Top

Published in:

01-05-2016 | Review

Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD

Authors: Helen L. Reeves, Marco Y. W. Zaki, Christopher P. Day

Published in: Digestive Diseases and Sciences | Issue 5/2016

Abstract

Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. Rather than falling as a result of prevention and treatments for viral hepatitis, an increase is evident in developed nations consequent to the rising prevalence of obesity and type 2 diabetes mellitus (T2DM)—the two major risk factors for nonalcoholic fatty liver disease (NAFLD). The majority of patients with HCC complicating these conditions present with advanced disease as the tools for surveillance are inadequate, and the “at-risk” population is not well characterized. This review will summarize the epidemiological evidence linking obesity, T2DM, and NAFLD with HCC, what is known about the pathogenic mechanisms involved, as well as their relevance for clinicians managing patients at risk. There will also be an overview of the “unmet needs” surrounding this topic, with suggestions for the direction translational research should take in order to prevent progression of NAFLD to HCC, to improve early detection of HCC in those with NAFLD, as well as to improve outcomes for those affected.

Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–781.PubMedCrossRef

Tanaka H, et al. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003. Ann Intern Med. 2008;148:820–826.PubMedCrossRef

Armstrong GL, et al. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000;31:777–782.PubMedCrossRef

Cancer, I.A.f.R.o. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012; 2012.

Moller H, et al. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer. 1994;30A:344–350.PubMedCrossRef

Wolk A, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001;12:13–21.PubMedCrossRef

Calle EE, et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348:1625–1638.PubMedCrossRef

Marrero JA, et al. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002;36:1349–1354.PubMedCrossRef

Dyson J, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60:110–117.PubMedCrossRef

10.

Friedman SL. Focus. J Hepatol. 2014;60:1–2.PubMedCrossRef

11.

Marengo A, Rosso C, Bugianesi E. Liver cancer: connections with obesity, fatty liver, and cirrhosis. Annu Rev Med. 2016;67:103–117.PubMedCrossRef

12.

Margini C, Dufour JF. The story of HCC in NAFLD: from epidemiology, across pathogenesis, to prevention and treatment. Liver Int. 2016;36:317–324.PubMedCrossRef

13.

Giovannucci E, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–1685.PubMedPubMedCentralCrossRef

14.

Tsilidis KK, et al. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. BMJ. 2015;350:g7607.PubMedCrossRef

15.

El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–468.PubMedCrossRef

16.

Nordenstedt H, White DL, El-Serag HB. The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis. 2010;42 Suppl 3:S206–S214.PubMedCrossRef

17.

Ascha MS, et al. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51:1972–1978.PubMedCrossRef

18.

Sanyal A, et al. Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin. 2010;26:2183–2191.PubMedCrossRef

19.

International Working P. Terminology of nodular hepatocellular lesions. Hepatology. 1995;22:983–993.CrossRef

20.

Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–1219.PubMedCrossRef

21.

Farrell GC. The liver and the waistline: fifty years of growth. J Gastroenterol Hepatol. 2009;24 Suppl 3:S105–S118.PubMedCrossRef

22.

Younossi ZM, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–1730.PubMedCrossRef

23.

Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med. 2000;108:9–13.PubMedCrossRef

24.

Willner IR, et al. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol. 2001;96:2957–2961.PubMedCrossRef

25.

Anstee QM, Daly AK, Day CP. Genetic modifiers of non-alcoholic fatty liver disease progression. Biochim Biophys Acta. 2011;1812:1557–1566.PubMedCrossRef

26.

Grarup N, et al. Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond. Diabetologia. 2014;57:1528–1541.PubMedCrossRef

27.

Larter CZ, et al. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010;25:672–690.PubMedCrossRef

28.

Anstee QM, Daly A, Day CP. Genetics of alcoholic and non-alcoholic fatty liver disease. Semin Liver Dis. 2011;31:128–146.PubMedCrossRef

29.

Romeo S, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465.PubMedPubMedCentralCrossRef

30.

Kotronen A, et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia. 2009;52:1056–1060.PubMedCrossRef

31.

Burza MA, et al. PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals. Dig Liver Dis. 2012;44:1037–1041.PubMedCrossRef

32.

