Fat and hepatocellular carcinoma

Clara Balsano , Cristiana Porcu , Silvia Sideri , Simona Tavolaro

Hepatoma Research ›› 2018, Vol. 4 : 38

PDF
Hepatoma Research ›› 2018, Vol. 4:38 DOI: 10.20517/2394-5079.2018.51
Review
Review

Fat and hepatocellular carcinoma

Author information +
History +
PDF

Abstract

Obesity and diabetes are associated with the onset of hepatocellular carcinoma (HCC). These two illnesses correlate also with the development of non-alcoholic fatty liver disease (NAFLD). Currently, NAFL is considered the leading form of chronic liver disease in the Western industrialized countries. Insulin resistance is the common pathogenic factor among these three pathologies. NAFL is characterized by fat accumulation in the liver that involves greater than 5% of the liver parenchyma with no evidence of hepatocyte injury. However, NAFL may progress toward non-alcoholic steatohepatitis that in turn may lead to advanced fibrosis, cirrhosis and HCC. It is alarming that NAFLD related HCC has been, at present, considered as a growing burden worldwide, and its prevalence is tending to further increase together with the increasing incidence of obesity and diabetes. Worthy of note is that in the presence of chronic accumulation of fat in the liver it has been reported the emergence of HCC during chronic liver disease in absence of liver cirrhosis, usually the major risk factor for the development of HCC. Thus, in the future NAFLD related HCCs will place a growing strain on health-care systems from the need for their management. Unfortunately, most of the NAFLD related HCC patients are diagnosed at advanced stages and are characterized by a poor prognosis, because they are ineligible to radical treatments. Thus, it is urgent to boost up new screening policies to make early diagnoses, as well as to develop preventive-therapeutic strategies.

Keywords

Hepatocellular carcinoma / obesity / non-alcoholic fatty liver / non-alcoholic steatohepatitis / copper

Cite this article

Download citation ▾
Clara Balsano, Cristiana Porcu, Silvia Sideri, Simona Tavolaro. Fat and hepatocellular carcinoma. Hepatoma Research, 2018, 4: 38 DOI:10.20517/2394-5079.2018.51

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Siddique A.Insulin resistance and other metabolic risk factors in the pathogenesis of hepatocellular carcinoma.Clin Liver Dis2011;15:281-96 PMCID:PMC3874238

[2]

Araújo AR,Bedogni G,Bellentani S.Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: what we need in the future.Liver Int2018;38 Suppl 1:47-51

[3]

Younossi ZM,Abdelatif D,Henry L.Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology2016;64:73-84

[4]

White DL,Kanwal F,El-Serag HB.Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 2012.Gastroenterology2017;152:812-20.e5 PMCID:PMC5346030

[5]

Tsukuma H,Tanaka S,Yabuuchi T,Nakanishi K,Inoue A,Kawashima T.Risk factors for hepatocellular carcinoma among patients with chronic liver disease.N Engl J Med1993;328:1797-801

[6]

Ertle J,Sowa JP,Herzer K,Schlaak JF,Syn WK.Non-alcoholic fatty liver disease progresses to hepatocellular carcinoma in the absence of apparent cirrhosis.Int J Cancer2011;128:2436-43

[7]

Thorgeirsson SS.Molecular pathogenesis of human hepatocellular carcinoma.Nat Genet2002;31:339-46

[8]

Hanahan D.Hallmarks of cancer: the next generation.Cell2011;144:646-74

[9]

Farazi PA.Hepatocellular carcinoma pathogenesis: from genes to environment.Nat Rev Cancer2006;6:674-87

[10]

Margini C.The story of HCC in NAFLD: from epidemiology, across pathogenesis, to prevention and treatment.Liver Int2016;36:317-24

[11]

Karagozian R,Baffy G.Obesity-associated mechanisms of hepatocarcinogenesis.Metabolism2014;63:607-17

[12]

Rajendran P,Chen YF,Tamilselvi S,Day CH,Viswanadha VP,Huang CY.The multifaceted link between inflammation and human diseases.J Cell Physiol2018;233:6458-71

[13]

Sayre LM,Perry G.Chemistry and biochemistry of oxidative stress in neurodegenerative disease.Curr Med Chem2001;8:721-38

[14]

Palma-Duran SA,Vlassopoulos A,Margariti A,Papatheodoridis G.Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can discriminate non-alcoholic fatty liver disease in age-, sex- and BMI-matched normo-glycemic adults.Metabolism2018;83:120-7

[15]

Said A.Epidemic of non-alcoholic fatty liver disease and hepatocellular carcinoma.World J Clin Oncol2017;8:429-36 PMCID:PMC5740098

[16]

Jemal A,Center MM,Ward E.Global cancer statistics.CA Cancer J Clin2011;61:69-90

[17]

GLOBOCAN. Estimated cancer incidence: mortality andprevalence worldwide 2012. Available from: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx [Last accessed on 17 Jul 2018].

