Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Causes of Mortality in Non-Alcoholic Fatty Liver Disease (NAFLD) and Alcohol Related Fatty Liver Disease (AFLD)

Author(s): Michael P. Johnston*, Janisha Patel and Christopher D. Byrne

Volume 26, Issue 10, 2020

Page: [1079 - 1092] Pages: 14

DOI: 10.2174/1381612826666200128094231

Price: $65

Abstract

Non-alcoholic fatty liver disease (NAFLD) and alcohol related fatty liver disease (AFLD) both represent a spectrum of liver disease severity from hepatic steatosis to fibrosis and cirrhosis. Both NAFLD and AFLD are common diseases in the general population. NAFLD affects ~25% of the adult global population whilst AFLD has become the commonest indication for liver transplantation in the United States. It is often not possible to distinguish between NAFLD and AFLD on examination of liver histology, consequently, differentiation between NAFLD and AFLD is heavily reliant on a history of alcohol consumption.

Age, smoking, alcohol consumption and sex appear to influence the risk of mortality in NAFLD or AFLD. In NAFLD and AFLD, the key causes of increased liver-related mortality are advanced liver fibrosis and cirrhosis leading to complications such as hepatocellular carcinoma and decompensated cirrhosis. NAFLD and AFLD are also associated with an increased risk of all-cause mortality including an increased risk of extra-hepatic malignancy. Non-invasive biomarkers of liver disease severity in NAFLD and AFLD perform poorly to predict mortality. However, alanine aminotransferase, gamma-glutamyl transpeptidase, FIB-4 and the NAFLD Fibrosis Score are independently associated with increased mortality in NAFLD.

Both NAFLD and AFLD are associated with extra-hepatic risk factors and complications such as metabolic syndrome encompassing obesity, hypertension, type 2 diabetes mellitus, and chronic kidney disease. AFLD is associated with hypertension and cardiovascular disease as well as other organ damage.

This narrative review discusses the associations, risk factors and diagnostic biomarkers linking NAFLD and AFLD with increased mortality.

Keywords: Alcoholic fatty liver disease, alcoholic steatohepatitis, metabolic syndrome, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, T2DM, CVD, mortality.

« Previous Next »
[1]
Thursz M, Gual A, Lackner C, et al. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018; 69(1): 154-81.
[http://dx.doi.org/10.1016/j.jhep.2018.03.018] [PMID: 29628280]
[2]
Levene AP, Goldin RD. The epidemiology, pathogenesis and histopathology of fatty liver disease. Histopathology 2012; 61(2): 141-52.
[http://dx.doi.org/10.1111/j.1365-2559.2011.04145.x] [PMID: 22372457]
[3]
Scaglioni F, Ciccia S, Marino M, Bedogni G, Bellentani S. ASH and NASH. Dig Dis 2011; 29(2): 202-10.
[http://dx.doi.org/10.1159/000323886] [PMID: 21734385]
[4]
Williams R, Alexander G, Armstrong I, et al. Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK. Lancet 2018; 391(10125): 1097-107.
[http://dx.doi.org/10.1016/S0140-6736(17)32866-0] [PMID: 29198562]
[5]
Younossi Z, Henry L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology 2016; 150(8): 1778-85.
[http://dx.doi.org/10.1053/j.gastro.2016.03.005] [PMID: 26980624]
[6]
Bellentani S, Saccoccio G, Costa G, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. Gut 1997; 41(6): 845-50.
[http://dx.doi.org/10.1136/gut.41.6.845] [PMID: 9462221]
[7]
Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis c virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol 2018; 16(8): 1356-8.
[http://dx.doi.org/10.1016/j.cgh.2017.11.045] [PMID: 29199144]
[8]
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.
[http://dx.doi.org/10.1002/hep.28431] [PMID: 26707365]
[9]
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(6): 2005-23.
[http://dx.doi.org/10.1002/hep.25762] [PMID: 22488764]
[10]
Shingina A, DeWitt PE, Dodge JL, et al. Future trends in demand for liver transplant: birth cohort effects among patients with NASH and HCC. Transplantation 2019; 103(1): 140-8.
[http://dx.doi.org/10.1097/TP.0000000000002497] [PMID: 30451739]
[11]
Ong J, Younossi ZM, Reddy V, et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl 2001; 7(9): 797-801.
[http://dx.doi.org/10.1053/jlts.2001.24644] [PMID: 11552214]
[12]
Golabi P, Bush H, Stepanova M, et al. Liver transplantation (LT) for cryptogenic cirrhosis (CC) and nonalcoholic steatohepatitis (NASH) cirrhosis data from the Scientific Registry of Transplant Recipients (SRTR): 1994 to 2016. Medicine (Baltimore) 2018; 97(31): e11518
[http://dx.doi.org/10.1097/MD.0000000000011518] [PMID: 30075518]
[13]
Lee BP, Vittinghoff E, Dodge JL, Cullaro G, Terrault NA. National trends and long-term outcomes of liver transplant for alcohol-associated liver disease in the United States. JAMA Intern Med 2019; 179(3): 340-8.
