Fatty liver disease and primary liver cancer: disease mechanisms, emerging therapies and the role of bariatric surgery

References

• Torres DM, Harrison SA. Nonalcoholic fatty liver disease: fibrosis portends a worse prognosis. Hepatology. 2015;61:1462–1464.
   PubMed Web of Science ®Google Scholar
• Ekstedt M, Hagstrom 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;61:1547–1554.
   PubMed Web of Science ®Google Scholar
• Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol. 2012;56:1384–1391.
   PubMed Web of Science ®Google Scholar
• Wongjarupong N, Assavapongpaiboon B, Susantitaphong P, et al. Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis. BMC Gastroenterol. 2017;17:149.
   PubMed Web of Science ®Google Scholar
• Brunt EM, Wong VW, Nobili V, et al. Nonalcoholic fatty liver disease. Nat Rev Dis Primers. 2015;1:15080.
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30:1212–1218.
   PubMed Web of Science ®Google Scholar
• Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.
   PubMed Web of Science ®Google Scholar
• Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140:124–131.
   PubMed Web of Science ®Google Scholar
• Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis. 2007;11:1–16, vii.
   PubMedGoogle Scholar
• Yki-Jarvinen H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol. 2014;2:901–910.
   PubMed Web of Science ®Google Scholar
• Maher JJ, Leon P, Ryan JC. Beyond insulin resistance: innate immunity in nonalcoholic steatohepatitis. Hepatology. 2008;48:670–678.
   PubMed Web of Science ®Google Scholar
• Samuel VT, Liu ZX, Wang A, et al. Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest. 2007;117:739–745.
   PubMed Web of Science ®Google Scholar
• Lambert JE, Ramos-Roman MA, Browning JD, et al. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014;146:726–735.
   PubMed Web of Science ®Google Scholar
• Koliaki C, Szendroedi J, Kaul K, et al. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab. 2015;21:739–746.
   PubMed Web of Science ®Google Scholar
• Johnson ES, Lindblom KR, Robeson A, et al. Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis. J Biol Chem. 2013;288:14463–14475.
   PubMed Web of Science ®Google Scholar
• Cazanave SC, Mott JL, Bronk SF, et al. Death receptor 5 signaling promotes hepatocyte lipoapoptosis. J Biol Chem. 2011;286:39336–39348.
   PubMed Web of Science ®Google Scholar
• Lawan A, Bennett AM. Mitogen-activated protein kinase regulation in hepatic metabolism. Trends Endocrinol Metab. 2017;28:868–878.
   PubMed Web of Science ®Google Scholar
• Anstee QM, Reeves HL, Kotsiliti E, et al. From NASH to HCC: current concepts and future challenges. Nat Clin Pract Gastroenterol Hepatol. 2019;16:411–428.
   Google Scholar
• Cholankeril G, Patel R, Khurana S, et al. Hepatocellular carcinoma in non-alcoholic steatohepatitis: current knowledge and implications for management. World J Hepatol. 2017;9:533–543.
   PubMed Web of Science ®Google Scholar
• Teoh NC, Dan YY, Swisshelm K, et al. Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology. 2008;47:2078–2088.
   PubMed Web of Science ®Google Scholar
• Tanaka S, Miyanishi K, Kobune M, et al. Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma. J Gastroenterol. 2013;48:1249–1258.
   PubMed Web of Science ®Google Scholar
• Kawada N, Imanaka K, Kawaguchi T, et al. Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis. J Gastroenterol. 2009;44:1190–1194.
   PubMed Web of Science ®Google Scholar
• Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often develop without significant liver fibrosis: a pathological analysis. Hepatology. 2009;49:851–859.
   PubMed Web of Science ®Google Scholar
• Patel A, Harrison SA. Hepatitis C virus infection and nonalcoholic steatohepatitis. Gastroenterol Hepatol. 2012;8:305–312.
   Google Scholar
• Moyer VA. Screening for hepatitis C virus infection in adults: U.S. preventive services task force recommendation statement. Ann Intern Med. 2013;159:349–357.
   PubMed Web of Science ®Google Scholar
• Meguid C, Ryan CE, Edil BH, et al. Establishing a framework for building multidisciplinary programs. J Multidiscip Healthc. 2015;8:519–526.
   PubMed Web of Science ®Google Scholar
• Vennarecci G, Laurenzi A, Santoro R, et al. The ALPPS procedure: a surgical option for hepatocellular carcinoma with major vascular invasion. World J Surg. 2014;38:1498–1503.
   PubMed Web of Science ®Google Scholar
• Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334:693–699.
   PubMed Web of Science ®Google Scholar
• Pavel MC, Fuster J. Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: future directions. World J Gastroenterol. 2018;24:3626–3636.
   PubMed Web of Science ®Google Scholar
• Lemoinne S, Friedman SL. New and emerging anti-fibrotic therapeutics entering or already in clinical trials in chronic liver diseases. Curr Opin Pharmacol. 2019;49:60–70.
   PubMed Web of Science ®Google Scholar
• Bowlus C, Pockros P, Kremer AE, et al. Long-Term obeticholic acid (OCA) treatment associated with reversal or stabilization of fibrosis/cirrhosis in patients with primary biliary cholangitis (PBC). J Hepatol. 2018;68:S111–S112.
   Web of Science ®Google Scholar
• 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;385:956–965.
   PubMed Web of Science ®Google Scholar
• Younossi Z, Ratziu V, Loomba R, et al. GS-06-Positive Results from REGENERATE: a phase 3 international, randomized, placebo-controlled study evaluating obeticholic acid treatment for NASH. J Hepatol. 2019;70.
   PubMed Web of Science ®Google Scholar
• Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an agonist of the peroxisome proliferator-activated receptor-alpha and -delta, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening. Gastroenterology. 2016;150:1147–1159.e5.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Seghieri M, Christensen AS, Andersen A, et al. Future perspectives on GLP-1 receptor agonists and GLP-1/glucagon receptor co-agonists in the treatment of NAFLD. Front Endocrinol (Lausanne). 2018;9:649.
   PubMed Web of Science ®Google Scholar
• Jung CH, Mok JO. The effects of hypoglycemic agents on non-alcoholic fatty liver disease: focused on sodium-glucose cotransporter 2 Inhibitors and glucagon-like peptide-1 receptor agonists. J Obesity Metab Syndrome. 2019;28:18–29.
   PubMed Web of Science ®Google Scholar
• Petit JM, Cercueil JP, Loffroy R, et al. Effect of liraglutide therapy on liver fat content in patients with inadequately controlled type 2 diabetes: the Lira-NAFLD study. J Clin Endocrinol Metab. 2017;102:407–415.
   PubMed Web of Science ®Google Scholar
• Yu P, Xu X, Zhang J, et al. Liraglutide attenuates nonalcoholic fatty liver disease through adjusting lipid metabolism via SHP1/AMPK signaling pathway. Int J Endocrinol. 2019;2019:1567095.
   PubMedGoogle Scholar
• Bril F, Kalavalapalli S, Clark VC, et al. Response to pioglitazone in patients with nonalcoholic steatohepatitis with vs without type 2 diabetes. Clin Gastroenterol Hepatol. 2018;16:558–566.e2.
   PubMed Web of Science ®Google Scholar
• Leoni S, Tovoli F, Napoli L, et al. Current guidelines for the management of non-alcoholic fatty liver disease: a systematic review with comparative analysis. World J Gastroenterol. 2018;24:3361–3373.
   PubMed Web of Science ®Google Scholar
• NICE tNIfHaCE. Non-alcoholic fatty liver disease (NAFLD): assessment and management.
   Google Scholar
• EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–1402.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Hirth DA, Jones EL, Rothchild KB, et al. Laparoscopic sleeve gastrectomy: long-term weight loss outcomes. Surg Obesity Related Dis. 2015;11:1004–1007.
   PubMed Web of Science ®Google Scholar
• Obeid NR, Dimick JB, Telem DA. Sexual function after bariatric surgery: a new level of comorbidity improvement. JAMA Surg. 2019;154:499.
   PubMed Web of Science ®Google Scholar
• Lyo V, Schafer AL, Stewart L. Roux-en-Y gastric bypass is a safe and effective option that improves major Co-Morbidities associated with obesity in an older, veteran population. Am J Surg. 2019;218:684–688.
   PubMed Web of Science ®Google Scholar
• Shubeck S, Dimick JB, Telem DA. Long-term outcomes following bariatric surgery. JAMA. 2018;319:302–303.
   PubMed Web of Science ®Google Scholar
• Kwak M, Mehaffey JH, Hawkins RB, et al. Bariatric surgery is associated with reduction in non-alcoholic steatohepatitis and hepatocellular carcinoma: a propensity matched analysis. Am J Surg. 2019.doi: 10.1016/j.amjsurg.2019.09.006. [Epub ahead of print]
   PubMedGoogle Scholar
• Cherla DV, Rodriguez NA, Vangoitsenhoven R, et al. Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease. Surg Endosc. 2019.doi: 10.1007/s00464-019-07017-0. [Epub ahead of print]
   Google Scholar
• Salman MA, Salman AA, Abdelsalam A, et al. Laparoscopic sleeve gastrectomy on the horizon as a promising treatment modality for NAFLD. Obes Surg. 2019.doi: 10.1007/s11695-019-04118-6. [Epub ahead of print]
   Google Scholar
• Michelotti GA, Machado MV, Diehl AM. NAFLD, NASH and liver cancer. Nat Clin Pract Gastroenterol Hepatol. 2013;10:656–665.
   Google Scholar
• Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362:1675–1685.
   PubMed Web of Science ®Google Scholar
• Gulliford MC, Charlton J, Prevost T, et al. Costs and outcomes of increasing access to bariatric surgery: cohort study and cost-effectiveness analysis using electronic health records. Value Health. 2017;20:85–92.
   PubMed Web of Science ®Google Scholar
• Aminian A, Zajichek A, Arterburn DE, et al. Association of metabolic surgery with major adverse cardiovascular outcomes in patients with type 2 diabetes and obesity. Jama. 2019;322:1271.
   Web of Science ®Google Scholar
• Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric surgery and the risk of cancer in a large multisite cohort. Ann Surg. 2019;269:95–101.
   PubMed Web of Science ®Google Scholar
• Brantley PJ, Waldo K, Matthews-Ewald MR, et al. Why patients seek bariatric surgery: does insurance coverage matter? Obes Surg. 2014;24:961–964.
   PubMed Web of Science ®Google Scholar