[18]

El-Serag HB.Hepatocellular carcinoma.N Engl J Med2011;365:1118-27

[19]

Ringelhan M,Protzer U.Viral hepatitis and liver cancer.Philos Trans R Soc Lond B Biol Sci2017;372:20160274 PMCID:PMC5597741

[20]

Marot A,Knebel JF,Deltenre P.Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: an observational study.PLoS One2017;12:e0186715 PMCID:PMC5659599

[21]

Reeves HL,Day CP.Hepatocellular carcinoma in obesity, type 2 diabetes, and NAFLD.Dig Dis Sci2016;61:1234-45

[22]

Calle EE,Walker-Thurmond K.Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults..N Engl J Med2003;348:1625-38

[23]

Calzadilla Bertot L.The natural course of non-alcoholic fatty liver disease.Int J Mol Sci2016;17:E774 PMCID:PMC4881593

[24]

Cholankeril G.Alcoholic liver disease replaces HCV infection as the leading indication for liver transplantation in the United States.Clin Gastroenterol Hepatol2017;

[25]

Musso G,Gambino R,Molinaro F.Interactions among bone, liver, and adipose tissue predisposing to diabesity and fatty liver.Trends Mol Med2013;19:522-35

[26]

Alisi A,Oliveira FL,Nobili V.The role of tissue macrophage-mediated inflammation on NAFLD pathogenesis and its clinical implications.Mediators Inflamm2017;2017:8162421 PMCID:PMC5237469

[27]

Ouchi N,Lugus JJ.Adipokines in inflammation and metabolic disease.Nat Rev Immunol2011;11:85-97 PMCID:PMC3518031

[28]

Seo YY,Bae JC,Park SE,Park CY,Park SW.Tumor necrosis factor-α as a predictor for the development of nonalcoholic fatty liver disease: a 4-year follow-up study.Endocrinol Metab (Seoul).2013;28:41-5 PMCID:PMC3811803

[29]

Hui JM,Farrell GC,Kriketos A.Beyond insulin resistance in NASH: TNF-alpha or adiponectin?.Hepatology2004;40:46-54

[30]

Abiru S,Maeda Y,Ito M,Nagaoka S,Takii Y,Nakamura M,Yano K,Eguchi K.Serum cytokine and soluble cytokine receptor levels in patients with non-alcoholic steatohepatitis.Liver Int2006;26:39-45

[31]

Hotamisligil GS,Spiegelman BM.Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.Science1993;259:87-91

[32]

Uysal KT,Marino MW.Protection from obesity-induced insulin resistance in mice lacking TNF-α function.Nature1997;389:610-4

[33]

Xu H,Yang Q,Yang D,Sole J,Ross JS,Chen H.Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.J Clin Invest2003;112:1821-30 PMCID:PMC296998

[34]

Onyekwere CA,Samaila AA,Abdulkareem FB.Nonalcoholic fatty liver disease: synopsis of current developments.Niger J Clin Pract2015;18:703-12

[35]

Huang CY,Chen MY,Chen YH,Hsu HC,Tang CH.Stromal cell-derived factor-1/CXCR4 enhanced motility of human osteosarcoma cells involves MEK1/2, ERK and NF-kappaB-dependent pathways.J Cell Physiol2009;221:204-12

[36]

Liu H,Tillman B,French BA.TLR3/4 signaling is mediated via the NFκB-CXCR4/7 pathway in human alcoholic hepatitis and non-alcoholic steatohepatitis which formed Mallory-Denk bodies.Exp Mol Pathol2014;97:234-40 PMCID:PMC4177360

[37]

Day CP.Steatohepatitis: a tale of two "hits"?.Gastroenterology1998;114:842-5

[38]

Ascha MS,Lopez R,Feldstein AF.The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.Hepatology2010;51:1972-8

