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Larsen FS, Saliba F. Liver support systems and liver transplantation in acute liver failure. Liver Int 2025; 45:e15633. [PMID: 37288706 PMCID: PMC11815598 DOI: 10.1111/liv.15633] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/15/2023] [Accepted: 05/24/2023] [Indexed: 06/09/2023]
Abstract
Acute liver failure (ALF) results in a multitude of complications that result in multi-organ failure. This review focuses on the pathophysiological processes and how to manage with these with artificial liver support and liver transplantation (LT). The pathophysiological sequence of events behind clinical deterioration in ALF comes down to two profound consequences of the failing liver. The first is the development of hyperammonemia, as the liver can no longer synthesize urea. The result is that the splanchnic system instead of removing ammonia becomes an ammonia-producing organ system that causes hepatic encephalopathy (HE) and cerebral oedema. The second complication is caused by the necrotic liver cells that release large molecules that originate from degrading proteins, that is damage associated molecular patterns (DAMPs) which causes inflammatory activation of intrahepatic macrophages and an overflow of DAMPs molecules into the systemic circulation resulting in a clinical picture that resembles septic shock. In this context the combined use of continuous renal replacement therapy (CRRT) and plasma exchange are rational and simple ways to remove ammonia and DAMPS molecules. This combination improve survival for ALF patients deemed not appropriate for LT, despite poor prognostic criteria, but also ensure a better stability of vital organs while awaiting LT. The combination of CRRT with albumin dialysis tends to have a similar effect. Currently, the selection criteria for LT for non-paracetamol cases appear robust while the criteria for paracetamol-intoxicated patients have become more unreliable and now consist of more dynamic prognostic systems. For patients that need LT for survival, a tremendous improvement in the post-LT results has been achieved during the last decade with a survival that now reach merely 90% which is mirroring the results seen after LT for chronic liver disease.
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Affiliation(s)
- Fin S. Larsen
- Department of Intestinal Failure and Liver DiseasesRigshospitalet, University Hospital CopenhagenCopenhagenDenmark
| | - Faouzi Saliba
- AP‐HP Hôpital Paul Brousse, Hepato‐Biliary Center and Liver Transplant ICUUniversity Paris Saclay, INSERM unit N°1193VillejuifFrance
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Zhang H, Yang L. Ureaplasma urealyticum infection following organ transplantation: a case report and narrative review. Ren Fail 2024; 46:2395466. [PMID: 39192626 PMCID: PMC11360648 DOI: 10.1080/0886022x.2024.2395466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 08/16/2024] [Accepted: 08/17/2024] [Indexed: 08/29/2024] Open
Abstract
OBJECTIVE One case of Ureaplasma urealyticum (UU) infection after kidney transplantation was reported, and relevant literature was collected to provide a scientific reference basis for clinical diagnosis and treatment. METHODS A case of UU infection after renal transplantation in our hospital was analyzed retrospectively. PubMed, Embase and Cochrane databases were searched for case reports of UU infection after organ transplantation before 30 June 2024. The clinical and laboratory characteristics, treatment and prognosis of UU infection were summarized and analyzed. RESULTS A 65-year-old man underwent renal transplantation on 26 January 2022 due to chronic renal disease (grade 2) caused by focal sclerosing glomerulonephritis. Hyperammonaemia and coma occurred after the operation, and the patient died. A total of 38 case reports or series of cases were included in this study, involving 44 patients. The case reports included 22 cases of kidney transplantation, 11 cases of lung transplantation, 4 cases of heart transplantation,1 case of liver transplantation and 6 cases of multiple organ transplantation. Ureaplasma urealyticum infection occurred in 74.47% of cases within 1 month after transplantation, and the main symptoms after the infection were mental. After the onset of the disease, the most abnormal examination index was the increase of blood ammonia, followed by the increase of white blood cells. Therapeutic drugs included tetracyclines (doxycycline or minocycline), quinolones and azithromycin. The clinical symptoms could be significantly improved after 24 h of taking the fastest-acting medication. The highest mortality rate was in patients infected with Ureaplasma after lung transplantation. CONCLUSION Early identification of UU and timely and correct drug treatment are essential to saving the lives of patients.
