Evaluation and impact of different biomarkers for early detection of hepatocellular carcinoma

Jan Best , Svenja Sydor , Lars P. Bechmann , Ali Canbay

Hepatoma Research ›› 2020, Vol. 6 : 62

PDF
Hepatoma Research ›› 2020, Vol. 6:62 DOI: 10.20517/2394-5079.2020.56
Review
Review

Evaluation and impact of different biomarkers for early detection of hepatocellular carcinoma

Author information +
History +
PDF

Abstract

Worldwide, hepatocellular carcinoma (HCC) is a frequent complication of liver diseases and remains a major cause of cancer-related mortality. In addition, the prevalence of nonalcoholic steatohepatitis (NASH) as prerequisite of hepatocarcinogenesis, even in the absence of cirrhosis, is rising rapidly. The early detection of HCC has been crucial in improving the survival outcomes of those patients. However, in the mostly obese NASH population, diagnostic sensitivity of ultrasound-based HCC screening approaches is limited. On the other hand, biomarkers for HCC show promising potential to improve early detection, providing reproducible, investigator-independent results that can be used either alone or integrated with other biomarkers for scoring models. In the past, validation has been limited due to a lack of prospective longitudinal cohort studies. At present, large-scale retrospective phase-III- biomarker- development gives hope for the availability of biomarker-based screening approaches in the near future. This review focuses on the potential impact of biomarkers on surveillance strategies, potentially allowing for earlier HCC diagnosis.

Keywords

Nonalcoholic steatohepatitis / hepatocellular carcinoma / alpha fetoprotein / AFP-L3 / des-gamma-carboxy-prothrombin / Gender / Age / GALAD-score / Glypican-3 / microbiome

Cite this article

Download citation ▾
Jan Best, Svenja Sydor, Lars P. Bechmann, Ali Canbay. Evaluation and impact of different biomarkers for early detection of hepatocellular carcinoma. Hepatoma Research, 2020, 6: 62 DOI:10.20517/2394-5079.2020.56

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

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

[2]

El-Serag HB.Epidemiology of hepatocellular carcinoma in the United States: where are we? Where do we go?.Hepatology2014;60:1767-75 PMCID:PMC4211957

[3]

Rich NE,Odewole M,Parikh ND.Racial and ethnic differences in presentation and outcomes of hepatocellular carcinoma..Clin Gastroenterol Hepatol2019;17:551-9.e1 PMCID:PMC6274621

[4]

De Minicis S,Rychlicki C,Saccomanno S.HCC development is associated to peripheral insulin resistance in a mouse model of NASH..PLoS One2014;9:e97136 PMCID:PMC4031080

[5]

White DL,El-Serag HB.Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review..Clin Gastroenterol Hepatol2012;10:1342-59.e2 PMCID:PMC3501546

[6]

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

[7]

Kudo M.Early detection and curative treatment of early-stage hepatocellular carcinoma..Clin Gastroenterol Hepatol2005;3:S144-8

[8]

Weinmann A,Niederle IM,Konig J.Trends in epidemiology, treatment, and survival of hepatocellular carcinoma patients between 1998 and 2009: an analysis of 1066 cases of a German HCC Registry..J Clin Gastroenterol2014;48:279-89

[9]

Shah SA,Li Y,Carroll JE.Underutilization of therapy for hepatocellular carcinoma in the medicare population..Cancer2011;117:1019-26

[10]

Sonnenday CJ,Schulick RD.Racial and geographic disparities in the utilization of surgical therapy for hepatocellular carcinoma..J Gastrointest Surg2007;11:1636-46discussion 46

[11]

Wang Y,Li Y,Wei S.Radiofrequency ablation versus hepatic resection for small hepatocellular carcinomas: a meta-analysis of randomized and nonrandomized controlled trials..PLoS One2014;9:e84484 PMCID:PMC2914087

[12]

Zheng SS,Wu J,Wang WL.Liver transplantation for hepatocellular carcinoma: Hangzhou experiences..Transplantation2008;85:1726-32

[13]

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

[14]

Altekruse SF,Reichman ME.Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005..J Clin Oncol2009;27:1485-91 PMCID:PMC2668555

[15]

Arends J, Bartenstein P, Bechstein W, Bernatik T, Bitzer M, et al. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe,AWMF): Diagnostik und Therapie des hepatozellulären Karzinoms, Kurzversion 1.0, AWMF Registrierungsnummer: 032-053OL,2013. Available from: https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/HCC/S3-HCC-OL-Langversion-V1.0.pdf. [Last accessed on 14 Aug 2020]

[16]