[39]

Zoller H.Nonalcoholic fatty liver disease and hepatocellular carcinoma.Metabolism2016;65:1151-60

[40]

Del Ben M,Brancorsini M,D'Erasmo L,Loffredo L,Pignatelli P,Arca M.Non-alcoholic fatty liver disease, metabolic syndrome and patatin-like phospholipase domain-containing protein3 gene variants.Eur J Intern Med2014;25:566-70

[41]

Seko Y,Itoh Y.The genetic backgrounds in nonalcoholic fatty liver disease.Clin J Gastroenterol2018;11:97-102

[42]

Guichard C,Imbeaud S,Pelletier L,Calderaro J,Letexier M,Clément B,Chevet E,Couchy G,Calvo F.Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.Nat Genet2012;44:694-8 PMCID:PMC3819251

[43]

Bartel DP.MicroRNAs: genomics, biogenesis, mechanism, and function.Cell2004;116:281-97

[44]

Qu H,Huang Y.Circulating miRNAs: promising biomarkers of human cancer.Asian Pac J Cancer Prev2011;12:1117-25

[45]

Sayed D.MicroRNAs in development and disease.Physiol Rev2011;91:827-87

[46]

Khoshnaw SM,Abdel-Fatah TM,Hodi Z,Ellis IO.Loss of Dicer expression is associated with breast cancer progression and recurrence.Breast Cancer Res Treat2012;135:403-13

[47]

Zeng S,Zhao J,Rong M,Gao W.Silencing Dicer expression enhances cellular proliferative and invasive capacities in human tongue squamous cell carcinoma.Oncol Rep2014;31:867-73

[48]

Zhu Y,Guo J,Yi X,Cai J.Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression.Tumour Biol2016;37:14009-23

[49]

Lei L,Yang X.Down-regulation of microRNA-375 regulates adipokines and inhibits inflammatory cytokines by targeting AdipoR2 in non-alcoholic fatty liver disease.Clin Exp Pharmacol Physiol2018;

[50]

Gori M,Balsano C.MicroRNAs in nonalcoholic fatty liver disease: novel biomarkers and prognostic tools during the transition from steatosis to hepatocarcinoma.Biomed Res Int2014;2014:741465 PMCID:PMC3972908

[51]

Becker PP,Schmitt J,Hammer C,Müllhaupt B.Performance of serum microRNAs -122, -192 and -21 as biomarkers in patients with non-alcoholic steatohepatitis.PLoS One2015;10:e0142661 PMCID:PMC4643880

[52]

Yamada H,Ichino N,Sawada A,Sugimoto K,Teradaira R,Hamajima N.Associations between circulating microRNAs (miR-21, miR-34a, miR-122 and miR-451) and non-alcoholic fatty liver.Clin Chim Acta2013;424:99-103

[53]

Wang Y,Yu W,Liu L,Li S.MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1.Biochem Biophys Res Commun2017;493:227-32

[54]

Jampoka K,Khongnomnan K,Tangkijvanich P.Serum miR-29a and miR-122 as potential biomarkers for non-alcoholic fatty liver disease (NAFLD)..Microrna2018;

[55]

Latorre J,Mercader JM,Rovira ò,Ricart W,Ortega FJ.Decreased lipid metabolism but increased FA biosynthesis are coupled with changes in liver microRNAs in obese subjects with NAFLD.Int J Obes (Lond).2017;41:620-30

[56]

Wang L,Wang Z,Cao ZY.Decreased miR-155 level in the peripheral blood of non-alcoholic fatty liver disease patients may serve as a biomarker and may influence LXR activity.Cell Physiol Biochem2016;39:2239-48

[57]

Cheung O,Eicken C,Mirshahi F,Kellum JM,Luketic VA.Nonalcoholic steatohepatitis is associated with altered hepatic microRNA expression.Hepatology2008;48:1810-20 PMCID:PMC2717729

[58]

Hur W,Kim SW,Bae SH,Hwang D,Park T,Song BJ.Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the AMPK/AKT pathway.Int J Biochem Cell Biol2015;64:265-76

[59]

Sharma H,Birerdinc A,Moazzez A,Goodman Z,Baranova A.Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease.J Gastroenterol Hepatol2013;28:1410-5

[60]

