Hepatic Encephalopathy: From the Pathogenesis to the New Treatments

Overview

Journal ISRN Hepatol

Specialty Gastroenterology

Date 2016 Jun 24

PMID 27335836

Citations 13

Authors

Juan Cordoba

Affiliations

Soon will be listed here.

Abstract

Hepatic encephalopathy is a frequent and serious complication of liver cirrhosis; the pathophysiology of this complication is not fully understood although great efforts have been made during the last years. There are few prospective studies on the epidemiology of this complication; however, it is known that it confers with high short-term mortality. Hepatic encephalopathy has been classified into different groups depending on the degree of hepatic dysfunction, the presence of portal-systemic shunts, and the number of episodes. Due to the large clinical spectra of overt EH and the complexity of cirrhotic patients, it is very difficult to perform quality clinical trials for assessing the efficacy of the treatments proposed. The physiopathology, clinical manifestation, and the treatment of HE is a challenge because of the multiple factors that converge and coexist in an episode of overt HE.

Citing Articles

PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease.

Kumar M, Sharma A, Datusalia A, Khatik G Med Chem. 2024; 20(8):781-798.

PMID: 38726789 DOI: 10.2174/0115734064295063240422100615.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions.

Shah Y, Ali H, Tiwari A, Guevara-Lazo D, Nombera-Aznaran N, Pinnam B World J Hepatol. 2024; 16(1):17-32.

PMID: 38313244 PMC: 10835490. DOI: 10.4254/wjh.v16.i1.17.

Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis.

Hoilat G, Ayas M, Hoilat J, Abu-Zaid A, Durer C, Durer S BMJ Open Gastroenterol. 2021; 8(1).

PMID: 34006606 PMC: 8137169. DOI: 10.1136/bmjgast-2021-000648.

Hyponatremia and Its Correlation With Hepatic Encephalopathy and Severity of Liver Disease.

Younas A, Riaz J, Chughtai T, Maqsood H, Saim M, Qazi S Cureus. 2021; 13(2):e13175.

PMID: 33717720 PMC: 7939097. DOI: 10.7759/cureus.13175.

Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner.

Drews L, Zimmermann M, Westhoff P, Brilhaus D, Poss R, Bergmann L Dis Model Mech. 2020; 13(10).

PMID: 32917661 PMC: 7657470. DOI: 10.1242/dmm.047134.

References

ZIEVE L, DOIZAKI W, Zieve J . Synergism between mercaptans and ammonia or fatty acids in the production of coma: a possible role for mercaptans in the pathogenesis of hepatic coma. J Lab Clin Med. 1974; 83(1):16-28. View

Rose C, Butterworth R, Zayed J, Normandin L, Todd K, Michalak A . Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterology. 1999; 117(3):640-4. DOI: 10.1016/s0016-5085(99)70457-9. View

Banares R, Nevens F, Larsen F, Jalan R, Albillos A, Dollinger M . Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology. 2012; 57(3):1153-62. DOI: 10.1002/hep.26185. View

Michalak A, Rose C, Butterworth J, Butterworth R . Neuroactive amino acids and glutamate (NMDA) receptors in frontal cortex of rats with experimental acute liver failure. Hepatology. 1996; 24(4):908-13. DOI: 10.1002/hep.510240425. View

Munoz S . Difficult management problems in fulminant hepatic failure. Semin Liver Dis. 1993; 13(4):395-413. DOI: 10.1055/s-2007-1007368. View

Cordoba J, Gottstein J, Blei A . Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis. J Hepatol. 1998; 29(4):589-94. DOI: 10.1016/s0168-8278(98)80154-2. View

Romero-Gomez M, Jover M, Del Campo J, Royo J, Hoyas E, Galan J . Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. Ann Intern Med. 2010; 153(5):281-8. DOI: 10.7326/0003-4819-153-5-201009070-00002. View

Mas A, Rodes J, Sunyer L, Rodrigo L, Planas R, Vargas V . Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2002; 38(1):51-8. DOI: 10.1016/s0168-8278(02)00350-1. View

Donovan J, Schafer D, Shaw Jr B, Sorrell M . Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet. 1998; 351(9104):719-21. DOI: 10.1016/S0140-6736(97)07373-X. View

10.

Butterworth R . Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. Neurochem Int. 2010; 57(4):383-8. DOI: 10.1016/j.neuint.2010.03.012. View

11.

Kircheis G, Wettstein M, Timmermann L, Schnitzler A, Haussinger D . Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology. 2002; 35(2):357-66. DOI: 10.1053/jhep.2002.30957. View

12.

Erceg S, Monfort P, Hernandez-Viadel M, Rodrigo R, Montoliu C, Felipo V . Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology. 2005; 41(2):299-306. DOI: 10.1002/hep.20565. View

13.

Simon-Talero M, Garcia-Martinez R, Torrens M, Augustin S, Gomez S, Pereira G . Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: a randomized double-blind study. J Hepatol. 2013; 59(6):1184-92. DOI: 10.1016/j.jhep.2013.07.020. View

14.

Blei A, Larsen F . Pathophysiology of cerebral edema in fulminant hepatic failure. J Hepatol. 1999; 31(4):771-6. DOI: 10.1016/s0168-8278(99)80361-4. View

15.

Nolte W, Wiltfang J, Schindler C, Unterberg K, Finkenstaedt M, Niedmann P . Bright basal ganglia in T1-weighted magnetic resonance images are frequent in patients with portal vein thrombosis without liver cirrhosis and not suggestive of hepatic encephalopathy. J Hepatol. 1998; 29(3):443-9. DOI: 10.1016/s0168-8278(98)80063-9. View

16.

Ortiz M, Cordoba J, Doval E, Jacas C, Pujadas F, Esteban R . Development of a clinical hepatic encephalopathy staging scale. Aliment Pharmacol Ther. 2007; 26(6):859-67. DOI: 10.1111/j.1365-2036.2007.03394.x. View

17.

Florent C, Flourie B, Leblond A, RAUTUREAU M, BERNIER J, Rambaud J . Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study). J Clin Invest. 1985; 75(2):608-13. PMC: 423537. DOI: 10.1172/JCI111738. View

18.

Moore J, Dunk A, Crawford J, Deans H, Besson J, de Lacey G . Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently healthy non-encephalopathic patients with cirrhosis. A controlled study. J Hepatol. 1989; 9(3):319-25. DOI: 10.1016/0168-8278(89)90140-2. View

19.

Barbaro G, Di Lorenzo G, Soldini M, Giancaspro G, Bellomo G, Belloni G . Flumazenil for hepatic encephalopathy grade III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo-controlled, cross-over study. Hepatology. 1998; 28(2):374-8. DOI: 10.1002/hep.510280212. View

20.

Schomerus H, Hamster W, Blunck H, Reinhard U, Mayer K, Dolle W . Latent portasystemic encephalopathy. I. Nature of cerebral functional defects and their effect on fitness to drive. Dig Dis Sci. 1981; 26(7):622-30. DOI: 10.1007/BF01367675. View