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Affiliation(s)
- Hongru Zhang
- Department of Pharmacy, ZhangJiakou First Hospital, Zhangjiakou, Hebei Province, China
| | - Liping Yang
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing, China
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Cui FP, Miao Y, Liu AX, Deng YL, Liu C, Zhang M, Zeng JY, Li YF, Liu HY, Liu CJ, Zeng Q. Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 269:115741. [PMID: 38029584 DOI: 10.1016/j.ecoenv.2023.115741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 11/15/2023] [Accepted: 11/23/2023] [Indexed: 12/01/2023]
Abstract
BACKGROUND Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.
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Affiliation(s)
- Fei-Peng Cui
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Yu Miao
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - A-Xue Liu
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Yan-Ling Deng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Chong Liu
- Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Jia-Yue Zeng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Yu-Feng Li
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Hai-Yi Liu
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China
| | - Chang-Jiang Liu
- NHC Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, PR China.
| | - Qiang Zeng
- Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
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Villanueva VB, Barrera Amorós DA, Castillo Echeverria EI, Budar-Fernández LF, Salas Nolasco OI, Juncos LA, Rizo-Topete L. Extracorporeal blood purification in patients with liver failure: Considerations for the low-and-middle income countries of Latin America. FRONTIERS IN NEPHROLOGY 2023; 3:938710. [PMID: 37675369 PMCID: PMC10479632 DOI: 10.3389/fneph.2023.938710] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 01/04/2023] [Indexed: 09/08/2023]
Abstract
Severe liver failure is common in Low-and-Medium Income Countries (LMIC) and is associated with a high morbidity, mortality and represents an important burden to the healthcare system. In its most severe state, liver failure is a medical emergency, that requires supportive care until either the liver recovers or a liver transplant is performed. Frequently the patient requires intensive support until their liver recovers or they receive a liver transplant. Extracorporeal blood purification techniques can be employed as a strategy for bridging to transplantation or recovery. The most common type of extracorporeal support provided to these patients is kidney replacement therapy (KRT), as acute kidney injury is very common in these patients and KRT devices more readily available. However, because most of the substances that the liver clears are lipophilic and albumin-bound, they are not cleared effectively by KRT. Hence, there has been much effort in developing devices that more closely resemble the clearance function of the liver. This article provides a review of various non-biologic extracorporeal liver support devices that can be used to support these patients, and our perspective keeping in mind the needs and unique challenges present in the LMIC of Latin America.
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Affiliation(s)
- Vladimir Barrera Villanueva
- Division of Nephrology, Instituto Mexicano del Seguro Social, Unidad Médica de Alta Especialidad 14, Universidad Veracruz, Veracruz, Mexico
| | - Daniel Alejandro Barrera Amorós
- Division of Nephrology, Instituto Mexicano del Seguro Social, Unidad Médica de Alta Especialidad 14, Universidad Veracruz, Veracruz, Mexico
| | | | - Luis F. Budar-Fernández
- Division of Nephrology, Instituto Mexicano del Seguro Social, Unidad Médica de Alta Especialidad 14, Universidad Veracruz, Veracruz, Mexico
| | | | - Luis A. Juncos
- Division of Nephrology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, Arkansas, EUA, United States
| | - Lilia Rizo-Topete
- Division of Nephrology, Hospital Unniversitario “Dr. José Eleuterio Gonzalez”, Universidad Autónoma de Nuevo León (UANL), Nuevo León, Mexico
- Division Internal Medicine, Hospital Christus Muguerza Alta Especialidad, Universidad de Monterrey (UDEM), Monterrey, Nuevo Leon, Mexico
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Wang J, Li W. Improvement Effect of PERMA Model-Based Nursing Intervention plus Music Therapy on Patients with Acute Liver Failure Undergoing Plasma Exchange Therapy. Emerg Med Int 2022; 2022:2485056. [PMID: 35811606 PMCID: PMC9259328 DOI: 10.1155/2022/2485056] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/01/2022] [Indexed: 12/02/2022] Open
Abstract
Objective To explore the improvement effect of PERMA model-based nursing intervention plus music therapy (MT) on patients with acute liver failure (AHF) undergoing plasma exchange therapy (PET). Methods This research included 100 AHF patients treated with PET in our hospital, between January 2020 and December 2021, including 54 cases receiving PERMA model-based nursing intervention plus MT (observation group, OG) and 46 cases receiving routine nursing (control group, CG). Clinical efficacy and liver function (LF) were compared between the groups. Prenursing and postnursing psychology, treatment compliance, sleep, pain, and quality of life were assessed, and patient satisfaction was investigated at discharge. Results The postnursing overall efficacy showed no evident difference between the groups (P > 0.05). The clinical efficacy was mainly markedly significant (50.00%) in OG and effective (43.48%) in CG. The overall response rate was not statistically different between groups (χ 2 = 1.392, P > 0.05). OG presented better LF, treatment compliance, and sleep quality after nursing, with milder negative emotions and pain than CG (P < 0.05). A higher patient satisfaction rate was also determined in OG at discharge (P < 0.05). Conclusions PERMA model-based nursing intervention plus MT can effectively improve the psychological state, treatment compliance, and quality of life of AHF patients with PET and reduce pain sensation, which has promising clinical application value in the future.
