Advances in early diagnosis of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most recurrent hepatic malignancy and the third in the cancer-related casualties in the west. The frequently-documented causes of HCC are chronic liver infections by hepatitis B virus or hepatitis C virus, nonalcoholic fatty liver disease, cirrhosis, exposure to aflatoxins and tobacco smocking, etc. Clinical presentation of this fatal disease ranges from asymptomatic to upper abdominal pain or common health conditions like weight loss or lethargy. Among current surveillance strategy for suspected patients, liver imaging and serum alpha fetoprotein estimation has been regularly recommended. However, sensitivity of this diagnostic methodology especially in early detections, often suffers from compromised sensitivity and selectivity. Various image based and serological biomarkers for HCC has been introduced in recent decades with varied sensitivity as stand-alone or combined diagnostic protocol. The current article will review the status of HCC diagnosis with respect to common diagnostic protocol, and upcoming novel biomarkers.

Keywords

Alpha fetoprotein / extracellular vehicles / hepatocellular carcinoma / indocyanine green / magnetic resonance imaging / non-coding RNA

References

[1] Massarweh NN.Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma..Cancer Control2017;24:1073274817729245 PMCID:PMC5937247

[2] Howe HL,Ries LA,Ahmed F.Annual report to the nation on the status of cancer, 1975-2003, featuring cancer among U.S. Hispanic/Latino populations..Cancer2006;107:1711-42

[3] 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

[4] Marrero JA,Wang Y,Befeler AS.Alpha-fetoprotein, des-γ carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma..Gastroenterology2009;137:110-8 PMCID:PMC2704256

[5] Ghanaati H,Jafarian A,Nassiri-Toosi M.Imaging and imaging-guided interventions in the diagnosis and management of hepatocellular carcinoma (HCC)-review of evidence..Iran J Radiol2012;9:167-77 PMCID:PMC3569547

[6] Haug AR.Comparison of liver biopsy and noninvasive methods for diagnosis of hepatocellular carcinoma Imaging of primary liver tumors with positron-emission tomography..Q J Nucl Med Mol Imaging2017;61:292-300

[7] 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

[8] Navin PJ.Hepatocellular carcinoma: state of the art imaging and recent advances..J Clin Transl Hepatol2019;7:72-85 PMCID:PMC6441649

[9] Jang HJ,Burns PN.Enhancement patterns of hepatocellular carcinoma at contrast-enhanced US: comparison with histologic differentiation..Radiology2007;244:898-906

[10] Wu B,Tan H.Value of ¹⁸F-FDG PET/CT in the diagnosis of portal vein tumor thrombus in patients with hepatocellular carcinoma..Abdom Radiol (NY)2019;

[11] Park MS,Patel J,Do RK.Hepatocellular carcinoma: detection with diffusion weighted versus contrast-enhanced magnetic resonance imaging in pretransplant patients..Hepatology2012;56:140-8

[12] Ishizawa T,Urano Y,Satou S.Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma..Ann Surg Oncol2014;21:440-8

[13] Hester CA,Singal AG.Comparative analysis of nonalcoholic steatohepatitis versus viral hepatitis and alcohol-related liver disease-related hepatocellular carcinoma..J Natl Compr Canc Netw2019;17:322-9

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

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

[16] Wang B,Ma X,Qiu S.Platelet activation status in the diagnosis and postoperative prognosis of hepatocellular carcinoma..Clin Chim Acta2019;495:191-7

[17] Ono M,Ohhira M,Namiki M.Measurements of immunoreative prothrombin, des-γ-carboxy prothrombin and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma..Am J Gastroenterol1990;85:1149-54

[18] Tsai SL,Yang PM,Sung JL.Plasma des-gamma-carboxyprothrombin in the early stages of hepatocellular carcinoma..Hepatology1990;11:481-8

[19] Pote N,Albuquerque M,Belghiti J.Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion..J Hepatol2015;62:848-54

[20] Lim TS,Han KH,Shin SH.Combined use of AFP, PIVKA-II, and AFP-L3 as tumor markers enhances diagnostic accuracy for hepatocellular carcinoma in cirrhotic patients..Scand J Gastroenterol2016;51:344-53

