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Nonalcoholic Fatty Liver Disease: A Wide Spectrum Disease

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Liver Diseases

Abstract

Nonalcoholic Liver Disease (NAFLD) is considered a wide spectrum progressive disease and has emerged as a major cause of chronic liver disease worldwide. It has a global prevalence of 24%, an increasing incidence in both adults and children, in parallel with the pandemic burden of obesity, Type 2 Diabetes Mellitus (T2DM) and Metabolic Syndrome (MS). The pathogenic drivers are still unknown and are not likely to be identical among all patients. The natural history of NAFLD is not linear: it progresses to Nonalcoholic Steatohepatitis (NASH) in 10–30% of the cases, and about 10–15% of NASH patients progress to cirrhosis. The major cause of mortality of NAFLD patients is cardiovascular disease (CVD), being liver-related mortality only the third cause. New valid markers to distinguish patients who progress to either cirrhosis or CVD and new treatments are still to be developed. In spite of the great efforts devoted to achieving these goals, real options for new non-invasive markers for the diagnosis of NASH-cirrhosis and new therapeutic agents are still limited. This chapter will discuss the most updated data about the epidemiology, risk factors, pathogenesis, available experimental models, new diagnostic tools and new treatment options for NAFLD and NASH.

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References

  1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–8.

    CAS  PubMed  Google Scholar 

  2. Bellentani S, Tiribelli C. Is it time to change NAFLD and NASH nomenclature? Lancet Gastroenterol Hepatol. 2017;2:547–8.

    Article  Google Scholar 

  3. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2018;15(1):11–20.

    Article  Google Scholar 

  4. Younossi ZM, Henry L, Bush H, Mishra A. Clinical and economic burden of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Clin Liver Dis. 2018;22:1–10.

    Article  Google Scholar 

  5. Welsh JA, Karpen S, Vos MB. Increasing prevalence of nonalcoholic fatty liver disease among United States adolescents, 1988–1994 to 2007–2010. J Pediatr. 2013;162:496–500.e1.

    Article  Google Scholar 

  6. Piscaglia F, Svegliati-Baroni G, Barchetti A, Pecorelli A, Marinelli S, Tiribelli C, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology. 2016;63:827–38.

    Article  Google Scholar 

  7. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–5.

    Article  CAS  Google Scholar 

  8. Valenti L, Al-Serri A, Daly AK, Galmozzi E, Rametta R, Dongiovanni P, et al. Homozygosity for the patatin-like phospholipase-3/adiponutrin I148M polymorphism influences liver fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2010;51:1209–17.

    Article  CAS  Google Scholar 

  9. Mancina RM, Dongiovanni P, Petta S, Pingitore P, Meroni M, Rametta R, et al. The MBOAT7-TMC4 variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent. Gastroenterology. 2016;150:1219–1230.e6.

    Article  CAS  Google Scholar 

  10. Anstee QM, Seth D, Day CP. Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease. Gastroenterology. 2016;150:1728–1744.e7.

    Article  Google Scholar 

  11. Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, Stevis P, et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N Engl J Med. 2018;378:1096–106.

    Article  CAS  Google Scholar 

  12. Zarrinpar A, Gupta S, Maurya MR, Subramaniam S, Loomba R. Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study. Gut. 2016;65:1546–54.

    Article  CAS  Google Scholar 

  13. Leung JC-F, Loong TC-W, Wei JL, Wong GL-H, Chan AW-H, Choi PC-L, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology. 2017;65:54–64.

    Article  CAS  Google Scholar 

  14. Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016;126:12–22.

    Article  Google Scholar 

  15. Yki-Järvinen H. Nutritional modulation of non-alcoholic fatty liver disease and insulin resistance. Nutrients. 2015;7:9127–38.

    Article  Google Scholar 

  16. Mouzaki M, Comelli EM, Arendt BM, Bonengel J, Fung SK, Fischer SE, et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology. 2013;58:120–7.

    Article  CAS  Google Scholar 

  17. Alegre F, Pelegrin P, Feldstein AE. Inflammasomes in liver fibrosis. Semin Liver Dis. 2017;37:119–27.

    Article  CAS  Google Scholar 

  18. Mazza G, Al-Akkad W, Rombouts K. Engineering in vitro models of hepatofibrogenesis. Adv Drug Deliv Rev. 2017;121:147–57.

    Article  CAS  Google Scholar 

  19. van Grunsven LA. 3D in vitro models of liver fibrosis. Adv Drug Deliv Rev. 2017;121:133–46.

    Article  Google Scholar 

  20. Van Herck MA, Vonghia L, Francque SM. Animal models of nonalcoholic fatty liver disease—a starter’s guide. Nutrients. 2017;9 https://doi.org/10.3390/nu9101072.

    Article  Google Scholar 

  21. Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, 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  Google Scholar 

  22. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, 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  Google Scholar 

Related Published Articles

  • Araújo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S. Global epidemiology of NAFLD/NASH: what we need in the future. Liver Int. 2018;38(Suppl 1):47–51.

