Hepatik Ensefalopati

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(3):716-721. doi: 10.1053/jhep.2002.31250. PMID: 11870389.

Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P. Hepatic encephalopathy in chronic liver disease:2014 practice guidelines by the american association for the study of liver diseases and the European association for the study of the liver. Hepatology 2014;60 (2): 715-735.https://doi.org/10.1002/hep.27210.

American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 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 Sep;61(3):642-59. doi: 10.1016/j.jhep.2014.05.042. Epub 2014 Jul 8. Erratum in: J Hepatol. 2015 Oct;63(4):1055. PMID: 25015420.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022 Sep;77(3):807-824. doi: 10.1016/j.jhep.2022.06.001. Epub 2022 Jun 17. Erratum in: J Hepatol. 2023 Nov;79(5):1340. doi: 10.1016/j.jhep.2023.09.004. PMID: 35724930.

Özbaş B, Keskin O, Hecker H, Karahan I, Özbaş C, Kalkan Ç, Kartal A, Önder FO, Öncü BK, Gençdal G, Akyildiz M, Günşar F, Idilman R, Weissenborn K, Özütemiz Ö, Yurdaydin C. Determination of Turkish norms of psychometric tests for diagnosing minimal hepatic encephalopathy and proposal of a high sensitive screening test battery. Hepatol Int. 2021 Dec;15(6):1442-1455. doi: 10.1007/s12072-021-10207-5. Epub 2021 Jun 3. PMID: 34085147.

Campagna F, Montagnese S, Ridola L, Senzolo M, Schiff S, De Rui M, et al. The animal naming test: an easy tool for the assessment of hepatic encephalopathy. Hepatology. 2017;66(1):198–208. https:// doi.org/10.1002/hep.29146.

Gil-Gómez A, Ampuero J, Rojas Á, Gallego-Durán R, Muñoz-Hernández R, Rico MC, Millán R, García-Lozano R, Francés R, Soriano G, Romero-Gómez M. Development and Validation of a Clinical-Genetic Risk Score to Predict Hepatic Encephalopathy in Patients With Liver Cirrhosis. Am J Gastroenterol. 2021 Jun 1;116(6):1238-1247. doi: 10.14309/ajg.0000000000001164. PMID: 33852451.

Weissenborn K. Hepatic encephalopathy: definition, clinical grading and diagnostic principles. Drugs. 2019; 79:5-9, http://dx.doi.org/10.1007/s40265-018-1018-z.

Vaquero J, Butterworth RF. Mechanisms of brain edema in acute liver failure and impact of novel therapeutic interventions. Neurol Res. 2007 Oct;29(7):683-90. doi: 10.1179/016164107X240099. PMID: 18173908.

Wijdicks EF. Hepatic Encephalopathy. N Engl J Med. 2016 Oct 27;375(17):1660-1670. doi: 10.1056/NEJMra1600561. PMID: 27783916.

Häussinger D, Dhiman RK, Felipo V, Görg B, Jalan R, Kircheis G, Merli M, Montagnese S, Romero-Gomez M, Schnitzler A, Taylor-Robinson SD, Vilstrup H. Hepatic encephalopathy. Nat Rev Dis Primers. 2022 Jun 23;8(1):43. doi: 10.1038/s41572-022-00366-6. PMID: 35739133.

Lu K. Cellular Pathogenesis of Hepatic Encephalopathy: An Update. Biomolecules. 2023 Feb 19;13(2):396. doi: 10.3390/biom13020396. PMID: 36830765; PMCID: PMC9953810.

Rose CF, Amodio P, Bajaj JS, Dhiman RK, Montagnese S, Taylor-Robinson SD, Vilstrup H, Jalan R. Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy. J Hepatol. 2020 Dec;73(6):1526-1547. doi: 10.1016/j.jhep.2020.07.013. Epub 2020 Oct 21. PMID: 33097308.

Ryu AJ, Rahimi RS, Leise MD. The Current Hepatic Encephalopathy Pipeline. J Clin Exp Hepatol. 2020 Jul-Aug;10(4):377-385. doi: 10.1016/j.jceh.2020.01.001. Epub 2020 Jan 14. PMID: 32655239; PMCID: PMC7335727.

Fiati Kenston SS, Song X, Li Z, Zhao J. Mechanistic insight, diagnosis, and treatment of ammonia-induced hepatic encephalopathy. J Gastroenterol Hepatol. 2019 Jan;34(1):31-39. doi: 10.1111/jgh.14408. Epub 2018 Aug 19. PMID: 30070387.

Higuera-de-la-Tijera F, Velarde-Ruiz Velasco JA, Raña-Garibay RH, Castro-Narro GE, Abdo-Francis JM, Moreno-Alcántar R, Pérez-Hernández JL, Torre A, Contreras-Omaña R, Cano-Contreras A, Castillo-Barradas M, Pérez-Escobar J, Aldana-Ledesma JM, Cerda-Reyes E, Fernández-Pérez NJ, Meza-Cardona J, Flores-García NC, Reyes-Bastidas M, Lira-Vera JE, García-Jiménez ES, Santana-Vargas D, Páez-Zayas VM, Chávez-Tapia NC, Márquez-Guillén E. Current vision on diagnosis and comprehensive care in hepatic encephalopathy. Rev Gastroenterol Mex (Engl Ed). 2023 Apr-Jun;88(2):155-174. doi: 10.1016/j.rgmxen.2023.04.006. Epub 2023 Apr 29. PMID: 37127462.

Nyarko-Danquah I., Pajarillo E., Digman A., Soliman K.F.A., Aschner M., Lee E. Manganese Accumulation in the Brain via Various Transporters and Its Neurotoxicity Mechanisms. Molecules. 2020; 25:5880. doi: 10.3390/molecules25245880

Merry T.L., Ristow M. Nuclear factor erythroid-derived 2-like 2 (NFE2L2, Nrf2) mediates exercise-induced mitochondrial biogenesis and the anti-oxidant response in mice. J. Physiol. Lond. 2016; 594:5195–5207. doi: 10.1113/JP271957.

Kim Y.H. High signal intensities on T1-weighted MRI as a biomarker of exposure to manganese. Ind. Health. 2004; 42:111–115. doi: 10.2486/indhealth.42.111

Görg B., Foster N., Reinehr R., Bidmon H.J., Hongen A., Häussinger D., Schliess F. Benzodiazepine-induced protein tyrosine nitration in rat astrocytes. Hepatology. 2003; 37:334–342. doi: 10.1053/jhep.2003.50061.

Sinke A.P., Jayakumar A.R., Panickar K.S., Moriyama M., Reddy P.V.B., Norenberg M.D. NF kappa B in the mechanism of ammonia-induced astrocyte swelling in culture. J. Neurochem. 2008; 106:2302–2311. doi: 10.1111/j.1471-4159.2008.05549.x.

Jin X, Chen D, Wu F, Zhang L, Huang Y, Lin Z, Wang X, Wang R, Xu L, Chen Y. Hydrogen Sulfide Protects Against Ammonia-Induced Neurotoxicity Through Activation of Nrf2/ARE Signaling in Astrocytic Model of Hepatic Encephalopathy. Front Cell Neurosci. 2020 Oct 22; 14:573422. doi: 10.3389/fncel.2020.573422. PMID: 33192318; PMCID: PMC7642620.

Amirshahrokhi K, Niapour A. Carvedilol attenuates brain damage in mice with hepatic encephalopathy. Int Immunopharmacol. 2022 Oct; 111:109119. doi: 10.1016/j.intimp.2022.109119. Epub 2022 Aug 4. PMID: 35933745.

Bjerring PN, Larsen FS. Changes in cerebral oxidative metabolism in patients with acute liver failure. Metab Brain Dis. 2013 Jun;28(2):179-82. doi: 10.1007/s11011-012-9346-2. Epub 2012 Oct 26. PMID: 23099996.