Liu YL, et al. Carriage of the PNPLA3 rs738409 C>G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81.PubMedCrossRef

33.

Pirazzi C, et al. PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells. Hum Mol Genet. 2014;23:4077–4085.PubMedPubMedCentralCrossRef

34.

Ballestri S, et al. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20:1724–1745.PubMedPubMedCentralCrossRef

35.

Zimmermann R, et al. Fate of fat: the role of adipose triglyceride lipase in lipolysis. Biochim Biophys Acta. 2009;1791:494–500.PubMedCrossRef

36.

Musso G, Gambino R, Cassader M. Non-alcoholic fatty liver disease from pathogenesis to management: an update. Obes Rev. 2010;11:430–445.PubMedCrossRef

37.

Cheung O, Sanyal AJ. Abnormalities of lipid metabolism in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:351–359.PubMedCrossRef

38.

Joost HG. Diabetes and cancer: epidemiology and potential mechanisms. Diab Vasc Dis Res. 2014;11:390–394.PubMedCrossRef

39.

Xu Y, Qian SY. Anti-cancer activities of omega-6 polyunsaturated fatty acids. Biomed J. 2014;37:112–119.PubMedPubMedCentralCrossRef

40.

Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301–316.PubMedCrossRef

41.

Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem. 2009;107:1053–1062.PubMedCrossRef

42.

Bedogni B, et al. The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation. Cancer Cell. 2005;8:443–454.PubMedCrossRef

43.

Trayhurn P, Wang B, Wood IS. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity? Br J Nutr. 2008;100:227–235.PubMedCrossRef

44.

Ahmed MH, Byrne CD. Obstructive sleep apnea syndrome and fatty liver: association or causal link? World J Gastroenterol. 2010;16:4243–4252.PubMedPubMedCentralCrossRef

45.

Weisberg SP, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–1808.PubMedPubMedCentralCrossRef

46.

Sun K, et al. Fibrosis and adipose tissue dysfunction. Cell Metab. 2013;18:470–477.PubMedPubMedCentralCrossRef

47.

Keophiphath M, et al. Macrophage-secreted factors promote a profibrotic phenotype in human preadipocytes. Mol Endocrinol. 2009;23:11–24.PubMedCrossRef

48.

McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity. 2014;41:36–48.PubMedCrossRef

49.

Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–246.PubMedCrossRef

50.

Solinas G, Karin M. JNK1 and IKKbeta: molecular links between obesity and metabolic dysfunction. FASEB J. 2010;24:2596–2611.PubMedCrossRef

51.

Fischer-Posovszky P, Wabitsch M, Hochberg Z. Endocrinology of adipose tissue—an update. Horm Metab Res. 2007;39:314–321.PubMedCrossRef

52.

Anstee QM, Goldin RD. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol. 2006;87:1–16.PubMedPubMedCentralCrossRef

53.

Zhang Y, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432.PubMedCrossRef

54.

Zimmet P, et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ. 1996;313:965–969.PubMedPubMedCentralCrossRef

55.

de Courten M, et al. Hyperleptinaemia: the missing link in the, metabolic syndrome? Diabet Med. 1997;14:200–208.PubMedCrossRef

56.

Wauters M, et al. Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion. Horm Metab Res. 2003;35:92–96.PubMedCrossRef

57.

Wang SN, Lee KT, Ker CG. Leptin in hepatocellular carcinoma. World J Gastroenterol. 2010;16:5801–5809.PubMedPubMedCentralCrossRef

58.

Uddin S, et al. Role of leptin and its receptors in the pathogenesis of thyroid cancer. Int J Clin Exp Pathol. 2011;4:637–643.PubMedPubMedCentral

59.

Berg AH, et al. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001;7:947–953.PubMedCrossRef

60.

Saxena NK, et al. Adiponectin modulates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma. Gastroenterology. 2010;139:1762–1773. (1773 e1–1773 e5).PubMedPubMedCentralCrossRef

61.

Sharma D, et al. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Hepatology. 2010;52:1713–1722.PubMedPubMedCentralCrossRef

62.

Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev. 2012;33:547–594.PubMedPubMedCentralCrossRef

63.

Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36:461–470.PubMedCrossRef

64.

Ganeshan K, Chawla A. Metabolic regulation of immune responses. Annu Rev Immunol. 2014;32:609–634.PubMedCrossRef

65.

Tanaka S, et al. T lymphopenia in genetically obese-diabetic Wistar fatty rats: effects of body weight reduction on T cells. Metabolism. 2000;49:1261–1266.PubMedCrossRef

66.

Macia L, et al. Impairment of dendritic cell functionality and steady-state number in obese mice. J Immunol. 2006;177:5997–6006.PubMedCrossRef

67.

Lamas O, Marti A, Martinez JA. Obesity and immunocompetence. Eur J Clin Nutr. 2002;56:S42–S45.PubMedCrossRef

68.

Sheridan PA, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes (Lond). 2012;36:1072–1077.CrossRef

69.

Schwabe RF, Jobin C. The microbiome and cancer. Nat Rev Cancer. 2013;13:800–812.PubMedPubMedCentralCrossRef

70.

Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol. 2014;12:661–672.PubMedCrossRef

71.

McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis. 2004;8:521–533. (viii).PubMedCrossRef

72.

Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:370–379.PubMedCrossRef

73.

Maeda S, et al. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Cell. 2005;121:977–990.PubMedCrossRef

74.

He G, et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 2013;155:384–396.PubMedPubMedCentralCrossRef

75.

Nakagawa H, et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 2014;26:331–343.PubMedPubMedCentralCrossRef

76.

Tal-Kremer S, Day CP, Reeves HL. The genetic basis of hepatocellular cancer. In: Ali S, Mann DA, Friedman SL, eds. Liver Diseases: Biochemical Mechanisms and New Therapeutic Insights. Enfield, New Hampshire: Science Publishers; 2006. pp. 273–308.

77.

Guy CD, et al. Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease. Hepatology. 2012;55:1711–1721.PubMedPubMedCentralCrossRef

78.

Kubes P, Mehal WZ. Sterile inflammation in the liver. Gastroenterology. 2012;143:1158–1172.PubMedCrossRef

79.

McDonald B, Kubes P. Neutrophils and intravascular immunity in the liver during infection and sterile inflammation. Toxicol Pathol. 2012;40:157–165.PubMedCrossRef

80.

Wilson CL, et al. NFkappaB1 is a suppressor of neutrophil-driven hepatocellular carcinoma. Nat Commun. 2015;6:6818.PubMedPubMedCentralCrossRef

81.

Wolf MJ, et al. Metabolic activation of intrahepatic CD8+ T cells and NKT cells causes nonalcoholic steatohepatitis and liver cancer via cross-talk with hepatocytes. Cancer Cell. 2014;26:549–564.PubMedCrossRef

82.

Wolf MJ, et al. The unexpected role of lymphotoxin beta receptor signaling in carcinogenesis: from lymphoid tissue formation to liver and prostate cancer development. Oncogene. 2010;29:5006–5018.PubMedCrossRef

83.

Bajaj JS, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60:940–947.PubMedPubMedCentralCrossRef

84.

Aron-Wisnewsky J, et al. Gut microbiota and non-alcoholic fatty liver disease: new insights. Clin Microbiol Infect. 2013;19:338–348.PubMedCrossRef

85.

Dumas ME, et al. Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci USA. 2006;103:12511–12516.PubMedPubMedCentralCrossRef

86.

Wang X, et al. Bile acid receptors and liver cancer. Curr Pathobiol Rep. 2013;1:29–35.PubMedPubMedCentralCrossRef

87.

Lade A, Noon LA, Friedman SL. Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer. Curr Opin Oncol. 2014;26:100–107.PubMedPubMedCentralCrossRef

88.

Neuschwander-Tetri BA, 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.PubMedPubMedCentralCrossRef

89.

Wu AL, et al. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PLoS One. 2011;6:e17868.PubMedPubMedCentralCrossRef

90.

Ravikumar B, et al. Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev. 2010;90:1383–1435.PubMedCrossRef

91.