Vega-Badillo J,Hernández-Pérez HA,León-Mimila P,Morán-Ramos S,Fernández-Silva I,Tovar AR,Villarreal-Molina T,Aguilar-Salinas CA.Hepatic miR-33a/miR-144 and their target gene ABCA1 are associated with steatohepatitis in morbidly obese subjects.Liver Int2016;36:1383-91

[61]

Mohamed AA,Elbedewy TA,Ali-Eldin FA.MicroRNAs and clinical implications in hepatocellular carcinoma.World J Hepatol2017;9:1001-7 PMCID:PMC5569275

[62]

De Conti A,Tryndyak V,Moreno FS,Beland FA.MicroRNA deregulation in nonalcoholic steatohepatitis-associated liver carcinogenesis.Oncotarget2017;8:88517-28 PMCID:PMC5687623

[63]

Ge W,Li QG,Zhang CY.Expression of serum miR-16, let-7f, and miR-21 in patients with hepatocellular carcinoma and their clinical significances.Clin Lab2014;60:427-34

[64]

Karakatsanis A,Gazouli M,Polymeneas G.Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance.Mol Carcinog2013;52:297-303

[65]

Ashmawy AM,Abdel Salam ET,Kobaisi MH,Sharawy SK.Crosstalk between liver-related microRNAs and Wnt/β-catenin pathway in hepatocellular carcinoma patients.Arab J Gastroenterol2017;18:144-50

[66]

Wang F,Chen H,Zhang J,Yang H.Prognostic value of hsa-mir-299 and hsa-mir-7706 in hepatocellular carcinoma.Oncol Lett2018;16:815-20

[67]

An Y,Zhao WC,Xia NX,Fan ZP.Novel serum microRNAs panel on the diagnostic and prognostic implications of hepatocellular carcinoma.World J Gastroenterol2018;24:2596-604 PMCID:PMC6021775

[68]

Porcu C,Barbaro B,Nasi S,Licata A,Grieco A.Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.Oncotarget2018;9:9325-43 PMCID:PMC5823635

[69]

Manz DH,Paul BT,Torti SV.Iron and cancer: recent insights.Ann N Y Acad Sci2016;1368:149-61 PMCID:PMC4870095

[70]

Tirnitz-Parker JE,Olynyk JK.Iron and hepatic carcinogenesis.Crit Rev Oncog2013;18:391-407

[71]

Antonucci L,Iannucci G,Barbaro B.Non-alcoholic fatty liver disease and nutritional implications: special focus on Copper.Nutrients2017;9:E1137 PMCID:PMC5691753

[72]

Tarantino G,Arciello M,Balsano C.Prediction of carotid intima-media thickness in obese patients with low prevalence of comorbidities by serum copper bioavailability.J Gastroenterol Hepatol2018;33:1511-7

[73]

Marshall KM,Estacio O,Kalitsis P,Baldwin GS.Activation by zinc of the human gastrin gene promoter in colon cancer cells in vitro and in vivo.Metallomics2015;7:1390-8

[74]

Ranasinghe WK,Bolton D,Ischia J.HIF1alpha expression under normoxia in prostate cancer--which pathways to target?.J Urol2015;193:763-70

[75]

Alam S.Cellular mechanisms of zinc dysregulation: a perspective on zinc homeostasis as an etiological factor in the development and progression of breast cancer.Nutrients2012;4:875-903 PMCID:PMC3448077

[76]

Sorrentino P,Ferbo U,Bracigliano A.Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis.J Hepatol2009;50:351-7

[77]

Fargion S,Fracanzani AL.Role of iron in hepatocellular carcinoma.Clin Liv Dis2014;3:108-10

[78]

Ye Q,Yin WL,Han T.Association between the HFE C282Y, H63D polymorphisms and the risks of non-alcoholic fatty liver disease, liver cirrhosis and hepatocellular carcinoma: an updated systematic review and meta-analysis of 5,758 cases and 14,741 controls.PLoS One2016;11:e0163423 PMCID:PMC5033482

[79]

Yao M,Leung PSC,Liu S,Guo X,Yan Y,Chen X,Liu T,Gershwin ME,Zhao J.The clinical significance of GP73 in immunologically mediated chronic liver diseases: experimental data and literature review.Clin Rev Allergy Immunol2018;54:282-94

[80]

Turati F,Pelucchi C,Franceschi S,Izzo F,Boffetta P.Metabolic syndrome and hepatocellular carcinoma risk.Br J Cancer2013;108:222-8 PMCID:PMC3553509

