Younossi ZM. Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2019;70(3):531–44.

Article  PubMed  Google Scholar 

Estes C, Anstee QM, Arias-Loste MT, Bantel H, Bellentani S, Caballeria J, 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(4):896–904.

Article  PubMed  Google Scholar 

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(1):73–84.

Article  PubMed  Google Scholar 

Sanyal AJ, Harrison SA, Ratziu V, Abdelmalek MF, Diehl AM, Caldwell S, et al. The natural history of Advanced Fibrosis due to nonalcoholic steatohepatitis: data from the Simtuzumab trials. Hepatology. 2019;70(6):1913–27.

Article  CAS  PubMed  Google Scholar 

Targher G, Byrne CD, Tilg H. NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications. Gut. 2020;69(9):1691–705.

Article  CAS  PubMed  Google Scholar 

Simon TG, Roelstraete B, Khalili H, Hagstrom H, Ludvigsson JF. Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort. Gut. 2021;70(7):1375–82.

Article  PubMed  Google Scholar 

Spengler EK, Loomba R. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Mayo Clinic Proceedings. 2015;90(9):1233-46.

Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, 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(1):328–57.

Article  PubMed  Google Scholar 

Torres DM, Williams CD, HarrisonO SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology. 2012;10(8):837–58.

Article  PubMed  Google Scholar 

Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, Torres-Gonzalez A, Gra-Oramas B, Gonzalez-Fabian L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):367-+.

Article  PubMed  Google Scholar 

Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB, et al. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol. 2011;106(3):460–8; quiz 9.

Article  PubMed  PubMed Central  Google Scholar 

Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148(3):547–55.

Article  PubMed  Google Scholar 

Samuel VT, Shulman GI. Nonalcoholic fatty liver disease as a Nexus of metabolic and hepatic Diseases. Cell Metabolism. 2018;27(1):22–41.

Article  CAS  PubMed  Google Scholar 

Jia W, Xie G, Jia W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nature Reviews Gastroenterology & Hepatology. 2018;15(2):111–28.

Article  CAS  Google Scholar 

Eslam M, Sanyal AJ, George J, Int Consensus P. MAFLD: A Consensus-Driven proposed nomenclature for metabolic Associated fatty liver disease. Gastroenterology. 2020;158(7):1999-+.

Article  CAS  PubMed  Google Scholar 

Chitturi S, Wong VW-S, Chan W-K, Wong GL-H, Wong SK-H, Sollano J, et al. The Asia-Pacific Working Party on non-alcoholic fatty liver Disease guidelines 2017Part 2: management and special groups. Journal of Gastroenterology and Hepatology. 2018;33(1):86–98.

Article  PubMed  Google Scholar 

Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. American Journal of Physiology-Endocrinology and Metabolism. 2005;288(2):E462-E8.

Article  Google Scholar 

Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and Meta-analysis of Paired-Biopsy Studies. Clinical Gastroenterology and Hepatology. 2015;13(4):643-+.

Article  PubMed  Google Scholar 

Loomba R, Adams LA. The 20% rule of NASH Progression: the natural history of Advanced Fibrosis and Cirrhosis caused by NASH. Hepatology. 2019;70(6):1885–8.

Article  PubMed  Google Scholar 

Zhou Y-Y, Zhou X-D, Wu S-J, Fan D-H, Van Poucke S, Chen Y-P, et al. Nonalcoholic fatty liver Disease contributes to subclinical atherosclerosis: a systematic review and Meta-analysis. Hepatology Communications. 2018;2(4):376–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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(2):389-+.

Article  PubMed  Google Scholar 

Xu L, Ma H, Miao M, Li Y. Impact of subclinical hypothyroidism on the development of non-alcoholic fatty liver disease: a prospective case-control study. J Hepatol. 2012;57(5):1153–4.

Article  CAS  PubMed  Google Scholar 

Xu C, Yu C, Xu L, Miao M, Li Y. High serum uric acid increases the risk for nonalcoholic fatty liver disease: a prospective observational study. Plos One. 2010;5(7).