Sørensen M, Andersen JV, Bjerring PN, Vilstrup H. Hepatic encephalopathy as a result of ammonia-induced increase in GABAergic tone with secondary reduced brain energy metabolism. Metab Brain Dis. 2024 Nov 19;40(1):19. doi: 10.1007/s11011-024-01473-x. PMID: 39560844.

Ntuli Y, Shawcross DL. Infection, inflammation and hepatic encephalopathy from a clinical perspective. Metab Brain Dis. 2024 Dec;39(8):1689-1703. doi: 10.1007/s11011-024-01402-y. Epub 2024 Aug 30. PMID: 39212845; PMCID: PMC11535002.

Norenberg MD, Rama Rao KV, Jayakumar AR. Signaling factors in the mechanism of ammonia neurotoxicity. Metab Brain Dis. 2009 Mar;24(1):103-17. doi: 10.1007/s11011-008-9113-6. Epub 2008 Dec 23. PMID: 19104923.

Llansola M, Arenas YM, Sancho-Alonso M, Mincheva G, Palomares-Rodriguez A, Doverskog M, Izquierdo-Altarejos P, Felipo V. Neuroinflammation alters GABAergic neurotransmission in hyperammonemia and hepatic encephalopathy, leading to motor incoordination. Mechanisms and therapeutic implications. Front Pharmacol. 2024 Mar 15; 15:1358323. doi: 10.3389/fphar.2024.1358323. PMID: 38560359; PMCID: PMC10978603.

Groiss SJ, Butz M, Baumgarten TJ, Füllenbach ND, Häussinger D, Schnitzler A. GABA-ergic tone hypothesis in hepatic encephalopathy - Revisited. Clin Neurophysiol. 2019 Jun;130(6):911-916. doi: 10.1016/j.clinph.2019.03.011. Epub 2019 Mar 30. PMID: 30981176.

Chen Z, Ruan J, Li D, Wang M, Han Z, Qiu W, Wu G. The Role of Intestinal Bacteria and Gut-Brain Axis in Hepatic Encephalopathy. Front Cell Infect Microbiol. 2021 Jan 21; 10:595759. doi: 10.3389/fcimb.2020.595759. PMID: 33553004; PMCID: PMC7859631.

Katayama K, Saito M, Kawaguchi T, Endo R, Sawara K, Nishiguchi S, et al. Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. Nutrition 2014;30(11-12):1409–1414.

Kumar R, Anand U, Priyadarshi RN. Liver transplantation in acute liver failure: Dilemmas and challenges. World J Transplant. 2021 Jun 18;11(6):187-202. doi: 10.5500/ wjt.v11.i6.187. PMID: 34164294; PMCID: PMC8218344.

Germani G, Theocharidou E, Adam R, Karam V, Wendon J, O'Grady J, Burra P, Senzolo M, Mirza D, Castaing D, Klempnauer J, Pollard S, Paul A, Belghiti J, Tsochatzis E, Burroughs AK. Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database. J Hepatol. 2012 Aug;57(2):288-96. doi: 10.1016/j.jhep.2012.03.017. Epub 2012 Apr 18. PMID: 22521347.

Rajajee V, Fontana RJ, Courey AJ, Patil PG. Protocol based invasive intracranial pressure monitoring in acute liver failure: feasibility, safety and impact on management. Crit Care. 2017; 21:178. doi: 10.1186/s13054-017-1762-6.

Mendoza Vasquez LE, Payne S, Zamper R. Intracranial pressure monitoring in the perioperative period of patients with acute liver failure undergoing orthotopic liver transplantation. World J Transplant. 2023 Jun 18;13(4):122-128. doi: 10.5500/ wjt.v13.i4.122. PMID: 37388394; PMCID: PMC10303411.

Jinadasa SP, Ruan QZ, Bayoumi AB, Sharma SV, Boone MD, Malik R, Chen CC, Kasper EM. Hemorrhagic Complications of Invasive Intracranial Pressure Monitor Placement in Acute Liver Failure: Outcomes of a Single-Center Protocol and Comprehensive Literature Review. Neurocrit Care. 2021 Aug;35(1):87-102. doi: 10.1007/s12028-020-01143-7. Epub 2020 Nov 18. PMID: 33205356.

