Hyperammonemia in Hepatic Encephalopathy
Open accessAbstract
The precise mechanism underlying the neurotoxicity of Hepatic Encephalopathy (HE) is remains unclear. The dominant view has been that gut-derived nitrogenous toxins are not extracted by the diseased liver and thereby enter the brain. Among the various toxins proposed, the case for ammonia is most compelling. Events that lead to increased levels of blood or brain ammonia have been shown to worsen HE, whereas reducing blood ammonia levels alleviates HE. Clinical, pathological, and biochemical changes observed in HE can be reproduced by increasing blood or brain ammonia levels in experimental animals, while exposure of cultured astrocytes to ammonium salts reproduces the morphological and biochemical findings observed in HE. However, factors other than ammonia have recently been proposed to be involved in the development of HE, including cytokines and other blood and brain immune factors. Moreover, recent studies have questioned the critical role of ammonia in the pathogenesis of HE since blood ammonia levels do not always correlate with the level/severity of encephalopathy. This review summarizes the vital role of ammonia in the pathogenesis of HE in humans, as well as in experimental models of acute and chronic liver failure. It further emphasizes recent advances in the molecular mechanisms involved in the progression of neurological complications that occur in acute and chronic liver failure.
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The aged liver secretes fewer neuroprotective molecules and eliminates fewer neurotoxic substances (e.g., superoxide radicals), exacerbating the accumulation of excessive oxidation products in the brain.
“The aged liver secretes fewer neuroprotective molecules and eliminates fewer neurotoxic substances (e.g., superoxide radicals), exacerbating the accumulation of excessive oxidation products in the brain.225”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [225]
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Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma
El‐Serag, H. B. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.12.061 · Cited by 3,384 · see citing works
Glutamine Synthetase: Glial Localization in Brain
Martinez-Hernandez, A., Bell, K. P., & Norenberg, M. D. (1977) · Science · doi:10.1126/science.14400 · Cited by 1,183 · see citing works
Self-citationTau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806 · see citing works
Clemmesen, J. O., Larsen, F. S., Kondrup, J., Hansen, B. A., & Ott, P. (1999) · Hepatology · doi:10.1002/hep.510290309 · Cited by 666 · see citing works
Control of excitatory CNS synaptogenesis by astrocyte-secreted proteins Hevin and SPARC
Kucukdereli, H., Allen, N. J., Lee, A. T., Feng, A., Ozlu, M. I., Conatser, L. M., Chakraborty, C., Workman, G., Weaver, M., Sage, E. H., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104977108 · Cited by 642 · see citing works
Correlation between ammonia levels and the severity of hepatic encephalopathy
Ong, J. P., Aggarwal, A., Krieger, D. W., Easley, K. A., Karafa, M., Lente, F. V., Arroliga, A. C., & Mullen, K. D. (2003) · The American Journal of Medicine · doi:10.1016/s0002-9343(02)01477-8 · Cited by 534 · see citing works
Wang, D. D., & Bordey, A. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.09.015 · Cited by 517 · see citing works
Bernal, W. E., Hall, C., Karvellas, C. J., Auzinger, G. M., Sizer, E., & Wendon, J. A. (2007) · Hepatology · doi:10.1002/hep.21838 · Cited by 475 · see citing works
Ammonia: Key factor in the pathogenesis of hepatic encephalopathy
Butterworth, R. F., Giguère, J., Michaud, J., Lavoie, J., & Pomier–Layrargues, G. (1987) · Neurochemical Pathology · doi:10.1007/bf02833598 · Cited by 412 · see citing works
Role for glia in synaptogenesis
Ullian, E. M., Christopherson, K. S., & Barres, B. A. (2004) · Glia · doi:10.1002/glia.20082 · Cited by 370 · see citing works
Cerebral Ammonia Metabolism in Patients with Severe Liver Disease and Minimal Hepatic Encephalopathy
Lockwood, A. H., Yap, E. W. H., & Wong, W. (1991) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1991.67 · Cited by 335 · see citing works
Predictive value of arterial ammonia for complications and outcome in acute liver failure
Bhatia, V., Singh, R., & Acharya, S. K. (2005) · Gut · doi:10.1136/gut.2004.061754 · Cited by 273 · see citing works
Kramer, J. R., Davila, J. A., MILLER, E. D., Richardson, P., Giordano, T. P., & EL‐SERAG, H. B. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03572.x · Cited by 269 · see citing works
GLIA-NEURON INTERCOMMUNICATIONS AND SYNAPTIC PLASTICITY
Vernadakis, A. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00012-3 · Cited by 268 · see citing works
Ammonia-induced brain edema and intracranial hypertension in rats after portacaval anastomosis
Blei, A. T., Olafsson, S., Therrien, G., & Butterworth, R. F. (1994) · Hepatology · doi:10.1002/hep.1840190619 · Cited by 243 · see citing works
RELATION OF RENAL IMPAIRMENT AND HAEMORRHAGIC DIATHESIS TO ENDOTOXAEMIA IN FULMINANT HEPATIC FAILURE
Wilkinson, S. P., Gazzard, B., Arroyo, V., Moodie, H., & Williams, R. L. (1974) · The Lancet · doi:10.1016/s0140-6736(74)92711-1 · Cited by 210 · see citing works
Pathophysiology of cerebral edema in fulminant hepatic failure
Blei, A. T., & Larsen, F. S. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80361-4 · Cited by 202 · see citing works
Quero, J. C., Hartmann, I. J. C., Meulstee, J., et al. (1996) · Hepatology · doi:10.1002/hep.510240316 · Cited by 199 · see citing works
Norenberg, M. D. (1977) · PubMed · Cited by 193 · see citing works
Self-citationNew concepts in the mechanism of ammonia-induced astrocyte swelling
Norenberg, M. D., Jayakumar, A. R., Rao, K. V. R., & Panickar, K. S. (2007) · Metabolic Brain Disease · doi:10.1007/s11011-007-9062-5 · Cited by 176 · see citing works
Self-citationAstrocytic-Ammonia Interactions in Hepatic Encephalopathy
Norenberg, M. D. (1996) · Seminars in Liver Disease · doi:10.1055/s-2007-1007237 · Cited by 176 · see citing works
Self-citationPartial pressure of ammonia versus ammonia in hepatic encephalopathy
Kramer, L., Tribl, B., Gendo, A., et al. (2000) · Hepatology · doi:10.1002/hep.510310107 · Cited by 169 · see citing works
Astroglial Dysfunction in Hepatic Encephalopathy
Norenberg, M. D. (1998) · Metabolic Brain Disease · doi:10.1023/a:1020688925901 · Cited by 168 · see citing works
Self-citationEffect of ammonium ions on synaptic transmission in the mammalian central nervous system
Szerb, J. C., & Butterworth, R. F. (1992) · Progress in Neurobiology · doi:10.1016/0301-0082(92)90008-3 · Cited by 166 · see citing works
Morphologic Effects of Ammonia on Primary Astrocyte Cultures. I. Light Microscopic Studies
Gregorios, J. B., Mozes, L. W., Norenberg, L.-O. B., & Norenberg, M. D. (1985) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198507000-00003 · Cited by 159 · see citing works
Self-citationNeurotrophic factor gene expression in astrocytes during development and following injury
Schwartz, J. P., & Nishiyama, N. (1994) · Brain Research Bulletin · doi:10.1016/0361-9230(94)90151-1 · Cited by 157 · see citing works
Glutamatergic and gabaergic neurotransmission and neuronal circuits in hepatic encephalopathy
Cauli, O., Rodrigo, R., Llansola, M., Montoliu, C., Monfort, P., Piedrafita, B., Mlili, N. E., Boix, J., Agustí, A., & Felipo, V. (2008) · Metabolic Brain Disease · doi:10.1007/s11011-008-9115-4 · Cited by 144 · see citing works
The Astrocyte in Liver Disease
Norenberg, M. D. (1981) · Advances in cellular neurobiology · doi:10.1016/b978-0-12-008302-2.50013-4 · Cited by 141 · see citing works
Self-citationJones, E. A., & Weißenborn, K. (1997) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.63.3.279 · Cited by 135 · see citing works
Basile, A. S., & Jones, E. A. (1997) · Hepatology · doi:10.1002/hep.510250636 · Cited by 134 · see citing works
Neuroinflammation in Hepatic Encephalopathy: Mechanistic Aspects
Jayakumar, A. R., Rao, K. V. R., & Norenberg, M. D. (2014) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2014.07.006 · Cited by 134 · see citing works
Self-citationA randomized controlled trial of acarbose in hepatic encephalopathy
Gentile, S., Guarino, G., Romano, M., et al. (2005) · Clinical Gastroenterology and Hepatology · doi:10.1016/s1542-3565(04)00667-6 · Cited by 132 · see citing works