[http://dx.doi.org/10.1001/jamainternmed.2018.6536] [PMID: 30667468]
[14]
Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015; 62(6): 1723-30.
[http://dx.doi.org/10.1002/hep.28123] [PMID: 26274335]
[15]
Pais R, Lebray P, Rousseau G, et al. Nonalcoholic fatty liver disease increases the risk of hepatocellular carcinoma in patients with alcohol-associated cirrhosis awaiting liver transplants. Clin Gastroenterol Hepatol 2015; 13(5): 992-9.e2.
[http://dx.doi.org/10.1016/j.cgh.2014.10.011] [PMID: 25459558]
[16]
Adams LA, Anstee QM, Tilg H, Targher G. Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 2017; 66(6): 1138-53.
[http://dx.doi.org/10.1136/gutjnl-2017-313884] [PMID: 28314735]
[17]
Stefan N, Fritsche A, Schick F, Häring HU. Phenotypes of prediabetes and stratification of cardiometabolic risk. Lancet Diabetes Endocrinol 2016; 4(9): 789-98.
[http://dx.doi.org/10.1016/S2213-8587(16)00082-6] [PMID: 27185609]
[18]
Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015; 62(1)(Suppl.): S47-64.
[http://dx.doi.org/10.1016/j.jhep.2014.12.012] [PMID: 25920090]
[19]
Mathurin P, Beuzin F, Louvet A, et al. Fibrosis progression occurs in a subgroup of heavy drinkers with typical histological features. Aliment Pharmacol Ther 2007; 25(9): 1047-54.
[http://dx.doi.org/10.1111/j.1365-2036.2007.03302.x] [PMID: 17439505]
[20]
Deleuran T, Grønbaek H, Vilstrup H, Jepsen P. Cirrhosis and mortality risks of biopsy-verified alcoholic pure steatosis and steatohepatitis: a nationwide registry-based study. Aliment Pharmacol Ther 2012; 35(11): 1336-42.
[http://dx.doi.org/10.1111/j.1365-2036.2012.05091.x] [PMID: 22490057]
[21]
Jepsen P, Vilstrup H, Mellemkjaer L, et al. Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort study. Hepatogastroenterology 2003; 50(54): 2101-4.
[PMID: 14696473]
[22]
Parker R, Aithal GP, Becker U, et al. Natural history of histologically proven alcohol-related liver disease: A systematic review. J Hepatol 2019; 71(3): 586-93.
[http://dx.doi.org/10.1016/j.jhep.2019.05.020] [PMID: 31173814]
[23]
Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med 2015; 372(17): 1619-28.
[http://dx.doi.org/10.1056/NEJMoa1412278] [PMID: 25901427]
[24]
Dam-Larsen S, Becker U, Franzmann MB, Larsen K, Christoffersen P, Bendtsen F. Final results of a long-term, clinical follow-up in fatty liver patients. Scand J Gastroenterol 2009; 44(10): 1236-43.
[http://dx.doi.org/10.1080/00365520903171284] [PMID: 19670076]
[25]
FDA/CDER.. Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing Drugs for Treatment Guidance for Industry DRAFT GUIDANCE FDA 2018.Available from: https://www.fda.gov/ Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/default.htm
[26]
Rafiq N, Bai C, Fang Y, et al. Long-term follow-up of patients with nonalcoholic fatty liver. Clin Gastroenterol Hepatol 2009; 7(2): 234-8.
[http://dx.doi.org/10.1016/j.cgh.2008.11.005] [PMID: 19049831]
[27]
Dulai PS, Singh S, Patel J, et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta-analysis. Hepatology 2017; 65(5): 1557-65.
[http://dx.doi.org/10.1002/hep.29085] [PMID: 28130788]
[28]
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(2): 389-97.e10.
[http://dx.doi.org/10.1053/j.gastro.2015.04.043] [PMID: 25935633]
[29]
Younossi ZM, Stepanova M, Rafiq N, et al. Pathologic criteria for nonalcoholic steatohepatitis: interprotocol agreement and ability to predict liver-related mortality. Hepatology 2011; 53(6): 1874-82.
[http://dx.doi.org/10.1002/hep.24268] [PMID: 21360720]
[30]
Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013; 57(4): 1357-65.
[http://dx.doi.org/10.1002/hep.26156] [PMID: 23175136]
[31]
Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94(9): 2467-74.
[http://dx.doi.org/10.1111/j.1572-0241.1999.01377.x] [PMID: 10484010]
[32]
McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol 2015; 62(5): 1148-55.
[http://dx.doi.org/10.1016/j.jhep.2014.11.034] [PMID: 25477264]
[33]
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(5): 1547-54.
[http://dx.doi.org/10.1002/hep.27368] [PMID: 25125077]
[34]
Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol 2017; 67(6): 1265-73.