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Affiliation(s)
- Jinhua Wang
- The Nanhua Affiliated Hospital, Department of Ultrasonography, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
| | - Wei Li
- The Affiliated Nanhua Hospital, Department of Gastroenterology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
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Chen X, Shao B, Yu C, Yao Q, Ma P, Li H, Li B, Sun C. Energy disorders caused by mitochondrial dysfunction contribute to α-amatoxin-induced liver function damage and liver failure. Toxicol Lett 2021; 336:68-79. [PMID: 33098907 DOI: 10.1016/j.toxlet.2020.10.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 09/06/2020] [Accepted: 10/12/2020] [Indexed: 02/07/2023]
Abstract
Mushroom toxicity is the main branch of foodborne poisoning, and liver damage caused by amatoxin poisoning accounts for more than 90 % of deaths due to mushroom poisoning. Alpha-amatoxin (α-AMA) has been considered the primary toxin from amatoxin-containing mushrooms, which is responsible for hepatotoxicity and death. However, the mechanism underlying liver failure due to α-AMA remains unclear. This study constructed animal and cell models. In the animal experiments, we investigated liver injury in BALB/c mice at different time points after α-AMA treatment, and explored the process of inflammatory infiltration using immunohistochemistry and western blotting. Then, a metabonomics method based on gas chromatography mass spectrometry (GCMS) was established to study the effect of α-AMA on liver metabonomics. The results showed a significant difference in liver metabolism between the exposed and control mice groups that coincided with pathological and biochemical indicators. Moreover, 20 metabolites and 4 metabolic pathways related to its mechanism of action were identified, which suggested that energy disorders related to mitochondrial dysfunction may be one of the causes of death. The significant changes of trehalose and the fluctuation of LC3-II and sqstm1 p62 protein levels indicated that autophagy was also involved in the damage process, suggesting that autophagy may participate in the clearance process of damaged mitochondria after poisoning. Then, we constructed an α-AMA-induced human normal liver cells (L-02 cells) injury model. The above hypothesis was further verified by detecting cell necrosis, mitochondrial reactive oxygen species (mtROS), mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (Δψ m), and cellular ATP level. Collectively, our results serve as direct evidence of elevated in vivo hepatic mitochondrial metabolism in α-AMA-exposed mice and suggest that mitochondrial dysfunction plays an important role in the early stage of α-AMA induced liver failure.
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Affiliation(s)
- Xiao Chen
- Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.
| | - Bing Shao
- Beijing Center for Disease Control and Prevention Beijing, China.
| | - Chengmin Yu
- Yunnan Chuxiong People's Hospital, Chuxiong, Yunnan, China.
| | - Qunmei Yao
- Yunnan Chuxiong People's Hospital, Chuxiong, Yunnan, China.
| | - Peibin Ma
- Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.
| | - Haijiao Li
- Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.
| | - Bin Li
- Chinese Center for Disease Control and Prevention, Beijing, Beijing, China.
| | - Chengye Sun
- Chinese Center for Disease Control and Prevention, 29th Nanwei Road, Xicheng District, Beijing, 102206, China.
