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Fettleversykdom, ikke alkoholisk

Sist oppdatert: Sist revidert:
Sist revidert av:


Definisjon:
Økt infiltrasjon av fett i lever hos personer som bruker lite eller er avholdende fra alkohol. Assosiert med metabolsk syndrom: Økt insulinresistens, overvekt og diabetes
Forekomst:
Den hyppigst forekommende kroniske leversykdom, økende forekomst med økende alder. Spesielt høy forekomst ved type 2-diabetes
Symptomer:
Kan være uten symptomer over lang tid. Noen utvikler allmennsymptomer og tyngdefølelse i leverområdet
Funn:
Ved us. forstørret lever. Som regel overvekt
Diagnostikk:
Forhøyet ALAT i blod, oftest dette som fører til diagnosen. Leverbiopsi er nødvendig for sikker diagnose
Behandling:
Viktigste behandling er vektreduksjon. Tilleggsbehandling med vitamin-E og antidiabetika er aktuelt
  1. Wilkins T, Tadkod A, Hepburn I, Schade RR. Nonalcoholic fatty liver disease: diagnosis and management. Am Fam Physician 2013; 88: 35-42. American Family Physician  
  2. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263-2273. PubMed  
  3. Sheka AC, Adeyi O, Thompson J, et al. Nonalcoholic Steatohepatitis A Review. JAMA 2020; 323: 1175-83. doi:10.1001/jama.2020.2298 DOI  
  4. Kaya E, Yilmaz Y. Metabolic-associated Fatty Liver Disease (MAFLD): A Multi-systemic Disease Beyond the Liver. J Clin Transl Hepatol. 2022 Apr 28;10(2):329-338. Epub 2021 Oct 19. PMID: 35528971 PubMed  
  5. Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2022. pmid:35798021 PubMed  
  6. Stål P. Liver fibrosis in non-alcoholic fatty lliver disease - diagnostic challenge with prognostic significance. World J Gastroenterol 2015; 21: 11077-87. doi:10.3748/wjg.v21.i39.11077 DOI  
  7. Kanwal F, Shubrook JH, Adams LA, et al. Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2021; 161: 1657-69. pmid:34602251 PubMed  
  8. Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract 2022; 28: 528-562. pmid:35569886 PubMed  
  9. Baker JL, Farpour-Lambert NJ, Nowicka P, Pietrobelli A, Weiss R. Evaluation of the overweight/obese child - practical tips for the primary health care provider: recommendations from the Childhood Obesity Task Force of the European Association for the Study of Obessity. Obes Facts 2010; 3: 131-7. PubMed  
  10. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents. JAMA 2011; 305: 1659-68. Journal of the American Medical Association  
  11. DiNicolantonio JJ, Subramonian AM, O'Keefe JH. Added fructose as a principal driver on non-alcoholic fatty liver disease: a public health crisis. Open Heart 2017. pmid:29118995 PubMed  
  12. Diehl AM, Day C. Cause, pathogenesis, and treatment of Non-alcoholic steatohepatitis. N Eng J Med 2017; 377: 2063-72. pmid:29166236 PubMed  
  13. Petersen KF, Dufour S, Hariri A, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. New Engl J Med 2010; 362: 1082-9. PubMed  
  14. Imajo K, Kessoku T, Honda Y, et al. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology 2016; 150: 626-37. pmid:26677985 PubMed  
  15. Koot BG, van der Baan-Slootweg OH, Bohte AE, et al. Accuracy of prediction scores and novel biomarkers for predicting nonalcoholic fatty liver disease in obese children. Obesity 2013; 21: 583-90. pmid:23592667 PubMed  
  16. Paul S, Davis AM. JAMA Clinical Guidelines Synopsis. Diagnosis and management of Nonalcoholic Fatty Liver Disease. JAMA 2018. doi:10.1001/jama.2018.17365 DOI  
  17. Koutoukidis DA, Astbury NM, Tudor KE, et al. Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease A Systematic Review and Meta-analysis. JAMA Intern Med 2019. pmid:31260026 PubMed  
  18. van der Windt DJ, Sud V, Zhang H, Tsung A, Huang H. The effects of physical exercise on fatty liver disease. Gene Expr. 2018;18(2):89-101. PMID: 29212576 PubMed  
  19. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010; 51: 121. PubMed  
  20. Wong VW-S, Wong GL-H, Choi PC-L, et al. Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut 2010; 59: 969-74. Gut  
  21. Zhang HJ, He J, Pan LL, et al. Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial. JAMA Intern Med. 2016. doi: 10.1001/jamainternmed.2016.3202. DOI  
  22. Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical acticity intervention in non-alcoholic fatty liver disease. BMJ Open Gastroenterol 2017; 4: e000139. pmid:28761689 PubMed  
  23. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010; 362: 1675-85. New England Journal of Medicine  
  24. Harrison SA, Torgersen S, Hayashi P, et al. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 2003; 98: 2485. PubMed  
  25. Singh S, Kera R, Allen AM, et al. Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta-analysis. Hepatology 2015. PMID: 26189925 PubMed  
  26. Miller ER, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005; 142: 37-46. Annals of Internal Medicine  
