elevated liver enzymes, low platelets
- sALI, severe acute liver injury
- viral hepatitis
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Affiliation(s)
- Anil C. Anand
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Bhaskar Nandi
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Anil Arora
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sethu Babu
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad 500003, India
| | - Yogesh Batra
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Abhijit Chowdhury
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
| | - Ashok Chaoudhuri
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Eapen C. Eapen
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
| | - RadhaKrishan Dhiman
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Ajay Duseja
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
| | | | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Mohamad S. Khuroo
- Department of Gastroenterology, Dr Khuroo’ S Medical Clinic, Srinagar, Kashmir, India
| | - Ashish Kumar
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Kaushal Madan
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
| | - Bipadabhanjan Mallick
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Rakhi Maiwall
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the Medicity Hospital, Sector – 38, Gurgaon, Haryana, India
| | - Aabha Nagral
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Preetam Nath
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Sarat C. Panigrahi
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Ankush Pawar
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
| | - Cyriac A. Philips
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, 682028, Kerala, India
| | - Dibyalochan Prahraj
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
| | - Pankaj Puri
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
| | - Amit Rastogi
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Sanjiv Saigal
- Department of Hepatology, Department of Liver Transplantation, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
| | - Akash Shukla
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Thomas Verghese
- Department of Gastroenterology, Government Medical College, Kozikhode, India
| | - Manav Wadhawan
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
| | - The INASL Task-Force on Acute Liver Failure
- Department of Gastroenterology, Kaliga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Department of Gastroenterology, Sarvodaya Hospital and Research Centre, Faridababd, Haryana, India
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
- Institute of Liver Gastroenterology &Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
- Department of Gastroenterology, Krishna Institute of Medical Sciences, Hyderabad 500003, India
- Department of Gastroenterology, Indraprastha Apollo Hospital, SaritaVihar, New Delhi, 110 076, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
- Department of Hepatology, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, 700020, India
- Hepatology and Liver Transplant, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Hepatology, Christian Medical College, Vellore, India
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, 560034, India
- Department of Hepatology, Post graduate Institute of Medical Education and Research, Chandigarh, 160 012, India
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chrompet, Chennai, 600044, India
- Gleneagles Global Hospitals, Hyderabad, Telangana, India
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
- Department of Gastroenterology, Dr Khuroo’ S Medical Clinic, Srinagar, Kashmir, India
- Gastroenterology and Hepatology, Max Smart Super Specialty Hospital, Saket, New Delhi, India
- Department of Gastroenterology, Kalinga Institute of Medical Sciences, Bhubaneswar, 751024, India
- Hepatology Incharge Liver Intensive Care, Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, New Delhi, India
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation, Medanta – the Medicity Hospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Apollo and Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
- Liver & Digestive Diseases Institute, Fortis Escorts Hospital, Okhla Road, New Delhi, 110 025, India
- The Liver Unit and Monarch Liver Lab, Cochin Gastroenterology Group, Ernakulam Medical Centre, Kochi, 682028, Kerala, India
- Department of Hepatology and Gastroenterology, Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
- Department of Liver Transplantation, Medanta – the MedicityHospital, Sector – 38, Gurgaon, Haryana, India
- Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh, 226 014, India
- Department of Hepatology, Department of Liver Transplantation, India
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, 29, India
- Department of Gastroenterology, LTM Medical College & Sion Hospital, India
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
- Department of Gastroenterology, Government Medical College, Kozikhode, India
- Institute of Liver & Digestive Diseases and Head of Hepatology & Liver Transplant (Medicine), BLK Super Speciality Hospital, Delhi, India
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Development of a Prognostic Score to Predict Mortality in Patients With Pediatric Acute Liver Failure. J Pediatr Gastroenterol Nutr 2020; 70:777-782. [PMID: 32443030 DOI: 10.1097/mpg.0000000000002625] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES This study aims to develop a new prognostic score based on changes in serial laboratory data from patients with pediatric acute liver failure (PALF). METHODS We retrospectively reviewed data on 146 patients with PALF at the Seoul National University Children Hospital (SNUCH) and the Asan Medical Center (AMC). Daily morning laboratory records were obtained for up to 7 days after diagnosis of PALF: total bilirubin (TB) (mg/dL), international normalized ratio for prothrombin time (INR) at enrolment; peak TB, peak INR, peak ammonia (μmol/L); the difference between the peak TB and TB at enrollment (ie, Δpeak TB), the difference between the peak INR and INR at enrollment (ie, Δpeak INR), the maximum change in serial TB (ie, Δdaily TB), the maximum change in serial INR level (ie, Δdaily INR). We assigned nontransplanted patients in SNUCH and AMC to derivation and validation cohorts, respectively. RESULTS Δpeak TB, Δdaily TB, Δpeak INR, and Δdaily INR were significantly higher in the nonsurvival group. We developed a new score that can predict mortality in nontransplanted patients (derivation cohort n = 42, validation cohort n = 33). PALF-Delta score (PALF-Ds) = [0.232 × Δpeak TB (mg/dL)] + [2.263 × Δdaily INR] + [0.013 × peak ammonia (μmol/L)] - 4.498. The score yielded AUC 0.918 in the derivation cohort (sensitivity 81%, specificity 91%) and AUC 0.947 in the validation cohort (sensitivity 100%, specificity 89%). CONCLUSION A prognostic scoring system using the change of TB/INR may be useful for predicting mortality in patients with PALF.
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Abstract
PURPOSE OF REVIEW This review describes the current intensive care management of acute liver failure (ALF) and the latest evidence for emerging therapies. RECENT FINDINGS Mortality from ALF continues to improve and in some cases, medical therapy can negate the need for liver transplantation because of protocolized management in specialist centres. Liver transplantation remains the cornerstone of management for poor prognosis ALF. The reduced use of blood products in ALF reflects growing evidence of balanced haemostasis in severe liver disease. Prophylactic therapeutic hypothermia is no longer recommended for neuroprotection. In cases not suitable for liver transplantation, high-volume plasma exchange (HVP) has potential benefit, although further research on the optimal timing and dosing is needed. Although sepsis remains an important complication in ALF, the use of prophylactic antimicrobials is being questioned in the era of emerging bacterial resistance. SUMMARY ICU management of ALF has improved such that liver transplantation is not required in some cases. HVP has emerged as a potential therapy for patients who may not be good liver transplantation candidates. Nevertheless in suitable patients with poor prognosis liver transplantation remains the optimal therapy.
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Shalimar, Rout G, Kumar R, Singh AD, Sharma S, Gunjan D, Saraya A, Nayak B, Acharya SK. Persistent or incident hyperammonemia is associated with poor outcomes in acute decompensation and acute-on-chronic liver failure. JGH OPEN 2020; 4:843-850. [PMID: 33102753 PMCID: PMC7578315 DOI: 10.1002/jgh3.12314] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Revised: 12/04/2019] [Accepted: 02/12/2020] [Indexed: 12/13/2022]
Abstract
Background and Aim The effect of elevated ammonia on organ failures (OF), apart from hepatic encephalopathy, in patients with acute decompensation (AD) of cirrhosis and acute‐on‐chronic liver failure (ACLF) is unclear. We aimed to assess the effect of persistent or incident hyperammonemia on OF and outcomes in patients with AD and ACLF. Methods A total of 229 patients with ACLF and 83 with AD were included. Arterial ammonia was measured on day 1 and day 3 of admission. Persistent or incident hyperammonemia was defined as a level of ≥79.5 μmol/L on day 3. The changes in ammonia levels during the first 3 days were analyzed with respect to the complications and outcomes. Results At admission, the median level of arterial ammonia was higher in ACLF compared to AD patients (103 vs 86 μmol/L, P < 0.001). Persistent or incident hyperammonemia was noted in 206 (66.0%) patients and was more frequent in ACLF compared to AD patients (70.7 vs 53.0%, P = 0.013). Patients with persistent or incident hyperammonemia, compared to those without it, developed a higher proportion of new‐onset OF during hospitalization involving liver (P = 0.018), kidney (P = 0.001), brain (P = 0.005), coagulation (P = 0.036), circulation (P = 0.002), and respiratory (P = 0.003) issues and had higher 28‐day mortality (log‐rank test, P < 0.001). After adjustment for chronic liver failure consortium ACLF score, persistent or incident hyperammonemia (hazard ratio, 3.174) was independently associated with 28‐day mortality. The presence of infection was an independent predictor of persistent or incident hyperammonemia. Conclusion Persistent or incident hyperammonemia during first 3 days of hospitalization in patients with AD or ACLF is associated with increased risk of OF and death.
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Affiliation(s)
- Shalimar
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Gyanranjan Rout
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Ramesh Kumar
- Department of Gastroenterology All India Institute of Medical Sciences Patna India
| | - Achintya D Singh
- Department of Internal Medicine Cleveland Clinic Cleveland Ohio USA
| | - Sanchit Sharma
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Deepak Gunjan
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Anoop Saraya
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Baibaswata Nayak
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
| | - Subrat K Acharya
- Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India
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Management of liver failure in general intensive care unit. Anaesth Crit Care Pain Med 2020; 39:143-161. [PMID: 31525507 DOI: 10.1016/j.accpm.2019.06.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 06/30/2019] [Indexed: 12/11/2022]
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Diabetes mellitus increases the risk of hepatic encephalopathy after a transjugular intrahepatic portosystemic shunt in cirrhotic patients. Eur J Gastroenterol Hepatol 2019; 31:1264-1269. [PMID: 31136318 DOI: 10.1097/meg.0000000000001452] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aim of this study was to examine the effect of diabetes mellitus (DM) on the rate of hepatic encephalopathy (HE) in patients with decompensated liver cirrhosis after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). PATIENTS AND METHODS This study retrospectively reviewed 436 consecutive patients with cirrhosis receiving TIPS in our department from 2008 to 2016. By comparing two groups of patients, with or without DM, the incidence of developing overt HE after TIPS, as well as the correlation between diabetes and HE, was analyzed. Data were analyzed using the χ-tests, unpaired t-tests, logistic regression, and Kaplan-Meier curves. After the initial data processing, we used a regression model to analyze whether or not DM is associated with the development of HE after TIPS. RESULTS Of the 436 patients who underwent TIPS, 85 (19.5%) had diabetes at admission and 126 (28.9%) had HE after TIPS. Patients with DM more frequently had HE compared with those without DM (44.7 vs. 25.1%; P = 0.000). The logistic regression analysis showed that DM (P = 0.015) and age (P = 0.002) were independent risk factors for HE after TIPS. Finally, using the Kaplan-Meier curves, we found that diabetes significantly increases the incidence of overt HE (log-rank P = 0.026). CONCLUSION Similar to old age, DM may increase the risk of HE in cirrhotic patients after the creation of TIPS.