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7
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Dahl RH, Berg RMG, Taudorf S, Bailey DM, Lundby C, Christensen M, Larsen FS, Møller K. Transcerebral exchange kinetics of large neutral amino acids during acute inspiratory hypoxia in humans. Scandinavian Journal of Clinical and Laboratory Investigation 2019; 79:595-600. [PMID: 31657241 DOI: 10.1080/00365513.2019.1683762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Hypoxaemia is present in many critically ill patients, and may contribute to encephalopathy. Changes in the passage of large neutral amino acids (LNAAs) across the blood-brain barrier (BBB) with an increased cerebral influx of aromatic amino acids into the brain may concurrently be present and also contribute to encephalopathy, but it has not been established whether hypoxaemia per se may trigger such changes. We measured cerebral blood flow (CBF) in 11 healthy men using the Kety-Schmidt technique and obtained paired arterial and jugular-venous blood samples for the determination of LNAAs by high performance liquid chromatography at baseline and after 9 hours of poikilocapnic normobaric hypoxia (12% O2). Transcerebral net exchange was determined by the Fick principle, and transport of LNAAs across the BBB was determined mathematically. Hypoxia increased both the systemic and corresponding cerebral delivery of the aromatic amino acid phenylalanine, and the branched-chain amino acids leucine and isoleucine. Despite this, the transcerebral net exchange values and mathematically derived brain extracellular concentrations for all LNAAs were unaffected. In conclusion, the observed changes in circulating LNAAs triggered by hypoxaemia do not affect the transcerebral exchange kinetics of LNAAs to such an extent that their brain extracellular concentrations are affected.
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Affiliation(s)
- Rasmus H Dahl
- Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark
| | - Ronan M G Berg
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen, Denmark.,Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontyprid, UK
| | - Sarah Taudorf
- Department of Neurology 2082, University Hospital Rigshospitalet, Copenhagen, Denmark
| | - Damian M Bailey
- Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Pontyprid, UK
| | - Carsten Lundby
- Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark
| | - Mette Christensen
- Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark
| | - Fin S Larsen
- Department of Hepatology, Rigshospitalet, Copenhagen, Denmark
| | - Kirsten Møller
- Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark
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Abstract
Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased intracranial pressure (ICP), and subsequent neurologic complications; it is the most important cause of morbidity and mortality in fulminant hepatic failure. The goal of therapy should be early diagnosis and treatment of HE with measures to reduce CE. A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment. Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation.
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Weingarten MA, Sande AA. Acute liver failure in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2015; 25:455-73. [PMID: 25882813 DOI: 10.1111/vec.12304] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 01/26/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To define acute liver failure (ALF), review the human and veterinary literature, and discuss the etiologies and current concepts in diagnostic and treatment options for ALF in veterinary and human medicine. ETIOLOGY In veterinary medicine ALF is most commonly caused by hepatotoxin exposure, infectious agents, inflammatory diseases, trauma, and hypoxic injury. DIAGNOSIS A patient may be deemed to be in ALF when there is a progression of acute liver injury with no known previous hepatic disease, the development of hepatic encephalopathy of any grade that occurs within 8 weeks after the onset of hyperbilirubinemia (defined as plasma bilirubin >50 μM/L [>2.9 mg/dL]), and the presence of a coagulopathy. Diagnostic testing to more specifically characterize liver dysfunction or pathology is usually required. THERAPY Supportive care to aid the failing liver and compensate for the lost functions of the liver remains the cornerstone of care of patients with ALF. Advanced therapeutic options such as extracorporeal liver assist devices and transplantation are currently available in human medicine. PROGNOSIS The prognosis for ALF depends upon the etiology, the degree of liver damage, and the response to therapy. In veterinary medicine, the prognosis is generally poor.
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Therapeutic plasma exchange does not reduce vasopressor requirement in severe acute liver failure: a retrospective case series. BMC Anesthesiol 2015; 15:30. [PMID: 25774091 PMCID: PMC4359494 DOI: 10.1186/s12871-015-0017-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 02/24/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND In acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy. METHODS Physiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation. The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model. RESULTS Thirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 - 147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score 8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively). CONCLUSION In this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.
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Kruitwagen HS, Spee B, Schotanus BA. Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies. BMC Vet Res 2014; 10:137. [PMID: 24946932 PMCID: PMC4089933 DOI: 10.1186/1746-6148-10-137] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Accepted: 12/31/2013] [Indexed: 12/17/2022] Open
Abstract
New curative therapies for severe liver disease are urgently needed in both the human and veterinary clinic. It is important to find new treatment modalities which aim to compensate for the loss of parenchymal tissue and to repopulate the liver with healthy hepatocytes. A prime focus in regenerative medicine of the liver is the use of adult liver stem cells, or hepatic progenitor cells (HPCs), for functional recovery of liver disease. This review describes recent developments in HPC research in dog and cat and compares these findings to experimental rodent studies and human pathology. Specifically, the role of HPCs in liver regeneration, key components of the HPC niche, and HPC activation in specific types of canine and feline liver disease will be reviewed. Finally, the potential applications of HPCs in regenerative medicine of the liver are discussed and a potential role is suggested for dogs as first target species for HPC-based trials.