    Article  Google Scholar 

  • Barbero-Becerra VJ, Giraudi PJ, Chávez-Tapia NC, Uribe M, Tiribelli C, Rosso N. The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH. Toxicol In Vitro. 2015;29(7):1753–8. https://doi.org/10.1016/j.tiv.2015.07.010. PMID: 26187275.

    Article  CAS  PubMed  Google Scholar 

  • Chavez-Tapia NC, Rosso N, Tiribelli C. In vitro models for the study of non-alcoholic fatty liver disease. Curr Med Chem. 2011;18(7):1079–84.

    Article  CAS  Google Scholar 

  • Giraudi PJ, Barbero Becerra VJ, Marin V, Chavez-Tapia NC, Tiribelli C, Rosso N. The importance of the interaction between hepatocyte and hepatic stellate cells in fibrogenesis induced by fatty accumulation. Exp Mol Pathol. 2014;98(1):85–92. https://doi.org/10.1016/j.yexmp.2014.12.006.

    Article  CAS  PubMed  Google Scholar 

  • Marin V, Rosso N, Dal Ben M, Raseni A, Boschelle M, Degrassi C, et al. An animal model for the juvenile non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. PLoS One. 2016;11(7):e0158817.

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Fondazione Italiana Fegato, Basovizza, Trieste, Italy

    Natalia Rosso

  2. Clinica Santa Chiara SA, Locarno, Switzerland

    Stefano Bellentani

Authors
  1. Natalia Rosso
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  2. Stefano Bellentani
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Corresponding authors

Correspondence to Natalia Rosso or Stefano Bellentani .

Editor information

Editors and Affiliations

  1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Florentina Radu-Ionita

  2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

    Nikolaos T. Pyrsopoulos

  3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Mariana Jinga

  4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

    Ion C. Tintoiu

  5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

    Zhonghua Sun

  6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

    Ecaterina Bontas

Self Study

Self Study

1.1 Questions

  1. 1.

    Which statement is true?

    1. (a)

      NAFLD/NASH treatment is nowadays based only on lifestyle changes, but it is enough to reach at least a reduction of 10% of the body weight to obtain a normalization of liver enzymes.

    2. (b)

      The diagnosis of NASH could be reached with non-invasive diagnostic markers.

    3. (c)

      The average prevalence of NAFLD worldwide is 35%.

    4. (d)

      Metformin, the most prescribed oral antidiabetic drugs, cannot be used in patients with NASH.

  1. 2.

    Which statement is true?

    1. (a)

      Lean NAFLD has a relatively benign clinical course with lower risk than NAFLD in obese subjects.

    2. (b)

      Among the experimental models, the in vitro systems are the best alternatives to reproduce the events involved in the progression of the disease.

    3. (c)

      In vivo models have played a vital role in the elucidation of the pathophysiological mechanisms of NAFLD; and there is wide variety of animal models to study this disease mimicking the human scenario.

    4. (d)

      The multifactorial nature of NAFLD hampers the progression in the field of pathophysiology and treatment.

1.2 Answers

  1. 1.

    Which statement is true?

    1. (a)

      CORRECT ANSWER: There are more than 200 clinical trials ongoing which explore different molecules belonging to different family of drugs, but still no drugs are approved to be used in the market worldwide.

    2. (b)

      The only possibility to make diagnosis of NASH is to perform liver biopsy, which remains still the gold standard for the diagnosis of NASH.

    3. (c)

      The real prevalence of NAFLD in the general population is ranging between 25% to 30% and could varies according to ethnicity, aged, sex, and the presence of co-morbidities such as type 2 diabetes mellitus, obesity, hypercholesterolemia, hypertension, etc.

    4. (d)

      All the drugs that are currently used in patients with type 2 diabetes mellitus and NAFLD/NASH should be continued even in the presence of NASH.

  2. 2.

    Which statement is true?

    1. (a)

      Lean NAFLD usually presents fewer comorbidities, for this reason, is commonly believed that this subgroup would follow a relatively benign clinical course. However, NASH prevalence in obese and nonobese has been reported to be similar. Moreover, the presence of advanced fibrosis in nonobese NASH patients is similar to the observed in obese subjects.

    2. (b)

      The currently available in vitro models cover a wide spectrum of variables, spanning from a simple cell culture or co-cultures (of two or more cells) exposed to different lipid mixtures, to more sophisticated 3D systems. However none of this experimental systems fulfil the all the events involved in the progression of the disease.

    3. (c)

      Due to the complex, multidirectional pathophysiology involved in NAFLD, the perfect animal model representing the complete spectrum of the disease in a workable time frame does not exist and translation of the results to human scenario has repeatedly failed.

    4. (d)

      CORRECT ANSWER: The complexity in the field of NAFLD is not limited to its pathophysiology, but also to the development of valid platforms for the discovery of therapeutic agents.

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Rosso, N., Bellentani, S. (2020). Nonalcoholic Fatty Liver Disease: A Wide Spectrum Disease. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_26

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  • DOI: https://doi.org/10.1007/978-3-030-24432-3_26

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-24431-6

  • Online ISBN: 978-3-030-24432-3

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