Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Hepatology International
Published in: Hepatology International 1/2018

Open Access 01-02-2018 | Special Issue - Portal Hypertension

Hepatic encephalopathy: a critical current review

Authors: Anna Hadjihambi, Natalia Arias, Mohammed Sheikh, Rajiv Jalan

Published in: Hepatology International | Special Issue 1/2018

Login to get access

Abstract

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of cirrhosis and/or porto-systemic shunting. The clinical symptoms are widely variable, extending from subtle impairment in mental state to coma. The utility of categorizing the severity of HE accurately and efficiently serves not only to provide practical functional information about the current clinical status of the patient but also gives valuable prognostic information. In the past 20–30 years, there has been rapid progress in understanding the pathophysiological basis of HE; however, the lack of direct correlation between pathogenic factors and the severity of HE make it difficult to select appropriate therapy for HE patients. In this review, we will discuss the classification system and its limitations, the neuropsychometric assessments and their challenges, as well as the present knowledge on the pathophysiological mechanisms. Despite the many prevalent hypotheses around the pathogenesis of the disease, most treatments focus on targeting and lowering the accumulation of ammonia as well as inflammation. However, treatment of minimal HE remains a huge unmet need and a big concerted effort is needed to better define this condition to allow the development of new therapies. We review the currently available therapies and future approaches to treat HE as well as the scientific and clinical data that support their effectiveness.
Literature
1.
American Association for the Study of Liver D, European Association for the Study of the L. Hepatic encephalopathy in chronic liver disease. Practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014;2014(61):642–59.
2.
3.
Parsons-Smith BG, Summerskill WH, Dawson AM, Sherlock S. The electroencephalograph in liver disease. Lancet. 1957;273:867–71.PubMedCrossRef
4.
Rikkers L, Jenko P, Rudman D, Freides D. Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology. 1978;75:462–9.PubMed
5.
Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy–definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35:716–21.PubMedCrossRef
6.
7.
Bajaj JS, Cordoba J, Mullen KD, Amodio P, Shawcross DL, Butterworth RF, Morgan MY, et al. Review article: the design of clinical trials in hepatic encephalopathy—an International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) consensus statement. Aliment Pharmacol Ther. 2011;33:739–47.PubMedPubMedCentralCrossRef
8.
Hassanein TI, Hilsabeck RC, Perry W. Introduction to the hepatic encephalopathy scoring algorithm (HESA). Dig Dis Sci. 2008;53:529–38.PubMedCrossRef
9.
Hassanein T, Blei AT, Perry W, Hilsabeck R, Stange J, Larsen FS, Brown RS Jr, et al. Performance of the hepatic encephalopathy scoring algorithm in a clinical trial of patients with cirrhosis and severe hepatic encephalopathy. Am J Gastroenterol. 2009;104:1392–400.PubMedCrossRef
10.
Ortiz M, Cordoba J, Doval E, Jacas C, Pujadas F, Esteban R, Guardia J. Development of a clinical hepatic encephalopathy staging scale. Aliment Pharmacol Ther. 2007;26:859–67.PubMedCrossRef
11.
Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in cirrhosis: implications for the assessment of hepatic encephalopathy. Hepatology. 2009;50:2014–21.PubMedCrossRef
12.
