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Neuroinflammation in liver disease: sessional talks from ISHEN

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Abstract

At the recent ISHEN (‘International Symposium of Hepatic Encephalopathy & Nitrogen Metabolism’) conference in London, a whole session was dedicated to our increasing awareness of the importance of inflammation in the brain - termed ‘neuroinflammation’, in the development of Hepatic Encephalopathy (HE) - the neurological manifestations of advanced liver disease. In this review our ISHEN speakers further discuss the content of their sessional presentations and more broadly we discuss our understanding of the role of neuroinflammation in HE pathogenesis.

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References

  • Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK (2009) Efficacy of L-ornithine L-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology 136:2159–2168

    Article  CAS  PubMed  Google Scholar 

  • Albrecht J, Norenberg MD (2006) Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology 44:788–794

    Article  CAS  PubMed  Google Scholar 

  • Annane D, Sharshar T (2015) Cognitive decline after sepsis. Lancet Respir Med 3:61–69

    Article  CAS  PubMed  Google Scholar 

  • Antoniades CG, Berry PA, Davies ET, Hussain M, Bernal W, Vergani D, Wendon J (2006) Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure. Hepatology 44:34–43

    Article  CAS  PubMed  Google Scholar 

  • Bai G, Rama Rao KV, Murthy CR, Panickar KS, Jayakumar AR, Norenberg MD (2001) Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes. J Neurosci Res 66:981–991

    Article  CAS  PubMed  Google Scholar 

  • Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, Sigal S, Sheikh MY, Beavers K, Frederick T, Teperman L, Hillebrand D, Huang S, Merchant K, Shaw A, Bortey E, Forbes WP (2010) Rifaximin treatment in hepatic encephalopathy. N Engl J Med 362(12):1071–1081

  • Bemeur C, Qu H, Desjardins P, Butterworth RF (2010) IL-1 or TNF receptor gene deletion delays onset of encephalopathy and attenuates brain edema in experimental acute liver failure. Neurochem Int 56:213–215

    Article  CAS  PubMed  Google Scholar 

  • Bernal W, Donaldson N, Wyncoll D, Wendon J (2002) Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study. Lancet 359:558–563

    Article  CAS  PubMed  Google Scholar 

  • Bernal W, Hall C, Karvellas CJ, Auzinger G, Sizer E, Wendon J (2007) Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure. Hepatology 46:1844–1852

    Article  CAS  PubMed  Google Scholar 

  • Bernal W, Hyyrylainen A, Gera A, Audimoolam VK, McPhail MJ, Auzinger G, Rela M et al (2013) Lessons from look-back in acute liver failure? A single centre experience of 3300 patients. J Hepatol 59:74–80

    Article  PubMed  Google Scholar 

  • Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V (2015) Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol 63:1272–1284

    Article  CAS  PubMed  Google Scholar 

  • Bernuau J, Goudeau A, Poynard T, Dubois F, Lesage G, Yvonnet B, Degott C et al (1986) Multivariate analysis of prognostic factors in fulminant hepatitis B. Hepatology 6:648–651

    Article  CAS  PubMed  Google Scholar 

  • Bismuth H, Samuel D, Gugenheim J, Castaing D, Bernuau J, Rueff B, Benhamou JP (1987) Emergency liver transplantation for fulminant hepatitis. Ann Intern Med 107:337–341

    Article  CAS  PubMed  Google Scholar 

  • Bjerring PN, Hauerberg J, Frederiksen HJ, Jorgensen L, Hansen BA, Tofteng F, Larsen FS (2008) Cerebral glutamine concentration and lactate-pyruvate ratio in patients with acute liver failure. Neurocrit Care 9:3–7

    Article  PubMed  Google Scholar 

  • Bjerring PN, Hauerberg J, Jorgensen L, Frederiksen HJ, Tofteng F, Hansen BA, Larsen FS (2010) Brain hypoxanthine concentration correlates to lactate/pyruvate ratio but not intracranial pressure in patients with acute liver failure. J Hepatol 53:1054–1058