Signaling factors in the mechanism of ammonia neurotoxicity
Norenberg, M. D., Rao, K. V. R., & Jayakumar, A. R. (2008) · Metabolic Brain Disease · doi:10.1007/s11011-008-9113-6 · Cited by 131 · see citing works
Self-citationKundra, A., Jain, A., Banga, A., Bajaj, G., & Kar, P. (2005) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2005.04.013 · Cited by 131 · see citing works
蒋文雷, Desjardins, P., & Butterworth, R. F. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.18 · Cited by 124 · see citing works
The Na–K–Cl Co-transporter in astrocyte swelling
Jayakumar, A. R., & Norenberg, M. D. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9180-3 · Cited by 124 · see citing works
Self-citationInteraction of oxidative stress, astrocyte swelling and cerebral ammonia toxicity
Häussinger, D., & Görg, B. (2009) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328333b829 · Cited by 124 · see citing works
McMillin, M., Frampton, G. A., Seiwell, A. P., Patel, N. S., Jacobs, A., & DeMorrow, S. (2015) · Laboratory Investigation · doi:10.1038/labinvest.2015.70 · Cited by 117 · see citing works
Görg, B., Karababa, A., Shafigullina, A. K., Bidmon, H. J., & Häussinger, D. (2014) · Glia · doi:10.1002/glia.22731 · Cited by 115 · see citing works
Bémeur, C., Qu, H., Desjardins, P., et al. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.11.010 · Cited by 111 · see citing works
Increased aquaporin-4 expression in ammonia-treated cultured astrocytes
Rao, K. V. R., Chen, M., Simard, J. M., et al. (2003) · Neuroreport · doi:10.1097/00001756-200312190-00018 · Cited by 111 · see citing works
McKinney, A. M., Lohman, B. D., Sarıkaya, B., et al. (2010) · American Journal of Neuroradiology · doi:10.3174/ajnr.a2112 · Cited by 109 · see citing works
Cerebral effects of ammonia in liver disease: current hypotheses
Ott, P., & Vilstrup, H. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9494-7 · Cited by 106 · see citing works
Blood ammonia levels in liver cirrhosis: a clue for the presence of portosystemic collateral veins
Tarantino, G., Citro, V., Esposito, P. B., et al. (2009) · BMC Gastroenterology · doi:10.1186/1471-230x-9-21 · Cited by 105 · see citing works
Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes
Rao, K. V. R., Jayakumar, A. R., Tong, X., et al. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-66 · Cited by 98 · see citing works
Self-citationMorphologic Effects of Ammonia on Primary Astrocyte Cultures. II. Electron Microscopic Studies
Gregorios, J. B., Mozes, L. W., & Norenberg, M. D. (1985) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198507000-00004 · Cited by 92 · see citing works
Self-citationThe pathophysiology of brain edema in acute liver failure
Blei, A. T. (2005) · Neurochemistry International · doi:10.1016/j.neuint.2005.04.009 · Cited by 89 · see citing works
Lichter‐Konecki, U., Mangin, J., Gordish‐Dressman, H., et al. (2008) · Glia · doi:10.1002/glia.20624 · Cited by 86 · see citing works
Ueber den Ammoniakgehalt des Blutes und der Organe und die Harnstoffbildung bei den Säugethieren
Nencki, M. V., Pawlow, J. P., & Zaleski, J. (1895) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/bf01966135 · Cited by 86 · see citing works
Weißenborn, K., Ahl, B., Fischer-Wasels, D., et al. (2007) · Gut · doi:10.1136/gut.2006.110569 · Cited by 85 · see citing works
Mardini, H. A., Saxby, B. K., & Record, C. O. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.06.043 · Cited by 80 · see citing works
Kanamori, K., Ross, B. D., Chung, J. C., & Kuo, E. L. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.67041584.x · Cited by 80 · see citing works
THE PLASMA “AMMONIA” AND GLUTAMINE CONTENT IN PATIENTS WITH HEPATIC COMA 1
Seegmiller, J. E., Schwartz, R. H., & Davidson, C. S. (1954) · Journal of Clinical Investigation · doi:10.1172/jci102976 · Cited by 74 · see citing works
Dhanda, S., & Sandhir, R. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.01.042 · Cited by 74 · see citing works
Management options for minimal hepatic encephalopathy
Bajaj, J. S. (2008) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/17474124.2.6.785 · Cited by 71 · see citing works