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Affiliation(s)
- Hedwig S Kruitwagen
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, 3584 CM, Utrecht, The Netherlands.
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12
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Wang DW, Yin YM, Yao YM. Advances in the management of acute liver failure. World J Gastroenterol 2013; 19:7069-7077. [PMID: 24222950 PMCID: PMC3819542 DOI: 10.3748/wjg.v19.i41.7069] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Revised: 08/05/2013] [Accepted: 09/13/2013] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure (ALF) is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver. The causes of ALF encompass a wide variety of toxic, viral, metabolic, vascular and autoimmune insults to the liver, and identifying the correct cause can be difficult or even impossible. Many patients with ALF develop a cascade of serious complications involving almost every organ system, and death is mostly due to multi-organ failure, hemorrhage, infection, and intracranial hypertension. Fortunately, the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology, and the advanced intensive care management. For most severely affected patients who fail to recover after treatment, rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop. This review focuses on the recent advances in the understanding of various contributing etiologies, the administration of etiology-specific treatment to alleviate the liver injury, and the management of complications (e.g., encephalopathy, coagulopathy, cardiovascular instability, respiratory failure, renal failure, sepsis and metabolic disturbance) in patients with ALF. Assessment of the need for liver transplantation is also presented.
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Intraoperative predictors of short-term mortality in living donor liver transplantation due to acute liver failure. Transplant Proc 2013; 45:236-40. [PMID: 23375307 DOI: 10.1016/j.transproceed.2012.06.077] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 05/23/2012] [Accepted: 06/19/2012] [Indexed: 12/28/2022]
Abstract
BACKGROUND Acute liver failure (ALF) is a rare and fatal disease with rapidly deteriorating clinical features. Many predictive models for ALF outcomes have been tested, but none have been adopted as definitive guidelines for prognosis because of inconsistencies in accuracy. Most prognostic models for ALF are based on preoperative patient conditions, thus ignoring various specific intraoperative features relevant to postoperative outcomes. We investigated whether intraoperative factors predicted short-term mortality due to ALF in living donor liver transplantations (LDLT). METHODS We retrospectively collected intraoperative data, including surgical time, fluctuations in mean blood pressure (MBP) and heart rate, mean pulmonary arterial pressure (PAP), central venous pressure (CVP), urine output, laboratory data, oxygen indices (PaO(2)/FiO(2)), administered drugs, and transfusion of packed red blood cells (PRBCs) from 101 patients with ALF who underwent LDLT. After simple relationships of individual intraoperative variables with 1-month posttransplant mortality were analyzed, we examined potentially significant intraoperative variables (P < .10) by a multivariate adjustment process with preoperative indicators of ALF prognosis. RESULTS Intraoperative MBP fluctuations, first mean PAP and CVP, last oxygen index, administered calcium chloride, and PRBC transfusion showed individual associations with posttransplant mortality of ALF patients (P < .05). After multivariate adjustment, PRBC transfusion of ≥ 10 pints (odds ratio 4.73; 95% confidence interval [CI] 1.06-21.16) and MBP fluctuations (odds ratio 1.26; 95% CI 1.00-1.58) were identified to be independent predictors of 1-month posttransplant mortality, together with preoperative factors, including severe hepatic encephalopathy, and a Model for End-stage Liver Disease score ≥ 30 points (area under the curve 0.82, P < .001). CONCLUSION MBP fluctuations and large blood transfusions were intraoperative predictors of short-term mortality after LDLT due to ALF. Increased attention to intraoperative manifestations should provide valuable prognostic information for ALF.
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Abstract
Liver failure is associated with a high morbidity and mortality rate and is the seventh leading cause of death worldwide. Orthotopic liver transplantation remains the definitive treatment; however, because of the limited number of available organs many patients expire while on the transplant list. Currently, there are no established means for providing liver support as a means of bridging patients to transplantation or allowing for recovery from liver injury. Analogous to the clinical situation of renal failure, there is great interest in developing liver support systems that replace the metabolic and waste removal functions of the liver. These support systems are of two general types: artificial and bioartificial livers. In this review, based on a presentation from the 57th American Society of Artificial Internal Organs Annual Meeting (Washington, D.C., June 2011), we review the current status of liver support systems.
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Artificial liver support system reduces intracranial pressure more effectively than bioartificial system: an experimental study. Int J Artif Organs 2012; 35:503-10. [PMID: 22476878 DOI: 10.5301/ijao.5000099] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/08/2012] [Indexed: 01/09/2023]
Abstract
OBJECTIVES Extracorporeal liver support (ELS) may play a role in bridging therapy in patients with acute liver failure (ALF). The aim of this study was to compare the influence of nonbiological and biological methods on intracranial pressure (ICP) in an animal model of ALF. METHODS A surgical devascularization model of ALF in pigs (35-40 kg) was used. Elimination therapy started after the onset of hypoglycemia. Biochemical parameters (bilirubin, ammonia, lactate, etc.) as well as ICP and cerebral perfusion pressure (CPP) were monitored for 12 hours. Of the total 31 pigs with ALF, 14 animals were treated by fractionated plasma separation and absorption (FPSA), 10 were treated with a bioartificial liver (BAL), and 7 animals were used as a control group. RESULTS FPSA and BAL treatment started on average 3 hours 17 minutes and 2 hours 21 minutes, after devascularization and lasted for 5 hours 54 minutes and 5 hours 43 minutes, respectively. Ammonia levels were lower in the FPSA group, and bilirubin levels differed significantly in both the FPSA and BAL groups compared with controls. However, ICP values were reduced more effectively in pigs treated by FPSA: 19.1 vs. 27.0 mm Hg at 9 hours, 22.5 vs. 28.7 mm Hg at 11 hours, and 24.0 vs. 33.0 mm Hg at 12 hours (p<0.05). CONCLUSIONS The artificial liver support system FPSA reduced ICP values more effectively than the Performer O. Liver RanD BAL system. Compared with this BAL system, the nonbiological elimination method of FPSA is a simpler application with the advantage that it can be applied in a more continuous way.
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Abstract
OBJECTIVE Angiopoietin-2, an antagonistic ligand of the endothelial Tie2 receptor, has been identified as a gatekeeper of endothelial activation. We examined whether the release of Angiopoietin-2 correlates with surrogates of organ dysfunction and outcome in patients with acute liver failure. DESIGN Retrospective clinical and immunohistological study. SETTING Intensive care unit of a university hospital. PATIENTS Thirty-seven patients with acute liver failure and 20 healthy control subjects. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Angiopoietin-2 levels were measured in sera from 37 patients with acute liver failure on admission and from 20 healthy control subjects. Median age of patients with acute liver failure was 34 yrs, 29 were female, and 21 developed encephalopathy grade 3 or greater. Nine patients survived to day 28 without transplantation, five died without transplantation, and 23 received a transplant. Median (interquartile range) Angiopoietin-2 serum concentrations steadily increased across the following groups: healthy control subjects (1.4 [0.9-1.7] ng/mL), patients with transplant-free recovery (10.0 [4.7-12.1] ng/mL), and patients who reached the composite end point of death or emergency liver transplantation (16.8 [11.3-39.5] ng/mL). Angiopoietin-2 release correlated strongly with surrogate markers of organ dysfunction and disease severity measures (lactate, platelet count, Sequential Organ Failure Assessment score, and Simplified Acute Physiology Score III). Angiopoietin-2 levels were higher in patients with acute kidney injury and patients on mechanical ventilation. Furthermore, Angiopoietin-2 levels were closely associated with Bilirubin-Lactate-Etiology score but not with other liver-specific markers. Unadjusted and adjusted Cox's proportional hazards analyses identified Angiopoietin-2 as a predictor of the composite end point of death or transplantation. Finally, immunohistological studies showed that Angiopoietin-2 protein was upregulated in acute liver failure explants compared with matched liver biopsies obtained at baseline. CONCLUSIONS Collectively, our data show that circulating Angiopoietin-2, which potentially originates from the injured liver, correlates with several features of multiple organ dysfunction syndrome and independently predicts outcome. Tie2 agonists may have potential as an endothelium-targeted therapy to ameliorate multiple organ dysfunction syndrome and improve outcome in acute liver failure.