    Article  CAS  PubMed  Google Scholar 

  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H et al (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  CAS  PubMed  Google Scholar 

  • Bradley MMM, Galindo C, Frampton G, Pae H, Quinn M, DeMorrow S (2013) CCR2 and CCR4 activation via CCL2/MCP-1 contributes to neurological decline and microglia activation associated with hepatic encephalopathy pathogenesis. Gastroenterology 144:S1026–S1027

    Article  Google Scholar 

  • Butterworth RF (2011) Hepatic encephalopathy: a central neuroinflammatory disorder? Hepatology 53:1372–1376

    Article  PubMed  Google Scholar 

  • Butterworth RF (2013) The liver-brain axis in liver failure: neuroinflammation and encephalopathy. Nat Rev Gastroenterol Hepatol 10:522–528

    Article  CAS  PubMed  Google Scholar 

  • Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V (2007) Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with chronic liver failure. Hepatology 46(2):514–519

    Article  CAS  PubMed  Google Scholar 

  • Clemmesen JO, Larsen FS, Kondrup J, Hansen BA, Ott P (1999) Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration. Hepatology 29:648–653

    Article  CAS  PubMed  Google Scholar 

  • Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P et al (2014) Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol 60:275–281

    Article  PubMed  Google Scholar 

  • Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S, Duan SX et al (2013) The UDP-glucuronosyltransferase (UGT) 1 A polymorphism c.2042C > G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. J Pharmacol Exp Ther 345:297–307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crippin JS, Gross JB Jr, Lindor KD (1992) Increased intracranial pressure and hepatic encephalopathy in chronic liver disease. Am J Gastroenterol 87:879–882

  • D’Mello C, Swain MG (2014) Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders. Brain Behav Immun 35:9–20

    Article  PubMed  Google Scholar 

  • D’Mello C, Le T, Swain MG (2009) Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J Neurosci 29:2089–2102

    Article  PubMed  Google Scholar 

  • D’Mello C, Riazi K, Le T, Stevens KM, Wang A, McKay DM, Pittman QJ et al (2013) P-selectin-mediated monocyte-cerebral endothelium adhesive interactions link peripheral organ inflammation to sickness behaviors. J Neurosci 33:14878–14888

    Article  PubMed  Google Scholar 

  • De Deyn PP, Vanholder R, Eloot S, Glorieux G (2009) Guanidino compounds as uremic (neuro)toxins. Semin Dial 22:340–345

    Article  PubMed  Google Scholar 

  • Demetriou AA, Brown RS, Jr., Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS, 2nd, et al. Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Ann Surg 2004; 239:660–667; discussion 667-670.

  • Deng X, Wang X, Andersson R (1995) Endothelial barrier resistance in multiple organs after septic and nonseptic challenges in the rat. J Appl Physiol (1985) 78:2052–2061

    CAS  Google Scholar 

  • Deshmukh DR, Ghole VS, Marescau B, De Deyn PP (1997) Effect of endotoxemia on plasma and tissue levels of nitric oxide metabolites and guanidino compounds. Arch Physiol Biochem 105:32–37

    Article  CAS  PubMed  Google Scholar 

  • Dhiman RK, Rana B, Agrawal S, Garg A, Chopra M, Thumburu KK, Khattri A et al (2014) Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: a randomized, controlled trial. Gastroenterology 147:1327–1337 e1323

    Article  CAS  PubMed  Google Scholar 

  • Domenicali M, Baldassarre M, Giannone FA, Naldi M, Mastroroberto M, Biselli M, Laggetta M et al (2014) Posttranscriptional changes of serum albumin: clinical and prognostic significance in hospitalized patients with cirrhosis. Hepatology 60:1851–1860

    Article  CAS  PubMed  Google Scholar 

  • Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF (1998) Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet 351:719–721