[21] Han C,Bai H.Identification of a role for serum aldoketo reductase family 1-member B10 in early detection of hepatocellular carcinoma..Oncology Letters2018;16:7123-30 PMCID:PMC6256343

[22] DiStefano JK.Diagnostic and prognostic potential of AKR1B10 in human hepatocellular carcinoma..Cancers (Basel)2019;11:E486 PMCID:PMC6521254

[23] Conigliaro A,Lo Dico A,Buccheri S.CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA..Mol Cancer2015;14:155 PMCID:PMC4536801

[24] Wang H,Li A,Gao H.Expression of serum exosomal microRNA-21 in human hepatocellular carcinoma..Biomed Res Int2014;2014:864894 PMCID:PMC4052145

[25] Qu Z,Wu J,Qiang G.Exosomal miR-665 as a novel minimally invasive biomarker for hepatocellular carcinoma diagnosis and prognosis..Oncotarget2017;8:80666-78 PMCID:PMC5655229

[26] Sugimachi K,Hirata H,Ueda M.Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation..Br J Cancer2015;112:532-8 PMCID:PMC4453648

[27] Liu W,Zhou K,Wang Z.Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma..OncoTargets Ther2017;10:3843-51 PMCID:PMC5546809

[28] Arbelaiz A,Krawczyk M,Lapitz A.Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma..Hepatology2017;66:1125-43

[29] Wang W,Zhou Y.Peripheral blood microvesicles are potential biomarkers for hepatocellular carcinoma..Cancer Biomark2013;13:351-7

[30] Świtlik WZ,Karbownik MS,Jabłkowski M.Forms of diagnostic material as sources of miRNA biomarkers in hepatocellular carcinoma: a preliminary study..Biomark Med2019;

[31] Panzitt K,Guelly C,Stradner M.Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA..Gastroenterology2007;132:330-42

[32] Liu Y,Liu L,Liu J.A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population,.PLoS One2012;7:e35145 PMCID:PMC3320879

[33] Smaldone MC.BC-819, a plasmid comprising the H19 gene regulatory sequences and diphtheria toxin A, for the potential targeted therapy of cancers..Curr Opin Mol Ther2010;12:607-16

[34] Yang L,Li H.The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma..Mol Biosyst2016;12:2605-12

[35] Lai MC,Zhou L,Xie HY.Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation..Med Oncol2012;29:1810-6

[36] Braconi C,Valeri N,Nuovo G.MicroRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer..Oncogene2011;30:4750-6 PMCID:PMC4292930

[37] Tu ZQ,Mei JZ.Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma..Int J Clin Exp Pathol2014;7:4303-9 PMCID:PMC4129048

[38] Wang F,He BS,Deng QW.Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway..Oncotarget2015;6:7899-917 PMCID:PMC4480724

[39] Tsang FH,Wei L,Lee JM.Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b..Liver Int2015;35:1597-606

[40] Zhuang LK,Ma X,Wang ZS.MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST..Cell Death Dis2016;7:e2203 PMCID:PMC4855645

[41] Zhang C,Zhang B.The predictive powers of plasma trefoil factor 3 or its related micro RNAs for patients with hepatocellular carcinoma..BMC Cancer2018;18:1110 PMCID:PMC6234585

[42] Ezzat WM,Elhosary YA,Fahim HH.Detection of DNA methylated microRNAs in hepatocellular carcinoma..Gene2019;702:153-7

[43] Xu RH,Krawczyk M,Luo H.Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma..Nat Mater2017;16:1155-61

[44] Kisiel JB,Kanipakam RVSR.Hepatocellular carcinoma detection by plasma methylated DNA: discovery, phase I pilot, and phase II clinical validation..Hepatology2019;69:1180-92 PMCID:PMC6429916

[45] Li Y,Yu S,He X.Extracellular Vesicles Long RNA Sequencing Reveals Abundant mRNA, circRNA, and lncRNA in Human Blood as Potential Biomarkers for Cancer Diagnosis..Clin Chem2019;