Singh R, et al. Autophagy regulates lipid metabolism. Nature. 2009;458:1131–1135.PubMedPubMedCentralCrossRef

92.

Kim J, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132–141.PubMedPubMedCentralCrossRef

93.

Aghajan M, Li N, Karin M. Obesity, autophagy and the pathogenesis of liver and pancreatic cancers. J Gastroenterol Hepatol. 2012;27 Suppl 2:10–14.PubMedCrossRef

94.

Komatsu M, et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol. 2010;12:213–223.PubMed

95.

Inami Y, et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J Cell Biol. 2011;193:275–284.PubMedPubMedCentralCrossRef

96.

Lee YJ, Jang BK. The role of autophagy in hepatocellular carcinoma. Int J Mol Sci. 2015;16:26629–26643.PubMedPubMedCentralCrossRef

97.

Czaja MJ, et al. Functions of autophagy in normal and diseased liver. Autophagy. 2013;9:1131–1158.PubMedPubMedCentralCrossRef

98.

Jain D, et al. Steatohepatitic hepatocellular carcinoma, a morphologic indicator of associated metabolic risk factors: a study from India. Arch Pathol Lab Med. 2013;137:961–966.PubMedCrossRef

99.

Salomao M, et al. Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol. 2010;34:1630–1636.PubMed

100.

Brenner C, et al. Decoding cell death signals in liver inflammation. J Hepatol. 2013;59:583–594.PubMedCrossRef

101.

McKee C, et al. Amphiregulin activates human hepatic stellate cells and is upregulated in non alcoholic steatohepatitis. Sci Rep. 2015;5:8812.PubMedPubMedCentralCrossRef

102.

Gori M, Arciello M, Balsano C. MicroRNAs in nonalcoholic fatty liver disease: novel biomarkers and prognostic tools during the transition from steatosis to hepatocarcinoma. Biomed Res Int. 2014;2014:741465.PubMedPubMedCentralCrossRef

103.

Shah N, Nelson JE, Kowdley KV. MicroRNAs in liver disease: bench to bedside. J Clin Exp Hepatol. 2013;3:231–242.PubMedPubMedCentralCrossRef

104.

Morishita A, Masaki T. miRNA in hepatocellular carcinoma. Hepatol Res. 2015;45:128–141.PubMedCrossRef

105.

Reddy SK, et al. Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease. Hepatology. 2012;55:1809–1819.PubMedCrossRef

106.

European Association For The Study Of The Liver, European Organisation For Research And Treatment Of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56:908–943.

107.

Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.PubMedPubMedCentralCrossRef

108.

Saran U, et al. Hepatocellular carcinoma and lifestyles. J Hepatol. 2016;64:203–214.PubMedCrossRef

109.

Turati F, et al. Mediterranean diet and hepatocellular carcinoma. J Hepatol. 2014;60:606–611.PubMedCrossRef

110.

Piguet AC, et al. Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis. J Hepatol. 2015;62:1296–1303.PubMedCrossRef

111.

El-Serag HB, et al. Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009;136:1601–1608.PubMedPubMedCentralCrossRef

112.

Dongiovanni P, et al. Statin use and non-alcoholic steatohepatitis in at risk individuals. J Hepatol. 2015;63:705–712.PubMedCrossRef

113.

Hoki T, et al. Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis. Hepatology. 2015;62:751–761.PubMedCrossRef

114.

Sorrentino P, et al. Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis. J Hepatol. 2009;50:351–357.PubMedCrossRef

115.

Williamson RM, et al. Prevalence and markers of advanced liver disease in type 2 diabetes. QJM. 2012;105:425–432.PubMedCrossRef

Title: Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD
Authors: Helen L. Reeves
Marco Y. W. Zaki
Christopher P. Day
Publication date: 01-05-2016
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 5/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-016-4085-6

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2016

Innate Immunity and Inflammation in NAFLD/NASH

Novel Pharmacotherapy Options for NASH

Editors’ Introduction to the NAFLD and NASH Special Issue

Natural History of Nonalcoholic Fatty Liver Disease

Medical and Surgical Treatment Options for Nonalcoholic Steatohepatitis

Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage