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Bozon-Rivière P, Rudler M, Weiss N, Thabut D. TIPS and hepatic encephalopathy in patients with cirrhosis. Metab Brain Dis 2025; 40:117. [PMID: 39903376 DOI: 10.1007/s11011-025-01541-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 01/17/2025] [Indexed: 02/06/2025]
Abstract
Despite a better understanding in its prognosis and pathogenesis, hepatic encephalopathy (HE) remains one of the major complications of Transjugular Intrahepatic Portosystemic Shunt (TIPS) with a prevalence ranging from 35 to 50%. Its epidemiology differs according to the indication for TIPS (salvage/rescue TIPS, preemptive (pTIPS) or elective TIPS). In salvage/rescue TIPS, the prognosis is linked to that of bleeding, and HE should not be a contraindication to TIPS, especially as bleeding is a common precipitating factor of HE. In pTIPS, i.e. TIPS performed within the 72 h after stabilization of acute variceal bleeding in high-risk patients, the risk rebleeding and HE is reduced, when compared to endoscopic and drugs treatment. As a consequence, the Baveno VII recommendations state that HE at admission should not be considered as a contraindication to pTIPS placement. In elective situations, such as refractory (intractable ascites (intolerance to diuretics) or resistant ascites (i.e. despite optimal diuretic treatment (spironolactone 400 mg/d and Furosemide 160 mg/d combined with low-salt treatment (< 5.2 g/day) or recurrent ascites (the need for at least 3 paracenteses per year) and secondary prophylaxis of variceal bleeding, it is recommended to systematically look for risk factors for HE, and chronic or refractory HE remain not recommended to TIPS in most centers. Chronic HE involves persistent neurological symptoms with fluctuating acute episodes. Recurrent HE refers to repeated episodes occurring within 6 months, while refractory HE is resistant to standard treatments, often requiring more aggressive management (Vilstrup et al. 2014). A careful selection of patients is mandatory before elective TIPS decision. Risk factors must be identified and corrected if possible before any TIPS decision is made. Management of HE after TIPS is based on identification of precipitating factors, curative treatment with lactulose as first-line therapy and rifaximin as second-line therapy, and nutritional management. In elective TIPS, prophylactic administration of rifaximin is recommended in order to decrease the risk of further HE development in selected patients (not in everyone, at least according to Baveno VII). Liver transplantation (LT) should be discussed with a multidisciplinary team as an alternative option to TIPS in case of high-risk of post-TIPS HE, and in case of refractory HE after TIPS.
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Affiliation(s)
- Pauline Bozon-Rivière
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France
| | - Marika Rudler
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Nicolas Weiss
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Neurology Intensive Care Unit, Neurology Department, AP-HP, Sorbonne Université, La Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
| | - Dominique Thabut
- Brain-Liver Pitié-Salpêtrière Study Group (BLIPS), Hôpital de la Pitié Salpétrière, INSERM UMR_S 938, CDR Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France.
- Liver Intensive Care Unit, Hepatogastroenterology Department, AP-HP, Sorbonne Université, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris, 75013, France.
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Weiss N, Tripon S, Mallet M, Imbert-Bismut F, Sakka M, Bonnefont-Rousselot D, Sultanik P, Mouri S, Rudler M, Thabut D. Protein-S-100-beta is increased in patients with decompensated cirrhosis admitted to ICU. JOURNAL OF INTENSIVE MEDICINE 2024; 4:222-230. [PMID: 38681783 PMCID: PMC11043635 DOI: 10.1016/j.jointm.2023.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 08/09/2023] [Accepted: 08/16/2023] [Indexed: 05/01/2024]
Abstract
Background Hepatic encephalopathy (HE) is highly prevalent in patients with liver diseases. The pathophysiology of HE is centered on the synergic role of hyperammonemia and systemic inflammation. However, some data suggest altered functioning of the blood-brain barrier (BBB). Assessing BBB function is challenging in clinical practice and at the bedside. Protein-S-100 Beta (PS100-Beta) could be a useful peripheral marker of BBB permeability in HE. This study aimed to assess plasmatic PS100-Beta levels in a prospective cohort of patients admitted to the intensive care unit (ICU) with decompensated cirrhosis with and without overt HE. Methods We retrospectively evaluated a prospective cohort of cirrhotic patients admitted to the ICU from October 2013 to September 2015 that had an available plasmatic PS100-Beta measurement. Patients with previous neurological impairment or limitation of intensive or resuscitative measures were excluded. Overt HE was defined as West-Haven grades 2 to 4. The patients were compared to a control cohort of outpatient clinic cirrhotic and non-cirrhotic patients explored for isolated elevation of liver enzymes. After ICU discharge, the patients were followed for at least 3 months for the occurrence of overt HE. Adverse outcomes (liver transplantation or death) were collected. The ability of PS100-Beta - in combination with other factors - to predict overt HE was evaluated in a multivariate analysis using logistic regression. Likelihood ratios were used to determine the effects and calculate odds ratios (OR). Survival analysis was performed by using the Kaplan-Meier method and survival between groups was compared using a Log-rank test. Results A total of 194 ICU patients and 207 outpatients were included in the study. Increased levels of plasmatic PS100-Beta were detected in the ICU decompensated cirrhotic patients compared with the outpatients ([0.15±0.01] mg/L vs. [0.08±0] mg/L, P <0.001). ICU patients with overt HE had higher levels of PS100-Beta ([0.19±0.03] mg/L) compared with the ICU patients without overt HE ([0.13±0.01] mg/L) (P=0.003). PS100-Beta levels did not differ in outpatients with F 0-3 compared to F 4 fibrosis (P=0.670). PS100-Beta values were correlated with Child-Pugh score (P <0.001), Model for End-Stage Liver Disease (MELD) score (P=0.004), C-reactive protein (P <0.001), ammonemia (P <0.001), and chronic liver failure consortium (CLIF-C) organ failure (P <0.001) and CLIF-C acute-on-chronic (P=0.038) scores, but not with leukocytes (P=0.053), procalcitonin (PCT) (P=0.107), or the lymphocyte-to-neutrophil ratio in ICU patients (P=0.522). In a multivariate model including age, ammonemia, PS100-Beta, PCT, MELD, presence of transjugular portosystemic shunt, and sodium level, the diagnostic performance was 0.765 for the diagnosis of overt HE. Patients with a PS100-Beta level <0.12 mg/L had a better overall survival (P=0.019) and a better survival without liver transplantation (P=0.013). Conclusions Serum levels of PS100-Beta are elevated in ICU patients with decompensated cirrhosis, and even more so in those displaying overt HE, and the levels are correlated with outcome. This suggests an increase in the permeability of the BBB in these patients.