Role of aquaporin-4 in the development of brain oedema in liver failure
Wright, G. A. K., Soper, R., Brooks, H. F., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.02.020 · Cited by 68 · see citing works
Shah, N. K., de Oca, M. M., Jover‐Cobos, M., Tanamoto, K., Muroi, M., Sugiyama, K., Davies, N. A., Mookerjee, R. P., Dhar, D. K., & Jalan, R. (2013) · Liver Transplantation · doi:10.1002/lt.23655 · Cited by 67 · see citing works
Microglial proliferation in the brain of chronic alcoholics with hepatic encephalopathy
Dennis, C. V., Sheahan, P. J., Graeber, M. B., Sheedy, D. L., Kril, J. J., & Sutherland, G. T. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9469-0 · Cited by 67 · see citing works
Skowrońska, M., Zielińska, M., Stanaszek, L., Ruszkiewicz, J. A., Milatović, D., Aschner, M., & Albrecht, J. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07669.x · Cited by 67 · see citing works
Neuroinflammation in acute liver failure: Mechanisms and novel therapeutic targets
Butterworth, R. F. (2011) · Neurochemistry International · doi:10.1016/j.neuint.2011.07.014 · Cited by 66 · see citing works
Chastre, A., Jiang, W., Desjardins, P., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9185-y · Cited by 66 · see citing works
Calcium in the mechanism of ammonia‐induced astrocyte swelling
Jayakumar, A. R., Rao, K. V. R., Tong, X., & Norenberg, M. D. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05842.x · Cited by 65 · see citing works
Self-citationSynaptic transmission in ammonia intoxication
Raabe, W. A. (1987) · Neurochemical Pathology · doi:10.1007/bf02833604 · Cited by 63 · see citing works
Jayakumar, A. R., Tong, X., Curtis, K. M., Ruiz‐Cordero, R., Abreu, M. T., & Norenberg, M. D. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12516 · Cited by 63 · see citing works
Self-citationJayakumar, A. R., Tong, X., Curtis, K. M., Ruiz‐Cordero, R., Shamaladevi, N., Abuzamel, M., Johnstone, J. T., Gaidosh, G., Rao, K. V. R., & Norenberg, M. D. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12810 · Cited by 61 · see citing works
Self-citationChastre, A., Bélanger, M., Nguyen, B., et al. (2013) · Liver International · doi:10.1111/liv.12252 · Cited by 61 · see citing works
Beste, L. A., & Ioannou, G. N. (2015) · Epidemiologic Reviews · doi:10.1093/epirev/mxu002 · Cited by 60 · see citing works
Siddiqui, T. A., Lively, S. S., & Schlichter, L. C. (2016) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0531-9 · Cited by 59 · see citing works
Brain Aquaporin-4 in Experimental Acute Liver Failure
Rao, K. V. R., Jayakumar, A. R., Tong, X., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181ebe581 · Cited by 57 · see citing works
Self-citationChapter 22: Hepatic encephalopathy: a disorder in glial-neuronal communication
Norenberg, M. D., Neary, J. T., Bender, A. S., et al. (1992) · Progress in brain research · doi:10.1016/s0079-6123(08)61756-2 · Cited by 56 · see citing works
Self-citationBrain Edema in Acute Liver Failure
Blei, A. T. (2008) · Critical Care Clinics · doi:10.1016/j.ccc.2007.11.001 · Cited by 53 · see citing works
Ammonia-induced activation of p53 in cultured astrocytes: Role in cell swelling and glutamate uptake
Panickar, K. S., Jayakumar, A. R., Rao, K. V. R., et al. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2008.12.022 · Cited by 52 · see citing works
Self-citationRao, K. V. R., Verkman, A. S., Curtis, K. M., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.11.018 · Cited by 51 · see citing works
Jayakumar, A. R., Tong, X. Y., Ospel, J. M., & Norenberg, M. D. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.05.006 · Cited by 49 · see citing works
Self-citationThe Na–K–Cl cotransporter in the brain edema of acute liver failure
Jayakumar, A. R., Valdes, V., & Norenberg, M. D. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.06.041 · Cited by 49 · see citing works
Self-citationSulfonylurea Receptor 1 Contributes to the Astrocyte Swelling and Brain Edema in Acute Liver Failure
Jayakumar, A. R., Valdes, V., Tong, X., et al. (2014) · Translational Stroke Research · doi:10.1007/s12975-014-0328-z · Cited by 45 · see citing works
Self-citationAmmonia levels and the severity of hepatic encephalopathy.
Qureshi, M. O., Khokhar, N., & Shafqat, F. (2014) · PubMed · Cited by 45 · see citing works
Capocaccia, L., & Angelico, M. (1991) · Digestive Diseases and Sciences · doi:10.1007/bf01311236 · Cited by 43 · see citing works
Cauli, O., Mlili, N. E., Llansola, M., & Felipo, V. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05435.x · Cited by 43 · see citing works
Cabrera‐Pastor, A., Malaguarnera, M., Taoro‐González, L., et al. (2016) · Scientific Reports · doi:10.1038/srep33124 · Cited by 43 · see citing works
Butterworth, R. F. (2015) · Metabolic Brain Disease · doi:10.1007/s11011-015-9747-0 · Cited by 42 · see citing works
Dezonne, R. S., Stipursky, J., Araújo, A. P. B., Nones, J., Pavão, M. S. G., Porcionatto, M. A., & Gomes, F. C. A. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00125 · Cited by 42 · see citing works
Panickar, K. S., Jayakumar, A. R., Rao, K. V. R., & Norenberg, M. D. (2007) · Glia · doi:10.1002/glia.20584 · Cited by 41 · see citing works
Self-citationOral Acetyl-L-Carnitine treatment in hepatic encephalopathy: view of evidence-based medicine
Jiang, Q., Jiang, G., Shi, K., et al. (2013) · Annals of Hepatology · doi:10.1016/s1665-2681(19)31323-7 · Cited by 41 · see citing works
Ammonia-induced brain swelling and neurotoxicity in an organotypic slice model
Back, A., Tupper, K. Y., Bai, T., et al. (2011) · Neurological Research · doi:10.1179/1743132811y.0000000046 · Cited by 40 · see citing works
Naderian, M., Akbari, H., Saeedi, M., et al. (2017) · Middle East Journal of Digestive Diseases · doi:10.15171/mejdd.2016.46 · Cited by 40 · see citing works
Synaptic plasticity, astrocytes and morphological homeostasis
Ślęzak, M., Pfrieger, F. W., & Sołtys, Z. (2006) · Journal of Physiology-Paris · doi:10.1016/j.jphysparis.2005.12.082 · Cited by 39 · see citing works
The neurosteroid system: an emerging therapeutic target for hepatic encephalopathy
Ahboucha, S., & Butterworth, R. F. (2007) · Metabolic Brain Disease · doi:10.1007/s11011-007-9065-2 · Cited by 38 · see citing works
Thumburu, K. K., Dhiman, R. K., Vasishta, R. K., et al. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12511 · Cited by 38 · see citing works
McMillin, M., Grant, S. M., Frampton, G. A., Petrescu, A. D., Kain, J., Williams, E., Haines, R., Canady, L., & DeMorrow, S. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.02.008 · Cited by 38 · see citing works
Microglia contribute to ammonia-induced astrocyte swelling in culture
Rao, K. V. R., Brahmbhatt, M., & Norenberg, M. D. (2012) · Metabolic Brain Disease · doi:10.1007/s11011-012-9339-1 · Cited by 37 · see citing works
Self-citationWright, G. A. K., Sharifi, Y., Newman, T. A., Davies, N. A., Vairappan, B., Perry, V. H., & Jalan, R. (2014) · Liver International · doi:10.1111/liv.12481 · Cited by 36 · see citing works
Jao, T., Schröter, M. S., Chen, C. L., Cheng, Y.-F., Lo, C. Z., Chou, K., Patel, A. X., Lin, W., Lin, C., & Bullmore, E. T. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.07.068 · Cited by 35 · see citing works
Zielińska, M., Ruszkiewicz, J. A., Hilgier, W., Fręśko, I., & Albrecht, J. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.11.015 · Cited by 33 · see citing works
Karababa, A., Görg, B., Schliess, F., et al. (2013) · Metabolic Brain Disease · doi:10.1007/s11011-013-9454-7 · Cited by 33 · see citing works
Kim, J. E., Go, J., Sung, J. E., Lee, H. A., Yun, W. B., Hong, J. T., & Hwang, D. Y. (2017) · BMC Gastroenterology · doi:10.1186/s12876-017-0576-y · Cited by 33 · see citing works
Méndez, M., Méndez-López, M., López, L., et al. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.06.013 · Cited by 30 · see citing works
Bajaj, J. S., Thacker, L. R., Heuman, D. M., Sterling, R. K., Stravitz, R. T., Sanyal, A. J., Luketic, V. A., Fuchs, M. A., Gilles, H., & Wade, J. B. (2012) · Liver Transplantation · doi:10.1002/lt.23484 · Cited by 30 · see citing works
Diagnostic methods in hepatic encephalopathy
Guillén, J. C. Q., & Gutiérrez, J. M. H. (2005) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.08.003 · Cited by 30 · see citing works
Kitzberger, R., Funk, G., Holzinger, U., Miehsler, W., Kramer, L., Kaider, A., Ferenci, P., & Madl, C. (2009) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2009.05.019 · Cited by 30 · see citing works
Cognitive dysfunction and hepatitis C virus infection
Solinas, A. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i7.922 · Cited by 30 · see citing works
Zhang, G., Cheng, Y., & Liu, B. (2016) · Brain Imaging and Behavior · doi:10.1007/s11682-016-9553-2 · Cited by 29 · see citing works
Assessment of the spectrum of hepatic encephalopathy: A multicenter study
Reuter, B., Walter, K., Bissonnette, J., et al. (2018) · Liver Transplantation · doi:10.1002/lt.25032 · Cited by 29 · see citing works
Hilgier, W., Oja, S. S., Saransaari, P., et al. (2004) · Brain Research · doi:10.1016/j.brainres.2004.05.014 · Cited by 26 · see citing works
Obara‐Michlewska, M., Pannicke, T., Karl, A., Bringmann, A., Reichenbach, A., Szeliga, M., Hilgier, W., Wrzosek, A., Szewczyk, A. M., & Albrecht, J. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22656 · Cited by 26 · see citing works
Monfort, P., Muñoz, M.-D., & Felipo, V. (2005) · Metabolic Brain Disease · doi:10.1007/s11011-005-7905-5 · Cited by 26 · see citing works
Hertz, L., Peng, L., & Song, D. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1352-9 · Cited by 25 · see citing works
Fukuzawa, T., Matsutani, S., Maruyama, H., et al. (2006) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2006.04226.x · Cited by 25 · see citing works
Zheng, G., Lu, H., Yu, W., et al. (2017) · European Radiology · doi:10.1007/s00330-017-4809-9 · Cited by 23 · see citing works
Multifactorial Effects on Different Types of Brain Cells Contribute to Ammonia Toxicity
Hertz, L., Song, D., Peng, L., & Chen, Y. (2016) · Neurochemical Research · doi:10.1007/s11064-016-1966-1 · Cited by 22 · see citing works
Jayakumar, A. R., Tong, X., Shamaladevi, N., Barcelona, S., Gaidosh, G., Agarwal, A. N., & Norenberg, M. D. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13867 · Cited by 21 · see citing works
Self-citationSobczyk, K., Jördens, M. S., Karababa, A., et al. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1389-9 · Cited by 20 · see citing works
Jördens, M. S., Keitel, V., Karababa, A., et al. (2015) · Glia · doi:10.1002/glia.22879 · Cited by 18 · see citing works
Melatonin Levels in Serum and Ascitic Fluid of Patients with Hepatic Encephalopathy
Chojnacki, C. J., Romanowski, M., Winczyk, K., et al. (2012) · Gastroenterology Research and Practice · doi:10.1155/2012/510764 · Cited by 16 · see citing works
Albrecht, J., & Zielińska, M. (2002) · Metabolic Brain Disease · doi:10.1023/a:1021901700493 · Cited by 14 · see citing works
Effects of raloxifene on portal hypertension and hepatic encephalopathy in cirrhotic rats
Chang, C.-C., Lee, W.-S., Chuang, C., Hsin, I., Hsu, S., Chang, T. T., Huang, H., Lee, F., & Lee, S. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.02.039 · Cited by 14 · see citing works
Park, J., Masaki, T., Mezaki, Y., Yokoyama, H., Nakamura, M., Maehashi, H., Fujimi, T. J., Gouraud, S. S., Nagatsuma, K., Nakagomi, M., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0189346 · Cited by 14 · see citing works
Zwirner, K., Thiel, C., Thiel, K., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9222-x · Cited by 13 · see citing works
Endozepine-4 levels are increased in hepatic coma
Malaguarnera, G. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i30.9103 · Cited by 13 · see citing works
Endothelial-astrocytic interactions in acute liver failure
Jayakumar, A. R., & Norenberg, M. D. (2012) · Metabolic Brain Disease · doi:10.1007/s11011-012-9344-4 · Cited by 12 · see citing works
Self-citationDai, H., Jia, G., Wang, W., et al. (2017) · Metabolic Brain Disease · doi:10.1007/s11011-017-9975-6 · Cited by 11 · see citing works
Chikamori, F., Okamoto, H., & Kuniyoshi, N. (2014) · Digestion · doi:10.1159/000357494 · Cited by 8 · see citing works
Ikeda, O., Inoue, S., Tamura, Y., et al. (2017) · Acta Radiologica · doi:10.1177/0284185117722810 · Cited by 5 · see citing works
Decreased STAT3 Phosphorylation Mediates Cell Swelling in Ammonia-Treated Astrocyte Cultures
Jayakumar, A., Curtis, K. M., Panickar, K., Shamaladevi, N., & Nörenberg, M. (2016) · Biology · doi:10.3390/biology5040048 · Cited by 4 · see citing works
Self-citationJaber, S. M., & Polster, B. M. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.13906 · Cited by 3 · see citing works
[Effect of amino acid solutions on the blood ammonia level].
Sanjo, K., Harihara, Y., Kawasaki, S., et al. (1985) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Nencki M, Pawlow J, Zaleski J. Ueber den ammoniakgehalt des blutes under der organe und die harnstoffbildung bei den sau- gethieren. Arch Fuer Exp Pathol Pharmakol. 1896;37:26-51.
- Tarantino G, Citro V, Esposito P, et al. BMC Gastroenterol. 2009;17(9):21.
- Jayakumar AR, Norenberg MD. Endothelial-astrocytic interac- tions in acute liver failure. Metab Brain Dis. 2013;28:183-186.
- Shah N, Montes de Oca M, Jover-Cobos M, et al. Role of toll-like receptor 4 in mediating multiorgan dysfunction in mice with acetaminophen induced acute liver failure. Liver Transpl. 2013;19:751-761.
Cited by
Sorted by citations
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165 · see citing works
- Authors
- Jayakumar, A. R., & Norenberg, M. D.
- Affiliations
- Veterans Health Administration (US)
- University of Miami (US)
- Corresponding author
- Jayakumar, A.R.
- Norenberg, Michael D.
- ORCID
- Jayakumar, A.R.
- Venue
- Journal of Clinical and Experimental Hepatology
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 8
- Issue
- 3
- Pages
- 272-280
- ISSN
- 0973-6883 (ISSN-L)
- PMC
- PMC6175739
- OpenAlex
- W2808917216
- Cited by
- 115
- References
- 126
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 16 · 2023: 18 · 2022: 21 · 2021: 14 · 2020: 9 · 2019: 4 · 2018: 3
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical and Experimental Hepatology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- US Department of Veterans Affairs (MDN)
- AASLD/ALF
- Stanley J. Glaser grant
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- hepatic encephalopathy, hyperammonemia, ammonia neurotoxicity, pathogenesis, acute liver failure, chronic liver failure, astrocytes, cytokines, neurological complications
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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