Skip to main content
SpringerLink
Log in

Hepatische Enzephalopathie

Hepatic encephalopathy

  • Schwerpunkt
  • Published:
Der Gastroenterologe Aims and scope

Zusammenfassung

Die hepatische Enzephalopathie (HE) ist ein neuropsychiatrisches Krankheitsbild, das im Gefolge akuter und chronischer Leberkrankheiten auftreten kann. Pathophysiologisch ist die Erkrankung die klinische Manifestation eines geringgradigen, chronischen Gliaödems, welches zu Änderungen der Astrozytenfunktion mit nachfolgender Störung der glioneuronalen Kommunikation führt. Die Veränderungen weisen auf eine primäre Störung oszillatorischer Netzwerke hin, welche durch neurotoxin- und schwellungssensitive thalamische Strukturen getriggert werden und in einem abnormalen niedrigfrequenten und rigiden thalamokortikalen und kortikomuskulären Coupling resultieren. Während die Diagnose der höhergradigen Formen der Erkrankung anhand des klinischen Bildes erfolgt, sind zur Aufdeckung der geringgradigen Formen der HE psychometrische und neurophysiologische Tests erforderlich. Dabei hat sich die Bestimmung der kritischen Flimmerfrequenz (CFF) zur Quantifizierung und Verlaufsbeurteilung der neuropsychiatrischen Defizite der HE als einfaches und objektives semiquantitatives Testverfahren erwiesen. Die Erkennung und konsequente Behandlung der auslösenden Faktoren ist die wichtigste therapeutische Maßnahme, die durch diätetische und medikamentöse Maßnahmen ergänzt wird.

Abstract

Hepatic encephalopathy (HE) is a neuropsychiatric disorder which can appear as a complication of acute or chronic liver disorders. Pathophysiologically the disorder is a clinical manifestation of a low-grade chronic cerebral edema, which leads to changes in astrocytic function with disturbances of glioneuronal communication. The findings point to a disturbance of cerebral oscillatory networks in HE that is triggered by possible neurotoxic- and hydration-sensitive, thalamic structures and results in an abnormally low-frequency and rigid thalamocortical and corticomuscular coupling. While the diagnosis of high-grade HE will be done exclusively by the clinical picture, psychometric and neurophysiological tests are necessary to diagnose the low-grade forms. Yet, the analysis of the critical flicker frequency (CFF) has been shown to be an easy and simple semi-quantitative test procedure for the quantification and follow-up of neuropsychiatric deficits in HE. The recognition and consequent treatment of the precipitating factors are the most important therapeutic measures. These are complemented by dietetic and pharmaceutical treatment..

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Als-Nielsen B, Gluud LL, Gluud C (2004) Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials BMJ 328: 1046–1050

  2. Blei AT, Larsen FS (1999) Pathophysiology of cerebral edema in fulminant hepatic failure. J Hepatol 31: 771–776

    Article  PubMed  CAS  Google Scholar 

  3. Bustamante J, Rimola A et al. (1999) Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol 30: 890–895

    Article  PubMed  CAS  Google Scholar 

  4. Butterworth RF (2000) The astrocytic („peripheral-type“) benzodiazepine receptor: role in the pathogenesis of portal-systemic encephalopathy. Neurochem Int 36: 411–416

    Article  PubMed  CAS  Google Scholar 

  5. Conn HO (1993) Quantifying the severity of hepatic encephalopathy. In: Conn HO, Bircher J (eds) Hepatic encephalopathy: syndromes and therapies. Medi-Ed, East Lansing, Michigan, pp 13–26

  6. Cordoba J, Alonso J et al. (2001) 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 35: 598–604

    Article  PubMed  CAS  Google Scholar 

  7. Cordoba J, Lopez-Hellin J, Planas M et al. (2004) Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol 41: 38-43

    Article  PubMed  CAS  Google Scholar 

  8. Cordoba J, Raguer N, Flavia M et al. (2003) T2 hyperintensity along the cortico-spinal tract in cirrhosis relates to functional abnormalities. Hepatology 38: 1026–1033

    Article  PubMed  Google Scholar 

  9. Ferenci P, Lockwood A et al. (2002) Hepatic encephalopathy – definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna 1998. Hepatology 35: 716–721