Montagnese S, Balistreri E, Schiff S, De Rui M, Angeli P, Zanus G, Cillo U, et al. Covert hepatic encephalopathy: agreement and predictive validity of different indices. World J Gastroenterol. 2014;20:15756–62.PubMedPubMedCentralCrossRef
13.
Thomsen KL, Macnaughtan J, Tritto G, Mookerjee RP, Jalan R. Clinical and pathophysiological characteristics of cirrhotic patients with grade 1 and minimal hepatic encephalopathy. PLoS ONE. 2016;11:e0146076.PubMedPubMedCentralCrossRef
14.
Montagnese S, De Rui M, Angeli P et al. Neuropsychiatric performance in patients with cirrhosis: who is "normal"? J Hepatol 2017;66:825–835.
15.
Prakash RK, Mullen KD. Is poor quality of life always present with minimal hepatic encephalopathy? Liver Int. 2011;31:908–10.PubMedCrossRef
16.
Agrawal S, Umapathy S, Dhiman RK. Minimal hepatic encephalopathy impairs quality of life. J Clin Exp Hepatol. 2015;5:S42–8.PubMedCrossRef
17.
Roman E, Cordoba J, Torrens M, Torras X, Villanueva C, Vargas V, Guarner C, et al. Minimal hepatic encephalopathy is associated with falls. Am J Gastroenterol. 2011;106:476–82.PubMedCrossRef
18.
Wein C, Koch H, Popp B, Oehler G, Schauder P. Minimal hepatic encephalopathy impairs fitness to drive. Hepatology. 2004;39:739–45.PubMedCrossRef
19.
Schomerus H, Hamster W. Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain Dis. 2001;16:37–41.PubMedCrossRef
20.
Romero-Gomez M, Boza F, Garcia-Valdecasas MS, Garcia E, Aguilar-Reina J. Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol. 2001;96:2718–23.PubMedCrossRef
21.
Ampuero J, Simon M, Montoliu C, Jover R, Serra MA, Cordoba J, Romero-Gomez M. Minimal hepatic encephalopathy and critical flicker frequency are associated with survival of patients with cirrhosis. Gastroenterology. 2015;149:1483–9.PubMedCrossRef
22.
Dhiman RK, Kurmi R, Thumburu KK, Venkataramarao SH, Agarwal R, Duseja A, Chawla Y. Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci. 2010;55:2381–90.PubMedCrossRef
23.
24.
Bajaj JS. Diagnosing minimal hepatic encephalopathy: from the ivory tower to the real world. Gastroenterology. 2015;149:1330–3.PubMedCrossRef
25.
26.
Bocarsly ME, Fasolino M, Kane GA, LaMarca EA, Kirschen GW, Karatsoreos IN, McEwen BS, et al. Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. Proc Natl Acad Sci USA. 2015;112:15731–6.PubMedPubMedCentral
27.
McAndrews MP, Farcnik K, Carlen P, Damyanovich A, Mrkonjic M, Jones S, Heathcote EJ. Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology. 2005;41:801–8.PubMedCrossRef
28.
Moreau R, Jalan R, Gines P, Pavesi M, Angeli P, Cordoba J, Durand F, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426–37.PubMedCrossRef
29.
Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P, et al. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014;60:275–81.PubMedCrossRef
30.
Merli M, Lucidi C, Pentassuglio I, Giannelli V, Giusto M, Di Gregorio V, Pasquale C, et al. Increased risk of cognitive impairment in cirrhotic patients with bacterial infections. J Hepatol. 2013;59:243–50.PubMedCrossRef
31.
Romero-Gomez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol. 2015;62:437–47.PubMedCrossRef
32.
Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol. 2004;41:613–20.PubMedCrossRef
33.
Bosoi CR, Rose CF. Oxidative stress: a systemic factor implicated in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2013;28:175–8.PubMedCrossRef
34.
Rama Rao KV, Norenberg MD. Brain energy metabolism and mitochondrial dysfunction in acute and chronic hepatic encephalopathy. Neurochem Int. 2012;60:697–706.PubMedCrossRef
35.
Zwingmann C. The anaplerotic flux and ammonia detoxification in hepatic encephalopathy. Metab Brain Dis. 2007;22:235–49.PubMedCrossRef