Gasco J, Rangel-Castilla L, Franklin B, Thomas PG, Patterson JT. State-of-the-art management and monitoring of brain edema and intracranial hypertension in fulminant hepatic failure. A proposed algorithm. Acta Neurochir Suppl. 2010; 106:311–314. doi: 10.1007/978-3-211-98811-4_58.

Khalessi A, Pyrsopoulos NT. Pharmacologic Management of Hepatic Encephalopathy. Clin Liver Dis. 2024 May;28(2):287-296. doi: 10.1016/j.cld.2024.01.006. Epub 2024 Feb 1. PMID: 38548440.

Kalal CR, Maiwall R, Choudhary A, Premkumar M, Kumar G, Vyas AK, Sarin SK. Mannitol Is Comparable to Hypertonic Saline for Raised Intracranial Pressure in Acute Liver Failure (MAHAL Study): A Randomized Controlled Trial. Dig Dis. 2022;40(5):607-615. doi: 10.1159/000520229. Epub 2021 Nov 11. PMID: 34763338.

Banares R, Nevens F, Larsen FS, Jalan R, Albillos A, Dollinger M, Saliba F, Sauerbruch T, Klammt S, Ockenga J, Pares A, Wendon J, Brünner T, Kramer L, Mathurin P, de la Mata M, Gasbarrini A, Müllhaupt B, Wilmer A, Laleman W, Eefsen M, Sen S, Williams R, Arroyo V, RELIEF study group. Extracorporeal albümin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial. Hepatology 2013; 57(3):1153-1162. https://doi.org./10.1002/hep.26185.

Kulkarni AV, Gustot T, Reddy KR. Liver transplantation for acute liver failure and acute-on-chronic liver failure. Am J Transplant. 2024 Nov;24(11):1950-1962. doi: 10.1016/j.ajt.2024.07.012. Epub 2024 Jul 31. PMID: 39094950.

Amaris NR, Marenco-Flores A, Barba R, Rubio-Cruz D, Medina-Morales E, Goyes D, Saberi B, Patwardhan V, Bonder A. Acute Liver Failure Etiology Determines Long-Term Outcomes in Patients Undergoing Liver Transplantation: An Analysis of the UNOS Database. Journal of Clinical Medicine. 2024; 13(22):6642. https://doi.org/10.3390/jcm13226642

Moughames E, Gurakar M, Khan A, Alsaqa M, Ozturk NB, Bonder A, Gurakar A, Saberi B. Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States. J Clin Med. 2024 Mar 17;13(6):1729. doi: 10.3390/jcm13061729. PMID: 38541954; PMCID: PMC10971084.

Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for liver cirrhosis: Varices, hepatic encephalopathy, and related complications. Clin Mol Hepatol. 2020 Apr;26(2):83-127. doi: 10.3350/cmh.2019.0010n. Epub 2020 Jan 10. PMID: 31918536; PMCID: PMC7160350.

Bai M, Qi XS, Yang M, Fan DM, Han GH. TIPS improves liver transplantation-free survival in cirrhotic patients with refractory ascites:an updated meta-analysis. World J Gastroenterol 2014; 20:2704-14. https://doi.org/10.3748/wjg.v20.i10.2704.

Santana-Vargas AD, Higuera-de-la-Tijera F, Perez-Hernandez JL. Auditory and visual P300 event-related potentials to detect minimal hepatic encephalopathy. Rev Esp Enferm Dig.2022; 114:83-8, http://dx.doi.org/10.17235/reed.2021.7709/2020.

