Aktuelle und zukünftige Therapieoptionen bei NAFLD

Zusammenfassung

Für die nicht-alkoholische Fettlebererkrankung (NAFLD) gibt es aktuell keine zugelassene medikamentöse Therapie in Deutschland. Als Therapieziel wird bei NAFLD-Patienten die Einstellung der metabolischen Risikofaktoren empfohlen sowie die Therapie der einzelnen Komponenten des metabolischen Syndroms. In den letzten Jahren sind einige neue Therapieansätze im Rahmen von klinischen Studien bei NASH (nicht-alkoholische Steatohepatitis)-Patienten untersucht worden. Die Substanzen weisen unterschiedliche pathophysiologische Angriffspunkte auf von FXR-Agonisten über GLP-1-Analoga bis hin zu antifibrotisch wirksamen Substanzen. Die beiden Substanzen, die in ihrer Entwicklung am weitesten vorangeschritten sind, werden aktuell in zwei Phase- III-Studien untersucht. Dabei handelt es sich um einen FXR-Agonisten (Obeticholsäure) sowie einen dualen PPARα/δ-Agonist (Elafibranor). Bis zum Vorliegen der Ergebnisse der Phase-III-Studien und einem möglichen Eintritt dieser Substanzen in den klinischen Alltag wird noch einige Zeit vergehen. Bis dahin bleibt der Fokus auf der Identifizierung der Risikopatienten im klinischen Alltag.

Summary

In Germany, there are currently no drugs approved to treat patients with Non-alcoholic fatty liver disease (NAFLD). In the current guidelines of the Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, the therapeutic goal for NAFLD patients is the reduction of metabolic risk factors and the treatment of the metabolic syndrome. In the last years, different new drugs are under development and act on different pathophysiological processes to treat NASH patients. These substances include agonists of nuclear receptors such as FXR agonists or PPAR agonists as well as agonists of enterohepatic hormones such as GLP-1 agonist and other specific antifibrotic agents. Two drugs with the most advanced development are now tested in two global phase III studies. Obeticholic acid is a FXR agonist and Elafibranor a dual PPARα/δ agonist. It will take some time to have access to the results of phase III studies and to have these drugs available in clinical practice. Up to then, the focus should be put on the identification of patients at risk in daily clinical practice.

Schlüsselwörter

NAFLD - NASH - medikamentöse Therapie

Keywords

NAFLD - NASH - drug treatment

• Literatur

• 1 Weiss J, Rau M, Geier A. Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Deutsches Arzteblatt international 2014; 111 (26) 447-452.
• 2 Younossi ZM, Blissett D, Blissett R. et al. The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe. Hepatology (Baltimore, Md). 2016
• 3 Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64 (01) 73-84.
• 4 Chalasani N, Younossi Z, Lavine JE. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55 (06) 2005-2023.
• 5 Roeb E, Steffen HM, Bantel H, Baumann U, Canbay A, Demir M. et al. [S2k Guideline non-alcoholic fatty liver disease]. Z Gastroenterol 2015; 53 (07) 668-723.
• 6 Promrat K, Kleiner DE, Niemeier HM. et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology (Baltimore, Md) 2010; 51 (01) 121-129.
• 7 Mudaliar S, Henry RR, Sanyal AJ. et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145 (03) 574-582. e1.
• 8 Neuschwander-Tetri BA, Loomba R, Sanyal AJ. et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebocontrolled trial. Lancet 2015; 385 (9972): 956-965.
• 9 Charles EDML, Hompesch M, Luo Y, Wu CK. Christian R. A Phase 1 Study of BMS-986036 (Pegylated FGF21) in Healthy Obese Subjects. AASLD Liver Meeting. Boston: 2016 Abstract 1082.
• 10 Charles EDTB, Luo Y, Wu CK, Christian R. A Phase 2 Study of BMS-986036 (Pegylated FGF21) in Obese Adults with Type 2 Diabetes and a High Prevalence of Fatty Liver. AASLD Liver Meeting. Boston: 2016 Abstract 33.
• 11 Armstrong MJ, Gaunt P, Aithal GP. et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 2016; 387 (10019); 679-690.
• 12 Ratziu V, Harrison SA, Francque S. et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology 2016; 150 (05) 1147-1159. e5.
• 13 Abitbol JLBP, Junien JL. Metabolic effects and good tolerance of IVA337 a Pan-PPAR agonist in diabetic patients warrant further investigation in NASH. ILC. 2016 Abstract PS105.
• 14 Sanyal AJRV, Harrison S, Abdelmalek MF. et al. Cenicriviroc versus Placebo for the treatment of Nonalcoholic Steatohepatitis with liver fibrosis: Results from the year 1 primary analysis of the phase 2b CENTAUR study. AASLD Liver Meeting. Boston: 2016 Abstract LB-1.
• 15 Loomba RLE, Mantry PS, Jayakumar S. et al. GS-4497, an inhibitor of apoptosis signal-regulating kinase (ASK1), alone or in combination with simtuzumab for the treatment of nonalcoholic steatohepatitis (NASH): a randomized, phase 2 trial. AASLD Liver Meeting. Boston: 2016 Abstract LB-3.