    Article  PubMed  Google Scholar 

  10. Giguere JF, Hamel E, Butterworth RF (1992) Increased densities of binding sites for the ‚peripheral-type‘ benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis. Brain Res 585: 295–298

    Article  PubMed  CAS  Google Scholar 

  11. Goulenok C, Bernard B et al. (2002) Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis. Aliment Pharmacol Ther 16: 361–372

    Article  PubMed  CAS  Google Scholar 

  12. Groeneweg M, Quero JC et al. (1998) Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 28: 45–49

    Article  PubMed  CAS  Google Scholar 

  13. Häussinger D, Kircheis G, Fischer R et al. (2000) Hepatic encephalopathy in chronic liver disease: a clinical manifestation of astrocyte swelling and low-grade cerebral edema. J. Hepatol 32: 1035–1038

    Article  Google Scholar 

  14. Häussinger D, Laubenberger J, vom Dahl S et al. (1994) Proton magnetic resonance spectroscopy on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenetrology 107: 1475–1480

    Google Scholar 

  15. Häussinger D, Schliess F, Kircheis G (2002) Pathogenesis of hepatic encephalopathy. J Gastroenterol Hepatol 17.3: 256–259

    Google Scholar 

  16. Häussinger D (1984) Hepatocyte heterogeneity in ammonia metabolism: impairment of glutamine synthetase in CCl4-induced liver cell necrosis with no effect on urea syn¬thesis. Chem Biol Interact 48: 191–193

    Article  PubMed  Google Scholar 

  17. Häussinger D, Steeb R, Kaiser S et al. (1990) Nitrogen metabo¬lism in normal and cirrhotic liver. Adv-Exp-Med-Biol 272: 47–64

    Google Scholar 

  18. Kircheis G, Görtelmeyer R, Grafe S et al. (2006) Critical assessment of the PHES test battery in patients with low-grade hepatic encephalopathy. In Häussinger D, Kircheis G, Schliess F (eds) Hepatic encephalopathy and nitrogen metabolism. Springer, Dordrecht, The Netherlands, pp 495–504

  19. Kircheis G, Wettstein M et al. (2002) Critical flicker frequency for quantification of low-grade hepatic encephalopathy. Hepatology 35: 357–366

    Article  PubMed  Google Scholar 

  20. Kircheis G, Häussinger D (2002) Management of hepatic encephalopathy. J Gastroenterol Hepatol 17.3: S260–S267

    Google Scholar 

  21. Kircheis G, Wettstein M., vom Dahl S et al. (2002) Clinical efficacy of L-Ornithine–L-Aspartate in the management of hepatic encephalopathy. Metab Brain Dis 17: 453–463

    Article  PubMed  CAS  Google Scholar 

  22. Larsen FS, Gottstein J, Blei AT (2001) Cerebral hyperemia and nitric oxide synthase in rats with ammonia-induced brain edema. J.Hepatol 34: 548–554

    CAS  Google Scholar 

  23. Liu Q, Duan ZP, Ha DK et al. (2004) Symbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology 39: 1441–1449

    Article  PubMed  Google Scholar 

  24. Marchesini G et al. (1990) Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. J Hepatol 11: 1–10

    Article  Google Scholar 

  25. Marchesini G, Fabbri A, Bianchi G et al. (1996) Zinc supplementation and amino acid–nitrogen metabolism in patients with advanced cirrhosis. Hepatology 23: 1084–1092

    Article  PubMed  CAS  Google Scholar 

  26. Montoliu C, Piedrafita B, Serra MA et al. (2007) Activation of soluble guanylate cyclase by nitric oxide in lymphocytes correlates with minimal hepatic encephalopathy in cirrhotic patients. J Mol Med 85: 233–241

    Article  PubMed  CAS  Google Scholar 

  27. Naylor CD, O’Rourke K, Detsky AS, Baker JP (1989) Parenteral nutrition with branched-chain amino acids in hepatic encephalopathy. A meta-analysis. Gastroenterology 97: 1033–1042