[http://dx.doi.org/10.1016/j.jhep.2017.07.027] [PMID: 28803953]
[35]
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41(6): 1313-21.
[http://dx.doi.org/10.1002/hep.20701] [PMID: 15915461]
[36]
Younossi ZM, Stepanova M, Rafiq N, et al. Nonalcoholic steatofibrosis independently predicts mortality in nonalcoholic fatty liver disease. Hepatol Commun 2017; 1(5): 421-8.
[http://dx.doi.org/10.1002/hep4.1054] [PMID: 29404470]
[37]
Angulo P. Long-term mortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology 2010; 51(2): 373-5.
[http://dx.doi.org/10.1002/hep.23521] [PMID: 20101746]
[38]
Argo CK, Northup PG, Al-Osaimi AMS, Caldwell SH. Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. J Hepatol 2009; 51(2): 371-9.
[http://dx.doi.org/10.1016/j.jhep.2009.03.019] [PMID: 19501928]
[39]
Strader DB, Seeff LB. A brief history of the treatment of viral hepatitis C. Clin Liver Dis (Hoboken) 2012; 1(1): 6-11.
[http://dx.doi.org/10.1002/cld.1] [PMID: 31186837]
[40]
Bhagat V, Mindikoglu AL, Nudo CG, Schiff ER, Tzakis A, Regev A. Outcomes of liver transplantation in patients with cirrhosis due to nonalcoholic steatohepatitis versus patients with cirrhosis due to alcoholic liver disease. Liver Transpl 2009; 15(12): 1814-20.
[http://dx.doi.org/10.1002/lt.21927] [PMID: 19938128]
[41]
VanWagner LB, Lapin B, Skaro AI, Lloyd-Jones DM, Rinella ME. Impact of renal impairment on cardiovascular disease mortality after liver transplantation for nonalcoholic steatohepatitis cirrhosis. Liver Int 2015; 35(12): 2575-83.
[http://dx.doi.org/10.1111/liv.12872] [PMID: 25977117]
[42]
Liu Y, Zhong G-C, Tan H-Y, Hao F-B, Hu J-J. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Sci Rep 2019; 9(1): 11124.
[http://dx.doi.org/10.1038/s41598-019-47687-3] [PMID: 31366982]
[43]
Vilar-Gomez E, Calzadilla-Bertot L, Wai-Sun Wong V, et al. Fibrosis severity as a determinant of cause-specific mortality in patients with advanced nonalcoholic fatty liver disease: a multi-national cohort study. Gastroenterology 2018; 155(2): 443-457.e17.
[http://dx.doi.org/10.1053/j.gastro.2018.04.034] [PMID: 29733831]
[44]
Söderberg C, Stål P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010; 51(2): 595-602.
[http://dx.doi.org/10.1002/hep.23314] [PMID: 20014114]
[45]
Trimble G, Zheng L, Mishra A, Kalwaney S, Mir HM, Younossi ZM. Mortality associated with alcohol-related liver disease. Aliment Pharmacol Ther 2013; 38(6): 596-602.
[http://dx.doi.org/10.1111/apt.12432] [PMID: 23889765]
[46]
Zhou YJ, Li YY, Nie YQ, Huang CM, Cao CY. Natural course of nonalcoholic fatty liver disease in southern China: a prospective cohort study. J Dig Dis 2012; 13(3): 153-60.
[http://dx.doi.org/10.1111/j.1751-2980.2011.00571.x] [PMID: 22356310]
[47]
Mahfood Haddad T, Hamdeh S, Kanmanthareddy A, Alla VM. Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis. Diabetes Metab Syndr 2017; 11(Suppl. 1): S209-16.
[http://dx.doi.org/10.1016/j.dsx.2016.12.033] [PMID: 28017631]
[48]
Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J Hepatol 2016; 65(3): 589-600.
[http://dx.doi.org/10.1016/j.jhep.2016.05.013] [PMID: 27212244]
[49]
Wild SH, Walker JJ, Morling JR, et al. Cardiovascular disease, cancer, and mortality among people with type 2 diabetes and alcoholic or nonalcoholic fatty liver disease hospital admission. Diabetes Care 2018; 41(2): 341-7.
[http://dx.doi.org/10.2337/dc17-1590] [PMID: 29167212]
[50]
Chang Y, Ryu S, Sung KC, et al. Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study. Gut 2018; 68(9): 1667-75.
[51]
Keskin M, Hayıroğlu Mİ, Uzun AO, Güvenç TS, Şahin S, Kozan Ö. Effect of nonalcoholic fatty liver disease on in-hospital and long-term outcomes in patients with ST-segment elevation myocardial infarction. Am J Cardiol 2017; 120(10): 1720-6.
[http://dx.doi.org/10.1016/j.amjcard.2017.07.107] [PMID: 28867124]
[52]
Shahab O, Biswas R, Paik J, Bush H, Golabi P, Younossi ZM. Among patients with NAFLD, treatment of dyslipidemia does not reduce cardiovascular mortality. Hepatol Commun 2018; 2(10): 1227-34.