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Affiliation(s)
- Nicolas Weiss
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Paris, France
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Université, Paris, France
| | - Simona Tripon
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Paris, France
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
| | - Maxime Mallet
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
| | - Françoise Imbert-Bismut
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Service de Biochimie Métabolique, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, DMU BioGeM, Paris F-75013, France
| | - Mehdi Sakka
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Service de Biochimie Métabolique, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, DMU BioGeM, Paris F-75013, France
| | - Dominique Bonnefont-Rousselot
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Service de Biochimie Métabolique, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, DMU BioGeM, Paris F-75013, France
- Université Paris Cité, UFR de Pharmacie, CNRS, Inserm, UTCBS, Paris, France
| | - Philippe Sultanik
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
| | - Sarah Mouri
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
| | - Marika Rudler
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
| | - Dominique Thabut
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, Biliaires et Fibro-Inflammatoire du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Assistance Publique-Hôpitaux de Paris, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service d'hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépatologie, Paris, France
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Kurtz P, van den Boogaard M, Girard TD, Hermann B. Acute encephalopathy in the ICU: a practical approach. Curr Opin Crit Care 2024; 30:106-120. [PMID: 38441156 DOI: 10.1097/mcc.0000000000001144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2024]
Abstract
PURPOSE OF REVIEW Acute encephalopathy (AE) - which frequently develops in critically ill patients with and without primary brain injury - is defined as an acute process that evolves rapidly and leads to changes in baseline cognitive status, ranging from delirium to coma. The diagnosis, monitoring, and management of AE is challenging. Here, we discuss advances in definitions, diagnostic approaches, therapeutic options, and implications to outcomes of the clinical spectrum of AE in ICU patients without primary brain injury. RECENT FINDINGS Understanding and definitions of delirium and coma have evolved. Delirium is a neurocognitive disorder involving impairment of attention and cognition, usually fluctuating, and developing over hours to days. Coma is a state of unresponsiveness, with absence of command following, intelligible speech, or visual pursuit, with no imaging or neurophysiological evidence of cognitive motor dissociation. The CAM-ICU(-7) and the ICDSC are validated, guideline-recommended tools for clinical delirium assessment, with identification of clinical subtypes and stratification of severity. In comatose patients, the roles of continuous EEG monitoring and neuroimaging have grown for the early detection of secondary brain injury and treatment of reversible causes. SUMMARY Evidence-based pharmacologic treatments for delirium are limited. Dexmedetomidine is effective for mechanically ventilated patients with delirium, while haloperidol has minimal effect of delirium but may have other benefits. Specific treatments for coma in nonprimary brain injury are still lacking.
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Affiliation(s)
- Pedro Kurtz
- D'Or Institute of Research and Education
- Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
| | - Mark van den Boogaard
- Radboud University Medical Center, Department of Intensive Care, Nijmegen, The Netherlands
| | - Timothy D Girard
- Center for Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) in the Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Bertrand Hermann
- Medical Intensive Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique des Hôpitaux de Paris - Centre (APHP-Centre)
- INSERM UMR 1266, Institut de Psychiatrie et Neurosciences de Paris (IPNP), Université Paris Cité, Paris, France
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Zhou Z, Li K, Guo J, Wang Y, Wei Y, Duan J, Chen M, Shi L, Hu W. Green Tea Catechin EGCG Ameliorates Thioacetamide-Induced Hepatic Encephalopathy in Rats via Modulation of the Microbiota-Gut-Liver Axis. Mol Nutr Food Res 2022; 67:e2200821. [PMID: 36573265 DOI: 10.1002/mnfr.202200821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 11/23/2022] [Indexed: 12/28/2022]
Abstract
SCOPE Existing research suggests that (-)-epigallocatechin-3-gallate (EGCG), which is a natural tea catechin active substance, can protect against liver injury. However, its mechanism for hepatic encephalopathy (HE) treatment is still unclear. In this study, the role of EGCG in the amelioration of HE rats and the effect on the microbiota-gut-liver axis are mainly analyzed. METHODS AND RESULTS Thioacetamide (TAA) is employed to induce the HE model in rats. The results of open field test show that EGCG restores locomotor activity and exploratory behavior. Histological and biochemical results demonstrate that EGCG ameliorates brain and liver damage, decreases the expression of pro-inflammatory cytokines, and increases the activity of antioxidant enzymes. Meanwhile, EGCG modulates the Nrf2 pathway and TLR4/NF-κB pathway to mitigate TAA-induced oxidative stress and inflammatory responses. Immunohistochemistry reveals protection of the intestinal barrier by EGCG upregulating the expression of occludin and zonula occludens-1. Furthermore, serum levels of ammonia and LPS are reduced. 16S rRNA analysis shows that EGCG treatment increases the abundance of beneficial bacteria (e.g., Bifidobacterium, Lactobacillus, and Limosilactobacillus). CONCLUSION The above results reveal that EGCG has anti-oxidative stress and anti-inflammatory effects, and ameliorates the condition through the microbiota-gut-liver axis, with potential for the treatment of HE.
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Affiliation(s)
- Zhengming Zhou
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Ke Li
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Jiankui Guo
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yunfeng Wang
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Yaoyao Wei
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Juan Duan
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Muxi Chen
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Lei Shi
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Wen Hu
- Department of Clinical Nutrition, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
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Bouzbib C, El Mourabit H, Wendum D, Lasnier E, Mouri S, Housset C, Thabut D, Weiss N, Rudler M. ATP-binding cassette transporters expression in rats with cirrhosis and hepatic encephalopathy. Clin Res Hepatol Gastroenterol 2022; 46:101784. [PMID: 34384925 DOI: 10.1016/j.clinre.2021.101784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 08/06/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pathophysiology of acute encephalopathy in cirrhotic patients is not completely understood. Factors implicated include ammonia, inflammation, various metabolic disorders and drug toxicity. Recent studies have evidenced an increased permeability of the blood-brain barrier (BBB) in models of chronic liver disease and encephalopathy, either to solutes, or to leukocytes. A modification of the expression of BBB ATP-Binding Cassette (ABC) transporters, actively transporting endogenous and exogenous components through the BBB, has been described in models of acute liver failure. We hypothesized that a modification of ABC transporters expression may contribute to drug-induced acute encephalopathy in cirrhosis. MATERIEL AND METHODS A rat model of cirrhosis induced by Bile Duct Ligation (BDL) was studied, and compared to a SHAM rat model. Rats were sacrificed and brains studied after decapitation. Genic expression of ABC transporters, including P-gp, BCRP, MRP1, MRP2, MRP4 and MRP5 was evaluated by RT-qPCR on isolated brain microvessels. Encephalopathy was assessed 6 weeks after surgery by a trail suspension test and an Open Field Test. RESULTS BDL rats developed a histologically proven cirrhosis and displayed a higher ammonemia than SHAM rats (183 µmol/L vs 53 µmol/L, p = 0.0003). BDL rats presented with encephalopathy shown by neurobehavioral tests. MRP2 was not detected neither in BDL nor in SHAM rats. There was a decrease in the genic expression of MRP5 6 weeks after surgery. Expressions of P-gp, BCRP, MRP1 and MRP4 were not different between the 2 groups. CONCLUSION We suggest that acute encephalopathy in cirrhotic BDL rats may be associated to a modification of ABC transporter MRP5 on the BBB, that could be responsible for a decrease clearance of neurotoxic agents.
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Affiliation(s)
- Charlotte Bouzbib
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Haquima El Mourabit
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Wendum
- AP-HP.Sorbonne Université, Department of Pathology, Saint-Antoine Hospital, 184 rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Elisabeth Lasnier
- AP-HP.Sorbonne Université, Department of Biochemistry, Saint-Antoine Hospital, 184 rue du Faubourg-Saint-Antoine, 75012 Paris, France
| | - Sarah Mouri
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
| | - Chantal Housset
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
| | - Dominique Thabut
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France.
| | - Nicolas Weiss
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Neurological Intensive Care Unit, Neurology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France.
| | - Marika Rudler
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; Brain Liver Pitié-Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris, France; AP-HP.Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology department, Pitié-Salpêtrière Hospital, 47-83 boulevard de l'Hôpital 75013 Paris, France
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Ascher Bartlett JM, Yanni G, Kwon Y, Emamaullee J. Pediatric acute liver failure: Reexamining key clinical features, current management, and research prospects. Liver Transpl 2022; 28:1776-1784. [PMID: 35557028 PMCID: PMC9588650 DOI: 10.1002/lt.26500] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 04/13/2022] [Accepted: 05/04/2022] [Indexed: 01/01/2023]
Abstract
This review aims to synthesize the most updated research, outcomes, and trends in the field of pediatric liver transplantation (LT), specifically focusing on children who have suffered from acute liver failure. Pediatric acute liver failure is a dynamic, life-threatening condition that can either self-resolve or lead to death. LT is a lifesaving intervention. With the introduction of technical variant grafts and recent immunosuppression modifications, overall patient survival, graft survival, and waitlist mortality have improved. Furthermore, recent advances in the knowledge of immunologic mediators of acute liver failure offer the possibility of more detailed understanding of the pathophysiology and new areas for research. Given the success of living donor LT for pediatric patients with acute liver failure, this option should continue to be actively considered as an alternative treatment option for patients who are listed for transplantation and are managed at a multidisciplinary tertiary care transplant center.