Ma H, Xu C, Xu L, Yu C, Mao M, Li Y. Independent association of HbA1c and nonalcoholic fatty liver disease in an elderly chinese population. Bmc Gastroenterology. 2013;13.

Xu C, Wan X, Xu L, Miao M, Li Y, Yu C. Xanthine Oxidase promotes hyperuricemia and nonalcoholic fatty liver disease in patients and mice. Gastroenterology. 2015;148(4):S1053-S.

Article  Google Scholar 

Wehmeyer MH, Zyriax B-C, Jagemann B, Roth E, Windler E, Zur Wiesch JS, et al. Nonalcoholic fatty liver disease is associated with excessive calorie intake rather than a distinctive dietary pattern. Medicine. 2016;95(23).

Kwok R, Choi KC, Wong GL-H, Zhang Y, Chan HL-Y, Luk AO-Y, et al. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut. 2016;65(8):1359–68.

Article  CAS  PubMed  Google Scholar 

Leung C, Rivera L, Furness JB, Angus PW. The role of the gut microbiota in NAFLD. Nature Reviews Gastroenterology & Hepatology. 2016;13(7):412–25.

Article  CAS  Google Scholar 

Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222-+.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bian X, Liu R, Meng Y, Xing D, Xu D, Lu Z. Cancer focus lipid metabolism and cancer. Journal of Experimental Medicine. 2021;218(1).

Hirsova P, Ibrabim SH, Gores GJ, Malhi H. Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis. J Lipid Res. 2016;57(10):1758–70.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ralston JC, Lyons CL, Kennedy EB, Kirwan AM, Roche HM. Fatty acids and NLRP3 inflammasome-mediated inflammation in metabolic tissues. Annu Rev Nutr. 2017;37:77–102.

Article  CAS  PubMed  Google Scholar 

Lomonaco R, Ortiz-Lopez C, Orsak B, Webb A, Hardies J, Darland C, et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology. 2012;55(5):1389–97.

Article  CAS  PubMed  Google Scholar 

Fu S, Watkins SM, Hotamisligil GS. The role of endoplasmic reticulum in hepatic lipid homeostasis and stress signaling. Cell Metabolism. 2012;15(5):623–34.

Article  CAS  PubMed  Google Scholar 

Perry RJ, Samuel VT, Petersen KF, Shulman GI. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature. 2014;510(7503):84–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation. 2006;116(11):3015–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Turpin SM, Nicholls HT, Willmes DM, Mourier A, Brodesser S, Wunderlich CM, et al. Obesity-Induced CerS6-Dependent C-16:0 Ceramide Production promotes weight gain and glucose intolerance. Cell Metabolism. 2014;20(4):678–86.

Article  CAS  PubMed  Google Scholar 

Xia JY, Holland WL, Kusminski CM, Sun K, Sharma AX, Pearson MJ, et al. Targeted induction of Ceramide Degradation leads to Improved systemic metabolism and reduced hepatic steatosis. Cell Metabolism. 2015;22(2):266–78.

Article  CAS  PubMed  PubMed Central  Google Scholar 

GarciaRuiz C, Colell A, Mari M, Morales A, FernandezCheca JC. Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species - role of mitochondrial glutathione. Journal of Biological Chemistry. 1997;272(17):11369–77.

Article  CAS  PubMed  Google Scholar 

Martinez L, Torres S, Baulies A, Alarcon-Vila C, Elena M, Fabrias G, et al. Myristic acid potentiates palmitic acid-induced lipotoxicity and steatohepatitis associated with lipodystrophy by sustaning de novo ceramide synthesis. Oncotarget. 2015;6(39):41479–96.

Article  PubMed  PubMed Central  Google Scholar 

Perez-Carreras M, Del Hoyo P, Martin MA, Rubio JC, Martin A, Castellano G, et