  • Egea J, Buendia I, Parada E, Navarro E, Leon R, Lopez MG (2015) Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection. Biochem Pharmacol 97:463–472

    Article  CAS  PubMed  Google Scholar 

  • Erickson MA, Banks WA (2011) Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis. Brain Behav Immun 25:1637–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germani G, Theocharidou E, Adam R, Karam V, Wendon J, O’Grady J, Burra P et al (2012) Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol 57:288–296

    Article  PubMed  Google Scholar 

  • Guillemin GJ, Wang L, Brew BJ (2005) Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex. J Neuroinflammation 2:16

    Article  PubMed  PubMed Central  Google Scholar 

  • Gustot T, Fernandez J, Garcia E, Morando F, Caraceni P, Alessandria C, Laleman W et al (2015) Clinical course of acute-on-chronic liver failure syndrome and effects on prognosis. Hepatology 62:243–252

    Article  PubMed  Google Scholar 

  • Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, Larsen FS et al (2007) Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology 46:1853–1862

  • Hellstrom IC, Danik M, Luheshi GN, Williams S (2005) Chronic LPS exposure produces changes in intrinsic membrane properties and a sustained IL-beta-dependent increase in GABAergic inhibition in hippocampal CA1 pyramidal neurons. Hippocampus 15:656–664

    Article  CAS  PubMed  Google Scholar 

  • Hernandes MS, D'Avila JC, Trevelin SC, et al (2014) The role of Nox2-derived ROS in the development of cognitive impairment after sepsis. J Neuroinflammation 11:36

  • Ichai P, Legeai C, Francoz C, Boudjema K, Boillot O, Ducerf C, Mathurin P et al (2015) Patients with acute liver failure listed for superurgent liver transplantation in France: reevaluation of the Clichy-Villejuif criteria. Liver Transpl 21:512–523

    Article  PubMed  Google Scholar 

  • Jalan R, Bernuau J (2007) Induction of cerebral hyperemia by ammonia plus endotoxin: does hyperammonemia unlock the blood-brain barrier? J Hepatol 47:168–171

    Article  CAS  PubMed  Google Scholar 

  • Jalan R, Dabos K, Redhead DN, Lee A, Hayes PC (1997) Elevation of intracranial pressure following transjugular intrahepatic portosystemic stent-shunt for variceal haemorrhage. J Hepatol 27:928–933

    Article  CAS  PubMed  Google Scholar 

  • Jayakumar AR, Rama Rao KV, Schousboe A, Norenberg MD (2004) Glutamine-induced free radical production in cultured astrocytes. Glia 46:296–301

    Article  PubMed  Google Scholar 

  • Jayakumar AR, Rama Rao KV, Norenberg MD (2015) Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol 5:S21–S28

    Article  PubMed  Google Scholar 

  • Jiang W, Desjardins P, Butterworth RF (2009) Minocycline attenuates oxidative/nitrosative stress and cerebral complications of acute liver failure in rats. Neurochem Int 55:601–605

    Article  CAS  PubMed  Google Scholar 

  • Joshi D, O’Grady J, Patel A, Shawcross D, Connor S, Deasy N, Willars C et al (2014) Cerebral oedema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy. Liver Int 34:362–366

    Article  PubMed  Google Scholar 

  • Kato M, Sugihara J, Nakamura T, Muto Y (1989) Electron microscopic study of the blood-brain barrier in rats with brain edema and encephalopathy due to acute hepatic failure. Gastroenterol Jpn 24:135–142

    CAS  PubMed  Google Scholar 

  • Kato M, Hughes RD, Keays RT, Williams R (1992) Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure. Hepatology 15:1060–1066