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Shalimar, Sheikh MF, Mookerjee RP, Agarwal B, Acharya SK, Jalan R. Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology 2019; 70:982-994. [PMID: 30703853 DOI: 10.1002/hep.30534] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 01/15/2019] [Indexed: 12/18/2022]
Abstract
Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in patients with cirrhosis and acute decompensation is unknown. The aims of this study were to determine the relationship between ammonia levels and severity of HE and its association with organ dysfunction and short-term mortality. We identified 498 patients from two institutions as part of prospective observational studies in patients with cirrhosis. Plasma ammonia levels were measured on admission and Chronic Liver Failure-Sequential Organ Failure Assessment criteria were used to determine the presence of organ failures. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cutoff points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. The 28-day mortality was 43.4%. Plasma ammonia correlated with severity of HE (P < 0.001), was significantly higher in nonsurvivors (93 [73-121] versus 67 [55-89] µmol/L, P < 0.001), and was an independent predictor of 28-day mortality (hazard ratio, 1.009, P < 0.001). An ammonia level of 79.5 µmol/L had sensitivity of 68.1% and specificity of 67.4% for predicting 28-day mortality. An ammonia level of ≥79.5 µmol/L was associated with a higher frequency of organ failures (liver [P = 0.004], coagulation [P < 0.001], kidney [P = 0.004], and respiratory [P < 0.001]). Lack of improvement in baseline ammonia at day 5 was associated with high mortality (70.6%). Conclusion: Ammonia level correlates with not only the severity of HE but also the failure of other organs and is an independent risk factor for mortality; lack of improvement in ammonia level is associated with high risk of death, making it an important biomarker and a therapeutic target.
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Affiliation(s)
- Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Mohammed Faisal Sheikh
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, London, UK
| | - Rajeshwar P Mookerjee
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, London, UK
| | - Banwari Agarwal
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, London, UK.,Intensive Care Unit, Royal Free Hospital, London, UK
| | - Subrat Kumar Acharya
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Rajiv Jalan
- Liver Failure Group, UCL Institute for Liver and Digestive Health, Division of Medicine, UCL Medical School, Royal Free Hospital, London, UK
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22
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Shalimar, Sonika U, Kedia S, Mahapatra SJ, Nayak B, Yadav DP, Gunjan D, Thakur B, Kaur H, Acharya SK. Comparison of Dynamic Changes Among Various Prognostic Scores in Viral Hepatitis-Related Acute Liver Failure. Ann Hepatol 2019; 17:403-412. [PMID: 29735790 DOI: 10.5604/01.3001.0011.7384] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIM Multiple prognostic scores are available for acute liver failure (ALF). Our objective was to compare the dynamicity of model for end stage liver disease (MELD), MELD-sodium, acute liver failure early dynamic model (ALFED), chronic liver failure (CLIF)-consortium ACLF score and King's College Hospital Criteria (KCH) for predicting outcome in ALF. MATERIALS AND METHODS All consecutive patients with ALF at a tertiary care centre in India were included. MELD, MELD-Na, ALFED, CLIF-C ACLF scores and KCH criteria were calculated at admission and day 3 of admission. Area under receiver operator characteristic curves (AUROC) were compared with DeLong method. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and diagnostic accuracy (DA) were reported. RESULTS Of the 115 patients included in the study, 73 (63.5%) died. The discrimination of mortality with baseline values of prognostic scores (MELD, MELD-Na, ALFED, CLIF-C ACLF and KCH) was modest (AUROC: 0.65-0.77). The AUROC increased on day 3 for all scores, except KCH criteria. On day 3 of admission, ALFED score had the highest AUROC 0.95, followed by CLIF-C ACLF 0.88, MELD 0.81, MELD-Na 0.77 and KCH 0.52. The AUROC for ALFED was significantly higher than MELD, MELD-Na and KCH (P < 0.001 for all) and CLIF-C ACLF (P = 0.05). ALFED score ≥ 4 on day 3 had the best sensitivity (87.1%), specificity (89.5%), PPV (93.8%), NPV (79.1%), LR positive (8.3) and DA (87.9%) for predicting mortality. CONCLUSIONS Dynamic assessment of prognostic scores better predicts outcome. ALFED model performs better than MELD, MELD, MELD-Na, CLIF-C ACLF scores and KCH criteria for predicting outcome in viral hepatitis- related ALF.
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Affiliation(s)
- Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ujjwal Sonika
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Soumya J Mahapatra
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Baibaswata Nayak
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Dawesh P Yadav
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Deepak Gunjan
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Thakur
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Harpreet Kaur
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Subrat K Acharya
- Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, New Delhi, India
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TLR5 silencing reduced hyperammonaemia-induced liver injury by inhibiting oxidative stress and inflammation responses via inactivating NF-κB and MAPK signals. Chem Biol Interact 2018; 299:102-110. [PMID: 30508503 DOI: 10.1016/j.cbi.2018.11.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 11/20/2018] [Accepted: 11/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Liver injury is a serious threat for human health and life. Toll-like receptor 5 (TLR5) has reported to be a vital mediator in flagellin or tetrachloride (CCl4)-induced liver injury. However, the roles and etiology of TLR5 in hyperammonaemia (HA)-induced liver injury are poor defined. METHODS HA rats were generated by intragastric administration using ammonium chloride solution. Liver status was assessed by haematoxylin and eosin (H&E) staining and measuring serum levels of liver injury markers. Immunohistochemistry (IHC) assay was used to visualize protein expression in tissues. Apoptotic index in tissues was determined by TUNEL assay. RT-qPCR assay was employed to test mRNA expression. Oxidative stress responses was assessed by detecting levels of reactive oxygen species (ROS) and related indicators. NF-κB activity was examined by TransAM NF-κB colorimetric kit. RESULTS TLR5 was highly expressed in liver tissues of HA rats. TLR5 knockdown ameliorated HA-induced liver injury by inhibiting liver cell apoptosis. TLR5 depletion inhibited HA-induced pro-inflammatory cytokine expression in liver tissues, but had no effect on the infiltration of T and macrophage cells into liver tissues. TLR5 silencing impaired HA-induced oxidative stress responses in hepatocytes, but not in hepatic stellate cells (HSCs). TLR5 downregulation inhibited HA-induced activation on TLR5/NF-κB and TLR5/MAPK signaling pathways. CONCLUSION TLR5 silencing reduced HA-induced liver injury by inhibiting hepatocyte apoptosis, oxidative stress and inflammation responses via inactivating NF-κB and MAPK signals, deepening our understanding on the molecular mechanism of HA-induced liver injury and providing a potential therapeutic target for alleviating liver injury.