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Affiliation(s)
- Johanna M. Ascher Bartlett
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsChildren's Hospital Los AngelesCaliforniaLos AngelesUSA
| | - George Yanni
- Division of Gastroenterology, Hepatology and Nutrition, Department of PediatricsChildren's Hospital Los AngelesCaliforniaLos AngelesUSA
| | - Yong Kwon
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of SurgeryUniversity of Southern CaliforniaCaliforniaLos AngelesUSA
| | - Juliet Emamaullee
- Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of SurgeryUniversity of Southern CaliforniaCaliforniaLos AngelesUSA
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Weiss N, Thabut D. Ammonia rises again from the ashes! JHEP Rep 2022; 4:100559. [PMID: 36267870 PMCID: PMC9576878 DOI: 10.1016/j.jhepr.2022.100559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 08/09/2022] [Indexed: 11/30/2022] Open
Affiliation(s)
- Nicolas Weiss
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation à Orientation Neurologique, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et Fibro-inflammatoire Du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France & Groupe de Recherche Clinique en REanimation et Soins Intensifs Du Patient en Insuffisance Respiratoire AiguE (GRC-RESPIRE) Sorbonne Université, Paris, France
| | - Dominique Thabut
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Service D’hépato-gastroentérologie, Unité de Soins Intensifs D’hépatologie, Paris, France & Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de Recherche Saint-Antoine, Maladies Métaboliques, Biliaires et Fibro-inflammatoire Du Foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
- Corresponding author. Address: Sorbonne Université, Service d’hépato-gastroentérologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l’hôpital, 75013 Paris, France. Tel.: +33(0)1.42.16.00.00, fax : +33(0)1.42.16.00.01.
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Zellos A, Debray D, Indolfi G, Czubkowski P, Samyn M, Hadzic N, Gupte G, Fischler B, Smets F, de Cléty SC, Grenda R, Mozer Y, Mancell S, Jahnel J, Auzinger G, Worth A, Lisman T, Staufner C, Baumann U, Dhawan A, Alonso E, Squires RH, Verkade HJ. Proceedings of ESPGHAN Monothematic Conference 2020: "Acute Liver Failure in Children": Diagnosis and Initial Management. J Pediatr Gastroenterol Nutr 2022; 74:e45-e56. [PMID: 35226643 DOI: 10.1097/mpg.0000000000003341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) aims to educate pediatric gastroenterologists, members of ESPGHAN and professionals from other specialties promoting an exchange of clinical expertise in the field of pediatric hepatology. Herewith we have concentrated on detailing the recent advances in acute liver failure in infants and children. METHODS The 2020 ESPGHAN monothematic three-day conference on pediatric hepatology disease, entitled "acute liver failure" (ALF), was organized in Athens, Greece. ALF is a devastating disease with high mortality and most cases remain undiagnosed. As knowledge in diagnosis and treatment of ALF in infants and children has increased in the past decades, the objective was to update physicians in the field with the latest research and developments in early recognition, curative therapies and intensive care management, imaging techniques and treatment paradigms in these age groups. RESULTS In the first session, the definition, epidemiology, various causes of ALF, in neonates and older children and recurrent ALF (RALF) were discussed. The second session was dedicated to new aspects of ALF management including hepatic encephalopathy (HE), coagulopathy, intensive care interventions, acute on chronic liver failure, and the role of imaging in treatment and prognosis. Oral presentations by experts in various fields are summarized highlighting key learning points. CONCLUSIONS The current report summarizes the major learning points from this meeting. It also identifies areas where there is gap of knowledge, thereby identifying the research agenda for the near future.
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Affiliation(s)
- Aglaia Zellos
- First Department of Pediatrics, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dominique Debray
- Pediatric Hepatology Unit, Hôpital Necker-Enfants Malades, Reference Center for Rare Pediatric Liver Diseases, ERN Rare Liver and Transplant Child, Paris, France
| | - Giuseppe Indolfi
- Department Neurofarba University of Florence, Meyer Children's University Hospital of Florence, Florence, Italy
| | - Piotr Czubkowski
- Department of Gastroenterology, Hepatology and Nutritional Disorders and Pediatrics. The Children's Memorial Health Institute, Warsaw, Poland
| | - Marianne Samyn
- Paediatric Liver, GI & Nutrition Centre, King's College London School of Medicine at King's College Hospital
| | | | - Girish Gupte
- Birmingham Children's Hospital NHS Trust, Birmingham, UK
| | - Björn Fischler
- Department of Pediatrics, CLINTEC Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Françoise Smets
- Pediatrics, Cliniques universitaires Saint-Luc, Université Catholique de Louvain
| | - Stéphan Clément de Cléty
- Paediatric intensive care, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Ryszard Grenda
- Department of Nephrology, Kidney Transplantation & Hypertension, The Children's Memorial Health Institute, Warsaw, Poland
| | - Yael Mozer
- Schneider Children's Medical Center, Israel
| | | | | | - Georg Auzinger
- King's College Hospital, Department Chair, Critical Care Cleveland Clinic
| | - Austen Worth
- Great Ormond Street Hospital for Children, London, UK
| | - Ton Lisman
- Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Christian Staufner
- Division of Neuropediatrics and Pediatric Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany
| | | | - Anil Dhawan
- Variety Children Hospital, Director Paediatric Liver GI and Nutrition and Mowat Labs, King's College Hospital, London, UK
| | - Estelle Alonso
- Siragusa Transplant Center, Ann and Robert H. Lurie Children' Hospital, Feinberg School of Medicine, Northwestern University, Chicago, IL
| | - Robert H Squires
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital of Pittsburgh, Pittsburgh, PA
| | - Henkjan J Verkade
- Department of Paediatrics, University of Groningen, Beatrix Children's Hospital, University Medical Center, Groningen, The Netherlands
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9
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Le Guennec L, Marois C, Demeret S, Wijdicks EFM, Weiss N. Toxic-metabolic encephalopathy in adults: Critical discussion and pragmatical diagnostic approach. Rev Neurol (Paris) 2022; 178:93-104. [PMID: 34996631 DOI: 10.1016/j.neurol.2021.11.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/16/2021] [Accepted: 11/17/2021] [Indexed: 10/19/2022]
Abstract
Toxic-metabolic encephalopathy (TME) results from an acute cerebral dysfunction due to different metabolic disturbances including medications or illicit-drugs. It can lead to altered consciousness, going from delirium to coma, which may require intensive care and invasive mechanical ventilation. Even if it is a life-threatening condition, TME might have an excellent prognosis if its etiology is rapidly identified and treated adequately. This review summarizes the main etiologies, their differential diagnosis, and diagnostic strategy and management of TME with a critical discussion on the definition of TME.