    Article  CAS  PubMed  Google Scholar 

  • Kenney MJ, Ganta CK (2014) Autonomic nervous system and immune system interactions. Compr Physiol 4:1177–1200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SE, Lee EO, Yang JH, Kang JH, Suh YH, Chong YH (2012) 15-deoxy-Delta(1)(2),(1)(4) -prostaglandin J(2) inhibits human immunodeficiency virus-1 tat-induced monocyte chemoattractant protein-1/CCL2 production by blocking the extracellular signal-regulated kinase-1/2 signaling pathway independently of peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 in rat hippocampal slices. J Neurosci Res 90:1732–1742

    Article  CAS  PubMed  Google Scholar 

  • Koyama Y, Kotani M, Sawamura T, Kuribayashi M, Konishi R, Michinaga S (2013) Different actions of endothelin-1 on chemokine production in rat cultured astrocytes: reduction of CX3CL1/fractalkine and an increase in CCL2/MCP-1 and CXCL1/CINC-1. J Neuroinflammation 10:51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, Bernal W, Auzinger G, Shawcross D, Eefsen M, Bjerring PN, Clemmesen JO, Hockerstedt K, Frederiksen HJ, Hansen BA, Antoniades CG, Wendon J et al (2016) High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 64(1):69–78. doi: 10.1016/j.jhep.2015.08.018

  • Larsen RH, Kjaer MS, Eefsen M, Larsen FS, Bjerring PN (2013) Ciclosporin does not attenuate intracranial hypertension in rats with acute hyperammonaemia. World J Hepatol 5:513–520

    Article  PubMed  PubMed Central  Google Scholar 

  • Licinio J, Wong ML (1997) Pathways and mechanisms for cytokine signaling of the central nervous system. J Clin Invest 100:2941–2947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma Y, Li J, Chiu I, Wang Y, Sloane JA, Lü J, Kosaras B, Sidman RL, Volpe JJ, Vartanian T et al (2006) Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis. J Cell Biol 175(2):209–15

  • Mark KS, Miller DW (1999) Increased permeability of primary cultured brain microvessel endothelial cell monolayers following TNF-a exposure. Life Sci 64:1941–1953

    Article  CAS  PubMed  Google Scholar 

  • Markwick LJ, Riva A, Ryan JM, Cooksley H, Palma E, Tranah TH, Godhev K, Vijay M, Vergis N, Thursz M, Evans A, Wright G, Tarff S, O’Grady J, Williams R, Shawcross DL, Chokshi S (2014) Blockade of PD1 and TIM3 restores innate and adaptive immunity in patients with acute alcoholic hepatitis. Gastroenterology 148

  • Marzocco S, Popolo A, Bianco G, Pinto A, Autore G (2010) Pro-apoptotic effect of methylguanidine on hydrogen peroxide-treated rat glioma cell line. Neurochem Int 57:518–524

    Article  CAS  PubMed  Google Scholar 

  • McCusker RH, Kelley KW (2013) Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol 216:84–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLennan IS, Weible MW 2nd, Hendry IA, Koishi K (2005) Transport of transforming growth factor-beta 2 across the blood-brain barrier. Neuropharmacology 48:274–282

    Article  CAS  PubMed  Google Scholar 

  • McMillin M, Frampton G, Thompson M, Galindo C, Standeford H, Whittington E, Alpini G et al (2014a) Neuronal CCL2 is upregulated during hepatic encephalopathy and contributes to microglia activation and neurological decline. J Neuroinflammation 11:121

    Article  PubMed  PubMed Central  Google Scholar 

  • McMillin MFG, Galindo C, Standeford H, Alpini G, DeMorrow S (2014b) Microglia activation during hepatic encephalopathy is driven by an imbalance of monocyte chemoattractant protein 1/fractalkine due to bile acid signaling. Hepatology 60:202A

    Google Scholar 

  • Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F et al (2013) Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 144:1426–1437 1437 e1421–1429

    Article  PubMed  Google Scholar 

  • Moss RF, Parmar NK, Tighe D, Davies DC (2004) Adrenergic agents modify cerebral edema and microvessel ultrastructure in porcine sepsis. Crit Care Med 32:1916–1921

