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Non-alcoholic Fatty Liver Disease

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Liver Disease in Clinical Practice

Part of the book series: In Clinical Practice ((ICP))

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Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease closely associated with features of the metabolic syndrome. NAFLD represents the most common aetiology of liver disease globally and encompasses a histopathological spectrum of disease ranging from simple steatosis to inflammation with hepatocyte injury, and eventually to fibrosis and cirrhosis. Obesity and insulin resistance lead to hepatic steatosis through increased free fatty acid delivery from adipose tissue, decreased hepatic fatty acid clearance and enhanced de novo lipogenesis. Disease progression from steatosis to inflammation and fibrosis is variable and likely occurs through complex interplay of genetic, environmental and gut microbial factors. The evolution of fibrosis is an essential prognostic characteristic in NAFLD and represents the only histological feature to predict overall mortality, liver transplantation and liver-related events. Therefore, risk stratification for fibrosis is crucial to identify patients with advanced disease using non-invasive approaches such as transient elastography or validated scoring systems, combined in two-tiered risk assessment pathways. Management of NAFLD comprises a multidisciplinary framework with emphasis on reducing cardiovascular risk as well as improving liver-related morbidity and mortality through lifestyle adaptation and pharmacological intervention. While targeted, liver-specific pharmacotherapy for NAFLD remains deficient at present, multiple agents have shown promise and are undergoing late-stage development to supplement standard care in progressive NAFLD.

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  1. 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;55:2005–23.

    Article  PubMed  Google Scholar 

  2. Eslam M, Sanyal AJ, George J, et al. MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158:1999–2014.e1.

    Article  CAS  PubMed  Google Scholar 

  3. Haldar D, Kern B, Hodson J, et al. Outcomes of liver transplantation for non-alcoholic steatohepatitis: a European liver transplant registry study. J Hepatol. 2019;71:313–22.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Younossi ZM, Stepanova M, Ong J, et al. Nonalcoholic steatohepatitis is the Most rapidly increasing indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2021;19:580–589.e5.

    Article  PubMed  Google Scholar 

  5. Marjot T, Moolla A, Cobbold JF, et al. Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management. Endocr Rev. 2020;41:bnz009.

    Article  PubMed  Google Scholar 

  6. Koeckerling D, Tomlinson JW, Cobbold JF. Fighting liver fat. Endocr Connect. 2020;9:R173–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. McPherson S, Hardy T, Henderson E, et al. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62:1148–55.

    Article  PubMed  Google Scholar 

  8. 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.e10.

    Article  PubMed  Google Scholar 

  9. Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61:1547–54.

    Article  CAS  PubMed  Google Scholar 

  10. Singh S, Allen AM, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13:643–654.e9.

    Article  PubMed  Google Scholar 

  11. Alexopoulos A, Crowley MJ, Wang Y, et al. Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease. Hepatology. 2021;74(3):1220–33.

    Article  CAS  PubMed  Google Scholar 

  12. Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol. 2001;35:195–9.

    Article  CAS  PubMed  Google Scholar 

  13. Srivastava A, Gailer R, Tanwar S, et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J Hepatol. 2019;71:371–8.

    Article  PubMed  Google Scholar 

  14. Chalmers J, Wilkes E, Harris R, et al. Development and implementation of a commissioned pathway for the identification and stratification of liver disease in the community. Frontline Gastroenterol. 2019;11:86–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol. 2012;56:255–66.

    Article  PubMed  Google Scholar 

  16. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149:367–378.e5.

    Article  PubMed  Google Scholar 

  17. Musso G, Cassader M, Rosina F, et al. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia. 2012;55:885–904.

    Article  CAS  PubMed  Google Scholar 

  18. Bower G, Toma T, Harling L, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25:2280–9.

    Article  PubMed  Google Scholar 

  19. 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;387:679–90.

    Article  CAS  PubMed  Google Scholar 

  20. Newsome PN, Buchholtz K, Cusi K, et al. A placebo-controlled trial of subcutaneous Semaglutide in nonalcoholic steatohepatitis. N Engl J Med. 2021;384(12):1113–24.

    Article  CAS  PubMed  Google Scholar 

  21. Bonora BM, Avogaro A, Fadini GP. Extraglycemic effects of SGLT2 inhibitors: a review of the evidence. Diabetes Metab Syndr Obes. 2020;13:161–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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, placebo-controlled trial. Lancet. 2015;385:956–65.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Jeremy Cobbold .

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Koeckerling, D., Marjot, T., Cobbold, J. (2022). Non-alcoholic Fatty Liver Disease. In: Cross, T. (eds) Liver Disease in Clinical Practice. In Clinical Practice. Springer, Cham.

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  • Print ISBN: 978-3-031-10011-6

  • Online ISBN: 978-3-031-10012-3

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