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Affiliation(s)
- L Le Guennec
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, département de neurologie, unité de Médecine Intensive Réanimation à orientation neurologique, Paris, France; Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Université, Sorbonne, France
| | - C Marois
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, département de neurologie, unité de Médecine Intensive Réanimation à orientation neurologique, Paris, France
| | - S Demeret
- Sorbonne Université, AP-HP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, département de neurologie, unité de Médecine Intensive Réanimation à orientation neurologique, Paris, France
| | - E F M Wijdicks
- Mayo Clinic, Department of Neurology, 200 First Street SW, Rochester, MN 55905, USA
| | - N Weiss
- Groupe de Recherche Clinique en REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aiguE (GRC-RESPIRE) Sorbonne Université, Sorbonne, France; Sorbonne Université, AP-HP, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, département de neurologie, unité de Médecine Intensive Réanimation à orientation neurologique, Paris, France; Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
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10
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Wang RR, Gu HQ, Wei YY, Yang JX, Hou YX, Liu HM, Yang ZY, Wang XB, Jiang YY. Development and Validation of a Prognostic Model for One-year Survival of Cirrhosis Patients with First-ever Spontaneous Bacterial Peritonitis. J Clin Transl Hepatol 2021; 9:647-654. [PMID: 34722179 PMCID: PMC8516845 DOI: 10.14218/jcth.2021.00031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 04/09/2021] [Accepted: 04/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND AIMS Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP. METHODS A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model. RESULTS A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort. CONCLUSIONS This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival.
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Affiliation(s)
- Rui-Rui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Hong-Qiu Gu
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- National Center for Healthcare Quality Management in Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Ying-Ying Wei
- The first Clinical School, Beijing University of Chinese Medicine, Beijing, China
| | - Jin-Xiang Yang
- Department of Gastroenterology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Yi-Xin Hou
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hui-Min Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhi-Yun Yang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xian-Bo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yu-Yong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
- Correspondence to: Yu-Yong Jiang, Beijing Diantan Hospital, Capital Medical University, Beijing 100015, China. ORCID: https://orcid.org/0000-0002-6082-1180. Tel: +86-13552175162, E-mail:
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11
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da Silveira F, Soares PHR, Marchesan LQ, da Fonseca RSA, Nedel WL. Assessing the prognosis of cirrhotic patients in the intensive care unit: What we know and what we need to know better. World J Hepatol 2021; 13:1341-1350. [PMID: 34786170 PMCID: PMC8568574 DOI: 10.4254/wjh.v13.i10.1341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/11/2021] [Accepted: 09/27/2021] [Indexed: 02/06/2023] Open
Abstract
Critically ill cirrhotic patients have high in-hospital mortality and utilize significant health care resources as a consequence of the need for multiorgan support. Despite this fact, their mortality has decreased in recent decades due to improved care of critically ill patients. Acute-on-chronic liver failure (ACLF), sepsis and elevated hepatic scores are associated with increased mortality in this population, especially among those not eligible for liver transplantation. No score is superior to another in the prognostic assessment of these patients, and both liver-specific and intensive care unit-specific scores have satisfactory predictive accuracy. The sequential assessment of the scores, especially the Sequential Organ Failure Assessment (SOFA) and Chronic Liver Failure Consortium (CLIF)-SOFA scores, may be useful as an auxiliary tool in the decision-making process regarding the benefits of maintaining supportive therapies in this population. A CLIF-ACLF > 70 at admission or at day 3 was associated with a poor prognosis, as well as SOFA score > 19 at baseline or increasing SOFA score > 72. Additional studies addressing the prognostic assessment of these patients are necessary.
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Affiliation(s)
- Fernando da Silveira
- Programa de Pós-Graduação em Pneumologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
| | - Pedro H R Soares
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Neurociências, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil
| | - Luana Q Marchesan
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria 97105900, Brazil
| | | | - Wagner L Nedel
- Intensive Care Unit, Grupo Hospitalar Conceição, Porto Alegre 91430835, Brazil
- Programa de Pós-Graduação em Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre 91430835, Brazil.
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12
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Kim YK, Song J. Therapeutic Applications of Resveratrol in Hepatic Encephalopathy through Its Regulation of the Microbiota, Brain Edema, and Inflammation. J Clin Med 2021; 10:jcm10173819. [PMID: 34501267 PMCID: PMC8432232 DOI: 10.3390/jcm10173819] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/22/2021] [Accepted: 08/24/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol's effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.
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Affiliation(s)
- Young-Kook Kim
- Department of Biochemistry, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Korea;
| | - Juhyun Song
- Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Korea
- Correspondence: ; Tel.: +82-61-379-2706; Fax: +82-61-375-5834
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13
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Rudler M, Weiss N, Bouzbib C, Thabut D. Diagnosis and Management of Hepatic Encephalopathy. Clin Liver Dis 2021; 25:393-417. [PMID: 33838857 DOI: 10.1016/j.cld.2021.01.008] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatic encephalopathy (HE) is a severe complication of cirrhosis. The prevalence of overt HE (OHE) ranges from 30% to 45%, whereas the prevalence of minimal HE (MHE) is as high as 85% in some case series. Widespread use of transjugular intrahepatic portosystemic shunt to control complications related to portal hypertension is associated with an increase in HE incidence. If the diagnosis of OHE remains simple in most cases, then the diagnosis of MHE is less codified because of many differential diagnoses with different therapeutic implications. This review analyzes current knowledge about the pathophysiology, diagnosis, and different therapeutic options of HE.
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Affiliation(s)
- Marika Rudler
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Nicolas Weiss
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Neurological Intensive Care Unit, Neurology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France
| | - Charlotte Bouzbib
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France
| | - Dominique Thabut
- Brain Liver Salpêtrière Study Group, Sorbonne Université, INSERM UMR_S 938, Centre de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN), Paris 75013, France; AP-HP, Sorbonne Université, Liver Intensive Care Unit, Hepatogastroenterology Department, Pitié-Salpêtrière Hospital, 47-83 Boulevard de l'Hôpital, Paris 75013, France; Sorbonne Université, Paris F-75005, France.
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14
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Rackayová V, Flatt E, Braissant O, Grosse J, Capobianco D, Mastromarino P, McMillin M, DeMorrow S, McLin VA, Cudalbu C. Probiotics improve the neurometabolic profile of rats with chronic cholestatic liver disease. Sci Rep 2021; 11:2269. [PMID: 33500487 PMCID: PMC7838316 DOI: 10.1038/s41598-021-81871-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo 1H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.
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Affiliation(s)
- Veronika Rackayová
- Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
- Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland
| | - Emmanuelle Flatt
- Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Olivier Braissant
- Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland
| | - Jocelyn Grosse
- Laboratory of Behavioral Genetics, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Daniela Capobianco
- Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University of Rome, Rome, Italy
| | - Paola Mastromarino
- Department of Public Health and Infectious Diseases, Section of Microbiology, Sapienza University of Rome, Rome, Italy
| | - Matthew McMillin
- Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
- Central Texas Veterans Health Care System, Temple, TX, USA
| | - Sharon DeMorrow
- Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, Austin, TX, USA
- Central Texas Veterans Health Care System, Temple, TX, USA
- Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA
| | - Valérie A McLin
- Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva and University Hospitals Geneva, Geneva, Switzerland
| | - Cristina Cudalbu
- Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Vaud, Switzerland.
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15
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Hu C, Huang K, Zhao L, Zhang F, Wu Z, Li L. Serum ammonia is a strong prognostic factor for patients with acute-on-chronic liver failure. Sci Rep 2020; 10:16970. [PMID: 33046732 PMCID: PMC7550336 DOI: 10.1038/s41598-020-73603-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023] Open
Abstract
Ammonia is thought to be central to the pathogenesis of hepatic encephalopathy (HE), but its prognostic role in acute-on-chronic liver failure (ACLF) is still unknown. We aimed to determine the association between serum ammonia level and short-term prognosis in ACLF. Furthermore, we performed an in-depth evaluation of the independent effect of serum ammonia level on the short-term prognosis of hepatitis B virus (HBV) reactivation-induced ACLF patients. We identified 174 patients as part of prospective observational studies in patients with ACLF. Plasma ammonia levels were measured on admission, and several prognostic scores were used to determine the prognostic effect of ammonia. The 28-day patient survival was determined. Receiver operating characteristic analysis was used to identify the cut-off points for ammonia values, and multivariable analysis was performed using the Cox proportional hazard regression model. Plasma ammonia was significantly higher in nonsurvivors (83.53 ± 43.78 versus 67.13 ± 41.77 µmol/L, P = 0.013), and ACLF patients with hyperammonemia had significantly higher 28-day mortality than those without hyperammonemia. Ammonia was also closely related to ACLF grade (P < 0.001) and organ failure, including liver (P = 0.048), coagulation (P < 0.001) and brain (P < 0.001). HBV reactivation serves as the main precipitating factor in the ACLF population. Subgroup analysis showed that ammonia is also a strong prognostic factor in the HBV reactivation-induced ACLF population. Ammonia level is closely correlated with failure of other organs and is an independent risk factor for mortality in ACLF and the special population defined as HBV reactivation-related ACLF. Based on the results from our study, we measured serum ammonia in the population with ACLF, which strongly indicates their prognosis. It serves as an important biomarker and a therapeutic target.
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Affiliation(s)
- Chenxia Hu
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Kaizhou Huang
- Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, 515041, Guangdong, People's Republic of China
| | - Lingfei Zhao
- Key Laboratory of Kidney Disease Prevention and Control Technology, Kidney Disease Center, Institute of Nephrology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Fen Zhang
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Zhongwen Wu
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China
| | - Lanjuan Li
- Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China. .,National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
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Abstract
PURPOSE OF REVIEW Liver transplantation (LT) remains the only way to cure patients with severe liver diseases. Important questions about neurological sequelae and quality of life after LT have emerged. In this review, we discuss the neurocognitive changes associated with LT and we conclude with recommendations in this regard for patients, caregivers, and physicians. RECENT FINDINGS Compared with other solid organ recipients, LT patients tend to have a higher incidence (up to 30%) of neurological complications post-LT. Even in absence of previous episodes of hepatic encephalopathy (HE), some patients display new onset of neurological symptoms post-LT, raising the concern about the role of other factors that may have a direct impact on cognitive function. SUMMARY Different mechanisms have been postulated to explain these postoperative neurological symptoms. They include sequelae of HE, persistent impairment of cognitive function due to cirrhosis, or postoperative decompensation of an unknown or undiagnosed neurodegenerative disorder.
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Affiliation(s)
- Somaya A. M. Albhaisi
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0341 USA
| | - Jasmohan S. Bajaj
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA USA
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Boilève A, Thomas L, Lillo-Le Louët A, Gaboriau L, Chouchana L, Ducreux M, Malka D, Boige V, Hollebecque A, Hillaire-Buys D, Jozwiak M. 5-Fluorouracil-induced hyperammonaemic encephalopathy: A French national survey. Eur J Cancer 2020; 129:32-40. [PMID: 32120273 DOI: 10.1016/j.ejca.2020.01.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 01/15/2020] [Accepted: 01/15/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND 5-Fluorouracil (5-FU)-induced hyperammonaemic encephalopathy is a rare but serious 5-FU adverse drug reaction (ADR). Given the growing number of cancers treated with 5-FU and the paucity of data regarding this ADR, we performed a retrospective national survey to better characterise 5-FU-induced hyperammonaemic encephalopathy. PATIENTS AND METHODS Since inception of the French pharmacovigilance database, we identified all patients who experienced 5-FU-induced hyperammonaemic encephalopathy. Variables regarding demographics, characteristics, management and outcome of patients were collected. RESULTS From 1986 to 2018, 30 patients were included. 5-FU-induced hyperammonaemic encephalopathy started 2 [1-4] days after 5-FU infusion onset. Most common neurological disorders were consciousness impairment, seizures and confusion. hyperammonaemia tended to be higher in patients with the lowest Glasgow score and admitted in intensive care unit (ICU) compared to non-ICU patients (250 [133-522] versus 139 [68-220] μmol/L respectively, p = NS). Dihydropyrimidine dehydrogenase deficiency was found in 27% of tested patients (n = 3/11). Encephalopathy-induced mortality was 17%, 57% of patients were admitted in ICU and 70% had a complete neurological recovery within 5 [2-10] days. A 5-FU rechallenge was considered in 14 (67%) patients with neurological recovery and a relapse was observed in 57% of them. No 5-FU-induced hyperammonaemic encephalopathy relapse was observed as long as 5-FU rechallenge was performed with decreased 5-FU dosage. CONCLUSION We report the largest cohort of 5-FU-induced hyperammonaemic encephalopathy cases so far. This ADR should be suspected and ammonaemia measured in all patients experiencing neurological disorders after 5-FU administration. In patients with complete neurological recovery, a 5-FU rechallenge could be cautiously considered.
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Affiliation(s)
- Alice Boilève
- Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France.
| | - Laure Thomas
- Centre Régional de PharmacoVigilance, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Paris-Est, Hôpital Henri Mondor, Créteil, France
| | - Agnès Lillo-Le Louët
- Centre Régional de PharmacoVigilance, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Paris-Centre, Hôpital Européen Georges Pompidou, Paris, France
| | - Louise Gaboriau
- Centre Régional de PharmacoVigilance, Hôpital Universitaire de Lille, Lille, France
| | - Laurent Chouchana
- Centre Régional de PharmacoVigilance, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Paris-Centre, Hôpital Cochin, Paris, France
| | - Michel Ducreux
- Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France; Université Paris-Saclay, Villejuif, France
| | - David Malka
- Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France
| | - Valérie Boige
- Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France
| | - Antoine Hollebecque
- Département de Médecine Oncologique, Institut Gustave Roussy, Villejuif, France
| | - Dominique Hillaire-Buys
- Centre Régional de PharmacoVigilance, Hôpital Universitaire de Montpellier, Montpellier France
| | - Mathieu Jozwiak
- Service de Médecine Intensive Réanimation, Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Paris-Centre, Hôpital Cochin, Paris, France
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Hermann B, Rudler M, Galanaud D, Thabut D, Weiss N. Magnetic resonance spectroscopy: A surrogate marker of hepatic encephalopathy? J Hepatol 2019; 71:1055-1057. [PMID: 31500856 DOI: 10.1016/j.jhep.2019.07.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 07/12/2019] [Indexed: 12/24/2022]
Affiliation(s)
- Bertrand Hermann
- Sorbonne University, Brain and Spine Institute - Institut du Cerveau et de la Moelle Epinière, ICM, Inserm U 1127, CNRS UMR 7225, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Charles Foix Hospital, Department of Neurology, Neurological Intensive Care Unit, Paris, France
| | - Marika Rudler
- Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Service d'hépato-gastroentérologie, Service d'hépatologie, Unité de Soins Intensifs d'Hépato-gastroentérologie, Paris, France
| | - Damien Galanaud
- Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Service de neuroradiologie, Paris, France
| | - Dominique Thabut
- Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Service d'hépato-gastroentérologie, Service d'hépatologie, Unité de Soins Intensifs d'Hépato-gastroentérologie, Paris, France
| | - Nicolas Weiss
- Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, INSERM UMR_S 938, Centre de recherche Saint-Antoine, Maladies métaboliques, biliaires et fibro-inflammatoire du foie, Institute of Cardiometabolism and Nutrition (ICAN), Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Département de Neurologie, Unité de réanimation neurologique, Paris, France.
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19
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Frainay C, Aros S, Chazalviel M, Garcia T, Vinson F, Weiss N, Colsch B, Sedel F, Thabut D, Junot C, Jourdan F. MetaboRank: network-based recommendation system to interpret and enrich metabolomics results. Bioinformatics 2019; 35:274-283. [PMID: 29982278 PMCID: PMC6330003 DOI: 10.1093/bioinformatics/bty577] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Accepted: 07/04/2018] [Indexed: 12/19/2022] Open
Abstract
Motivation Metabolomics has shown great potential to improve the understanding of complex diseases, potentially leading to therapeutic target identification. However, no single analytical method allows monitoring all metabolites in a sample, resulting in incomplete metabolic fingerprints. This incompleteness constitutes a stumbling block to interpretation, raising the need for methods that can enrich those fingerprints. We propose MetaboRank, a new solution inspired by social network recommendation systems for the identification of metabolites potentially related to a metabolic fingerprint. Results MetaboRank method had been used to enrich metabolomics data obtained on cerebrospinal fluid samples from patients suffering from hepatic encephalopathy (HE). MetaboRank successfully recommended metabolites not present in the original fingerprint. The quality of recommendations was evaluated by using literature automatic search, in order to check that recommended metabolites could be related to the disease. Complementary mass spectrometry experiments and raw data analysis were performed to confirm these suggestions. In particular, MetaboRank recommended the overlooked α-ketoglutaramate as a metabolite which should be added to the metabolic fingerprint of HE, thus suggesting that metabolic fingerprints enhancement can provide new insight on complex diseases. Availability and implementation Method is implemented in the MetExplore server and is available at www.metexplore.fr. A tutorial is available at https://metexplore.toulouse.inra.fr/com/tutorials/MetaboRank/2017-MetaboRank.pdf. Supplementary information Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Clément Frainay
- Toxalim, Université de Toulouse, INRA, Université de Toulouse 3 Paul Sabatier, Toulouse, France
| | | | | | - Thomas Garcia
- Toxalim, Université de Toulouse, INRA, Université de Toulouse 3 Paul Sabatier, Toulouse, France
| | - Florence Vinson
- Toxalim, Université de Toulouse, INRA, Université de Toulouse 3 Paul Sabatier, Toulouse, France
| | - Nicolas Weiss
- Unité de Réanimation Neurologique, Département de Neurologie, Pôle des Maladies du Système Nerveux Central, Groupement Hospitalier Pitié-Salpêtrière Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France.,Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris & INSERM UMR_S 938, CDR Saint-Antoine Maladies Métaboliques, Biliaires et Fibro-inflammatoire du Foie & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France
| | - Benoit Colsch
- Service de Pharmacologie et Immunoanalyse (SPI), CEA, INRA, Université Paris-Saclay, MetaboHUB, Gif-sur-Yvette, France and
| | | | - Dominique Thabut
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris & INSERM UMR_S 938, CDR Saint-Antoine Maladies Métaboliques, Biliaires et Fibro-inflammatoire du Foie & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France.,Unité de Soins Intensifs d'Hépato-gastroentérologie, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris et Université Pierre et Marie Curie Paris 6, Paris, France
| | - Christophe Junot
- Service de Pharmacologie et Immunoanalyse (SPI), CEA, INRA, Université Paris-Saclay, MetaboHUB, Gif-sur-Yvette, France and
| | - Fabien Jourdan
- Toxalim, Université de Toulouse, INRA, Université de Toulouse 3 Paul Sabatier, Toulouse, France
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20
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CT Scan Is Still a Valuable Tool to Assess Hepatic Encephalopathy Pathophysiology in Both Acute and Chronic Liver Diseases. Crit Care Med 2019; 46:e728. [PMID: 29912129 DOI: 10.1097/ccm.0000000000003116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Braissant O, Rackayová V, Pierzchala K, Grosse J, McLin VA, Cudalbu C. Longitudinal neurometabolic changes in the hippocampus of a rat model of chronic hepatic encephalopathy. J Hepatol 2019; 71:505-515. [PMID: 31173812 DOI: 10.1016/j.jhep.2019.05.022] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 05/24/2019] [Accepted: 05/27/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS The sequence of events in hepatic encephalopathy (HE) remains unclear. Using the advantages of in vivo 1H-MRS (9.4T) we aimed to analyse the time-course of disease in an established model of type C HE by analysing the longitudinal changes in a large number of brain metabolites together with biochemical, histological and behavioural assessment. We hypothesized that neurometabolic changes are detectable very early, and that these early changes will offer insight into the primary events underpinning HE. METHODS Wistar rats underwent bile-duct ligation (BDL) and were studied before BDL and at post-operative weeks 2, 4, 6 and 8 (n = 26). In vivo short echo-time 1H-MRS (9.4T) of the hippocampus was performed in a longitudinal manner, as were biochemical (plasma), histological and behavioural tests. RESULTS Plasma ammonium increased early after BDL and remained high during the study. Brain glutamine increased (+47%) as early as 2-4 weeks post-BDL while creatine (-8%) and ascorbate (-12%) decreased. Brain glutamine and ascorbate correlated closely with rising plasma ammonium, while brain creatine correlated with brain glutamine. The increases in brain glutamine and plasma ammonium were correlated, while plasma ammonium correlated negatively with distance moved. Changes in astrocyte morphology were observed at 4 weeks. These early changes were further accentuated at 6-8 weeks post-BDL, concurrently with the known decreases in brain organic osmolytes. CONCLUSION Using a multimodal, in vivo and longitudinal approach we have shown that neurometabolic changes are already noticeable 2 weeks after BDL. These early changes are suggestive of osmotic/oxidative stress and are likely the premise of some later changes. Early decreases in cerebral creatine and ascorbate are novel findings offering new avenues to explore neuroprotective strategies for HE treatment. LAY SUMMARY The sequence of events in chronic hepatic encephalopathy (HE) remains unclear, therefore using the advantages of in vivo proton magnetic resonance spectroscopy at 9.4T we aimed to test the hypothesis that neurometabolic changes are detectable very early in an established model of type C HE, offering insight into the primary events underpinning HE, before advanced liver disease confounds the findings. These early, previously unreported neurometabolic changes occurred as early as 2 to 4 weeks after bile-duct ligation, namely an increase in plasma ammonium and brain glutamine, a decrease in brain creatine and ascorbate together with behavioural and astrocyte morphology changes, and continued to progress throughout the 8-week course of the disease.
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Affiliation(s)
- Olivier Braissant
- Service of Clinical Chemistry, University of Lausanne and University Hospital of Lausanne, Lausanne, Switzerland
| | - Veronika Rackayová
- Laboratory of Functional and Metabolic Imaging, Center for Biomedical Imaging, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Centre d'Imagerie Biomedicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Katarzyna Pierzchala
- Centre d'Imagerie Biomedicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Jocelyn Grosse
- Laboratory of Behavioral Genetics, Brain Mind Institute, School Of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - Valérie A McLin
- Swiss Pediatric Liver Center, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals Geneva, and University of Geneva Medical School, Switzerland
| | - Cristina Cudalbu
- Centre d'Imagerie Biomedicale (CIBM), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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22
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Vairappan B, Sundhar M, Srinivas BH. Resveratrol Restores Neuronal Tight Junction Proteins Through Correction of Ammonia and Inflammation in CCl 4-Induced Cirrhotic Mice. Mol Neurobiol 2019; 56:4718-4729. [PMID: 30377987 DOI: 10.1007/s12035-018-1389-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 10/11/2018] [Indexed: 12/31/2022]
Abstract
Systemic inflammation and ammonia (hyperammonemia) act synergistically in the pathogenesis of hepatic encephalopathy (HE), the neurobehavioral sequelae of advanced liver disease. In cirrhotic patients, we have recently observed elevated levels of circulating neuronal tight junction (TJ) protein, zonula occludens 1 (ZO-1), reflective of a change to blood-brain barrier (BBB) integrity. Moreover, ZO-1 levels positively correlated with hyperammonemia, although any potential relationship remains unclear. Using a carbon tetrachloride (CCl4)-induced mouse model of cirrhosis, we primarily looked to explore the relationship between neuronal TJ protein expression and hyperammonemia. Secondarily, we assessed the potential role of a natural antioxidant, resveratrol, on neuronal TJ protein expression and hyperammonemia. Over 12 weeks, male Swiss mice were randomized (n = 8/group) to either naïve controls or induced cirrhosis, using two doses of intraperitoneal CCl4 (0.5 ml/kg/week). After 12 weeks, naïve and cirrhotic mice were randomized to receive either 2 weeks of par-oral resveratrol (10 mg/kg). Plasma samples were analyzed for ammonia, liver biochemistry (ALT, AST, albumin, and bilirubin), and pro-inflammatory cytokines (TNF-α and IL-1β), and brain tissue for brain water content, TJ protein expression (e.g., ZO-1, claudin 5, and occludin), and tissue oxidative stress and inflammatory markers (NF-κB and iNOS) using western blotting. Compared to naïve mice, cirrhosis significantly increased circulating ammonia, brain water, ALT, AST, TNF-α, IL-1β, 4HNE, NF-κB, and iNOS levels, with a concomitant reduction in all TJ proteins (P < 0.05, respectively). In cirrhotic mice, resveratrol treatment ameliorated these changes significantly (P < 0.05, respectively). Our findings provide evidence for a causal association between hyperammonemia and inflammation in cirrhosis linked to TJ protein alterations, BBB disruption, and HE predilection. Moreover, this is the first report of a potential role for resveratrol as a novel therapeutic approach to managing neurological sequelae complicating cirrhosis.