[http://dx.doi.org/10.1002/hep4.1241] [PMID: 30288477]
[53]
Valbusa F, Agnoletti D, Scala L, et al. Non-alcoholic fatty liver disease and increased risk of all-cause mortality in elderly patients admitted for acute heart failure. Int J Cardiol 2018; 265: 162-8.
[http://dx.doi.org/10.1016/j.ijcard.2018.04.129] [PMID: 29739707]
[54]
Mantovani A, Dauriz M, Sandri D, et al. Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta-analysis. Liver Int 2019; 39(4): 758-69.
[http://dx.doi.org/10.1111/liv.14044] [PMID: 30657626]
[55]
Hu J, Xu Y, He Z, et al. Increased risk of cerebrovascular accident related to non-alcoholic fatty liver disease: a meta-analysis. Oncotarget 2017; 9(2): 2752-60.
[PMID: 29416808]
[56]
Alkagiet S, Papagiannis A, Tziomalos K. Associations between nonalcoholic fatty liver disease and ischemic stroke. World J Hepatol 2018; 10(7): 474-8.
[http://dx.doi.org/10.4254/wjh.v10.i7.474] [PMID: 30079133]
[57]
Lonardo A, Bellentani S, Argo CK, et al. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups. Dig Liver Dis 2015; 47(12): 997-1006.
[http://dx.doi.org/10.1016/j.dld.2015.08.004] [PMID: 26454786]
[58]
Stepanova M, Rafiq N, Makhlouf H, et al. Predictors of all-cause mortality and liver-related mortality in patients with non-alcoholic fatty liver disease (NAFLD). Dig Dis Sci 2013; 58(10): 3017-23.
[http://dx.doi.org/10.1007/s10620-013-2743-5] [PMID: 23775317]
[59]
Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2004; 2(3): 262-5.
[http://dx.doi.org/10.1016/S1542-3565(04)00014-X] [PMID: 15017611]
[60]
Björkström K, Franzén S, Eliasson B, et al. Risk factors for severe liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2019; 17(13): 2769-2775.e4.
[http://dx.doi.org/10.1016/j.cgh.2019.04.038] [PMID: 31009793]
[61]
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. Clin Gastroenterol Hepatol 2015; 13(4): 643-54.e1.
[http://dx.doi.org/10.1016/j.cgh.2014.04.014] [PMID: 24768810]
[62]
Zhang T, Zhang C, Zhang Y, et al. Metabolic syndrome and its components as predictors of nonalcoholic fatty liver disease in a northern urban Han Chinese population: a prospective cohort study. Atherosclerosis 2015; 240(1): 144-8.
[http://dx.doi.org/10.1016/j.atherosclerosis.2015.02.049] [PMID: 25785362]
[63]
Mantovani A, Byrne CD, Bonora E, Targher G. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: a meta-analysis. Diabetes Care 2018; 41(2): 372-82.
[http://dx.doi.org/10.2337/dc17-1902] [PMID: 29358469]
[64]
Sung KC, Wild SH, Byrne CD. Resolution of fatty liver and risk of incident diabetes. J Clin Endocrinol Metab 2013; 98(9): 3637-43.
[http://dx.doi.org/10.1210/jc.2013-1519] [PMID: 23873989]
[65]
Sung KC, Seo DC, Lee SJ, Lee MY, Wild SH, Byrne CD. Non alcoholic fatty liver disease and risk of incident diabetes in subjects who are not obese. Nutr Metab Cardiovasc Dis 2019; 29(5): 489-95.
[http://dx.doi.org/10.1016/j.numecd.2019.01.016] [PMID: 30940491]
[66]
Wild SH, Morling JR, McAllister DA, et al. Type 2 diabetes and risk of hospital admission or death for chronic liver diseases. J Hepatol 2016; 64(6): 1358-64.
[http://dx.doi.org/10.1016/j.jhep.2016.01.014] [PMID: 26812073]
[67]
Hazlehurst JM, Woods C, Marjot T, Cobbold JF, Tomlinson JW. Non-alcoholic fatty liver disease and diabetes. Metabolism 2016; 65(8): 1096-108.
[http://dx.doi.org/10.1016/j.metabol.2016.01.001] [PMID: 26856933]
[68]
Mantovani A, Zaza G, Byrne CD, et al. Nonalcoholic fatty liver disease increases risk of incident chronic kidney disease: A systematic review and meta-analysis. Metabolism 2018; 79: 64-76.
[http://dx.doi.org/10.1016/j.metabol.2017.11.003] [PMID: 29137912]
[69]
Chinnadurai R, Chrysochou C, Kalra PA. Increased risk for cardiovascular events in patients with diabetic kidney disease and non-alcoholic fatty liver disease. Nephron 2019; 141(1): 24-30.
[http://dx.doi.org/10.1159/000493472] [PMID: 30384370]
[70]
Önnerhag K, Dreja K, Nilsson PM, Lindgren S. Increased mortality in non-alcoholic fatty liver disease with chronic kidney disease is explained by metabolic comorbidities. Clin Res Hepatol Gastroenterol 2019; 43(5): 542-50.