    PubMed  CAS  Google Scholar 

  28. Ong JP, Aggarwal A et al. (2003) Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 114: 188–193

    Article  PubMed  CAS  Google Scholar 

  29. Riordan S, Williams R (1997) Treatment of hepatic encephalopathy. NEJM 337: 473–478

    Article  PubMed  CAS  Google Scholar 

  30. Romero-Gómez M, Córdoba J, Jover R et al. (2007) Value of the critical flicker frequency in patients with minimal hepatic encephalopathy. Hepatology 45: 879–885

    Article  PubMed  Google Scholar 

  31. Schliess F, Görg B, Fischer R et al. (2002) Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FASEB J 16: 739–741

    PubMed  CAS  Google Scholar 

  32. Schnitzler A, Timmermann L, Gross J (2006) Physiological and pathological oscillatory networks in the human motor system. J Physiol (Paris) 99: 3–7

    Google Scholar 

  33. Schomerus H, Hamster W, Blunck H et al. (1981) Latent portosystemic encephalopathy. Nature of cerebral function defects and their effect on fitness to drive. Dig Dis Sci 16: 321–328

    Google Scholar 

  34. Sharma P, Sharma BC, Puri V, Sarin SK (2007) Critical Flicker Frequency: Diagnostic Tool for Minimal hepatic encephalopathy. J Hepatol

  35. Shah NJ, Neeb H, Kircheis G et al. (2007) Quantitative cerebral water content mapping in hepatic encephalopathy. Neuro Image

  36. Shawcross D, Jalan R (2005) Dispelling myths in the treatment of hepatic encephalopathy Lancet 365: 431–433

  37. Srivastava A, Mehta R, Rothke SP et al. (1994) Fitness to drive in patients with cirrhosis and portal-systemic shunting: a pilot study evaluating driving performance. J Hepatol 21: 1023–1028

    Article  PubMed  CAS  Google Scholar 

  38. Strauss E, Tramote R, Silva EP (1992) Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. Hepato Gastroenterology 39: 542–545

    PubMed  CAS  Google Scholar 

  39. Timmermann L, Gross J, Butz M et al. (2004) Pathological oscillatory coupling within the human motor system in different tremor syndromes as revealed by magnetoencephalography. Neurol Clin Neurophysiol 26

  40. Timmerman L, Butz M, Gross J et al. (2005) Neural synchronization in hepatic encephalopathy. Metab Brain Dis 20: 337–346

    Article  Google Scholar 

  41. Uribe M, Campollo O et al. (1987) Acidifying enemas (lactitol and lactose) versus nonacidifying enemas (tap water) to treat acute portal-systemic encephalopathy: a double-blind randomized clinical trial. Hepatology 7: 639–643

    Article  PubMed  CAS  Google Scholar 

  42. Vogels BAP, Maas MAW, Daalhuisen J et al. (1997) Memantine, a non-competitive NMDA-receptor antagonist improves hyperammonia-induced encephalopathy and acute hepatic encephalopathy in rats. Hepatology 25: 820–827

    Article  PubMed  CAS  Google Scholar 

  43. Warskulat U, Kreuels S, Müller HW, Häussinger D (2001) Identification of osmosensitive and ammonia-regulated genes in rat astrocytes by Northern blotting and differential display RT-PCR. J Hepatol 35: 358–366

    Article  PubMed  CAS  Google Scholar 

  44. Wein C, Koch H, Popp B et al. (2004) Minimal hepatic encephalopathy impairs fitness to drive. Hepatology 39: 739–745

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

G. Kircheis ist an der Entwicklung des „Hepatonorm Analyzers“ zur Messung der Flimmerfrequenz beteiligt. Darüber hinaus erklärt der Autor, dass er keine finanziellen Verbindungen mit einer Firma hat, deren Produkt in dem Artikel eine wichtige Rolle spielt (oder mit einer Firma, die ein Konkurrenzprodukt vertreibt).

Author information

Authors and Affiliations

  1. Klinik für Gastroenterologie, Hepatologie und Infektiologie (Direktor der Klinik: Prof. Dr. D. Häussinger), Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    G. Kircheis

Authors
  1. G. Kircheis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Kircheis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kircheis, G. Hepatische Enzephalopathie. Gastroenterologe 2, 251–260 (2007). https://doi.org/10.1007/s11377-007-0088-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11377-007-0088-3

Schlüsselwörter

Keywords

Search

Navigation