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Affiliation(s)
- Balasubramaniyan Vairappan
- Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Dhanvantari Nagar, Pondicherry, 605 006, India.
| | - M Sundhar
- Liver Diseases Research Lab, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Dhanvantari Nagar, Pondicherry, 605 006, India
| | - B H Srinivas
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605006, India
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23
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Weiss N, Thabut D. Neurological Complications Occurring After Liver Transplantation: Role of Risk Factors, Hepatic Encephalopathy, and Acute (on Chronic) Brain Injury. Liver Transpl 2019; 25:469-487. [PMID: 30697911 DOI: 10.1002/lt.25420] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 12/19/2018] [Indexed: 02/06/2023]
Abstract
Orthotopic liver transplantation (LT) remains the only way to definitively cure patients with the most severe liver diseases. Because the survival rate is now fairly high, important questions about neurological sequelae or quality of life after LT have emerged. Indeed, LT represents a peculiar situation because up to 30% of patients present with neurological symptoms after LT compared with only 4% after cardiac transplant and 0.5% after renal transplant. These postoperative neurological symptoms have long been interpreted as sequelae of hepatic encephalopathy (HE). However, postoperative decompensation of an unknown cerebral condition due to the pathophysiology of cirrhosis or undiagnosed neurodegenerative disorders or aging constitute other possibilities that are underrecognized. Some patients who undergo LT for acute liver failure and patients with cirrhosis without episodes of HE and without any previous cerebral alteration also display post-LT neurological symptoms. This latter situation speaks in favor of a direct adverse effect of either general anesthesia, the surgical procedure, or factors related to the postoperative intensive care unit (ICU) environment. The role of inflammation, which has been described in the ICU setting, could also be a crucial determinant. In this review, we will discuss the neurological complications associated with LT, the neurocognitive complications after LT, and how to assess the LT-related neurological or neurocognitive complications. Furthermore, we will review the various hypotheses surrounding post-LT neurocognitive impairment and will conclude with recommendations for future directions.
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Affiliation(s)
- Nicolas Weiss
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Département de Neurologie, Unité de Réanimation Neurologique, Sorbonne Université, Paris, France.,Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université, INSERM, Paris, France
| | - Dominique Thabut
- Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université, INSERM, Paris, France.,Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Service d'Hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépato-Gastroentérologie, Sorbonne Université, Paris, France
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24
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Weiss N, Housset C, Thabut D. Hepatic encephalopathy: Another brick in the wall. J Hepatol 2019; 70:8-10. [PMID: 30414737 DOI: 10.1016/j.jhep.2018.10.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 10/18/2018] [Accepted: 10/21/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Nicolas Weiss
- Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Département de Neurologie, Unité de réanimation neurologique, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France.
| | - Chantal Housset
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France
| | - Dominique Thabut
- Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris, France; Sorbonne Université, Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Assistance Publique - Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Service d'Hépato-Gastroentérologie, Unité de Soins Intensifs d'Hépato-Gastroentérologie, Paris, France
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Alsaad AA, Stancampiano FF, Palmer WC, Henry AM, Jackson JK, Heckman MG, Diehl NN, Keaveny AP. Serum Electrolyte Levels and Outcomes in Patients Hospitalized with Hepatic Encephalopathy. Ann Hepatol 2018; 17:836-842. [PMID: 30145570 DOI: 10.5604/01.3001.0012.3144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND AIMS Serum electrolyte derangements are common in patients with decompensated cirrhosis hospitalized for hepatic encephalopathy. There are limited data describing the association between electrolyte levels and outcomes in hepatic encephalopathy. We assessed the association between initial serum electrolyte values and outcomes in patients with hepatic encephalopathy. MATERIAL AND METHODS A total of 385 consecutive patients hospitalized with encephalopathy were included in the study. Baseline electrolyte levels (sodium, potassium, chloride, bicarbonate, calcium and phosphorus) were measured at the time of admission and assessed for association with outcomes, which included survival, admission to the intensive care unit, requirement for mechanical ventilation, and length of hospital stay. P-values ≤ 0.0083 were considered significant after adjustment for multiple testing. RESULTS In unadjusted analysis, significant associations were identified regarding both bicarbonate and phosphorus (admission to intensive care unit), and calcium (mechanical ventilation); however these findings weakened and no longer approached statistical significance when adjusting for confounding variables. No other significant associations between serum electrolyte measurements and outcomes were observed. CONCLUSIONS Our findings suggest that in patients hospitalized with encephalopathy, serum electrolyte measurements are not strong predictors of patient outcome.
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Affiliation(s)
- Ali A Alsaad
- Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida, USA
| | | | - William C Palmer
- Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - April M Henry
- CRISP Program, Mayo Clinic, Jacksonville, Florida, USA
| | | | - Michael G Heckman
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA
| | - Nancy N Diehl
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA
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Boilève A, Osman D, Marthey L, Carbonnel F, Jozwiak M. Drug-induced coma after chemotherapy in intensive care unit: How to make the right diagnosis? J Neurol Sci 2018; 392:137-138. [PMID: 30059846 DOI: 10.1016/j.jns.2018.07.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 07/18/2018] [Accepted: 07/20/2018] [Indexed: 01/11/2023]
Affiliation(s)
- Alice Boilève
- Hôpitaux universitaires Paris-Sud, Hôpitaux de Paris, Hôpital de Bicêtre, service de réanimation médicale, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France; Inserm, UMR S_999, Univ Paris-Sud, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France.
| | - David Osman
- Hôpitaux universitaires Paris-Sud, Hôpitaux de Paris, Hôpital de Bicêtre, service de réanimation médicale, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France; Inserm, UMR S_999, Univ Paris-Sud, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France
| | - Lysiane Marthey
- Hôpitaux universitaires Paris-Sud, Hôpitaux de Paris, Hôpital de Bicêtre, service d'hépato-gastro-entérologie, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France
| | - Franck Carbonnel
- Hôpitaux universitaires Paris-Sud, Hôpitaux de Paris, Hôpital de Bicêtre, service d'hépato-gastro-entérologie, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France
| | - Mathieu Jozwiak
- Hôpitaux universitaires Paris-Sud, Hôpitaux de Paris, Hôpital de Bicêtre, service de réanimation médicale, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France; Inserm, UMR S_999, Univ Paris-Sud, 78, rue du Général Leclerc, Le Kremlin-Bicêtre F-94270, France
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Zhang XD, Zhang LJ. Multimodal MR imaging in hepatic encephalopathy: state of the art. Metab Brain Dis 2018; 33:661-671. [PMID: 29374342 DOI: 10.1007/s11011-018-0191-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 01/17/2018] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a neurological or neuropsychological complication due to liver failure or portosystemic shunting. The clinical manifestation is highly variable, which can exhibit mild cognitive or motor impairment initially, or gradually progress to a coma, even death, without treatment. Neuroimaging plays a critical role in uncovering the neural mechanism of HE. In particular, multimodality MR imaging is able to assess both structural and functional derangements of the brain with HE in focal or neural network perspectives. In recent years, there has been rapid development in novel MR technologies and applications to investigate the pathophysiological mechanism of HE. Therefore, it is necessary to update the latest MR findings regarding HE by use of multimodality MRI to refine and deepen our understanding of the neural traits in HE. Herein, this review highlights the latest MR imaging findings in HE to refresh our understanding of MRI application in HE.