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24
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Montrief T, Koyfman A, Long B. Acute liver failure: A review for emergency physicians. Am J Emerg Med 2018; 37:329-337. [PMID: 30414744 DOI: 10.1016/j.ajem.2018.10.032] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Revised: 10/15/2018] [Accepted: 10/17/2018] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION Acute liver failure (ALF) remains a high-risk clinical presentation, and many patients require emergency department (ED) management for complications and stabilization. OBJECTIVE This narrative review provides an evidence-based summary of the current data for the emergency medicine evaluation and management of ALF. DISCUSSION While ALF remains a rare clinical presentation, surveillance data suggest an overall incidence between 1 and 6 cases per million people every year, accounting for 6% of liver-related deaths and 7% of orthotopic liver transplants (OLT) in the U.S. The definition of ALF includes neurologic dysfunction, an international normalized ratio ≥ 1.5, no prior evidence of liver disease, and a disease course of ≤26 weeks, and can be further divided into hyperacute, acute, and subacute presentations. There are many underlying etiologies, including acetaminophen toxicity, drug induced liver injury, and hepatitis. Emergency physicians will be faced with several complications, including encephalopathy, coagulopathy, infectious processes, renal injury, and hemodynamic instability. Critical patients should be evaluated in the resuscitation bay, and consultation with the transplant team for appropriate patients improves patient outcomes. This review provides several guiding principles for management of acute complications. Using a pathophysiological-guided approach to the management of ALF associated complications is essential to optimizing patient care. CONCLUSIONS ALF remains a rare clinical presentation, but has significant morbidity and mortality. Physicians must rapidly diagnose these patients while evaluating for other diseases and complications. Early consultation with a transplantation center is imperative, as is identifying the underlying etiology and initiating symptomatic care.
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Affiliation(s)
- Tim Montrief
- University of Miami, Jackson Memorial Hospital/Miller School of Medicine, Department of Emergency Medicine, 1611 N.W. 12th Avenue, Miami, FL 33136, United States
| | - Alex Koyfman
- The University of Texas Southwestern Medical Center, Department of Emergency Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States
| | - Brit Long
- Brooke Army Medical Center, Department of Emergency Medicine, 3841 Roger Brooke Dr, Fort Sam Houston, TX 78234, United States.
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Savy N, Brossier D, Brunel-Guitton C, Ducharme-Crevier L, Du Pont-Thibodeau G, Jouvet P. Acute pediatric hyperammonemia: current diagnosis and management strategies. Hepat Med 2018; 10:105-115. [PMID: 30254497 PMCID: PMC6140721 DOI: 10.2147/hmer.s140711] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Acute hyperammonemia may induce a neurologic impairment leading to an acute life-threatening condition. Coma duration, ammonia peak level, and hyperammonemia duration are the main risk factors of hyperammonemia-related neurologic deficits and death. In children, hyperammonemia is mainly caused by severe liver failure and inborn errors of metabolism. In an acute setting, obtaining reliable plasma ammonia levels can be challenging because of the preanalytical difficulties that need to be addressed carefully. The management of hyperammonemia includes 1) identification of precipitating factors and cerebral edema presence, 2) a decrease in ammonia production by reducing protein intake and reversing catabolism, and 3) ammonia removal with pharmacologic treatment and, in the most severe cases, with extracorporeal therapies. In case of severe coma, transcranial Doppler ultrasound could be the method of choice to noninvasively monitor cerebral blood flow and titrate therapies.
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Affiliation(s)
- Nadia Savy
- Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada,
| | - David Brossier
- Department of Pediatrics, Pediatric Intensive Care Unit, CHU Caen, Caen, France
| | | | | | | | - Philippe Jouvet
- Department of Pediatrics, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada,
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Aquilina A, Pirotta T, Aquilina A. Acute liver failure and hepatic encephalopathy in exertional heat stroke. BMJ Case Rep 2018; 2018:bcr-2018-224808. [PMID: 30061127 PMCID: PMC6067139 DOI: 10.1136/bcr-2018-224808] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/14/2018] [Indexed: 01/06/2023] Open
Abstract
A 31-year-old man was brought to Accident & Emergency after collapsing during a race. On presentation, the patient had a temperature of 41.7°C (rectal). External cooling was started immediately. The patient was intubated in view of a Glasgow Coma Scale of 7 and was transferred to theintensive therapy unit. Laboratory results revealed an acute kidney injury, rhabdomyolysis, disseminated intravascular coagulopathy and acute liver failure. The patient was encephalopathic, jaundiced and difficult to sedate. His liver function continued to deteriorate with alanine aminotransferase (ALT) levels reaching 9207 U/L. King's Hospital Liver Centre, London was contacted for a possible liver transplant, and they advised an infusion of N-acetylcysteine. The following day liver function tests improved; thus, transplantation was not performed. The patient failed multiple sedation holds and required a tracheostomy. He continued to spike a fever. Despite no source of sepsis being found, the patient remained on broad spectrum antibiotics to cover for any potential infective causes until day 27. After 15 days, the patient's encephalopathy gradually improved. He was weaned off the ventilator and underwent intense physiotherapy. The patient was discharged from hospital one month after admission.
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Affiliation(s)
- Audrey Aquilina
- William Harvey Anaesthesia Department, East Kent Hospitals University NHS Foundation Trust, Ashford, UK
- Anaesthesia and Intensive Care, Mater Dei Hospital, Msida, Malta
| | - Tiziana Pirotta
- Anaesthesia and Intensive Care, Mater Dei Hospital, Msida, Malta
| | - Andrew Aquilina
- Anaesthesia and Intensive Care, Mater Dei Hospital, Msida, Malta
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Abstract
Acute liver failure is a rare but life-threatening disease that can lead to progressive encephalopathy, intracranial hypertension, and multiorgan failure. In the developed world, the most common cause remains acetaminophen overdose, but there are still many cases in which there is acute liver failure of unknown etiology. The mainstay of acute liver failure management remains supportive care in the critical care setting. If supportive treatment does not stabilize the disease process, the patient may require emergent liver transplantation. This article summarizes the current management of acute liver failure.
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Abstract
Hepatic encephalopathy (HE) is a common complication of liver dysfunction, including acute liver failure and liver cirrhosis. HE presents as a spectrum of neuropsychiatric symptoms ranging from subtle fluctuating cognitive impairment to coma. It is a significant contributor of morbidity in patients with liver disease. HE is observed in acute liver failure, liver bypass procedures, for example, shunt surgry and transjugular intrahepatic portosystemic shunt, and cirrhosis. These are classified as Type A, B and C HE, respectively. HE can also be classified according to whether its presence is overt or covert. The pathogenesis is linked with ammonia and glutamine production, and treatment is based on mechanisms to reduce the formation and/or removal of these compounds. There is no specific diagnostic test for HE, and diagnosis is based on clinical suspicion, excluding other causes and use of clinical tests that may support its diagnosis. Many tests are used in trials and experimentally, but have not yet gained universal acceptance. This review focuses on the definitions, pathogenesis and treatment of HE. Consideration will be given to existing treatment, including avoidance of precipitating factors and novel therapies such as prebiotics, probiotics, antibiotics, laxatives, branched-chain amino acids, shunt embolization and the importance of considering liver transplant in appropriate cases.
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Affiliation(s)
| | - Mark Alexander Ellul
- Faculty of Health and Life Sciences, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK
| | - Timothy JS Cross
- Department of Gastroenterology, Royal Liverpool University Hospital
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29
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Stravitz RT, Gottfried M, Durkalski V, Fontana RJ, Hanje AJ, Koch D, Hameed B, Ganger D, Subramanian RM, Bukofzer S, Ravis WR, Clasen K, Sherker A, Little L, Lee WM. Safety, tolerability, and pharmacokinetics of l-ornithine phenylacetate in patients with acute liver injury/failure and hyperammonemia. Hepatology 2018; 67:1003-1013. [PMID: 29080224 PMCID: PMC5826861 DOI: 10.1002/hep.29621] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Revised: 08/03/2017] [Accepted: 10/25/2017] [Indexed: 12/12/2022]
Abstract
Cerebral edema remains a significant cause of morbidity and mortality in patients with acute liver failure (ALF) and has been linked to elevated blood ammonia levels. l-ornithine phenylacetate (OPA) may decrease ammonia by promoting its renal excretion as phenylacetylglutamine (PAGN), decreasing the risk of cerebral edema. We evaluated the safety, tolerability, and pharmacokinetics of OPA in patients with ALF and acute liver injury (ALI), including those with renal failure. Forty-seven patients with ALI/ALF and ammonia ≥60 μM were enrolled. Patients received OPA in a dose escalation scheme from 3.3 g every 24 hours to 10 g every 24 hours; 15 patients received 20 g every 24 hours throughout the infusion for up to 120 hours. Plasma phenylacetate (PA) concentrations were uniformly below target (<75 μg/mL) in those receiving 3.3 g every 24 hours (median [interquartile range] 5.0 [5.0] μg/mL), and increased to target levels in all but one who received 20 g every 24 hours (150 [100] μg/mL). Plasma [PAGN] increased, and conversion of PA to PAGN became saturated, with increasing OPA dose. Urinary PAGN clearance and creatinine clearance were linearly related (r = 0.831, P < 0.0001). Mean ammonia concentrations based on the area under the curve decreased to a greater extent in patients who received 20 g of OPA every 24 hours compared with those who received the maximal dose of 3.3 or 6.7 g every 24 hours (P = 0.046 and 0.022, respectively). Of the reported serious adverse events (AEs), which included 11 deaths, none was attributable to study medication. The only nonserious AEs possibly related to study drug were headache and nausea/vomiting. CONCLUSION OPA was well-tolerated in patients with ALI/ALF, and no safety signals were identified. Target [PA] was achieved at infusion rates of 20 g every 24 hours, leading to ammonia excretion in urine as PAGN in proportion to renal function. Randomized, controlled studies of high-dose OPA are needed to determine its use as an ammonia-scavenging agent in patients with ALF. (Hepatology 2018;67:1003-1013).
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Affiliation(s)
| | | | | | | | | | - David Koch
- Medical University of South Carolina, Charleston, SC
| | - Bilal Hameed
- University of California at San Francisco, San Francisco, CA
| | | | | | | | | | | | - Averell Sherker
- National Institute of Diabetes, Digestive and Kidney Disease, Bethesda, MD
| | - Lanna Little
- University of Texas, Southwestern Medical Center, Dallas, TX
| | - William M. Lee
- University of Texas, Southwestern Medical Center, Dallas, TX
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30
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Shalimar, Kedia S, Sharma H, Vasudevan S, Sonika U, Upadhyaya AD, Acharya SK. Predictors of infection in viral-hepatitis related acute liver failure. Scand J Gastroenterol 2017; 52:1413-1419. [PMID: 28875762 DOI: 10.1080/00365521.2017.1374449] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Infections are common and associated with complications and mortality in acute liver failure (ALF). The temporal relationship between ammonia and infection in ALF patients is unclear. We aimed to evaluate the predictors of infection and its relationship with arterial ammonia levels. MATERIALS AND METHODS Consecutive ALF patients hospitalized between January 2004 and December 2015, without signs of infection at/within 48 h of admission, were included. Occurrence of infection after 48 h was documented and ammonia levels were estimated for five consecutive days. Multivariate logistic regression analysis was used to assess factors associated with development of infection. Generalized estimating equations (GEE) were used to evaluate five-day time trend of ammonia in patients with and without infection. RESULTS Of 540 consecutive patients, 120 were infected at admission/within 48 h and were excluded. Of the rest 420 patients, 144 (34.3%) developed infection after 48 h and 276 (65.7%) remained non-infected. Infected patients had higher mortality than non-infected patients (61.8% vs 40.0%, p < .001). On multivariate analysis, presence of cerebral edema(HR 2.049; 95%CI, 1.30-3.23), ammonia level on day 3 of admission (HR 1.006; 95%CI, 1.003-1.008), and model for end stage liver disease (MELD) score (HR 1.051; 95%CI, 1.026-1.078) were associated with development of infection. GEE showed group difference in serial ammonia values between infected and non-infected patients indicating lack of ammonia decline in infected patients. CONCLUSIONS Cerebral edema, elevated ammonia on day 3, and higher MELD score predict the development of infection in ALF. Ammonia persists at high levels in infected patients, and elevated ammonia on day 3 is associated with complications and death.
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Affiliation(s)
- Shalimar
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Saurabh Kedia
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Hanish Sharma
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Sreejith Vasudevan
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Ujjwal Sonika
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
| | - Ashish Dutt Upadhyaya
- b Department of Biostatistics , All India Institute of Medical Sciences , New Delhi , India
| | - Subrat K Acharya
- a Department of Gastroenterology and Human Nutrition , All India Institute of Medical Sciences , New Delhi , India
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Abstract
Acute liver failure, also known as fulminant hepatic failure, is a rare life-threatening disease that has a high mortality rate and affects many organ systems. Causes of acute liver failure vary-it can be attributed to drugs, viruses, and other uncommon sources. Complications of liver failure can include encephalopathy, cerebral edema, sepsis, renal failure, gastrointestinal bleeding, and respiratory failure. Fortunately, with advances in critical care medicine and emergent liver transplant, mortality rates have decreased in the past decade. This article reviews acute liver failure, its manifestations in different organ systems, and its treatment.
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Affiliation(s)
- Ami Grek
- Ami Grek is Nurse Practitioner, Department of Critical Care Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224 . Lisa Arasi is Nurse Practitioner, General Surgery, Mayo Clinic, Jacksonville, Florida
| | - Lisa Arasi
- Ami Grek is Nurse Practitioner, Department of Critical Care Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224 . Lisa Arasi is Nurse Practitioner, General Surgery, Mayo Clinic, Jacksonville, Florida
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Bernal W, Wang Y, Maggs J, Willars C, Sizer E, Auzinger G, Murphy N, Harding D, Elsharkawy A, Simpson K, Larsen FS, Heaton N, O'Grady J, Williams R, Wendon J. Development and validation of a dynamic outcome prediction model for paracetamol-induced acute liver failure: a cohort study. Lancet Gastroenterol Hepatol 2016; 1:217-225. [PMID: 28404094 DOI: 10.1016/s2468-1253(16)30007-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 05/13/2016] [Accepted: 05/13/2016] [Indexed: 01/07/2023]
Abstract
BACKGROUND Early, accurate prediction of survival is central to management of patients with paracetamol-induced acute liver failure to identify those needing emergency liver transplantation. Current prognostic tools are confounded by recent improvements in outcome independent of emergency liver transplantation, and constrained by static binary outcome prediction. We aimed to develop a simple prognostic tool to reflect current outcomes and generate a dynamic updated estimation of risk of death. METHODS Patients with paracetamol-induced acute liver failure managed at intensive care units in the UK (London, Birmingham, and Edinburgh) and Denmark (Copenhagen) were studied. We developed prognostic models, excluding patients who underwent transplantation, using Cox proportional hazards in a derivation dataset, and tested in initial and recent external validation datasets. Mortality was estimated in patients who had emergency liver transplantation. Model discrimination was assessed using area under receiver operating characteristic curve (AUROC) and calibration by root mean square error (RMSE). Admission (day 1) variables of age, Glasgow coma scale, arterial pH and lactate, creatinine, international normalised ratio (INR), and cardiovascular failure were used to derive an initial predictive model, with a second (day 2) model including additional changes in INR and lactate. FINDINGS We developed and validated new high-performance statistical models to support decision making in patients with paracetamol-induced acute liver failure. Applied to the derivation dataset (n=350), the AUROC for 30-day survival was 0·92 (95% CI 0·88-0·96) using the day 1 model and 0·93 (0·88-0·97) using the day 2 model. In the initial validation dataset (n=150), the AUROC for 30-day survival was 0·89 (0·84-0·95) using the day 1 model and 0·90 (0·85-0·95) using the day 2 model. Assessment of calibration using RMSE in prediction of 30-day survival gave values of 0·1642 for the day 1 model and 0·0626 for the day 2 model. In the external validation dataset (n=412), the AUROC for 30-day survival was 0·91 (0·87-0·94) using the day 1 model and 0·91 (0·88-0·95) using the day 2 model, and assessment of calibration using RMSE gave values of 0·079 for the day 1 model and 0·107 for the day 2 model. Applied to patients who underwent emergency liver transplantation (n=116), median predicted 30-day survival was 51% (95% CI 33-85). INTERPRETATION The models developed here show very good discrimination and calibration, confirmed in independent datasets, and suggest that many patients undergoing transplantation based on existing criteria might have survived with medical management alone. The role and indications for emergency liver transplantation in paracetamol-induced acute liver failure require re-evaluation. FUNDING Foundation for Liver Research.
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Affiliation(s)
- William Bernal
- Institute of Liver Studies, King's College Hospital, London, UK.
| | - Yanzhong Wang
- Division of Health and Social Care Research, King's College London, London, UK
| | - James Maggs
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Elizabeth Sizer
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Georg Auzinger
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Nicholas Murphy
- Departments of Liver Medicine, Anaesthesia and Critical Care, Queen Elizabeth Hospital, Birmingham, UK
| | - Damian Harding
- Departments of Liver Medicine, Anaesthesia and Critical Care, Queen Elizabeth Hospital, Birmingham, UK
| | - Ahmed Elsharkawy
- Departments of Liver Medicine, Anaesthesia and Critical Care, Queen Elizabeth Hospital, Birmingham, UK
| | - Kenneth Simpson
- Department of Hepatology, Edinburgh Royal Infirmary, Edinburgh, UK
| | - Fin Stolze Larsen
- Department of Hepatology, Rigshospitalet University Hospital Copenhagen, Copenhagen, Denmark
| | - Nigel Heaton
- Institute of Liver Studies, King's College Hospital, London, UK
| | - John O'Grady
- Institute of Liver Studies, King's College Hospital, London, UK
| | | | - Julia Wendon
- Institute of Liver Studies, King's College Hospital, London, UK
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Chen EQ, Zeng F, Zhou LY, Tang H. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure. World J Gastroenterol 2015; 21:11964-11973. [PMID: 26576085 PMCID: PMC4641118 DOI: 10.3748/wjg.v21.i42.11964] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/29/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.
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Abstract
PURPOSE OF REVIEW Acute liver failure (ALF) is a rare but life-threatening systemic disorder. Survival rates with or without emergency liver transplantation (ELT) are increasing. The benefit of ELT in some cases has been questioned and the potential for survival with medical management alone is changing our approach to the management of this disease. RECENT FINDINGS Survival rates for all causes of ALF are increasing because of improvements in the care of the critically ill patient. A multifactorial approach involving support of respiratory, circulatory and renal function together with measures to avoid intracranial hypertension, metabolic disequilibrium and sepsis are required. For those who do not respond to these measures or specific antidotes, the selection methods for those likely to benefit from transplantation remain imperfect and novel methods based on the prediction of hepatic regeneration are required. For patients with ALF secondary to acetaminophen overdose, some experts believe a randomized controlled trial is required to find those most likely to benefit from ELT. SUMMARY ALF remains a life-threatening condition with a high mortality rate requiring prompt support of multiorgan failure. Historical listing criteria for ELT are being questioned and improvement in medical management offers the option of continued improvements in transplant-free survival.
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Aldridge DR, Tranah EJ, Shawcross DL. Pathogenesis of hepatic encephalopathy: role of ammonia and systemic inflammation. J Clin Exp Hepatol 2015; 5:S7-S20. [PMID: 26041962 PMCID: PMC4442852 DOI: 10.1016/j.jceh.2014.06.004] [Citation(s) in RCA: 203] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 06/05/2014] [Indexed: 12/12/2022] Open
Abstract
The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review.
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Key Words
- ATP, adenosine triphosphate
- AoCLF, acute-on-chronic liver failure
- BBB, blood–brain barrier
- CBF, cerebral blood flow
- CNS, central nervous system
- GS, glutamine synthetase
- HE, hepatic encephalopathy
- ICH, intracranial hypertension
- MHE, minimal hepatic encephalopathy
- MPT, mitochondrial permeability transition
- PAG, phosphate-activated glutaminase
- PTP, permeability transition pore
- TLR, toll-like receptor
- ammonia
- hepatic encephalopathy
- iNOS, inducible nitric oxide synthase
- infection
- inflammation
- systemic inflammatory response syndrome
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Affiliation(s)
| | | | - Debbie L. Shawcross
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, King's College Hospital, Denmark Hill, London SE5 9RS, United Kingdom
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Kumar S, Asrani SK. Non-cirrhotic Hyperammonemia—When High Ammonia Is not Always from Cirrhosis. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0252-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Dharel N, Bajaj JS. Antibiotic prophylaxis in acute liver failure: friend or foe? Clin Gastroenterol Hepatol 2014; 12:1950-2. [PMID: 24842669 DOI: 10.1016/j.cgh.2014.05.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 05/10/2014] [Accepted: 05/12/2014] [Indexed: 02/07/2023]
Affiliation(s)
- Narayan Dharel
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, McGuire VA Medical Center, Richmond, Virginia
| | - Jasmohan S Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, McGuire VA Medical Center, Richmond, Virginia
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Seiden-Long I, Schnabl K, Skoropadyk W, Lennon N, McKeage A. Evaluation of a third party enzymatic ammonia method for use on the Roche Cobas 6000 (c501) automated platform. Clin Biochem 2014; 47:1116-20. [DOI: 10.1016/j.clinbiochem.2014.04.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 04/21/2014] [Accepted: 04/22/2014] [Indexed: 11/24/2022]
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Abstract
OPINION STATEMENT Hepatic encephalopathy management varies depending on the acuity of liver failure. However, in patients with either acute or chronic liver failure five basic steps in management are critical: stabilization, addressing modifiable precipitating factors, lowering blood ammonia, managing elevated intracranial pressure (ICP) (if present), and managing complications of liver failure that can contribute to encephalopathy, particularly hyponatremia. Because liver failure patients are prone to a variety of other medical problems that can lead to encephalopathy (such as coagulopathy associated intracranial hemorrhage, electrolyte disarray, renal failure, hypotension, hypoglycemia, and infection), a thorough history, physical and neurologic examination is mandated in all encephalopathic liver failure patients. There should be a low threshold for brain imaging in patients with focal neurological deficits given the propensity for spontaneous intracranial hemorrhage. In patients with acute liver failure and high grade encephalopathy, identification of the etiology of acute liver failure is essential to guide treatment and antidote administration, particularly in the case of acetaminophen poisoning. Equally critical is management of elevated ICP in acute liver failure. Intracranial hypertension can be treated with hypertonic saline and/or adjustment of the dialysis bath. Placement of an intracranial monitor to guide ICP therapy is risky because of concomitant coagulopathy and remains controversial. Continuous renal replacement therapy may help lower serum ammonia, treat coexisting uremia, and improve symptoms. Liver transplantation is the definitive treatment for patients with acute liver failure and hepatic encephalopathy. In patients with chronic hepatic encephalopathy, lactulose and rifaxamin remain a mainstay of therapy. In these patients, it is essential to identify reversible causes of hepatic encephalopathy such as increased ammonia production and/or decreased clearance (eg, infection, GI bleed, constipation, hypokalemia, dehydration). Chronic hyponatremia should be managed by gradual sodium correction of no more than 8‒12 meq/L per day to avoid central myelinolysis syndrome. Free water restriction and increased dietary sodium are reasonable, cost effective treatment options. Many emerging therapies, both pharmacologic and interventional, are currently being studied to improve management of hepatic encephalopathy.
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Affiliation(s)
- William Bernal
- From the Liver Intensive Therapy Unit, Institute of Liver Studies, King's College London, London
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Tsai HJ, Hsieh MY, Tsai YC, Liu ZY, Hsieh HY, Lee CM, Chien CH, Chiu YW, Chuang HY, Huang CT. Liver function tests may be useful tools for advanced cancer patient care: a preliminary single-center result. Kaohsiung J Med Sci 2013; 30:146-52. [PMID: 24581215 DOI: 10.1016/j.kjms.2013.09.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Accepted: 05/07/2013] [Indexed: 10/25/2022] Open
Abstract
Accurate prognostication in advanced cancer may facilitate better palliative care. An objective marker may be more applicable and appropriate than a subjective evaluation by physicians. The aim of this study was to evaluate liver function tests as useful prognostic factors for survival in patients with advanced cancer. We recruited advanced cancer patients from January 2007 to December 2009. Data on age, sex, cancer diagnosis, site of metastases, clinical symptoms, and performance status were collected at the time of admission to the palliative care unit. Analyzed laboratory data were obtained on the Day 1 of admission to the palliative care unit. A total of 522 patients were enrolled; 322 (61.7%) of them were males. The mean age was 60.6 ± 13.2 years. Multiple logistic regression analysis adjusting for age and sex demonstrated aspartate transaminase (AST) > 80 IU/L [odds ratio (OR) = 2.01, p = 0.010] and alanine transaminase > 80 IU/L (OR = 1.89, p = 0.047) were independently significant prognostic factors of death within 14 days. AST > 80 IU/L (OR = 3.67, p = 0.017) and albumin < 3.0 g/dL (OR = 1.98, p = 0.048) were independently significant prognostic factors of death within 6 months. Liver function tests may be useful prognostic factors for patients in the palliative care unit, in addition to being useful for patients with hepatobiliary cancer or liver metastasis. These biochemical tests of liver function with cutoff values can easily be used in palliative care.
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Affiliation(s)
- Hui-Ju Tsai
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Yi-Chun Tsai
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Zi-Yun Liu
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hui-Ya Hsieh
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiou-Mei Lee
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Hsin Chien
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Wen Chiu
- Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
| | - Hung-Yi Chuang
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Chia-Tsuan Huang
- Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Medicine, Kaohsiung Medical University, Taiwan
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Pathogenesis of hepatic encephalopathy. Gastroenterol Res Pract 2012; 2012:642108. [PMID: 23316223 PMCID: PMC3534214 DOI: 10.1155/2012/642108] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2012] [Revised: 11/16/2012] [Accepted: 11/16/2012] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.
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II. Ammonia in Acute Liver Failure: If the Level Does Not Decline, the Outcome of Acute Liver Failure Might. J Clin Exp Hepatol 2012; 2:194-5. [PMID: 25755430 PMCID: PMC3940552 DOI: 10.1016/s0973-6883(12)60112-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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