  27. Cusi K, Orsak B, Bril F, et al. Long-term pioglitazon treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus. Ann Intern Med 2016; 165: 305-15. pmid:27322798 PubMed  
  28. Musso G, Cassader M, Paschetta E, et al. Thiazolidinediones and Advanced Liver Fibrosis in Nonalcoholic Steatohepatitis: A Meta-analysis. JAMA Intern Med. 2017. PMID: 28241279 PubMed  
  29. 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: 328-57. pmid:28714183 PubMed  
  30. Francque SM, Bedossa P, Ratziu V, et al. A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. N Engl J Med 2021; 385: 1547-58. pmid:34670042 PubMed  
  31. Armstrong MJ, Gaunt P, Aithal GP, et al; LEAN trial team. 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. PMID: 26608256 PubMed  
  32. Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2020. pmid:33185364 PubMed  
  33. Younossi ZM, Ratziu V, Loomba R, et al. Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2019; 394: 2184-96. pmid:31813633 PubMed  
  34. Kramer JR, Natarajan Y, Dai J, et al . Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease.. Hepatology 2022; 75: 1420-28. pmid:34779535 PubMed  
  35. Bugianesi E, Gentilcore E, Manini R, et al. A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 2005; 100: 1082. PubMed  
  36. Simon TG, Henson J, Osganian S, et al. Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol 2019. pmid:31077838 PubMed  
  37. Malaguarnera M, Gargante MP, Russo C, et al. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis--a randomized and controlled clinical trial. Am J Gastroenterol 2010; 105: 1338-45. PubMed  
  38. Sanyal A, Charles ED, Neuschwander-Tetri BA, et al. Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet 2018. pmid:30554783 PubMed  
  39. Leuschner EF, Lindenthal B, Herrmann G, et al. High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double blind, randomized, placecbo-controlled trial. Hepatology 2010; 52: 472-9. PubMed  
  40. Alisi A, Bedogni G, Baviera G, et al. Randomised clinical trial: The beneficial effects of VSL#3 in obese children with nonalcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39:1276. PMID: 24738701 PubMed  
  41. Nobili V, Bedogni G, Alisi A, et al. Docosahexaenoic acid supplementation decreases liver fat content in children with non-alcoholic fatty liver disease: double blind randomised controlled clinical trial. Arch Dis Child 2011; 96: 350-3. PubMed  
  42. Shouhed D, Steggerda J, Burch M, Noureddin M. The role of bariatric surgery in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expert Rev Gastroenterol Hepatol 2018; 9: 797-811. pmid:28712339 PubMed  
  43. Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149(2):379-388. PMID: 25917783 PubMed  
  44. Aminian A, Al-Kurd A, Wilson R, et al. Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis. JAMA 2021; 326: 2031-42. pmid:34762106 PubMed  
  45. Sanyal A, Natta MLV, Clark J, et al. Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease. N Engl J Med 2021; 385: 1559-69. pmid:34670043 PubMed  
  46. Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol 2009; 51: 371. PubMed  
  47. Hossain N, Afendy A, Stepanova M, et al. Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1224. PubMed  
  48. Kim GA, Lee HC, Choe J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate. J Hepatol. 2017 PMID: 29150142 PubMed  
  49. Mantovani A, Csermely A, Petracca G, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021. pmid:34555346 PubMed  
  50. Powell EE, Cooksley WG, Hanson R, et al. The natural history of nonalcoholic steatohepatitis: A follow up study of forty-two patients for up to 21 years. Hepatology 1990; 11: 74. PubMed  
  51. Evans CD, Oien KA, MacSween RN, Mills PR. Non-alcoholic steatohepatitis: a commin cause of progressive chronic liver injury?. J Clin Pathol 2002; 55: 689. PubMed  
  52. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356. PubMed  
  53. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865-73. PubMed  
  54. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: 846-54. doi:10.1002/hep.21496 DOI  
  55. Long MT, Pedley A, Colantonio LD, et al. Development and Validation of the Framingham Steatosis Index to Identify Persons With Hepatic Steatosis. Clin Gastroenterol Hepatol 2016. pmid:27046482 PubMed  
  56. Younossi ZM, Loomba R, Anstee QM, et al. Diagnostic Modalities for Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Associated Fibrosis. Hepatology 2018. pmid:29222917 PubMed  
  • Ingard Løge, spesialist allmennmedisin, redaktør NEL

Tidligere fagmedarbeidere

  • Per Martin Kleveland, professor i gastroenterologi, Norges teknisk-naturvitenskapelige universitet og overlege gastroenterologisk avdeling St. Olavs Hospital, Trondheim