Heimbach JK,Finn RS,Abecassis MM.AASLD guidelines for the treatment of hepatocellular carcinoma..Hepatology2018;67:358-80

[17]

EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma..J Hepatol2018;56:908-43

[18]

Omata M,Kokudo N,Lee JM.Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update..Hepatol Int2017;11:317-70 PMCID:PMC5491694

[19]

Omata M,Tateishi R,Lin SM.Asian pacific association for the study of the liver consensus recommendations on hepatocellular carcinoma..Hepatol Int2010;4:439-74 PMCID:PMC2900561

[20]

Kudo M,Kokudo N,Sakamoto M.Management of hepatocellular carcinoma in Japan: Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version..Dig Dis2011;29:339-64

[21]

Bruix J.Management of hepatocellular carcinoma..Hepatology2005;42:1208-36

[22]

Bruix J.Management of hepatocellular carcinoma: an update..Hepatology2011;53:1020-2 PMCID:PMC3084991

[23]

Bolondi L,Siringo S,Casali A.Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis..Gut2001;48:251-9 PMCID:PMC1728189

[24]

Dyson J,Chattopadyhay D,Graham J.Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team..J Hepatol2014;60:110-7

[25]

Siegel AB.Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link..Cancer2009;115:5651-61 PMCID:PMC3397779

[26]

Tzartzeva K,Rich NE,Marrero JA.Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis..Gastroenterology2018;154:1706-18.e1 PMCID:PMC5927818

[27]

Araujo AR,Bedogni G,Bellentani S.Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: what we need in the future..Liver Int.2018;38 Suppl 1:47-51

[28]

Angulo P.Nonalcoholic fatty liver disease..N Engl J Med2002;346:1221-31

[29]

Vernon G,Younossi ZM.Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults..Aliment Pharmacol Ther2011;34:274-85

[30]

Wong RJ,Ahmed A.Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S..Hepatology2014;59:2188-95

[31]

Younossi Z,Ong JP,Bugianesi E.Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates..Clin Gastroenterol Hepatol2019;17:748-55.e3

[32]

Kanwal F,Mapakshi S,Chayanupatkul M.Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease..Gastroenterology2018;155:1828-37.e2 PMCID:PMC6279617

[33]

Weinmann A,Koch S,Duber C.Treatment and survival of non-alcoholic steatohepatitis associated hepatocellular carcinoma..BMC Cancer2015;15:210 PMCID:PMC4407550

[34]

Di Bisceglie AM.Elevations in serum alpha-fetoprotein levels in patients with chronic hepatitis B..Cancer1989;64:2117-20

[35]

Di Bisceglie AM,Chung RT,Dienstag JL.Serum alpha-fetoprotein levels in patients with advanced hepatitis C: results from the HALT-C trial..J Hepatol2005;43:434-41

[36]

Sherman M,Lee C.Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population..Hepatology1995;22:432-8

[37]

Li D,Satomura S.AFP-L3: a new generation of tumor marker for hepatocellular carcinoma..Clin Chim Acta2001;313:15-9

[38]

Liebman HA,Tong MJ,Lo KJ.Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma..N Engl J Med1984;310:1427-31

[39]

Shang S,Ge S,Rosen HR.Identification of osteopontin as a novel marker for early hepatocellular carcinoma..Hepatology2012;55:483-90 PMCID:PMC3914762

[40]

Wang XY,Dubois S,Allegretta M.Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas..Hum Pathol2006;37:1435-41

[41]

Abelev GI,Khramkova NI,Irlin IS.Production of embryonal alpha-globulin by transplantable mouse hepatomas..Transplantation1963;1:174-80

[42]

Daniele B,Megna AS.Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma..Gastroenterology2004;127:S108-12

[43]

Kumada T,Takeda I,Sone Y.Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis..J Hepatol1999;30:125-30

[44]

Yamashita F,Satomura S.Prognostic significance of Lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinomas..Gastroenterology1996;111:996-1001

[45]

Khien VV,Chinh TT,Bang MH.Clinical evaluation of lentil lectin-reactive alpha-fetoprotein-L3 in histology-proven hepatocellular carcinoma..Int J Biol Markers2001;16:105-11

[46]

Taketa K,Win N,Wind KM.Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar..Acta Med Okayama2002;56:317-20

[47]

Marrero JA,Wei W,Conjeevaram HS.Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients..Hepatology2003;37:1114-21

[48]

Volk ML,Su GL,Marrero JA.Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3..Cancer Biomark2007;3:79-87

[49]

Yuen MF.Serological markers of liver cancer..Best Pract Res Clin Gastroenterol2005;19:91-9

[50]