[81]

Sharma D,Fu PP,Nagalingam A,Handy J,Cohen C,Saxena NK.Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis.Hepatology2010;52:1713-22 PMCID:PMC2967627

[82]

Gan L,Sun C.Obesity linking to hepatocellular carcinoma: a global view.Biochim Biophys Acta2018;1869:97-102

[83]

Ley RE,Klein S.Microbial ecology: human gut microbes associated with obesity.Nature2006;444:1022-3

[84]

Da Silva HE,Comelli EM,Arendt BM,Lou W.Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance.Sci Rep2018;8:1466 PMCID:PMC5780381

[85]

Ponziani FR,Pecere S,Lopetuso L,Pompili M.Effect of rifaximin on gut microbiota composition in advanced liver disease and its complications.World J Gastroenterol2015;21:12322-33 PMCID:PMC4649116

[86]

Turnbaugh PJ,Mahowald MA,Mardis ER.An obesity-associated gut microbiome with increased capacity for energy harvest.Nature2006;444:1027-31

[87]

Zhu L,Gill C,Alkhouri R,Gill SR.Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH.Hepatology2013;57:601-9

[88]

Iannaccone R,Murakami T,Belghiti J,Kim T,Wakasa K,Nakamura H,Vilgrain V.Hepatocellular carcinoma in patients with nonalcoholic fatty liver disease: helical CT and MR imaging findings with clinical-pathologic comparison.Radiology2007;243:422-30

[89]

Farges O,Dokmak S,Bedossa P.Changing trends in malignant transformation of hepatocellular adenoma.Gut2011;60:85-9

[90]

Yasui K,Komorizono Y,Arii S,ShimaT,Saibara T,Kawata S,Takami S,Takamura T,Okanoue T.Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma.Clin Gastroenterol Hepatol2011;9:428-33

[91]

Dyson J,Chattopadyhay D,Graham J,Aslam T,Gaggar S,Sumpter K,Rose J,Manas D.Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team.J Hepatol2014;60:110-7

[92]

Chang CY,Roayaie S,Thung SN.Changing epidemiology of hepatocellular adenoma in the United States: review of the literature.Int J Hepatol2013;2013:604860 PMCID:PMC3595661

[93]

Schütte K,Poranzke J,Bornschein J,Arend J,Malfertheiner P.Characterization and prognosis of patients with hepatocellular carcinoma (HCC) in the non-cirrhotic liver.BMC Gastroenterol2014;14:117 PMCID:PMC4098694

[94]

Larsson SC.Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies.Br J Cancer2007;97:1005-8 PMCID:PMC2360408

[95]

Torres DM.Nonalcoholic steatohepatitis and noncirrhotic hepatocellular carcinoma: fertile soil.Semin Liver Dis2012;32:30-8

[96]

Angulo P,Marchesini G,George J,Enders F,Burt AD,Lindor K,Lenzi M,Kench J,Day CP.The NAFLD fibrosis score:a noninvasive system that identifies liver fibrosis in patients with NAFLD.Hepatology2007;45:846-54

[97]

Loomba R.The global NAFLD epidemic.Nat Rev Gastroenterol Hepatol2013;10:686-90

[98]

Rinella ME.Nonalcoholic fatty liver disease: a systematic review.JAMA2015;313:2263-73

[99]

Bertot LC,Wallace M,Garas G,Adams LA.Nonalcoholic fatty liver disease-related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma.Hepatol Commun2017;1:53-60 PMCID:PMC5747027

[100]

Sanyal AJ,Sargeant C,Sterling RK,Shiffman ML,Coterrell A,Contos MJ.Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C.Hepatology2006;43:682-9

[101]

Mofrad P,Haque M,Fisher RA,Sterling RK,Stravitz RT.Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.Hepatology2003;37:1286-92

[102]

Wieland AC,Truesdale A,Bambha KM.Identifying practice gaps to optimize medical care for patients with nonalcoholic fatty liver disease.Dig Dis Sci2013;58:2809-16

[103]

Simmons O,Yokoo T,Yopp A,Browning T.Editorial: ultrasound surveillance of hepatocellular carcinoma in the 21st century - authors' reply.Aliment Pharmacol Ther2017;45:562-3

PDF

41

Accesses

0

Citation

Detail

Sections
Recommended

/