Wang, Y., Yang, L., Shang, Y., Huang, Y., Ju, C., Zheng, H., Zhao, W. and Liu, J. (2025), Identifying Minimal Hepatic Encephalopathy: A New Perspective from Magnetic Resonance Imaging. J Magn Reson Imaging, 61: 11-24. https://doi.org/10.1002/jmri.29179

Tuo S, Yeo YH, Chang R, Wen Z, Ran Q, Yang L, Fan Q, Kang J, Si J, Liu Y, Shi H, Li Y, Yuan J, Liu N, Dai S, Guo X, Wang J, Ji F, Tantai X. Prevelance of and associated factors for sarcopenia in patients with liver cirrhosis: A systematic review and meta-analysis. Clin Nutr. 2024 Jan;43(1):84-94. doi:10.1016/j.clnu.2023.11.008.

Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: international society for hepatic encephalopathy and nitrogen metabolism consensus. Hepatology. 2013;58(1):325–36. https://doi.org/10.1002/hep.26370.

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on nutrition in chronic liver disease. J Hepatol. 2019 Jan;70(1):172-193. doi: 10.1016/j.jhep.2018.06.024. Epub 2018 Aug 23. PMID: 30144956; PMCID: PMC6657019.

Les I, Doval E, García-Martínez R, Planas M, Cárdenas G, Gómez P, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a random- ized study. Am J Gastroenterol 2011;106:1081–1088. https://doi.org/10. 1038/ajg.2011.9.

Gluud LL, Vilstrup H, Morgan MY. Nonabsorbable disaccharides versus placebo/no intervention and lactulose versus lactilol for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cohrane Database Syst Rev.2016;4:CD003044, https://dx.doi.org/10.1002/14651858.CD003044.pub3.

Haussinger D, Dhiman RK, Felipo V, et al. Hepatic encephalopathy. Nat Rev Dis Primers.2022;8:43,https://dx.doi.org/10.1038/ajg.2012.113.

Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2. PMID: 37467180; PMCID: PMC10360160.

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 Sep;108(9):1458-63. doi: 10.1038/ajg.2013.219. Epub 2013 Jul 23. PMID: 23877348.

Patel VC, Lee S, McPhail MJW, Da Silva K, Guilly S, Zamalloa A, Witherden E, Støy S, Manakkat Vijay GK, Pons N, Galleron N, Huang X, Gencer S, Coen M, Tranah TH, Wendon JA, Bruce KD, Le Chatelier E, Ehrlich SD, Edwards LA, Shoaie S, Shawcross DL. Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J Hepatol. 2022 Feb;76(2):332-342. doi: 10.1016/j.jhep.2021.09.010. Epub 2021 Sep 24. PMID: 34571050.

Bass NM, Mullen KD, Sanyal A, Poordad F, Neff G, Leevy CB, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010; 362(12):1071–81. https://doi.org/10.1056/NEJMoa0907893

He Q, Mao C, Chen Z, Zeng Y, Deng Y, Hu R. Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials. Arab J Gastroenterol. 2024 May;25(2):84-92. doi: 10.1016/j.ajg.2024.01.006. Epub 2024 Feb 24. PMID: 38403493.

Bajaj JS, Pompili E, Caraceni P. The burden of hepatic encephalopathy and the use of albümin as a potential treatment. Ann Hepatol.2024. Dec 3;30(1): 101751.doi:10.1016/j.aohep.2024.101751.

Laleman W, Simon‐Talero M, Maleux G, Perez M, Ameloot K, Sor- iano G, et al. Embolization of large spontaneous portosystemic shunts for refractory hepatic encephalopathy: a multicenter survey on safety and efficacy. Hepatology. 2013;57(6):2448–57. https://doi. org/10.1002/hep.26314.

Bureau C, Thabut D, Jezequel C, Archambeaud I, D’Alteroche L, Dharancy S, et al. The use of rifaximin in the prevention of overt hepatic encephalopathy after transjugular intrahepatic portosyste- mic shunt: a randomized controlled trial. Ann Intern Med. 2021; 174(5):633–40. https://doi.org/10.7326/M20‐0202.

Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: a randomized clinical trial. Hepatology. 2017; 66(6):1727–38. https://doi.org/10.1002/hep.29306.

Martin P, DiMartini A, Feng S, Brown R, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation: martin et al. Hepatology. 2014;59(3):1144–65. https://doi.org/10.1002/hep.26972.