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Sabaté A, Acosta Villegas F, Dalmau A, Koo M, Sansano Sánchez T, García Palenciano C. [Anesthesia in the patient with impaired liver function]. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2012; 58:574-81. [PMID: 22279877 DOI: 10.1016/s0034-9356(11)70142-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We review information on impaired liver function, focusing on concepts relevant to anesthesia and postoperative recovery. The effects of impaired function are analyzed by systems of the body, with attention to the complications the patient with liver cirrhosis may develop according to type of surgery. Approaches to correcting coagulation disorders in the cirrhotic patient are particularly controversial because an increase in volume may be a factor in bleeding owing to increased portal venous pressure and imbalances in the factors that favor or inhibit coagulation. Perioperative morbidity and mortality correlate closely to Child-Pugh class and the score derived from the model for end-stage liver disease (MELD). Patients in Child class A are at moderate risk and surgery is therefore not contraindicated. Patients in Child class C or with a MELD score over 20, on the other hand, are at high risk and should not undergo elective surgical procedures. Abdominal surgery is generally considered to put patients with impaired liver function at high risk because it causes changes in hepatic blood flow and increases intraoperative bleeding because of high portal venous pressures.
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Affiliation(s)
- A Sabaté
- Servicio de Anestesiología y Reanimación, Hospital Universitari de Bellvitge, IDIBELL, Hospitalet de Llobregat, Barcelona.
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Myeloid differentiation 2 as a therapeutic target of inflammatory disorders. Pharmacol Ther 2011; 133:291-8. [PMID: 22119168 DOI: 10.1016/j.pharmthera.2011.11.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Accepted: 11/04/2011] [Indexed: 02/07/2023]
Abstract
Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, activates the innate immunity system through a receptor complex of myeloid differentiation 2 (MD-2) and toll-like receptor 4 (TLR4). MD-2 directly recognizes the lipid A domain of LPS, which triggers MD-2/TLR4-mediated cellular response aimed at eliminating the invaded pathogen. However, excess production of inflammatory mediators is harmful to host tissue and this can cause septic death in extreme cases. MD-2 represents an attractive therapeutic target of inflammatory and immune diseases in human. In particular, eritoran is a synthetic tetraacylated lipid A that binds directly to MD-2 and antagonizes LPS binding to the same site, and it ameliorates various inflammatory conditions due to infection or sterile organ injury. In this review, we outline the recent advances in the structure biology of ligand interaction with MD-2/TLR4, and highlight the MD-2-directed LPS antagonists, which are natural and synthetic chemicals, under development to treat inflammatory diseases.
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Mpabanzi L, Jalan R. Neurological complications of acute liver failure: pathophysiological basis of current management and emerging therapies. Neurochem Int 2011; 60:736-42. [PMID: 22100567 DOI: 10.1016/j.neuint.2011.10.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Revised: 10/17/2011] [Accepted: 10/26/2011] [Indexed: 12/11/2022]
Abstract
One of the major causes of mortality in patients with acute liver failure (ALF) is the development of hepatic encephalopathy (HE) which is associated with increased intracranial pressure (ICP). High ammonia levels, increased cerebral blood flow and increased inflammatory response have been identified as major contributors to the development of HE and the related brain swelling. The general principles of the management of patients with ALF are straightforward. They include identifying the insult causing hepatic injury, providing organ systems support to optimize the patient's physical condition, anticipation and prevention of development of complications. Increasing insights into the pathophysiological mechanisms of ALF are contributing to better therapies. For instance, the evident role of cerebral hyperemia in the pathogenesis of increased ICP has led to a re-evaluation of established therapies such as hyperventilation, N-acetylcysteine, thiopentone sodium and propofol. The role of systemic inflammatory response in the pathogenesis of increased ICP has also gained importance supporting the concept that antibiotics given prophylactically reduce the risk of developing sepsis during the course of illness. Moderate hypothermia has also been established as a therapy able to reduce ICP in patients with uncontrolled intracranial hypertension and to prevent increases in ICP during orthopic liver transplantation. Ornithine phenylacetate, a new drug in the treatment of liver failure, and liver replacement therapies are still being investigated both experimentally and clinically. Despite many advances in the understanding of the pathophysiological basis and the management of intracranial hypertension in ALF, more clinical trials should be conducted to determine the best therapeutic management for this difficult clinical event.
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Affiliation(s)
- Liliane Mpabanzi
- Department of Surgery, Maastricht University Medical Centre, and NUTRIM School of Nutrition, Toxicology and Metabolism, Maastricht University, PO Box 5800, Maastricht, The Netherlands
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