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Entzündungsmechanismen im Rahmen der Progression der Fettleber als innovative molekulare Targets

Inflammatory mechanisms in the progression of fatty liver disease as innovative molecular targets

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Zusammenfassung

Multiple Schädigungsreize im Rahmen der nichtalkoholischen Fettlebererkrankungen (NAFLD) und daraus resultierende Veränderungen in der Leber, wie z. B. Lipideinlagerungen in den Hepatozyten, Akkumulation toxischer Metaboliten, oxidativer Stress oder Apoptose und Nekrose der Hepatozyten, bewirken eine Aktivierung des Immunsystems. Dies wiederum führt zu einer inflammatorischen Reaktion, die das Fortschreiten von der prognostisch günstigeren nichtalkoholischen Fettleber (NAFL) zur progressiven Verlaufsform der nichtalkoholischen Steatohepatitis (NASH) begünstigt. Die chronische Inflammation führt zur Fibrose, die der wesentliche Risikofaktor für die leberbezogene sowie die Gesamtmorbidität und Mortalität bei NAFLD ist. Aktuell gibt es keine zugelassenen medikamentösen Therapieoptionen, allerdings befinden sich zahlreiche Substanzen in der klinischen Prüfung. Das bessere Verständnis der Entzündungsprozesse in der Leber liefert neue innovative Ansatzpunkte für die Therapie der NAFLD und ihrer Komplikationen. Die immunologischen Mechanismen sowie daraus resultierende therapeutische Ansatzpunkte werden in dieser Übersicht dargestellt.

Abstract

Multiple injurious stimuli in the course of nonalcoholic fatty liver diseases (NAFLD) and the resulting changes in the liver such as hepatic lipid deposits, accumulation of toxic metabolites, oxidative stress or apoptosis and necrosis of hepatocytes lead to an activation of the immune system. This in turn leads to an inflammatory reaction that favors the progression from the prognostically more favorable nonalcoholic fatty liver (NAFL) to the progressive phenotype of nonalcoholic steatohepatitis (NASH). Chronic inflammation leads to fibrosis, which is the major risk factor for overall and liver-related morbidity and mortality in NAFLD. There are currently no approved drug treatments, but numerous substances are in clinical trials. A better understanding of the inflammatory processes in the liver provides new innovative therapeutic targets for the treatment of NAFLD and its complications. The immunological mechanisms and the resulting therapeutic approaches are presented in this review.

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Author information

Correspondence to Prof. Dr. F. Tacke.

Ethics declarations

Interessenkonflikt

M. Demir gibt an, dass kein Interessenkonflikt besteht und F. Tacke gibt an, dass seine Arbeitsgruppe Forschungsförderung der Firmen Allergan, Bristol Myers Squibb, Galapagos und Inventiva erhalten hat.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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C. Trautwein, Aachen

S. Zeuzem, Frankfurt am Main

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Demir, M., Tacke, F. Entzündungsmechanismen im Rahmen der Progression der Fettleber als innovative molekulare Targets. Gastroenterologe (2020). https://doi.org/10.1007/s11377-020-00418-x

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Schlüsselwörter

  • Nichtalkoholische Fettlebererkrankung
  • Medikamentöse Therapie
  • Immunsystem
  • Inflammation
  • Klinische Studie

Keywords

  • Nonalcoholic fatty liver disease
  • Drug therapy
  • Immune system
  • Inflammation
  • Clinical trial