    Article  CAS  PubMed  Google Scholar 

  • Nishioku T, Matsumoto J, Dohgu S, Sumi N, Miyao K, Takata F, et al (2010) Tumor necrosis factor-alpha mediates the blood-brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells. J Pharmacol Sci 112:251–254. doi:10.1254/jphs.09292sc

  • Nolan JP (1978) Bacteria and the liver. N Engl J Med 299:1069–1071

    Article  CAS  PubMed  Google Scholar 

  • Nolan JP (2010) The role of intestinal endotoxin in liver injury: a long and evolving history. Hepatology 52:1829–1835

    Article  CAS  PubMed  Google Scholar 

  • Norenberg MD, Martinez-Hernandez A (1979) Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res 161:303–310

    Article  CAS  PubMed  Google Scholar 

  • O’Grady JG, Alexander GJ, Hayllar KM, Williams R (1989) Early indicators of prognosis in fulminant hepatic failure. Gastroenterology 97:439–445

    Article  PubMed  Google Scholar 

  • Oettl K, Birner-Gruenberger R, Spindelboeck W, Stueger HP, Dorn L, Stadlbauer V, Putz-Bankuti C et al (2013) Oxidative albumin damage in chronic liver failure: relation to albumin binding capacity, liver dysfunction and survival. J Hepatol 59:978–983

    Article  CAS  PubMed  Google Scholar 

  • Papadopoulos MC, Lamb FJ, Moss RF, Davies DC, Tighe D, Bennett ED (1999) Faecal peritonitis causes oedema and neuronal injury in pig cerebral cortex. Clin Sci (Lond) 96:461–466

    Article  CAS  Google Scholar 

  • Rai R, Saraswat VA, Dhiman RK (2015) Gut microbiota: its role in hepatic encephalopathy. J Clin Exp Hepatol 5:S29–S36

    Article  PubMed  Google Scholar 

  • Rama Rao KV, Norenberg MD (2012) Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy. Neurochem Int 60:697–706

    Article  CAS  PubMed  Google Scholar 

  • Rama Rao KV, Reddy PV, Tong X, Norenberg MD (2010a) Brain edema in acute liver failure: inhibition by L-histidine. Am J Pathol 176:1400–1408

    Article  PubMed  PubMed Central  Google Scholar 

  • Rama Rao KV, Jayakumar AR, Tong X, Alvarez VM, Norenberg MD (2010b) Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes. J Neuroinflammation 7:66

    Article  PubMed  PubMed Central  Google Scholar 

  • Rama Rao KV, Jayakumar AR, Norenberg MD (2014) Brain edema in acute liver failure: mechanisms and concepts. Metab Brain Dis 29:927–936

    Article  CAS  PubMed  Google Scholar 

  • Rangroo Thrane V, Thrane AS, Chang J, Alleluia V, Nagelhus EA, Nedergaard M (2012) Real-time analysis of microglial activation and motility in hepatic and hyperammonemic encephalopathy. Neuroscience 220:247–255

    Article  CAS  PubMed  Google Scholar 

  • Riva A, Ryan JM, Williams R, Shawcross DL, Tarff S, Evans A, Wright G, Chokshi S (2015) PWE-088 frequency and function of anti-bacterial mait cells are significantly impaired in advanced alcoholic liver disease. J Hepatol 62:30

    Article  Google Scholar 

  • Rolando N, Wade J, Davalos M, Wendon J, Philpott-Howard J, Williams R (2000) The systemic inflammatory response syndrome in acute liver failure. Hepatology 32:734–739

    Article  CAS  PubMed  Google Scholar 

  • Rose C, Ytrebo LM, Davies NA, Sen S, Nedredal GI, Belanger M, Revhaug A et al (2007) Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure. Hepatology 46:1883–1892

    Article  CAS  PubMed  Google Scholar 

  • Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B, Barange K et al (2013) Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med 159:522–531