[http://dx.doi.org/10.1016/j.clinre.2019.02.004] [PMID: 30827925]
[71]
Mittal S, Sada YH, El-Serag HB, et al. Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population. Clin Gastroenterol Hepatol 2015; 13(3): 594-601.e1.
[http://dx.doi.org/10.1016/j.cgh.2014.08.013] [PMID: 25148760]
[72]
Hester D, Golabi P, Paik J, Younossi I, Mishra A, Younossi ZM. Among medicare patients with hepatocellular carcinoma, nonalcoholic fatty liver disease is the most common etiology and cause of mortality. J Clin Gastroenterol 2019.(Online ahead of print).
[http://dx.doi.org/10.1097/MCG.0000000000001172] [PMID: 30672817]
[73]
Wang YG, Wang P, Wang B, Fu ZJ, Zhao WJ, Yan SL. Diabetes mellitus and poorer prognosis in hepatocellular carcinoma: a systematic review and meta-analysis. PLoS One 2014; 9(5)e95485
[http://dx.doi.org/10.1371/journal.pone.0095485] [PMID: 24830459]
[74]
Kasmari AJ, Welch A, Liu G, Leslie D, McGarrity T, Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome. Am J Med 2017; 130(6): 746.e1-7.
[http://dx.doi.org/10.1016/j.amjmed.2016.12.029] [PMID: 28109969]
[75]
Kanwal F, Kramer JR, Mapakshi S, et al. Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease. Gastroenterology 2018; 155(6): 1828-1837.e2.
[http://dx.doi.org/10.1053/j.gastro.2018.08.024] [PMID: 30144434]
[76]
Yang JD, Ahmed F, Mara KC, et al. Diabetes is associated with increased risk of hepatocellular carcinoma in patients with cirrhosis from nonalcoholic fatty liver disease. Hepatology 2019.(Online ahead of print).
[http://dx.doi.org/10.1002/hep.30858]
[77]
Ioannou GN, Green P, Kerr KF, Berry K. Models estimating risk of hepatocellular carcinoma in patients with alcohol or NAFLD-related cirrhosis for risk stratification. J Hepatol 2019; 71(3): 523-33.
[http://dx.doi.org/10.1016/j.jhep.2019.05.008] [PMID: 31145929]
[78]
Mantovani A, Dauriz M, Byrne CD, et al. Association between nonalcoholic fatty liver disease and colorectal tumours in asymptomatic adults undergoing screening colonoscopy: a systematic review and meta-analysis. Metabolism 2018; 87: 1-12.
[http://dx.doi.org/10.1016/j.metabol.2018.06.004] [PMID: 29935236]
[79]
Murphy N, Jenab M, Gunter MJ. Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions. Nat Rev Gastroenterol Hepatol 2018; 15(11): 659-70.
[http://dx.doi.org/10.1038/s41575-018-0038-1] [PMID: 29970888]
[80]
Kim G-A, Lee HC, Choe J, et al. Association between non-alcoholic fatty liver disease and cancer incidence rate. J Hepatol 2017; 68: 140-6.
[http://dx.doi.org/10.1016/j.jhep.2017.09.012] [PMID: 29150142]
[81]
LoConte NK, Brewster AM, Kaur JS, Merrill JK, Alberg AJ. Alcohol and cancer: a statement of the american society of clinical oncology. J Clin Oncol 2018; 36(1): 83-93.
[http://dx.doi.org/10.1200/JCO.2017.76.1155] [PMID: 29112463]
[82]
Hydes TJ, Burton R, Inskip H, Bellis MA, Sheron N. A comparison of gender-linked population cancer risks between alcohol and tobacco: how many cigarettes are there in a bottle of wine? BMC Public Health 2019; 19(1): 316.
[http://dx.doi.org/10.1186/s12889-019-6576-9] [PMID: 30917803]
[83]
Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 2015; 112(3): 580-93.
[http://dx.doi.org/10.1038/bjc.2014.579] [PMID: 25422909]
[84]
Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34(3): 274-85.
[http://dx.doi.org/10.1111/j.1365-2036.2011.04724.x] [PMID: 21623852]
[85]
Golabi P, Otgonsuren M, de Avila L, Sayiner M, Rafiq N, Younossi ZM. Components of metabolic syndrome increase the risk of mortality in nonalcoholic fatty liver disease (NAFLD). Medicine (Baltimore) 2018; 97(13): e0214
[http://dx.doi.org/10.1097/MD.0000000000010214] [PMID: 29595666]
[86]
Golabi P, Paik J, Reddy R, Bugianesi E, Trimble G, Younossi ZM. Prevalence and long-term outcomes of non-alcoholic fatty liver disease among elderly individuals from the United States. BMC Gastroenterol 2019; 19(1): 56.
[http://dx.doi.org/10.1186/s12876-019-0972-6] [PMID: 30991959]
[87]
Hwang YC, Ahn HY, Park SW, Park CY. Nonalcoholic fatty liver disease associates with increased overall mortality and death from cancer, cardiovascular disease, and liver disease in women but not men. Clin Gastroenterol Hepatol 2018; 16(7): 1131-1137.e5.
[http://dx.doi.org/10.1016/j.cgh.2017.11.026] [PMID: 29158157]
[88]
Yang JD, Abdelmalek MF, Pang H, et al. Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology 2014; 59(4): 1406-14.
[http://dx.doi.org/10.1002/hep.26761] [PMID: 24123276]
[89]
Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Lonardo A. NAFLD as a sexual dimorphic disease: role of gender and reproductive status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk. Adv Ther 2017; 34(6): 1291-326.
[http://dx.doi.org/10.1007/s12325-017-0556-1] [PMID: 28526997]
[90]
Eguchi Y, Hyogo H, Ono M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study. J Gastroenterol 2012; 47(5): 586-95.
[http://dx.doi.org/10.1007/s00535-012-0533-z] [PMID: 22328022]
[91]
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(1): 124-31.
[http://dx.doi.org/10.1053/j.gastro.2010.09.038] [PMID: 20858492]
[92]
Di Cesare M, Bentham J, Stevens GA, et al. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants. Lancet 2016; 387(10026): 1377-96.
[http://dx.doi.org/10.1016/S0140-6736(16)30054-X] [PMID: 27115820]
[93]
Åberg F, Puukka P, Salomaa V, et al. Risks of light and moderate alcohol use in fatty liver disease: follow‐up of population cohorts. Hepatology 2019. (Online ahead of print).
[94]
Younossi ZM, Stepanova M, Negro F, et al. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine (Baltimore) 2012; 91(6): 319-27.
[http://dx.doi.org/10.1097/MD.0b013e3182779d49] [PMID: 23117851]
[95]
Cusi K. Nonalcoholic steatohepatitis in nonobese patients: Not so different after all. Hepatology 2017; 65(1): 4-7.
[http://dx.doi.org/10.1002/hep.28839] [PMID: 27650699]
[96]
Kim D, Kim WR. Nonobese fatty liver disease. Clin Gastroenterol Hepatol 2017; 15(4): 474-85.
[http://dx.doi.org/10.1016/j.cgh.2016.08.028] [PMID: 27581063]
[97]
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016; 64(6): 1388-402.
[http://dx.doi.org/10.1016/j.jhep.2015.11.004] [PMID: 27062661]
[98]
Leung JCF, Loong TCW, Wei JL, et al. Histological severity and clinical outcomes of nonalcoholic fatty liver disease in nonobese patients. Hepatology 2017; 65(1): 54-64.
[http://dx.doi.org/10.1002/hep.28697] [PMID: 27339817]
[99]
Fracanzani AL, Valenti L, Bugianesi E, et al. Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity. J Hepatol 2011; 54(6): 1244-9.
[http://dx.doi.org/10.1016/j.jhep.2010.09.037] [PMID: 21145841]
[100]
Saab S, Manne V, Nieto J, Schwimmer JB, Chalasani NP. Nonalcoholic fatty liver disease in Latinos. Clin Gastroenterol Hepatol 2016; 14(1): 5-12.
[http://dx.doi.org/10.1016/j.cgh.2015.05.001] [PMID: 25976180]
[101]
Kim D, Kim W, Adejumo AC, et al. Race/ethnicity-based temporal changes in prevalence of NAFLD-related advanced fibrosis in the United States, 2005-2016. Hepatol Int 2019; 13(2): 205-13.
[http://dx.doi.org/10.1007/s12072-018-09926-z] [PMID: 30694445]
[102]
Masuoka HC, Chalasani N. Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals. Ann N Y Acad Sci 2013; 1281: 106-22.
[http://dx.doi.org/10.1111/nyas.12016] [PMID: 23363012]
[103]
Rich NE, Oji S, Mufti AR, et al. Racial and ethnic disparities in nonalcoholic fatty liver disease prevalence, severity, and outcomes in the united states: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2018; 16(2): 198-210.e2.
[http://dx.doi.org/10.1016/j.cgh.2017.09.041] [PMID: 28970148]
[104]
Douds AC, Cox MA, Iqbal TH, Cooper BT. Ethnic differences in cirrhosis of the liver in a British city: alcoholic cirrhosis in South Asian men. Alcohol Alcohol 2003; 38(2): 148-50.
[http://dx.doi.org/10.1093/alcalc/agg040] [PMID: 12634262]
[105]
Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40(12): 1461-5.
[http://dx.doi.org/10.1038/ng.257] [PMID: 18820647]
[106]
Köpp J, Fleßa S, Lieb W, et al. Association of PNPLA3 rs738409 and TM6SF2 rs58542926 with health services utilization in a population-based study. BMC Health Serv Res 2016; 16: 41.
[http://dx.doi.org/10.1186/s12913-016-1289-6] [PMID: 26847197]
[107]
Chamorro AJ, Torres JL, Mirón-Canelo JA, González-Sarmiento R, Laso FJ, Marcos M. Systematic review with meta-analysis: the I148M variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is significantly associated with alcoholic liver cirrhosis. Aliment Pharmacol Ther 2014; 40(6): 571-81.
[http://dx.doi.org/10.1111/apt.12890] [PMID: 25060292]
[108]
Atkinson SR, Way MJ, McQuillin A, Morgan MY, Thursz MR. Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis. J Hepatol 2017; 67(1): 120-7.
[http://dx.doi.org/10.1016/j.jhep.2017.01.018] [PMID: 28161471]
[109]
Shen H, Rodriguez AC, Shiani A, et al. Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis. Therap Adv Gastroenterol 2016; 9(1): 113-20.
[http://dx.doi.org/10.1177/1756283X15593700] [PMID: 26770272]
[110]
Akhavan Rezayat A, Dadgar Moghadam M, Ghasemi Nour M, et al. Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis. SAGE Open Med 2018; 6: 2050312117745223
[http://dx.doi.org/10.1177/2050312117745223] [PMID: 29399359]
[111]
Wijarnpreecha K, Scribani M, Kim D, Kim WR. The interaction of nonalcoholic fatty liver disease and smoking on mortality among adults in the United States. Liver Int 2019; 39(7): 1202-6.
[http://dx.doi.org/10.1111/liv.14058] [PMID: 30697898]
[112]
Wood AM, Kaptoge S, Butterworth AS, et al. Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet 2018; 391(10129): 1513-23.
[http://dx.doi.org/10.1016/S0140-6736(18)30134-X] [PMID: 29676281]
[113]
Åberg F, Helenius-Hietala J, Puukka P, Färkkilä M, Jula A. Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population. Hepatology 2018; 67(6): 2141-9.
[http://dx.doi.org/10.1002/hep.29631] [PMID: 29164643]
[114]
Hajifathalian K, Torabi Sagvand B, McCullough AJ. Effect of alcohol consumption on survival in nonalcoholic fatty liver disease: a national prospective cohort study. Hepatology 2019; 70(2): 511-21.
[http://dx.doi.org/10.1002/hep.30226] [PMID: 30125379]
[115]
Younossi ZM, Stepanova M, Ong J, et al. Effects of alcohol consumption and metabolic syndrome on mortality in patients with nonalcoholic and alcohol-related fatty liver disease. Clin Gastroenterol Hepatol 2019; 17(8): 1625-1633.e1.
[http://dx.doi.org/10.1016/j.cgh.2018.11.033] [PMID: 30476585]
[116]
Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005; 42: 132-8.
[117]
Sung KC, Ryu S, Kim BS, et al. γ-Glutamyl transferase is associated with mortality outcomes independently of fatty liver. Clin Chem 2015; 61(9): 1173-81.
[http://dx.doi.org/10.1373/clinchem.2015.240424] [PMID: 26152752]
[118]
Peleg N, Sneh Arbib O, Issachar A, Cohen-Naftaly M, Braun M, Shlomai A. Noninvasive scoring systems predict hepatic and extra-hepatic cancers in patients with nonalcoholic fatty liver disease. PLoS One 2018; 13(8): e0202393
[http://dx.doi.org/10.1371/journal.pone.0202393] [PMID: 30106985]
[119]
Ito T, Ishigami M, Ishizu Y, et al. Utility and limitations of noninvasive fibrosis markers for predicting prognosis in biopsy-proven Japanese non-alcoholic fatty liver disease patients. J Gastroenterol Hepatol 2019; 34(1): 207-14.
[http://dx.doi.org/10.1111/jgh.14448] [PMID: 30144360]
[120]
Salomone F, Micek A, Godos J. Simple scores of fibrosis and mortality in patients with nafld: a systematic review with meta-analysis. J Clin Med 2018; 7: 219.
[http://dx.doi.org/10.3390/jcm7080219]
[121]
Xun YH, Guo JC, Lou GQ, et al. Non-alcoholic fatty liver disease (NAFLD) fibrosis score predicts 6.6-year overall mortality of Chinese patients with NAFLD. Clin Exp Pharmacol Physiol 2014; 41(9): 643-9.
[PMID: 24837195]
[122]
Hagström H, Nasr P, Ekstedt M, Stål P, Hultcrantz R, Kechagias S. Accuracy of noninvasive scoring systems in assessing risk of death and liver-related endpoints in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2019; 17(6): 1148-1156.e4.
[http://dx.doi.org/10.1016/j.cgh.2018.11.030] [PMID: 30471458]
[123]
De Vincentis A, Costanzo L, Vespasiani-Gentilucci U, et al. Association between non-invasive liver fibrosis scores and occurrence of health adverse outcomes in older people. Dig Liver Dis 2019; 51(9): 1330-6.
[http://dx.doi.org/10.1016/j.dld.2019.01.017] [PMID: 30808572]
[124]
Hsieh MH, Wu KT, Chen YY, et al. Higher NAFLD fibrosis score is associated with impaired eGFR. J Formos Med Assoc 2019. [Online ahead of print].
[PMID: 31353118]
[125]
Ze EY, Kim BJ, Jun DH, Kim JG, Kang H, Lee DY. The Fatty liver index: a simple and accurate predictor of colorectal adenoma in an average-risk population. Dis Colon Rectum 2018; 61(1): 36-42.
[http://dx.doi.org/10.1097/DCR.0000000000000973] [PMID: 29219920]
[126]
Munteanu M, Pais R, Peta V, et al. Long-term prognostic value of the FibroTest in patients with non-alcoholic fatty liver disease, compared to chronic hepatitis C, B, and alcoholic liver disease. Aliment Pharmacol Ther 2018; 48(10): 1117-27.
[http://dx.doi.org/10.1111/apt.14990] [PMID: 30334263]
[127]
Johnston MP, Patel J, Byrne CD. Multi-drug approaches to NASH: what’s in the development pipeline? Expert Opin Investig Drugs 2019; 1-8. [Online ahead of print]
[http://dx.doi.org/10.1080/13543784.2020.1668926] [PMID: 31524533]
[128]
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(9972): 956-65.
[http://dx.doi.org/10.1016/S0140-6736(14)61933-4] [PMID: 25468160]
[129]
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: e5
[http://dx.doi.org/10.1016/S0618-8278(19)30006-4]
[130]
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(10019): 679-90.
[http://dx.doi.org/10.1016/S0140-6736(15)00803-X] [PMID: 26608256]
[131]
Musso G, Cassader M, Paschetta E, Gambino R. Thiazolidinediones and advanced liver fibrosis in nonalcoholic steatohepatitis: a meta-analysis. JAMA Intern Med 2017; 177(5): 633-40.
[http://dx.doi.org/10.1001/jamainternmed.2016.9607] [PMID: 28241279]
[132]
Glen J, Floros L, Day C, Pryke R. Non-alcoholic fatty liver disease (NAFLD): summary of NICE guidance. BMJ 2016; 354: i4428.
[http://dx.doi.org/10.1136/bmj.i4428] [PMID: 27605111]
[133]
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(1): 328-57.
[http://dx.doi.org/10.1002/hep.29367] [PMID: 28714183]
[134]
Schulte L, Scheiner B, Voigtländer T, et al. Treatment with metformin is associated with a prolonged survival in patients with hepatocellular carcinoma. Liver Int 2019; 39(4): 714-26.
[http://dx.doi.org/10.1111/liv.14048] [PMID: 30663219]
[135]
Johnston MP, Patel J, Byrne CD. Diabetes is associated with increased risk of hepatocellular carcinoma in non-alcoholic steatohepatitis with cirrhosis - Implications for surveillance and future pharmacotherapy. Hepatobiliary Surg Nutr 2019. [Online ahead of print].
[136]
Mathurin P, Bataller R. Trends in the management and burden of alcoholic liver disease. J Hepatol 2015; 62(1)(Suppl.): S38-46.
[http://dx.doi.org/10.1016/j.jhep.2015.03.006] [PMID: 25920088]
[137]
Addolorato G, Mirijello A, Barrio P, Gual A. Treatment of alcohol use disorders in patients with alcoholic liver disease. J Hepatol 2016; 65(3): 618-30.
[http://dx.doi.org/10.1016/j.jhep.2016.04.029] [PMID: 27155530]
[138]
Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. JAMA 2014; 311(18): 1889-900.
[http://dx.doi.org/10.1001/jama.2014.3628] [PMID: 24825644]
[139]
Caputo F, Domenicali M, Bernardi M. Diagnosis and treatment of alcohol use disorder in patients with end-stage alcoholic liver disease. Hepatology 2019; 70(1): 410-7.
[http://dx.doi.org/10.1002/hep.30358] [PMID: 30471136]
[140]
Zhou Z, Zhong W. Targeting the gut barrier for the treatment of alcoholic liver disease. Liver Res 2017; 1(4): 197-207.
[http://dx.doi.org/10.1016/j.livres.2017.12.004] [PMID: 30034913]
[141]
Grander C, Adolph TE, Wieser V, et al. Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease. Gut 2018; 67(5): 891-901.
[http://dx.doi.org/10.1136/gutjnl-2016-313432] [PMID: 28550049]
[142]
Inokuchi S, Tsukamoto H, Park E, Liu ZX, Brenner DA, Seki E. Toll-like receptor 4 mediates alcohol-induced steatohepatitis through bone marrow-derived and endogenous liver cells in mice. Alcohol Clin Exp Res 2011; 35(8): 1509-18.
[http://dx.doi.org/10.1111/j.1530-0277.2011.01487.x] [PMID: 21463341]

Rights & Permissions Print Cite
Article Metrics
63
6
1
© 2024 Bentham Science Publishers | Privacy Policy