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Affiliation(s)
- Xiao Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Clinical School of Tianjin Medical University, Tianjin, 300192, People's Republic of China
| | - Long Jiang Zhang
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
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Carrier P, Loustaud-Ratti V. Treating hepatic encephalopathy in cirrhotic patients admitted to ICU with sodium phenylbutyrate: a preliminary study. Fundam Clin Pharmacol 2018; 32:206-208. [DOI: 10.1111/fcp.12353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Paul Carrier
- Hepatology and Gastroenterology Unit; Limoges Teaching Hospital; 2, avenue Martin Luther King 87042 Limoges France
- Faculté de Médecine et de Pharmacie de Limoges; INSERM; UMR-1248; 2, rue Docteur Marcland 87042 Limoges France
- FHU SUPORT (SUrvival oPtimization in ORgan Transplantation); 2, avenue Martin Luther King 87042 Limoges France
| | - Véronique Loustaud-Ratti
- Hepatology and Gastroenterology Unit; Limoges Teaching Hospital; 2, avenue Martin Luther King 87042 Limoges France
- Faculté de Médecine et de Pharmacie de Limoges; INSERM; UMR-1248; 2, rue Docteur Marcland 87042 Limoges France
- FHU SUPORT (SUrvival oPtimization in ORgan Transplantation); 2, avenue Martin Luther King 87042 Limoges France
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Fuhrmann V, Whitehouse T, Wendon J. The ten tips to manage critically ill patients with acute-on-chronic liver failure. Intensive Care Med 2018; 44:1932-1935. [DOI: 10.1007/s00134-018-5078-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2017] [Accepted: 01/24/2018] [Indexed: 12/25/2022]
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Weiss N, Attali V, Bouzbib C, Thabut D. Altered distal-proximal temperature gradient as a possible explanation for sleep-wake disturbances in cirrhotic patients. Liver Int 2017; 37:1776-1779. [PMID: 29149489 DOI: 10.1111/liv.13590] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Nicolas Weiss
- Sorbonne Universités, Université Pierre et Marie Curie Paris 6, Paris, France.,Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France.,INSERM UMR_S 938, CDR Saint-Antoine Maladies métaboliques, Biliaires et fibro-inflammatoire du foie & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France.,Unité de réanimation neurologique, Département de neurologie, pôle des maladies du système nerveux, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris et Institut de neurosciences translationnelles IHU-A-ICM, Paris, France
| | - Valérie Attali
- Sorbonne Universités, Université Pierre et Marie Curie Paris 6, Paris, France.,Service d'Exploration des Pathologies du Sommeil (Département "R3S"), Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris& Sorbonne Universités, UPMC Université Paris 06, INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Paris, France
| | - Charlotte Bouzbib
- Sorbonne Universités, Université Pierre et Marie Curie Paris 6, Paris, France.,Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France.,INSERM UMR_S 938, CDR Saint-Antoine Maladies métaboliques, Biliaires et fibro-inflammatoire du foie & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France.,Unité de Soins Intensifs d'Hépato-gastroentérologie, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France
| | - Dominique Thabut
- Sorbonne Universités, Université Pierre et Marie Curie Paris 6, Paris, France.,Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France.,INSERM UMR_S 938, CDR Saint-Antoine Maladies métaboliques, Biliaires et fibro-inflammatoire du foie & Institut de Cardiométabolisme et Nutrition, ICAN, Paris, France.,Unité de Soins Intensifs d'Hépato-gastroentérologie, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris, Paris, France
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Feng L, Cai L, He GL, Weng J, Li Y, Pan MX, Jiang ZS, Peng Q, Gao Y. Novel D-galactosamine-induced cynomolgus monkey model of acute liver failure. World J Gastroenterol 2017; 23:7572-7583. [PMID: 29204057 PMCID: PMC5698250 DOI: 10.3748/wjg.v23.i42.7572] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 09/17/2017] [Accepted: 10/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure having an appropriate treatment window.
METHODS Sixteen cynomolgus monkeys were randomly divided into four groups (A, B, C and D) after intracranial pressure (ICP) sensor implantation. D-galactosamine at 0.3, 0.25, 0.20 + 0.05 (24 h interval), and 0.20 g/kg body weight, respectively, was injected via the small saphenous vein. Vital signs, ICP, biochemical indices, and inflammatory factors were recorded at 0, 12, 24, 36, 48, 72, 96, and 120 h after D-galactosamine administration. Progression of clinical manifestations, survival times, and results of H&E staining, TUNEL, and Masson staining were recorded.
RESULTS Cynomolgus monkeys developed different degrees of debilitation, loss of appetite, and jaundice after D-galactosamine administration. Survival times of groups A, B, and C were 56 ± 8.7 h, 95 ± 5.5 h, and 99 ± 2.2 h, respectively, and in group D all monkeys survived the 144-h observation period except for one, which died at 136 h. Blood levels of ALT, AST, CK, LDH, TBiL, Cr, BUN, and ammonia, prothrombin time, ICP, endotoxin, and inflammatory markers [(tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6)] significantly increased compared with baseline values in different groups (P < 0.05). Pathological results showed obvious liver cell necrosis that was positively correlated with the dose of D-galactosamine.
CONCLUSION We successfully established a simplified, reproducible D-galactosamine-induced cynomolgus monkey model of acute liver failure, and the single or divided dosage of 0.25 g/kg is optimal for creating this model.
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Affiliation(s)
- Lei Feng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Lei Cai
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Guo-Lin He
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Jun Weng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Yang Li
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Ming-Xin Pan
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Ze-Sheng Jiang
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Qing Peng
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
| | - Yi Gao
- Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
- State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou 510282, Guangdong Province, China
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Weiss N, Colsch B, Fenaille F, Junot C, Thabut D. Reply to: "Serum metabolic signatures in patients with overt hepatic encephalopathy": Metabolic signature for severe cirrhosis with inflammation or hepatic encephalopathy: Do we really face two different entities? J Hepatol 2017; 67:1115-1116. [PMID: 28688802 DOI: 10.1016/j.jhep.2017.06.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 06/30/2017] [Indexed: 12/04/2022]
Affiliation(s)
- Nicolas Weiss
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France; Unité de réanimation neurologique, Fédération de neurologie 1, pôle des maladies du système nerveux, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris et Institut de neurosciences translationnelles IHU-A-ICM, Paris, France
| | - Benoit Colsch
- CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Etude du Métabolisme des Médicaments, MetaboHUB-Paris, 91191 Gif-sur-Yvette cedex, France
| | - François Fenaille
- CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Etude du Métabolisme des Médicaments, MetaboHUB-Paris, 91191 Gif-sur-Yvette cedex, France
| | - Christophe Junot
- CEA, iBiTec-S, Service de Pharmacologie et d'Immunoanalyse, Laboratoire d'Etude du Métabolisme des Médicaments, MetaboHUB-Paris, 91191 Gif-sur-Yvette cedex, France
| | - Dominique Thabut
- Brain Liver Pitié-Salpêtrière (BLIPS) Study Group, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France; Unité de Soins Intensifs d'Hépato-gastroentérologie, Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Assistance Publique - Hôpitaux de Paris et Université Pierre et Marie Curie Paris 6, Paris, France.
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