Toyoda H,Tada T,Maeda A.Clinical utility of highly sensitive Lens culinaris agglutinin-reactive alpha-fetoprotein in hepatocellular carcinoma patients with alpha-fetoprotein <20 ng/mL..Cancer Sci2011;102:1025-31

[51]

Choi JY,Kim HY,Kim Y.Diagnostic value of AFP-L3 and PIVKA-II in hepatocellular carcinoma according to total-AFP..World J Gastroenterol2013;19:339-46 PMCID:PMC3554817

[52]

Koike Y,Sato S,Teratani T.Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients..Cancer2001;91:561-9

[53]

Lok AS,Morgan TR,Sterling RK.Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease..Gastroenterology2009;136:138-48 PMCID:PMC3749922

[54]

Johnson PJ,Cox TF,Teng M.The detection of hepatocellular carcinoma using a prospectively developed and validated model based on serological biomarkers..Cancer Epidemiol Biomarkers Prev2014;23:144-53

[55]

Chan SL,Johnson PJ,Chan MH.Performance of serum alpha-fetoprotein levels in the diagnosis of hepatocellular carcinoma in patients with a hepatic mass..HPB (Oxford)2014;16:366-72 PMCID:PMC3967889

[56]

Berhane S,Tada T,Kagebayashi C.Role of the GALAD and BALAD-2 serologic models in diagnosis of hepatocellular carcinoma and prediction of survival in patients..Clin Gastroenterol Hepatol2016;14:875-86.e6

[57]

Best J,Heider D,Manka P.The GALAD scoring algorithm based on AFP, AFP-L3, and DCP significantly improves detection of BCLC early stage hepatocellular carcinoma..Z Gastroenterol2016;54:1296-305

[58]

Best J,Sowa JP,Dechene A.GALAD score detects early hepatocellular carcinoma in an international cohort of patients with nonalcoholic steatohepatitis..Clin Gastroenterol Hepatol2020;18:728-35.e4

[59]

Fedarko NS,Karadag A,Fisher LW.Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer..Clin Cancer Res2001;7:4060-6

[60]

Zhao J,Lu B,Xu D.Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis..Gastroenterology2008;135:956-68

[61]

Kim J,Lee SD,Kim YC.Elevated plasma osteopontin levels in patients with hepatocellular carcinoma..Am J Gastroenterol2006;101:2051-9

[62]

Wan HG,Gu YM,Xu W.Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis..Clin Res Hepatol Gastroenterol2014;38:706-14

[63]

Li J,Dai M,Chen J.Diagnostic accuracy of osteopontin plus alpha-fetoprotein in the hepatocellular carcinoma: a meta-analysis..Clin Res Hepatol Gastroenterol2017;41:543-53

[64]

Filmus J.The role of glypican-3 in the regulation of body size and cancer..Cell Cycle2008;7:2787-90

[65]

Capurro M,Sherman M,Shi W.Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma..Gastroenterology2003;125:89-97

[66]

Capurro MI,Lobe C.Glypican-3 promotes the growth of hepatocellular carcinoma by stimulating canonical Wnt signaling..Cancer Res2005;65:6245-54

[67]

Nakatsura T,Senju S,Komori H.Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker..Biochem Biophys Res Commun2003;306:16-25

[68]

Jia X,Gao Y,Du Z.Diagnosis accuracy of serum glypican-3 in patients with hepatocellular carcinoma: a systematic review with meta-analysis..Arch Med Res2014;45:580-8

[69]

Qiao SS,Gong L,Chen PC.Simultaneous measurements of serum AFP, GPC-3 and HCCR for diagnosing hepatocellular carcinoma..Hepatogastroenterology2011;58:1718-24

[70]

Yang JD,Mara KC,Dai J.GALAD score for hepatocellular carcinoma detection in comparison to liver ultrasound and proposal of GALADUS score..Cancer Epidemiol Biomarkers Prev2019;28:531-8 PMCID:PMC6401221

[71]

Hassan MM,Etzel CJ,Spitz MR.Genetic variation in the PNPLA3 gene and hepatocellular carcinoma in USA: risk and prognosis prediction..Mol Carcinog.2013;52 Suppl 1:E139-47 PMCID:PMC3808509

[72]

Tang S,Mei TT,Wei XH.Association of TM6SF2 rs58542926 T/C gene polymorphism with hepatocellular carcinoma: a meta-analysis..BMC Cancer2019;19:1128 PMCID:PMC6868855

[73]

Dongiovanni P,Longo M,Fracanzani AL.miRNA signature in NAFLD: a turning point for a non-invasive diagnosis..Int J Mol Sci2018;19: PMCID:PMC6320931

[74]