36.
Zwingmann C, Butterworth R. An update on the role of brain glutamine synthesis and its relation to cell-specific energy metabolism in the hyperammonemic brain: further studies using NMR spectroscopy. Neurochem Int. 2005;47:19–30.PubMedCrossRef
37.
38.
Joshi D, O’Grady J, Patel A, Shawcross D, Connor S, Deasy N, Willars C, et al. Cerebral edema is rare in acute-on-chronic liver failure patients presenting with high-grade hepatic encephalopathy. Liver Int. 2014;34:362–6.PubMedCrossRef
39.
Bosoi CR, Zwingmann C, Marin H, Parent-Robitaille C, Huynh J, Tremblay M, Rose CF. Increased brain lactate is central to the development of brain edema in rats with chronic liver disease. J Hepatol. 2014;60:554–60.PubMedCrossRef
40.
Hadjihambi A, De Chiara F, Hosford PS, Habtetion A, Karagiannis A, Davies N, Gourine AV, et al. Ammonia mediates cortical hemichannel dysfunction in rodent models of chronic liver disease. Hepatology. 2017;65:1306–18.PubMedPubMedCentralCrossRef
41.
Rackayova V, Braissant O, McLin VA, Berset C, Lanz B, Cudalbu C. 1H and 31P magnetic resonance spectroscopy in a rat model of chronic hepatic encephalopathy: in vivo longitudinal measurements of brain energy metabolism. Metab Brain Dis. 2016;31:1303–14.PubMedCrossRef
42.
Weiss N, Barbier Saint Hilaire P, Colsch B, Isnard F, Attala S, Schaefer A, Amador MD, et al. Cerebrospinal fluid metabolomics highlights dysregulation of energy metabolism in overt hepatic encephalopathy. J Hepatol. 2016;65:1120–30.PubMedCrossRef
43.
Shawcross DL, Shabbir SS, Taylor NJ, Hughes RD. Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology. 2010;51:1062–9.PubMedCrossRef
44.
Benyoub K, Muller M, Bonnet A, Simon R, Gazon M, Duperret S, Aubrun F, et al. Amounts of bile acids and bilirubin removed during single-pass albumin dialysis in patients with liver failure. Ther Apher Dial. 2011;15:504–6.PubMedCrossRef
45.
Tanaka N, Matsubara T, Krausz KW, Patterson AD, Gonzalez FJ. Disruption of phospholipid and bile acid homeostasis in mice with nonalcoholic steatohepatitis. Hepatology. 2012;56:118–29.PubMedCrossRef
46.
Cordoba J, Alonso J, Rovira A, Jacas C, Sanpedro F, Castells L, Vargas V, et al. The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation. J Hepatol. 2001;35:598–604.PubMedCrossRef
47.
Josephs KA, Ahlskog JE, Klos KJ, Kumar N, Fealey RD, Trenerry MR, Cowl CT. Neurologic manifestations in welders with pallidal MRI T1 hyperintensity. Neurology. 2005;64:2033–9.PubMedCrossRef
48.
Bezzi P, Domercq M, Vesce S, Volterra A. Neuron-astrocyte cross-talk during synaptic transmission: physiological and neuropathological implications. Prog Brain Res. 2001;132:255–65.PubMedCrossRef
49.
50.
McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation. 2008;5:45.PubMedPubMedCentralCrossRef
51.
Butterworth RF. The liver-brain axis in liver failure: neuroinflammation and encephalopathy. Nat Rev Gastroenterol Hepatol. 2013;10:522–8.PubMedCrossRef
52.
Shawcross DL, Wright G, Olde Damink SW, Jalan R. Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis. 2007;22:125–38.PubMedCrossRef
53.
Coltart I, Tranah TH, Shawcross DL. Inflammation and hepatic encephalopathy. Arch Biochem Biophys. 2013;536:189–96.PubMedCrossRef
54.
Prakash R, Mullen KD. Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol. 2010;7:515–25.PubMedCrossRef
55.
Hung TH, Lay CJ, Chang CM, Tsai JJ, Tsai CC, Tsai CC. The effect of infections on the mortality of cirrhotic patients with hepatic encephalopathy. Epidemiol Infect. 2013;141:2671–8.PubMedCrossRef
56.
Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G, Aagaard NK, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: What is the evidence? Metab Brain Dis. 2013;28:221–5.PubMedCrossRef
57.
Gluud LL, Vilstrup H, Morgan MY. Nonabsorbable disaccharides for hepatic encephalopathy: a systematic review and meta-analysis. Hepatology. 2016;64:908–22.PubMedCrossRef
58.
59.
Bajaj JS, Sanyal AJ, Bell D, Gilles H, Heuman DM. Predictors of the recurrence of hepatic encephalopathy in lactulose-treated patients. Aliment Pharmacol Ther. 2010;31:1012–7.PubMedCrossRef
60.
Sharma P, Sharma BC, Agrawal A, Sarin SK. Primary prophylaxis of overt hepatic encephalopathy in patients with cirrhosis: an open labeled randomized controlled trial of lactulose versus no lactulose. J Gastroenterol Hepatol. 2012;27:1329–35.PubMedCrossRef
61.
Rahimi RS, Singal AG, Cuthbert JA, Rockey DC. Lactulose vs polyethylene glycol 3350–electrolyte solution for treatment of overt hepatic encephalopathy: the HELP randomized clinical trial. JAMA Intern Med. 2014;174:1727–33.PubMedPubMedCentralCrossRef
62.
Conn HO, Leevy CM, Vlahcevic ZR, Rodgers JB, Maddrey WC, Seeff L, Levy LL. Comparison of lactulose and neomycin in the treatment of chronic portal-systemic encephalopathy. A double blind controlled trial. Gastroenterology. 1977;72:573–83.PubMed
63.
Strauss E, Tramote R, Silva EP, Caly WR, Honain NZ, Maffei RA, de Sa MF. Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepatogastroenterology. 1992;39:542–5.PubMed
64.
65.
Wu D, Wu SM, Lu J, Zhou YQ, Xu L, Guo CY. Rifaximin versus nonabsorbable disaccharides for the treatment of hepatic encephalopathy: a meta-analysis. Gastroenterol Res Pract. 2013;2013:236963.PubMedPubMedCentral
66.
Sharma BC, Sharma P, Lunia MK, Srivastava S, Goyal R, Sarin SK. A randomized, double-blind, controlled trial comparing rifaximin plus lactulose with lactulose alone in treatment of overt hepatic encephalopathy. Am J Gastroenterol. 2013;108:1458–63.PubMedCrossRef
67.
Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, Sigal S, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362:1071–81.PubMedCrossRef
68.
69.
Zullo A, Ridola L, Hassan C. Rifaximin therapy and Clostridium difficile infection: a note of caution. J Clin Gastroenterol. 2013;47:737.PubMedCrossRef
70.
Acharya SK, Bhatia V, Sreenivas V, Khanal S, Panda SK. Efficacy of l-ornithine l-aspartate in acute liver failure: a double-blind, randomized, placebo-controlled study. Gastroenterology. 2009;136:2159–68.PubMedCrossRef
71.
Bai M, Yang Z, Qi X, Fan D, Han G. l-ornithine-l-aspartate for hepatic encephalopathy in patients with cirrhosis: a meta-analysis of randomized controlled trials. J Gastroenterol Hepatol. 2013;28:783–92.PubMedCrossRef
72.
Hadjihambi A, Khetan V, Jalan R. Pharmacotherapy for hyperammonemia. Expert Opin Pharmacother. 2014;15:1685–95.PubMedCrossRef
73.
Ventura-Cots M, Arranz JA, Simon-Talero M, Torrens M, Blanco A, Riudor E, Fuentes I, et al. Safety of ornithine phenylacetate in cirrhotic decompensated patients: an open-label, dose-escalating, single-cohort study. J Clin Gastroenterol. 2013;47:881–7.PubMedCrossRef
74.
Jover-Cobos M, Noiret L, Lee K, Sharma V, Habtesion A, Romero-Gomez M, Davies N, et al. Ornithine phenylacetate targets alterations in the expression and activity of glutamine synthase and glutaminase to reduce ammonia levels in bile duct ligated rats. J Hepatol. 2014;60:545–53.PubMedCrossRef
75.
Ytrebo LM, Kristiansen RG, Maehre H, Fuskevag OM, Kalstad T, Revhaug A, Cobos MJ, et al. l-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. Hepatology. 2009;50:165–74.PubMedCrossRef
76.
