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Zielińska M, Popek M, Albrecht J. Neuroglia in hepatic encephalopathy. HANDBOOK OF CLINICAL NEUROLOGY 2025; 210:191-212. [PMID: 40148045 DOI: 10.1016/b978-0-443-19102-2.00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Neuroglia contribute to the pathophysiology of hepatic encephalopathy (HE) either beneficially or detrimentally. Pathogenesis of HE is linked to damage triggered by blood-derived toxins, with ammonia being the main causative factor. Neuroglial cells, especially astrocytes and microglia, respond to HE-associated systemic and central signals and undergo complex and variable changes in their metabolism, morphology, and function, which include ion and water dyshomeostasis in conjunction with neurotransmission imbalance and neuroinflammation. HE-induced alterations of astrocytes are defined as astrocytopathy, with aberrant astrocytes resulting in either gain or loss of functions. In the chronic HE, the presence of Alzheimer type II cells is a histologic hallmark, with asthenic astrocytes emerging as a newcomer. In acute HE, rapid swelling of astrocytes is a primary cause of cerebral edema and mortality. This chapter reviews the dominant role of astrocytes in the pathogenesis of HE resulting from acute and chronic liver failure, mainly in experimental models. The focus is on the loss of homeostatic function bearing upon the functioning of the glymphatic system, aberrant neurotransmission as a consequence of astrocyte-neuron miscommunication, and the concordant neuroinflammatory response of astrocytes and microglia. The chapter concludes with a delineation of concepts for future research.
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Affiliation(s)
- Magdalena Zielińska
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
| | - Mariusz Popek
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
| | - Jan Albrecht
- Department of Neurotoxicology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland
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Paschoal-Jr FM, Nogueira RC, Ronconi KDAL, de Lima Oliveira M, Almeida KJ, Rocha IS, Paschoal EHA, Paschoal JKSF, D'Albuquerque LAC, Teixeira MJ, Panerai RB, Bor-Seng-Shu E. TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation. Ann Hepatol 2024; 29:101167. [PMID: 37802415 DOI: 10.1016/j.aohep.2023.101167] [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: 05/29/2023] [Revised: 08/25/2023] [Accepted: 09/25/2023] [Indexed: 10/10/2023]
Abstract
INTRODUCTION AND OBJECTIVES Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.
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Affiliation(s)
- Fernando M Paschoal-Jr
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil; Department of Neurology, Federal University of Pará Medical School, Brazil.
| | - Ricardo C Nogueira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Karla de Almeida Lins Ronconi
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Marcelo de Lima Oliveira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Kelson James Almeida
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | | | | | | | | | - Manoel Jacobsen Teixeira
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
| | - Ronney B Panerai
- Department of Cardiovascular Sciences, University of Leicester, United Kingdom
| | - Edson Bor-Seng-Shu
- Laboratory for Neurosonology and Cerebral Hemodynamics, Division of Neurological Surgery, Hospital das Clinicas, Sao Paulo University Medical School, Brazil
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Muñoz-Martínez SG, Díaz-Hernández HA, Suárez-Flores D, Sánchez-Ávila JF, Gamboa-Domínguez A, García-Juárez I, Torre A. Atypical manifestations of hepatitis A virus infection. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2018; 83:134-143. [PMID: 29685743 DOI: 10.1016/j.rgmx.2017.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 09/13/2017] [Accepted: 10/05/2017] [Indexed: 02/07/2023]
Abstract
Acute hepatitis due to the hepatitis A virus usually has a short, benign and self-limited course, without causing chronic hepatitis. However, some cases have an atypical presentation, such as relapsing hepatitis, prolonged or persistent cholestasis, fulminant hepatic failure, or liver failure associated with autoimmune hepatitis. The typical clinical course of acute hepatitis A virus infection is spontaneous remission in 90% of the cases, but atypical cases have a prevalence that varies from less than 1 to 20%, depending on the manifestation (overall prevalence ∼7%). There is little information on the atypical clinical courses of hepatitis A virus infection and the lack of recognizing those presentations in clinical practice often results in carrying out numerous studies and treatments that not only are unnecessary, but can also be harmful. The aim of the present article was to describe 3 clinical cases of atypical hepatitis A infection and provide a literature review of such cases.
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Affiliation(s)
- S G Muñoz-Martínez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - H A Díaz-Hernández
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - D Suárez-Flores
- Departamento de Anatomía Patológica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - J F Sánchez-Ávila
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México; Unidad de Hepatología y Trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - A Gamboa-Domínguez
- Departamento de Anatomía Patológica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México; Unidad de Hepatología y Trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - A Torre
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México; Unidad de Hepatología y Trasplante hepático, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
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Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond. HEPATIC CRITICAL CARE 2018. [PMCID: PMC7122599 DOI: 10.1007/978-3-319-66432-3_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Occurrence of brain dysfunction is common in both chronic liver disease as well as acute liver failure. While brain dysfunction most commonly manifests as hepatic encephalopathy is chronic liver disease; devastating complications of cerebral edema and brain herniation syndromes may occur with acute liver failure. Ammonia seems to play a central role in the pathogenesis of brain dysfunction in both chronic liver disease and acute liver failure. In this chapter we outline the pathophysiology and clinical management of brain dysfunction in the critically ill patients with liver disease.
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Fu LL, Pang BY, Zhu Y, Wang L, Leng AJ, Chen HL. Yi Guan Jian decoction may enhance hepatic differentiation of bone marrow‑derived mesenchymal stem cells via SDF‑1 in vitro. Mol Med Rep 2017; 16:2511-2521. [PMID: 28677743 PMCID: PMC5548069 DOI: 10.3892/mmr.2017.6888] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/12/2016] [Indexed: 01/25/2023] Open
Abstract
A previous study reported that Yi Guan Jian (YGJ) may increase the proliferation and differentiation of hepatic oval cells in a rat liver cirrhosis model. The aim of the present study was to investigate the effect and mechanism of action of YGJ on inducing hepatic differentiation in bone marrow-derived mesenchymal stem cells (BM-MSCs) via stromal-cell derived factor-1 (SDF-1). Murine BM-MSCs were isolated with whole bone marrow adherence, then identified by immunocytochemical staining and flow cytometry. Passage 2 cells were divided into 8 groups and their differentiation was induced by cell factors added to the medium, including hepatocyte growth factor (HGF), SDF-1 and YGJ. Each of the cell factors was used alone and any two or three of them were combined to establish different cell microenvironments in the different treatment groups. Albumin (ALB) was selected as a hepatocellular marker and cytokeratin-18 (CK-18) as a cholangiocellular marker. The protein and mRNA expression levels of ALB and CK-18 were used to determine the differentiation of BM-MSCs using immunocytochemical staining, western blotting and reverse transcription-quantitative polymerase chain reaction on days 7, 14, 21 and 28 during induction. The relative expression levels of ALB and CK-18 resulted in time-dependent increases in the groups supplemented only with HGF, SDF-1 or YGJ. Combination treatment of any two HGF, SDF-1 and YGJ led to a higher expression of ALB and CK-18 compared with only one cell factor treatment. Additionally, when all three were used in a combined treatment the expression levels of ALB and CK-18 occurred at an earlier time and was higher overall. Therefore, the present study suggested that YGJ had an effect on inducing hepatic differentiation in BM-MSCs via SDF-1 and may act in a synergistic manner with HGF and SDF-1.
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Affiliation(s)
- Lin-Lin Fu
- Department of Infectious Disease, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Bing-Yao Pang
- Department of Infectious Disease, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Ying Zhu
- Department of Infectious Disease, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Ling Wang
- Department of Digestive Disease, Gansu Provincial Hospital, Lanzhou, Gansu 730000, P.R. China
| | - Ai-Jing Leng
- Department of Chinese Medicine, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Hai-Long Chen
- Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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Ndekwe P, Ghabril MS, Zang Y, Mann SA, Cummings OW, Lin J. Substantial hepatic necrosis is prognostic in fulminant liver failure. World J Gastroenterol 2017; 23:4303-4310. [PMID: 28694671 PMCID: PMC5483505 DOI: 10.3748/wjg.v23.i23.4303] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 03/21/2017] [Accepted: 05/19/2017] [Indexed: 02/07/2023] Open
Abstract
AIM To evaluate if any association existed between the extent of hepatic necrosis in initial liver biopsies and patient survival.
METHODS Thirty-seven patients with fulminant liver failure, whose liver biopsy exhibited substantial necrosis, were identified and included in the study. The histological and clinical data was then analyzed in order to assess the relationship between the extent of necrosis and patient survival, with and without liver transplantation. The patients were grouped based on the etiology of hepatic necrosis. Each of the etiology groups were then further stratified according to whether or not they had received a liver transplant post-index biopsy, and whether or not the patient survived.
RESULTS The core tissue length ranged from 5 to 44 mm with an average of 23 mm. Causes of necrosis included 14 autoimmune hepatitis, 10 drug induced liver injury (DILI), 9 hepatitis virus infection, and 4 unknown origin. Among them, 11 showed submassive (26%-75% of the parenchymal volume) and 26 massive (76%-100%) necrosis. Transplant-free survival was worse in patients with a higher extent of necrosis (40%, 71.4% and 100% in groups with necrosis of 76%-100%, 51%-75% and 26%-50%, respectively). Additionally, transplant-free survival rates were 66.7%, 57.1%, and 25.0% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively. Even after liver transplantation, the survival rate in patients as a result of viral hepatitis remained the lowest (80%, 100%, and 40% in groups of autoimmune hepatitis, DILI, and viral hepatitis, respectively).
CONCLUSION Adequate liver biopsy with more than 75% necrosis is associated with significant transplant-free mortality that is critical in predicting survival.
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Abstract
Hepatic encephalopathy occurs ubiquitously in all causes of advanced liver failure, however, its implications on mortality diverge and vary depending upon acuity and severity of liver failure. This associated mortality has decreased in subsets of liver failure over the last 20 years. Aside from liver transplantation, this improvement is not attributable to a single intervention but likely to a combination of practical advances in critical care management. Misconceptions surrounding many facets of hepatic encephalopathy exists due to heterogeneity in presentation, pathophysiology and outcome. This review is intended to highlight the important concepts, rationales and strategies for managing hepatic encephalopathy.
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Affiliation(s)
- Prem A Kandiah
- Division of Neuro Critical Care, Department of Neurosurgery, Co-appointment in Surgical Critical Care, Emory University Hospital, 1364 Clifton Road Northeast, 2nd Floor, 2D ICU-D264, Atlanta, GA 30322, USA.
| | - Gagan Kumar
- Department of Critical Care, Phoebe Putney Memorial Hospital, 417 Third Avenue, Albany, GA 31701, USA
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Liver transplantation for acute liver failure. Cir Esp 2017; 95:181-189. [PMID: 28433231 DOI: 10.1016/j.ciresp.2017.01.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2016] [Revised: 01/11/2017] [Accepted: 01/19/2017] [Indexed: 12/16/2022]
Abstract
Before liver transplantation became widely applicable as a treatment option, the mortality rate for acute liver failure was as high as 85%. Today, acute liver failure is a relatively common transplant indication in some settings, but the results of liver transplantation in this context appear to be worse than those for chronic forms of liver disease. In this review, we discuss the indications and contraindications for urgent liver transplantation. In particular, we consider the roles of auxiliary, ABO-incompatible, and urgent living donor liver transplantation and address the management of a «status 1» patient with total hepatectomy and portocaval shunt for toxic liver syndrome.
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Pannu AK, Bhalla A, Rao C, Singh C. Delta model for end-stage liver disease and delta clinical prognostic indicator as predictors of mortality in patients with viral acute liver failure. Int J Crit Illn Inj Sci 2017; 7:252-255. [PMID: 29291180 PMCID: PMC5737069 DOI: 10.4103/ijciis.ijciis_122_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Objective: The objective of the study is to compare the model for end-stage liver disease (MELD) with clinical prognostic indicators (CPI) specifically the change in these parameters after 48 h of admission in predicting the mortality in patients with acute liver failure (ALF) due to acute viral hepatitis. Materials and Methods: An open label, investigator-initiated prospective study was conducted that included 41 patients with acute viral hepatitis with ALF. The cases were followed prospectively till death or discharge. The MELD and CPI were calculated at admission and 48 h of admission. Results: Patients having no change or worsening in CPI score, i.e., delta CPI more negative had a higher mortality over the next 48 h compared to patients having an improvement in their respective CPI score. Delta CPI predicted adverse outcome better than the presence of any three CPI on admission (P = 0.019). Patients having no change or a worsening in MELD score, i.e., delta MELD more negative, had a higher mortality in the next 48 h compared to the patients having improvement in their respective MELD score. However, MELD >33 on admission was superior to delta MELD in predicting the adverse outcome (P = 0.019). Conclusion: Among the patients with ALF due to viral hepatitis, delta CPI was found to be superior to delta MELD in predicting the adverse outcome in patients with viral ALF (P < 0.0001).
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Affiliation(s)
- Ashok Kumar Pannu
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Bhalla
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Chelapati Rao
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Charanpreet Singh
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Abstract
PURPOSE OF REVIEW The objective of this article is to review the latest developments related to the treatment of patients with acute liver failure (ALF). RECENT FINDINGS As the treatment of ALF has evolved, there is an increasing recognition regarding the risk of intracranial hypertension related to advanced hepatic encephalopathy. Therefore, there is an enhanced emphasis on neuromonitoring and therapies targeting intracranial hypertension. Also, new evidence implicates systemic proinflammatory cytokines as an etiology for the development of multiorgan system dysfunction in ALF; the recent finding of a survival benefit in ALF with high-volume plasmapheresis further supports this theory. SUMMARY Advances in the critical care management of ALF have translated to a substantial decrease in mortality related to this disease process. The extrapolation of therapies from general neurocritical care to the treatment of ALF-induced intracranial hypertension has resulted in improved neurologic outcomes. In addition, recognition of the systemic inflammatory response and multiorgan dysfunction in ALF has guided current treatment recommendations, and will provide avenues for future research endeavors. With respect to extracorporeal liver support systems, further randomized studies are required to assess their efficacy in ALF, with attention to nonsurvival end points such as bridging to liver transplantation.
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Paschoal Jr FM, Nogueira RC, Ronconi KDAL, de Lima Oliveira M, Teixeira MJ, Bor-Seng-Shu E. Multimodal brain monitoring in fulminant hepatic failure. World J Hepatol 2016; 8:915-923. [PMID: 27574545 PMCID: PMC4976210 DOI: 10.4254/wjh.v8.i22.915] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Revised: 04/22/2016] [Accepted: 06/16/2016] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting.
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Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: an updated review. Arch Toxicol 2014; 89:193-9. [PMID: 25537186 DOI: 10.1007/s00204-014-1432-2] [Citation(s) in RCA: 192] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2014] [Accepted: 12/04/2014] [Indexed: 02/06/2023]
Abstract
As the most common cause of acute liver failure (ALF) in the USA and UK, acetaminophen-induced hepatotoxicity remains a significant public health concern and common indication for emergent liver transplantation. This problem is largely attributable to acetaminophen combination products frequently prescribed by physicians and other healthcare professionals, with unintentional and chronic overdose accounting for over 50 % of cases of acetaminophen-related ALF. Treatment with N-acetylcysteine can effectively reduce progression to ALF if given early after an acute overdose; however, liver transplantation is the only routinely used life-saving therapy once ALF has developed. With the rapid course of acetaminophen-related ALF and limited supply of donor livers, early and accurate diagnosis of patients that will require transplantation for survival is crucial. Efforts in developing novel treatments for acetaminophen-induced ALF are directed toward bridging patients to recovery. These include auxiliary, artificial, and bioartificial support systems. This review outlines the most recent developments in diagnosis and management of acetaminophen-induced ALF.
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Wijdicks EF, Hocker SE. Neurologic complications of liver transplantation. HANDBOOK OF CLINICAL NEUROLOGY 2014; 121:1257-66. [DOI: 10.1016/b978-0-7020-4088-7.00085-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/12/2023]
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Abstract
Fulminant hepatic failure presents with a hepatic encephalopathy and may progress to coma and often brain death from cerebral edema. This natural progression in severe cases contributes to early mortality, but outcome can be good if liver transplantation is appropriately timed and increased intracranial pressure (ICP) is managed. Neurologists and neurosurgeons have become more involved in these very challenging patients and are often asked to rapidly identify patients who are at risk of cerebral edema, to carefully select the patient population who will benefit from invasive ICP monitoring, to judge the correct time to start monitoring, to participate in treatment of cerebral edema, and to manage complications such as intracranial hemorrhage or seizures. This chapter summarizes the current multidisciplinary approach to fulminant hepatic failure and how to best bridge patients to emergency liver transplantation.
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Development of a new auxiliary heterotopic partial liver transplantation technique using a liver cirrhosis model in minipigs: Preliminary report of eight transplants. Exp Ther Med 2012; 3:865-868. [PMID: 22969983 DOI: 10.3892/etm.2012.507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 02/10/2012] [Indexed: 01/18/2023] Open
Abstract
This study aimed to develop a new auxiliary heterotopic partial liver transplantation (AHPLT) technique in minipigs using a model of liver cirrhosis. Based on our previous study, 14 minipigs were induced to cirrhosis by administration of carbon tetrachloride (CCl(4)) through intraperitoneal injection. All of the cirrhotic animals were utilized as recipients. The donor's liver was placed on the recipient's splenic bed, and the anastomosis was performed as follows: end-to-end anastomosis between the donor's portal vein and the recipient's splenic vein, end-to-side anastomosis between the donor's suprahepatic vena cava and the recipient's suprahepatic vena cava, and end-to-end anastomosis between the donor's hepatic artery and the recipient's splenic artery. The common bile duct of the donor was intubated and bile was collected with an extracorporeal bag. Vital signs, portal vein pressure (PVP), hepatic venous pressure (HVP) and portal vein pressure gradient (PVPG) were monitored throughout the transplantation. All 8 minipigs that developed liver cirrhosis were utilized to establish the new AHPLT; 7 cases survived. Following the surgical intervention, the PVP and PVPG of the recipients were lower than those prior to the operation (P<0.05), whereas the PVP and PVPG of the donors increased significantly compared to those of the normal animals (P<0.05). A new operative technique for AHPLT has been successfully described herein using a model of liver cirrhosis.
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Jin SZ, Liu BR, Xu J, Gao FL, Hu ZJ, Wang XH, Pei FH, Hong Y, Hu HY, Han MZ. Ex vivo-expanded bone marrow stem cells home to the liver and ameliorate functional recovery in a mouse model of acute hepatic injury. Hepatobiliary Pancreat Dis Int 2012; 11:66-73. [PMID: 22251472 DOI: 10.1016/s1499-3872(11)60127-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Stem cell transplantation provides a theoretical approach for liver regeneration medicine; it may promote liver regeneration and self-repair. However, the transplantation of bone marrow-mesenchymal stem cells expanded ex vivo as a therapy for liver disease has rarely been investigated. This study aimed to explore whether bone marrow stem cells expanded ex vivo home to the liver and foster hepatic recovery after CCl4 injury. METHODS Bone marrow cells from BALB/c mice were expanded ex vivo by multiple-passage cultivation, characterized by cytoflow immunofluorescence, and pre-labeled with PKH26 before intravenous infusion into animals treated with CCl4. The integration of bone marrow cells into the liver was examined microscopically, and plasma hepatic enzymes were determined biochemically. RESULTS Cultured bone marrow cells exhibited antigenic profiles comparable to those of primary medullary stem cells. Double immunofluorescence showed colocalization of these cells with proliferative activity and albumin expression in the liver of CCl4-treated mice. Densitometry showed increased in situ cell proliferation (50+/-14 vs 20+/-3 cells/high-power field, P<0.05) and albumin expression (149+/-25 vs 20+/-5 cells/high-power field, P<0.05) in the liver, as well as reduced serum aminotransferase levels (P<0.05) and better survival rates (P<0.05) in animals receiving cultured bone marrow cells relative to controls. CONCLUSIONS Ex vivo-expanded bone marrow cells are capable of relocating to and proliferating in the chemically-injured liver. Transplantation of these pluripotent stem cells appears to improve serum indices of liver function and survival rate in mice after CCl4-induced hepatic damage.
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Affiliation(s)
- Shi-Zhu Jin
- Department of Gastroenterology and Hepatology, Second Affiliated Hospital, Harbin Medical University, Harbin, China
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Gomes MAC, Ferreira ADSP, Silva AAMD, Souza ERD. Hepatite A: soroprevalência e fatores associados em escolares de São Luís (MA), Brasil. REVISTA BRASILEIRA DE EPIDEMIOLOGIA 2011. [DOI: 10.1590/s1415-790x2011000400002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVOS: Estimar a prevalência de anticorpos contra o vírus da hepatite A (antiVHA-IgG) em escolares de 7 a 14 anos de escolas públicas e privadas e identificar fatores demográficos, socioeconômicos e sanitários associados à prevalência de antiVHA-IgG. MÉTODOS: Estudo soroepidemiológico para detecção de antiVHA-IgG, de abril de 2002 a abril de 2004, em 462 escolares de São Luís, com idades compreendidas entre 7 e 14 anos, do ensino fundamental. Participaram 30 escolas aleatoriamente selecionadas, com probabilidade proporcional ao número de alunos matriculados, sendo 23 públicas e 7 privadas. Os dados foram obtidos por meio de questionário estruturado. Para se identificar variáveis independentemente associadas à prevalência do antiVHA-IgG, foi realizada análise de regressão de Poisson múltipla, sendo estimadas as RPs ajustadas e respectivos intervalos de confiança de 95%. Somente permaneceram no modelo final aquelas variáveis associadas com a prevalência da hepatite A com p < 0,10. Foi adotado o nível de significância de 0,05 (α = 0,05). RESULTADOS: A prevalência de antiVHA-IgG foi de 64%, sendo de 71,5% nas escolas públicas e de 36,5% nas privadas. Após análise multivariável, idade de 11 a 14 anos, mais de uma pessoa por dormitório e menos de dois banheiros por domicílio foi associada a maiores prevalências de antiVHA-IgG. Maior escolaridade dos pais esteve associada à menor prevalência de antiVHA-IgG. CONCLUSÕES: A hepatite A é endêmica nos escolares de São Luís, com taxa de prevalência semelhante àquela encontrada em outras regiões do país com condições socioeconômicas e sanitárias similares. Fatores historicamente associados à maior prevalência da hepatite A foram também identificados nesta população.
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Arkadopoulos N, Kostopanagiotou G, Nastos C, Papalois A, Papoutsidakis N, Kalimeris K, Defterevos G, Kanna T, Polyzois K, Kampouroglou G, Kypriotis D, Costopanagiotou C, Pafiti A, Tzanatos H, Smyrniotis V. Reversal of experimental posthepatectomy liver failure in pigs: a new application of hepatocyte bioreactors. Artif Organs 2011; 35:29-36. [PMID: 20618230 DOI: 10.1111/j.1525-1594.2010.01016.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post-hepatectomy liver failure. Our experimental model included a combination of a side-to-side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24-h autopsy. The extracorporeal circuit was well-tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.
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Affiliation(s)
- Nikolaos Arkadopoulos
- Experimental Surgical Unit, 2nd Department of Surgery, Medical School, University of Athens, Aretaieion Hospital, Greece
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Chen Y, Li J, Liu X, Zhao W, Wang Y, Wang X. Transplantation of immortalized human fetal hepatocytes prevents acute liver failure in 90% hepatectomized mice. Transplant Proc 2010; 42:1907-14. [PMID: 20620547 DOI: 10.1016/j.transproceed.2010.01.061] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2009] [Accepted: 01/25/2010] [Indexed: 12/14/2022]
Abstract
AIM The aim of this study was to investigate whether human fetal hepatocytes are amenable to simian virus 40 large T-antigen (SV40Tag) mediated immortalization and whether the immortalized cells rescue mice with acute liver failure induced by 90% hepatectomy. METHODS We constructed a retroviral vector expressing a thermolabile mutant SV40Tag for transfer into primary human fetal hepatocytes. We quantitatively detected the synthetic ability for albumin and urea by the immortalized cells, which were subcutaneously inoculated into mice with severe combined immunodeficiency (SCID) to evaluate tumorigenzcity. The immortalized cells were also transplanted into the spleens of mice with acute liver failure. RESULTS One clone resulting after selection, referred to as HepCL, was highly differentiated, growing steadily in a chemically defined serum-free medium. HepCL cells were positive for albumin, cytokeratin 18, and cytokeratin 19 immunocytochemical staining. The average synthetic efficacies of HepCL cells for albumin and urea were comparable to that of unmodified primary human fetal hepatocytes. The population doubling time of HepCL cells in the logarithmic growth phase was approximately 17 hours. HepCL cells showed no oncogenicity in immunodeficient mice at 16 months. Mice receiving HepCL cells (G1) and primary human fetal hepatocytes (G2) showed significantly lower blood ammonia levels after 90% hepatectomy. Pairwise comparisons between the 4 groups showed that xenotransplantation of HepCL (G1) or primary fetal hepatocytes (G2) significantly improved survivals of recipient mice. CONCLUSIONS HepCL may be useful as a source of hepatic function for cell-based therapeutics in acute liver failure.
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Affiliation(s)
- Y Chen
- Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China
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Abstract
PURPOSE OF REVIEW Acute liver failure (ALF) is a devastating syndrome afflicting previously healthy individuals. Early recognition of the illness is crucial, as aggressive treatment may improve outcomes. Despite significant advances in care, however, the mortality remains high (30-100%). This brief review will focus on the causes and overall management of the complications of ALF. RECENT FINDINGS Our knowledge of the causes of ALF has expanded significantly in the last decade. The mechanism of hepatic encephalopathy and cerebral edema in this setting continues to be elucidated and is discussed here. SUMMARY Improved outcomes can be achieved with the early recognition and aggressive management of ALF.
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Yan S, Tu Z, Lu W, Zhang Q, He J, Li Z, Shao Y, Wang W, Zhang M, Zheng S. Clinical utility of an automated pupillometer for assessing and monitoring recipients of liver transplantation. Liver Transpl 2009; 15:1718-27. [PMID: 19938127 DOI: 10.1002/lt.21924] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Pupil examination has been used as a basic measure in critically ill patients and has great importance for the prognosis and management of disease. An automated pupillometer is a computer-based infrared digital video system by which the accuracy and precision of the pupil examination are markedly improved. We conducted an observational study of pupil assessment with automated pupillometry in clinical liver transplantation settings, including pretransplant evaluations and posttransplant surveillance. Our results showed that unconscious patients (grade 4 hepatic encephalopathy) had a prolonged latency phase (left side: 283 +/- 80 milliseconds; right side: 295 +/- 96 milliseconds) and a reduced pupillary constrictive ratio (left direct response: 0.23 +/- 0.10; left indirect response: 0.21 +/- 0.07; right direct response: 0.20 +/- 0.08; right indirect response: 0.21 +/- 0.08) in comparison with normal and conscious patients. After liver transplantation, the recovery of pupillography in these patients was slower than that in conscious patients. However, the surviving recipients without major complications all had a gradual recovery of pupillary responses, which occurred on the first or second posttransplant day. We also reported 4 cases of futile LT in the absence of pretransplant pupillary responses and other pupillary abnormalities revealed by automated pupillometry in our study. In conclusion, patients with grade 4 hepatic encephalopathy had a sluggish pupil response and a delayed recovery pattern after LT. An automated pupillometer is potentially a supplementary device for pretransplant screening and posttransplant monitoring in patients undergoing LT, but further prospective studies are required.
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Affiliation(s)
- Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, Hangzhou, People's Republic of China
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Cell transplantation in the treatment of acute liver injury: effect but no clear mechanism. J Surg Res 2009; 157:2-3. [PMID: 19679318 DOI: 10.1016/j.jss.2009.05.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2009] [Revised: 04/28/2009] [Accepted: 05/11/2009] [Indexed: 11/24/2022]
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Arab JP, Pizarro M, Solis N, Sun H, Thevananther S, Arrese M. Mild hypothermia does not affect liver regeneration after partial hepatectomy in mice. Liver Int 2009; 29:344-8. [PMID: 18662277 PMCID: PMC2859296 DOI: 10.1111/j.1478-3231.2008.01834.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND The use of mild hypothermia has been suggested to be therapeutically useful in treating acute liver failure. It is not known if hypothermia influences liver regeneration. AIM To assess the effect of hypothermia on liver regeneration in mice. METHODS After partial (70%) hepatectomy (PHx), C57BL6/J mice were randomly assigned to either a hypothermic group or a normothermic group. Controlled mild hypothermia was maintained for up to 3 h after surgery. In addition, assessment of liver mass restitution was examined by studying the induction of key cell cycle proteins (cyclin A, D1 and E) and hepatocyte proliferation [assessment of proliferating cell nuclear antigen (PCNA) protein expression] by Western blotting and DNA synthesis by measuring 5-bromo-2-deoxyuridine (BrdU) incorporation by immunohistochemical techniques 45 h after PHx. RESULTS Partial hepatectomy induced a vigorous proliferative response in the remnant livers of both groups of mice (normothermic and hypothermic groups), as evidenced by the induction of key cyclins, PCNA and incorporation of BrdU after PHx. The liver/body weight ratio and both cyclin and PCNA protein expression as well as BrdU incorporation did not differ between the regenerating livers of hypothermic and normothermic groups. CONCLUSION Mild hypothermia does not influence liver regeneration in mice.
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Affiliation(s)
- Juan Pablo Arab
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Margarita Pizarro
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Nancy Solis
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile,CORRESPONDING AUTHOR: Marco Arrese, MD, Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile. Marcoleta 367. Postal Code: 833-0024 CHILE. Pone/Fax: 56-2-6397780;
| | - Hongdan Sun
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Texas Children’s Liver Center, Baylor College of Medicine Houston, TX, USA
| | - Sundararajah Thevananther
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Texas Children’s Liver Center, Baylor College of Medicine Houston, TX, USA
| | - Marco Arrese
- Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile,CORRESPONDING AUTHOR: Marco Arrese, MD, Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile. Marcoleta 367. Postal Code: 833-0024 CHILE. Pone/Fax: 56-2-6397780;
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Consolo F, Fiore GB, Truscello S, Caronna M, Morbiducci U, Montevecchi FM, Redaelli A. A Computational Model for the Optimization of Transport Phenomena in a Rotating Hollow-Fiber Bioreactor for Artificial Liver. Tissue Eng Part A 2008. [DOI: 10.1089/ten.tea.2008.0213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Abstract
PURPOSE OF REVIEW Significant changes have been witnessed recently in patients presenting for liver transplantation. The growing number of liver transplantations performed, the increasingly successful outcomes, the expansion of indications, and the implementation of the Model for End-Stage Liver Disease (MELD) system are driving forces for those changes. The purpose of this review is to examine those changes and their effect in perioperative management. RECENT FINDINGS Patients who present for liver transplantation today have higher MELD scores and more advanced liver disease. Studies show that high MELD score patients are associated with high perioperative risks and undergo a more difficult perioperative course than patients with low MELD score. More specifically, they have more preoperative comorbidities, more baseline laboratory abnormalities, and higher requirements for intraoperative transfusion and vasopressors. Progress has been also made in management in patients with hepatocellular carcinoma, fulminant hepatic failure, and coronary artery disease prior to liver transplantation. SUMMARY Patients who present for liver transplantation today are more acutely ill compared with a few years ago and have more comorbidities, higher perioperative risks, and a more difficult perioperative course. Further characterization of the changes and associated perioperative risks and strategies to manage those risks are needed.
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Ferreira CT, Vieira SMG, Kieling CO, Silveira TR. Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil. J Viral Hepat 2008; 15 Suppl 2:66-8. [PMID: 18837838 DOI: 10.1111/j.1365-2893.2008.01033.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.
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Affiliation(s)
- C T Ferreira
- Pediatric Liver Transplant Unit, Hospital de Clínicas, Porto Alegre, Brazil.
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Ananthakrishnan AN, McGinley EL, Saeian K. Effect of hospital volume and teaching status on outcomes of acute liver failure. Liver Transpl 2008; 14:1347-56. [PMID: 18756487 DOI: 10.1002/lt.21519] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Acute liver failure (ALF) often requires multidisciplinary support. Higher hospital volumes have been associated with better outcomes for surgical procedures, but whether such a relationship exists for ALF has not been explored previously. In this study, our aim was to examine if hospital volume affects mortality from ALF. Using data from the Nationwide Inpatient Sample for the years 2001 to 2004, we identified cases by the presence of a primary discharge diagnosis of ALF (International Classification of Diseases, 9th revision, Clinical Modification code 570.x). Hospitals were divided into low-, medium-, and high-volume hospitals on the basis of 1 to 5, 6 to 20, and more than 20 annual ALF discharges. There were 17,361, 6756, and 1790 discharges with ALF from low-, medium-, and high-volume hospitals, respectively. There was no difference in adjusted mortality between low- and high-volume hospitals (odds ratio 0.94, 95% confidence interval 0.68-1.28). Teaching hospitals had a trend toward lower mortality among patients with hepatic encephalopathy (odds ratio 0.69, 95% confidence interval 0.47-1.01). High-volume centers had a higher rate of orthotopic liver transplantation (OLT) primarily because they were transplant centers, had better in-hospital post-OLT survival, and showed a trend toward a shorter time to OLT. In conclusion, patients with ALF receiving care at teaching hospitals and high-volume centers tend to be sicker. However, teaching hospitals and high-volume centers have equivalent in-hospital survival despite caring for this more severely ill cohort.
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Affiliation(s)
- Ashwin N Ananthakrishnan
- Department of Population Health, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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Shiffman ML, Rockey DC. Role and support for hepatologists at liver transplant programs in the United States. Liver Transpl 2008; 14:1092-9. [PMID: 18668665 DOI: 10.1002/lt.21523] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Liver transplantation has evolved into a successful option for patients with end-stage liver disease. Transplant hepatologists are involved in the management of patients with end-stage liver disease both before and after liver transplantation. The goals of this study were to evaluate the roles that transplant hepatologists play at liver transplantation programs in the United States and the demand for and institutional support provided for these physicians. A web-based questionnaire was sent via e-mail to the medical directors of all 108 United Network for Organ Sharing-recognized liver transplant programs during the fall of 2006. Follow-up e-mails were sent and phone calls were made to those not completing the survey within 4 weeks. The survey was completed by 72 (67%) medical directors. The average number of liver transplants performed per center was 62, and a broad range of program sizes were represented. The number of transplant hepatologists increased in proportion to the number of transplants performed on an annual basis but lagged behind the number of surgeons and transplant coordinators. On average, 33 liver transplants were performed per year per transplant hepatologist. Transplant hepatologists were involved in all aspects of pretransplant and posttransplant care at all but 10% of these institutions; they provided virtually all pretransplant care at all of these programs and all long-term posttransplant care at 45% of these programs. Overall, 94% of liver transplant programs provided direct salary support and/or ancillary personnel for their transplant hepatologists. Despite this, over half of transplant hepatologists and 75% of those that received no direct salary support performed endoscopic procedures on a regular basis. Eighty-one percent of programs were recruiting additional transplant hepatologists. In conclusion, although the vast majority of transplant hepatologists receive institutional support, this support appears to be inadequate. The current shortage of transplant hepatologists is likely to increase if appropriate support mechanisms are not implemented.
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Affiliation(s)
- Mitchell L Shiffman
- Hepatology Section and Liver Transplant Program, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
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