    Article  PubMed  Google Scholar 

  • Sen S, Rose C, Ytrebo LM, Davies NA, Nedredal GI, Drevland SS, Kjonno M et al (2006) Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study. Crit Care Med 34:158–164

    Article  PubMed  Google Scholar 

  • Sharshar T, Gray F, Lorin de la Grandmaison G, Hopkinson NS, Ross E, Dorandeu A, Orlikowski D et al (2003) Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock. Lancet 362:1799–1805

    Article  CAS  PubMed  Google Scholar 

  • Shawcross DL, Davies NA, Williams R, Jalan R (2004) Systemic inflammatory response exacerbates the neuropsychological effects of induced hyperammonemia in cirrhosis. J Hepatol 40:247–254

    Article  CAS  PubMed  Google Scholar 

  • Shawcross DL, Wright G, Olde Damink SW, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138

    Article  CAS  PubMed  Google Scholar 

  • Shawcross DL, Wright GA, Stadlbauer V, Hodges SJ, Davies NA, Wheeler-Jones C, Pitsillides AA et al (2008) Ammonia impairs neutrophil phagocytic function in liver disease. Hepatology 48:1202–1212

    Article  CAS  PubMed  Google Scholar 

  • Stubbs DJ, Yamamoto AK, Menon DK (2013) Imaging in sepsis-associated encephalopathy--insights and opportunities. Nat Rev Neurol 9:551–561

    Article  CAS  PubMed  Google Scholar 

  • Sun D, Lytle C, O’Donnell ME (1997) IL-6 secreted by astroglial cells regulates Na-K-Cl cotransport in brain microvessel endothelial cells. Am J Phys 272:C1829–C1835

    CAS  Google Scholar 

  • Szerb JC, Butterworth RF (1992) Effect of ammonium ions on synaptic transmission in the mammalian central nervous system. Prog Neurobiol 39:135–153

    Article  CAS  PubMed  Google Scholar 

  • Traber PG, Ganger DR, Blei AT (1986) Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Regional differences and effects on intracranial pressure. Gastroenterology 91:1347–1356

    Article  CAS  PubMed  Google Scholar 

  • Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM et al (2003) Infection and the progression of hepatic encephalopathy in acute liver failure. Gastroenterology 125:755–764

    Article  PubMed  Google Scholar 

  • Waidmann O, Brunner F, Herrmann E, Zeuzem S, Piiper A, Kronenberger B (2013) Macrophage activation is a prognostic parameter for variceal bleeding and overall survival in patients with liver cirrhosis. J Hepatol 58:956–961

    Article  PubMed  Google Scholar 

  • Walsh TS, McLellan S, Mackenzie SJ, Lee A (1999) Hyperlactatemia and pulmonary lactate production in patients with fulminant hepatic failure. Chest 116:471–476

    Article  CAS  PubMed  Google Scholar 

  • Weberpals M1, Hermes M, Hermann S, et al (2009) NOS2 gene deficiency protects from sepsis-induced long-term cognitive deficits. J Neurosci 29:14177–84

  • Williams RGA (1984) An assessment of orthotopic liver transplantation in acute liver failure. Hepatology 4:22S–24S

    Article  CAS  PubMed  Google Scholar 

  • Wolf Y, Yona S, Kim KW, Jung S (2013) Microglia, seen from the CX3CR1 angle. Front Cell Neurosci 7:26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright G, Jalan R (2007) Ammonia and inflammation in the pathogenesis of hepatic encephalopathy: Pandora’s box? Hepatology 46:291–294

    Article  CAS  PubMed  Google Scholar 

  • Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, Mani AR et al (2007a) Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology 45:1517–1526

    Article  CAS  PubMed  Google Scholar 

  • Wright G, Shawcross D, Olde Damink SW, Jalan R (2007b) Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension. Metab Brain Dis 22:375–388