Ventura-Cots M, Concepcion M, Arranz JA, Simon-Talero M, Torrens M, Blanco-Grau A, Fuentes I, et al. Impact of ornithine phenylacetate (OCR-002) in lowering plasma ammonia after upper gastrointestinal bleeding in cirrhotic patients. Therap Adv Gastroenterol. 2016;9:823–35.PubMedPubMedCentralCrossRef
77.
Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Alexeeva O, Zupanets IA, et al. Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy. Hepatology. 2014;59:1073–83.PubMedPubMedCentralCrossRef
78.
Hassanein TI, Tofteng F, Brown RS Jr, McGuire B, Lynch P, Mehta R, Larsen FS, et al. Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis. Hepatology. 2007;46:1853–62.PubMedCrossRef
79.
Laleman W, Wilmer A, Evenepoel P, Elst IV, Zeegers M, Zaman Z, Verslype C, et al. Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care. 2006;10:R108.PubMedPubMedCentralCrossRef
80.
Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, Saliba F, et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2013;57:1153–62.PubMedCrossRef
81.
An J, Kim KW, Han S, Lee J, Lim YS. Improvement in survival associated with embolisation of spontaneous portosystemic shunt in patients with recurrent hepatic encephalopathy. Aliment Pharmacol Ther. 2014;39:1418–26.PubMedCrossRef
82.
Laleman W, Simon-Talero M, Maleux G, Perez M, Ameloot K, Soriano G, Villalba J, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013;57:2448–57.PubMedCrossRef
83.
84.
Bosoi CR, Parent-Robitaille C, Anderson K, Tremblay M, Rose CF. AST-120 (spherical carbon adsorbent) lowers ammonia levels and attenuates brain edema in bile duct-ligated rats. Hepatology. 2011;53:1995–2002.PubMedCrossRef
85.
Bajaj JS, Sheikh MY, Chojkier M, Balart L, Sherker AH, Vemuru R, Sussman NL, Vierling J, Morelli G, Anderson KE, Harris MS, Mullen KD. 190 AST-120 (spherical carbon adsorbent) in covert hepatic encephalopathy: results of the ASTUTE trial. J Hepatol. 2013;58:S84.CrossRef
86.
McGee RG, Bakens A, Wiley K, Riordan SM, Webster AC. Probiotics for patients with hepatic encephalopathy. Cochrane Database Syst Rev 2011:CD008716
87.
Zhao LN, Yu T, Lan SY, Hou JT, Zhang ZZ, Wang SS, Liu FB. Probiotics can improve the clinical outcomes of hepatic encephalopathy: an update meta-analysis. Clin Res Hepatol Gastroenterol. 2015;39:674–82.PubMedCrossRef
88.
Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label, randomized controlled trial of lactulose, probiotics, and no therapy. Am J Gastroenterol. 2012;107:1043–50.PubMedCrossRef
89.
Stein TP. Nutrition and protein turnover: a review. J Parenter Enteral Nutr. 1982;6:444–54.CrossRef
90.
Cunningham-Rundles S. Effect of nutritional status on immunological function. Am J Clin Nutr. 1982;35:1202–10.PubMedCrossRef
91.
Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? PINC (Policentrica Italiana Nutrizione Cirrosi). Hepatology. 1996;23:1041–6.PubMedCrossRef
92.
Cordoba J, Lopez-Hellin J, Planas M, Sabin P, Sanpedro F, Castro F, Esteban R, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41:38–43.PubMedCrossRef
93.
Dam G, Keiding S, Munk OL, Ott P, Buhl M, Vilstrup H, Bak LK, et al. Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects. Am J Physiol Gastrointest Liver Physiol. 2011;301:G269–77.PubMedCrossRef
94.
Gluud LL, Dam G, Borre M, Les I, Cordoba J, Marchesini G, Aagaard NK, et al. Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. J Nutr. 2013;143:1263–8.PubMedCrossRef
95.
Goulenok C, Bernard B, Cadranel JF, Thabut D, Di Martino V, Opolon P, Poynard T. Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis. Aliment Pharmacol Ther. 2002;16:361–72.PubMedCrossRef
96.
Als-Nielsen B, Gluud LL, Gluud C. Benzodiazepine receptor antagonists for hepatic encephalopathy. Cochrane Database of Systematic Reviews 2004
97.
Therrien G, Rose C, Butterworth J, Butterworth RF. Protective effect of l-carnitine in ammonia-precipitated encephalopathy in the portacaval shunted rat. Hepatology. 1997;25:551–6.PubMedCrossRef
98.
Jiang Q, Jiang G, Shi KQ, Cai H, Wang YX, Zheng MH. Oral acetyl-l-carnitine treatment in hepatic encephalopathy: view of evidence-based medicine. Ann Hepatol. 2013;12:803–9.PubMed
99.
Larsen FS, Hansen BA, Ejlersen E, Secher NH, Clemmesen JO, Tygstrup N, Knudsen GM. Cerebral blood flow, oxygen metabolism and transcranial Doppler sonography during high-volume plasmapheresis in fulminant hepatic failure. Eur J Gastroenterol Hepatol. 1996;8:261–5.PubMedCrossRef
100.
Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC, Triantafyllou E, et al. High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial. J Hepatol. 2016;64:69–78.PubMedCrossRef
101.
Ahboucha S, Layrargues GP, Mamer O, Butterworth RF. Increased brain concentrations of a neuroinhibitory steroid in human hepatic encephalopathy. Ann Neurol. 2005;58:169–70.PubMedCrossRef
102.
Bosman DK, van den Buijs CA, de Haan JG, Maas MA, Chamuleau RA. The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat. Gastroenterology. 1991;101:772–81.PubMedCrossRef
103.
Ahboucha S, Coyne L, Hirakawa R, Butterworth RF, Halliwell RF. An interaction between benzodiazepines and neuroactive steroids at GABA A receptors in cultured hippocampal neurons. Neurochem Int. 2006;48:703–7.PubMedCrossRef
104.
Kao D, Roach B, Park H, Hotte N, Madsen K, Bain V, Tandon P. Fecal microbiota transplantation in the management of hepatic encephalopathy. Hepatology. 2016;63:339–40.PubMedCrossRef
105.
Cauli O, Rodrigo R, Piedrafita B, Boix J, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology. 2007;46:514–9.PubMedCrossRef
106.
Jiang W, Desjardins P, Butterworth RF. Minocycline attenuates oxidative/nitrosative stress and cerebral complications of acute liver failure in rats. Neurochem Int. 2009;55:601–5.PubMedCrossRef
107.
Hernandez-Rabaza V, Agusti A, Cabrera-Pastor A, Fustero S, Delgado O, Taoro-Gonzalez L, Montoliu C, et al. Sildenafil reduces neuroinflammation and restores spatial learning in rats with hepatic encephalopathy: underlying mechanisms. J Neuroinflammation. 2015;12:195.PubMedPubMedCentralCrossRef
108.
Hadjihambi A, Rose CF, Jalan R. Novel insights into ammonia-mediated neurotoxicity pointing to potential new therapeutic strategies. Hepatology. 2014;60:1101–3.PubMedCrossRef
Metadata
Title
Hepatic encephalopathy: a critical current review
Authors
Anna Hadjihambi
Natalia Arias
Mohammed Sheikh
Rajiv Jalan
Publication date
01-02-2018
Publisher
Springer India
Published in
Hepatology International / Issue Special Issue 1/2018
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-017-9812-3

Other articles of this Special Issue 1/2018

Hepatology International 1/2018 Go to the issue

Special Issue - Portal Hypertension

Acute variceal bleeding: risk stratification and management (including TIPS)

Special Issue - Portal Hypertension

Biology of portal hypertension

Special Issue - Portal Hypertension

Balloon-occluded retrograde transvenous obliteration of varices: focusing on the portal hemodynamics and the recent techniques

Review Article

Invasive and non-invasive assessment of portal hypertension

Special Issue - Portal Hypertension

Pharmacologic prevention of variceal bleeding and rebleeding

Special Issue - Portal Hypertension

Budd–Chiari syndrome/hepatic venous outflow tract obstruction
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits