Z Gastroenterol 2019; 57(04): 508-517
DOI: 10.1055/a-0784-8827
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Nonalcoholic steatohepatitis (NASH) – current treatment recommendations and future developments

Nichtalkoholische Steatohepatitis (NASH) – aktuelle Behandlungsempfehlungen und zukünftige Entwicklungen
Elke Roeb
1   Department of Gastroenterology, Justus-Liebig-University & University-Hospital Giessen, Giessen
,
Andreas Geier
2   Division of Hepatology, University-Hospital Würzburg, Würzburg, Germany
› Author Affiliations
Further Information

Publication History

17 July 2018

05 November 2018

Publication Date:
09 April 2019 (online)

Abstract

Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL), nonalcoholic steato hepatitis (NASH) and NASH cirrhosis. NAFLD is the leading cause of liver diseases in the Western world (Central Europe, United States). The NAFLD incidence increases because of increasing type 2 diabetes and obesity. This article reviews the scientific findings of epidemiology, diagnostic, and therapeutic management of NAFLD. Lifestyle modifications (low-caloric Mediterranean diet and exercise training) to reduce weight are a major factor in the treatment of NAFLD.

Pharmacological therapies may be useful in patients with NASH and fibrosis as well as nonresponders to lifestyle modifications. Currently, however, no pharmacological substances are approved for the indication NASH.

Zusammenfassung

Die nichtalkoholische Fettlebererkrankung (NAFLD) umfasst die nichtalkoholische Fettleber (NAFL), die nichtalkoholische Steatohepatitis (NASH) und die NASH-Zirrhose. NAFLD ist die Hauptursache für Lebererkrankungen in der westlichen Welt (Mitteleuropa, USA). Die NAFLD-Inzidenz steigt aufgrund der Zunahme von Typ-2-Diabetes und Fettleibigkeit. Diese Übersicht fasst den aktuellen Wissensstand bezüglich Epidemiologie, Diagnose und klinischem Management von NAFLD sowie zukünftige Therapieansätze anhand aktueller Leitlinien und Studien zusammen. Life-Style-Modifikationen (kalorienarme mediterrane Diät und Ausdauertraining) zur Erzielung eines Gewichtsverlustes sind das Hauptziel im Rahmen aktueller therapeutischer Empfehlungen zu NAFLD. Eine pharmakologische Therapie könnte bei Patienten mit NASH und Fibrose sowie Non-Respondern der Life-Style-Modifikationen hilfreich sein. Aktuell sind allerdings noch keine pharmakologischen Substanzen für die Indikation NASH zugelassen.

 
  • References

  • 1 Allen AM, Terry TM, Larson JJ. et al. Nonalcoholic fatty liver disease incidence and impact on metabolic burden and death: a 20 year-community study. Hepatology 2018; 67: 1726-1736
  • 2 Roeb E, Steffen HM, Bantel H. et al. S2k Guideline non-alcoholic fatty liver disease. Z Gastroenterol 2015; 53: 668-723
  • 3 Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015; 62: S47-S64
  • 4 Targher G, Byrne CD, Lonardo A. et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 2016; 65: 589-600
  • 5 Dulai PS, Singh S, Patel J. et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 2017; 65: 1557-1565
  • 6 Ibrahim SH, Hirsova P, Gores GJ. Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a driver of liver inflammation. Gut 2018; 67: 963-972
  • 7 Weiss J, Rau M, Geier A. Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Dtsch Arztebl Int 2014; 111: 447-452
  • 8 Losurdo G, Castellaneta A, Rendina M. et al. Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease in liver-transplanted patients. Aliment Pharmacol Ther 2018; 47: 704-714
  • 9 Herzer K, Roeb E. Modernes Management und neue Herausforderungen bei Fettlebererkrankungen: Diagnostik, Therapie und Lebertransplantation. Klinikarzt 2016; 45: 596-601
  • 10 Wong RJ, Aguilar M, Cheung R. et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015; 148: 547-555
  • 11 Estes C, Anstee QM, Arias-Loste MT. et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol 2018; 69: 896-904
  • 12 Ertle J, Dechêne A, Sowa JP. et al. Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis. Int J Cancer 2011; 128: 2436-2443
  • 13 Kälsch J, Bechmann LP, Heider D. et al. Normal liver enzymes are correlated with severity of metabolic syndrome in a large population based cohort. Sci Rep 2015; 5: 13058 . doi: 10.1038/srep13058
  • 14 Loomba R. Role of imaging-based biomarkers in NAFLD: recent advances in clinical application and future research directions. J Hepatol 2018; 68: 296-304
  • 15 Tapper EB, Lok ASF. Use of liver imaging and biopsy in clinical practice. N Engl J Med 2017; 377: 756-768
  • 16 Daniels SJ, Leeming DJ, Eslam M. et al. ADAPT: An algorithm incorporating PRO-C3 accurately identifies patients with NAFLD and advanced fibrosis. Hepatology 2018; [Epub ahead of print]. DOI: 10.1002/hep.30163.
  • 17 Schuppan D, Surabattula R, Wang XY. Determinants of fibrosis progression and regression in NASH. J Hepatol 2018; 68: 238-250
  • 18 Boursier J, Vergniol J, Guillet A. et al. Diagnostic accuracy and prognostic significance of blood fibrosis tests and liver stiffness measurement by FibroScan in non-alcoholic fatty liver disease. J Hepatol 2016; 65: 570-578
  • 19 Angulo P, Kleiner DE, Dam-Larsen S. et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 2015; 149: 389-397
  • 20 Labenz C, Huber Y, Kalliga E. et al. Predictors of advanced fibrosis in non-cirrhotic non-alcoholic fatty liver disease in Germany. Aliment Pharmacol Ther 2018; 48: 1109-1116
  • 21 Park CC, Nguyen P, Hernandez C. et al. Magnetic resonance elastography vs transient elastography in detection of fibrosis and noninvasive measurement of steatosis in patients with biopsy-proven nonalcoholic fatty liver disease. Gastroenterology 2017; 152: 598-607
  • 22 Eddowes PJ, McDonald N, Davies N. et al. Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2018; 47: 631-644
  • 23 Dietrich CF, Bamber J, Berzigotti A. et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version). Ultraschall Med 2017; 38: e16-e47
  • 24 Dong Y, Sirli R, Ferraioli G. et al. Shear wave elastography of the liver – review on normal values. Z Gastroenterol 2017; 55: 153-166
  • 25 Younossi ZM, Loomba R, Anstee QM. et al. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology 2018; 68: 349-360
  • 26 Vilar-Gomez E, Yasells-Garcia A, Martinez-Perez Y. et al. Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention. Hepatology 2016; 63: 1875-1887
  • 27 Bedossa P. Diagnosis of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: why liver biopsy is essential. Liver Int 2018; 38 (Suppl. 01) 64-66
  • 28 Said A, Ghufran A. Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma. World J Clin Oncol 2017; 8: 429-436
  • 29 European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Diabetologia 2016; 64: 1388-1402
  • 30 Chiu S, Sievenpiper JL, de RJ Souza. et al. Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Eur J Clin Nutr 2014; 68: 416-423
  • 31 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: 679-690
  • 32 Chalasani N, Younossi Z, Lavine JE. et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67: 328-357
  • 33 Rau M, Geier A. Nicht-alkoholische Fettlebererkrankung – Entwicklung der medikamentösen Therapie. Arzneimitteltherapie 2017; 35: 479-484
  • 34 Geier A, Rau M. Emerging therapies for NASH – the future is now. Expert Rev Clin Pharmacol 2017; 10: 467-469