Zhang C,Li Y,Ni W.Role of MicroRNAs in the development of hepatocellular carcinoma in nonalcoholic fatty liver disease..Anat Rec (Hoboken)2019;302:193-200

[75]

Kutlu O,Ozer E.Molecular pathogenesis of nonalcoholic steatohepatitis- (NASH-) related hepatocellular carcinoma..Can J Gastroenterol Hepatol2018;2018:8543763 PMCID:PMC6136489

[76]

Chassaing B,Gewirtz AT.Microbiota-liver axis in hepatic disease..Hepatology2014;59:328-39 PMCID:PMC4084781

[77]

Konturek PC,Konturek K,Konturek T.Gut(-)Liver Axis: how do gut bacteria influence the liver?.Med Sci (Basel)2018;6: PMCID:PMC6165386

[78]

Kostic AD,Gevers D.The microbiome in inflammatory bowel disease: current status and the future ahead..Gastroenterology2014;146:1489-99 PMCID:PMC4034132

[79]

Bashiardes S,Rozin S,Elinav E.Non-alcoholic fatty liver and the gut microbiota..Mol Metab2016;5:782-94 PMCID:PMC5004228

[80]

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

[81]

Khoruts A.Understanding the mechanisms of faecal microbiota transplantation..Nat Rev Gastroenterol Hepatol2016;13:508-16 PMCID:PMC5909819

[82]

Zhou D,Shen F,Ding WJ.Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota..Sci Rep2017;7:1529 PMCID:PMC5431549

[83]

de Groot PF,de Clercq NC.Fecal microbiota transplantation in metabolic syndrome: History, present and future..Gut Microbes2017;8:253-67 PMCID:PMC5479392

[84]

Dapito DH,Gwak GY,Jang MK.Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4..Cancer Cell2012;21:504-16 PMCID:PMC3332000

[85]

Yoshimoto S,Atarashi K,Sato S.Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome..Nature2013;499:97-101

[86]

Ponziani FR,Castelli C,Rivoltini L.Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease..Hepatology2019;69:107-20

[87]

Schonewille M,Groen AK.Bile salts in control of lipid metabolism..Curr Opin Lipidol2016;27:295-301

[88]

Mouzaki M,Bandsma R,Arendt BM.Bile acids and dysbiosis in non-alcoholic fatty liver disease..PLoS One2016;11:e0151829 PMCID:PMC4874546

[89]

Neuschwander-Tetri BA,Tonascia J,Kleiner DE.Trials of obeticholic acid for non-alcoholic steatohepatitis - Authors’ reply..Lancet2015;386:28-9

[90]

Liu Q,Zhuang Y,Wang J.Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma..Gut Pathog2019;11:1 PMCID:PMC6337822

[91]

Sydor S,Messerschmidt I,Vilchez-Vargas R.Altered microbiota diversity and bile acid signaling in cirrhotic and noncirrhotic NASH-HCC..Clin Transl Gastroenterol2020;11:e00131 PMCID:PMC7145043

[92]

Jiao N,Chapa-Rodriguez A,Nugent CA.Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD..Gut2018;67:1881-91

[93]

Bechmann LP,Sowa JP,Best J.Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis..Hepatology2013;57:1394-406

[94]

Caussy C,Humphrey G,Singh S.A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease..Nat Commun2019;10:1406 PMCID:PMC6440960

[95]

Nowak A,Blasiak J.Anti-proliferative, pro-apoptotic and anti-oxidative activity of Lactobacillus and Bifidobacterium strains: a review of mechanisms and therapeutic perspectives..Crit Rev Food Sci Nutr2019;59:3456-67

[96]

Fujiwara N,Koneru B.Omics-derived hepatocellular carcinoma risk biomarkers for precision care of chronic liver diseases..Hepatol Res2020;50:817-30

[97]

Pei Y,Renault V.An overview of hepatocellular carcinoma study by omics-based methods..Acta Biochim Biophys Sin (Shanghai)2009;41:1-15

[98]

Del Poggio P,Ciccarese F,Rapaccini GL.Factors that affect efficacy of ultrasound surveillance for early stage hepatocellular carcinoma in patients with cirrhosis..Clin Gastroenterol Hepatol2014;12:1927-33.e2

[99]

Chagas AL,Oliveira CP,Mello ES.Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?.Braz J Med Biol Res2009;42:958-62

[100]

Kawada N,Kawaguchi T,Ishihara R.Hepatocellular carcinoma arising from non-cirrhotic nonalcoholic steatohepatitis..J Gastroenterol2009;44:1190-4

PDF

29

Accesses

0

Citation

Detail

Sections
Recommended

/