    Article  CAS  PubMed  Google Scholar 

  • Wright G, Sharifi Y, Jalan R (2010) Blood-brain barrier in liver failure: are cracks appearing in the wall? Liver Int 30:1087–1090

    Article  CAS  PubMed  Google Scholar 

  • Wright G, Sharifi Y, Jover-Cobos M, Jalan R (2014a) The brain in acute on chronic liver failure. Metab Brain Dis 29:965–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright GA, Sharifi Y, Newman TA, Davies N, Vairappan B, Perry HV, Jalan R (2014b) Characterisation of temporal microglia and astrocyte immune responses in bile duct-ligated rat models of cirrhosis. Liver Int 34:1184–1191

    Article  CAS  PubMed  Google Scholar 

  • Yao HL, Gao FH, Li ZZ, Wu HX, Xu MD, Zhang Z, Dai QY (2012) Monocyte chemoattractant protein-1 mediates angiotensin II-induced vascular smooth muscle cell proliferation via SAPK/JNK and ERK1/2. Mol Cell Biochem 366:355–362

    Article  CAS  PubMed  Google Scholar 

  • Zemtsova I, Gorg B, Keitel V, Bidmon HJ, Schror K, Haussinger D (2011) Microglia activation in hepatic encephalopathy in rats and humans. Hepatology 54:204–215

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann HW, Trautwein C, Tacke F (2012) Functional role of monocytes and macrophages for the inflammatory response in acute liver injury. Front Physiol 3:56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zwingmann C, Chatauret N, Leibfritz D, Butterworth RF (2003) Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H-C] nuclear magnetic resonance study. Hepatology 37:420–428

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Gastroenterology Department, Basildon & Thurrock University Hospitals, Basildon, UK

    Gavin Wright

  2. Hepatology and Hepatobiliary Medicine, The Royal Free Hospital, Pond Street, London, NW3 2QG, UK

    Gavin Wright

  3. University College London, Gower Street, London, WC1E 6BT, UK

    Gavin Wright

  4. Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Canada

    Mark Swain

  5. INSERM CIC IT 805, CHU Paris IdF Ouest - Hôpital Raymond Poincaré, 104 boulevard Raymond Poincaré, 92380, Garches, France

    Djillali Annane

  6. Centre Hépato-Biliaire, Hôpital Paul Brousse, 12, avenue Paul vaillant Couturier, 94800, Villejuif, France

    Faouzi Saliba

  7. GHU Paris-Sud - Hôpital Paul Brousse, 12 avenue Paul Vaillant-Couturier, 94804, Villejuif Cedex, France

    Didier Samuel

  8. Liver Unit, Instiute of Digestive and Metabolic Diseases, Hopsital Clinic, University of Barcelona, Barcelona, Spain

    Vicente Arroyo

  9. Department of Internal Medicine, Central Texas Veterans Healthcare System, VA Bld 205, 1901 South 1st Street, Temple, TX, 76504, USA

    Sharon DeMorrow

  10. Departement of Hepatology, Rigshospitalet, Blegdamsvej 9, 2100 København Ø, Copenhagen, Denmark

    Anne Witt

Authors
  1. Gavin Wright
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  2. Mark Swain
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  3. Djillali Annane
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  4. Faouzi Saliba
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  5. Didier Samuel
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  6. Vicente Arroyo
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  7. Sharon DeMorrow
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  8. Anne Witt
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Corresponding author

Correspondence to Gavin Wright.

Additional information

The work presented by Sharon DeMorrow was completed, in part, with resources and the use of facilities at the Central Texas Veterans Health Care System, Temple Texas. The views are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs.

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Wright, G., Swain, M., Annane, D. et al. Neuroinflammation in liver disease: sessional talks from ISHEN. Metab Brain Dis 31, 1339–1354 (2016). https://doi.org/10.1007/s11011-016-9918-7

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  • DOI: https://doi.org/10.1007/s11011-016-9918-7

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