Villanueva A, Hepatocellular Carcinoma N, Engl JM (2019) 380 (15),1450–1462. https://doi.org/10.1056/NEJMra1713263

Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero J (2018) A. AASLD Guidelines for the treatment of Hepatocellular Carcinoma: Heimbach et Al. Hepatology 67(1):358–380. https://doi.org/10.1002/hep.29086

Article  PubMed  Google Scholar 

El-Serag HB (2012) Epidemiology of viral Hepatitis and Hepatocellular Carcinoma. Gastroenterology 142(6):1264–1273. e1

Article  PubMed  Google Scholar 

Yang JD, Roberts LR, Hepatocellular Carcinoma (2010) A Global View. Nat Rev Gastroenterol Hepatol 7(8):448–458. https://doi.org/10.1038/nrgastro.2010.100

Article  PubMed  PubMed Central  Google Scholar 

Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR (2019) A Global View of Hepatocellular Carcinoma: Trends, Risk, Prevention and Management. Nat Rev Gastroenterol Hepatol 16(10):589–604. https://doi.org/10.1038/s41575-019-0186-y

Article  PubMed  PubMed Central  Google Scholar 

Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, Zoulim F, Tacke F EASL 2017 clinical practice guidelines on the management of Hepatitis B Virus infection. Journal of Hepatology 2017, 67 (2),370–398. https://doi.org/10.1016/j.jhep.2017.03.021

Wu X, Li J, Gassa A, Buchner D, Alakus H, Dong Q, Ren N, Liu M, Odenthal M, Stippel D, Bruns C, Zhao Y, Wahba R (2020) Circulating tumor DNA as an emerging Liquid Biopsy Biomarker for early diagnosis and therapeutic monitoring in Hepatocellular Carcinoma. Int J Biol Sci 16(9):1551–1562. https://doi.org/10.7150/ijbs.44024

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lang H, Sotiropoulos GC, Brokalaki EI, Schmitz KJ, Bertona C, Meyer G, Frilling A, Paul A, Malagó M, Broelsch CE (2007) Survival and recurrence rates after resection for Hepatocellular Carcinoma in noncirrhotic livers. J Am Coll Surg 205(1):27–36. https://doi.org/10.1016/j.jamcollsurg.2007.03.002

Article  PubMed  Google Scholar 

NCCN Guidelines for Hepatobiliary Cancers.

Tzartzeva K Surveillance imaging and alpha fetoprotein for early detection of Hepatocellular Carcinoma in patients with cirrhosis: a Meta-analysis. 34. https://doi.org/10.1053/j.gastro.2018.01.064

Zhang X, Wang Z, Tang W, Wang X, Liu R, Bao H, Chen X, Wei Y, Wu S, Bao H, Wu X, Shao Y, Fan J, Zhou J (2022) Ultrasensitive and affordable assay for early detection of primary Liver Cancer using plasma cell-free DNA fragmentomics. Hepatology 76(2):317–329. https://doi.org/10.1002/hep.32308

Article  CAS  PubMed  Google Scholar 

Guo J, Seo Y, Ren S, Hong S, Lee D, Kim S, Jiang Y (2016) Diagnostic performance of contrast-enhanced Multidetector Computed Tomography and Gadoxetic Acid Disodium-Enhanced magnetic resonance imaging in detecting Hepatocellular Carcinoma: direct comparison and a Meta-analysis. Abdom Radiol 41(10):1960–1972. https://doi.org/10.1007/s00261-016-0807-7

Article  Google Scholar 

The PreCar Team, Chen L, Abou-Alfa GK, Zheng B, Liu J-F, Bai J, Du L-T, Qian Y-S, Fan R, Liu X-L, Wu L, Hou J-L, Wang H-Y (2021) Genome-scale profiling of circulating cell-free DNA signatures for early detection of Hepatocellular Carcinoma in Cirrhotic Patients. Cell Res 31(5):589–592. https://doi.org/10.1038/s41422-020-00457-7

Article  CAS  Google Scholar 

Harris PS, Hansen RM, Gray ME, Massoud OI, McGuire BM, Shoreibah MG (2019) Hepatocellular Carcinoma Surveillance: an evidence-based Approach. WJG 25(13):1550–1559. https://doi.org/10.3748/wjg.v25.i13.1550

Article  PubMed  PubMed Central  Google Scholar 

Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid Biopsy: Monitoring Cancer-Genetics in the blood. Nat Rev Clin Oncol 10(8):472–484. https://doi.org/10.1038/nrclinonc.2013.110

Article  CAS  PubMed  Google Scholar 

Issa IA, Noureddine M (2017) Colorectal Cancer Screening: An Updated Review of the Available Options. WJG 23 (28), 5086. https://doi.org/10.3748/wjg.v23.i28.5086

Hench IB, Hench J, Tolnay M (2018) Liquid biopsy in clinical management of breast, lung, and Colorectal Cancer. Front Med 5:9. https://doi.org/10.3389/fmed.2018.00009

Article  Google Scholar 

Morrison GJ, Goldkorn A (2018) Development and application of Liquid Biopsies in metastatic prostate Cancer. Curr Oncol Rep 20(4):35. https://doi.org/10.1007/s11912-018-0683-0

Article  PubMed  PubMed Central  Google Scholar 

Chung JH, Pavlick D, Hartmaier R, Schrock AB, Young L, Forcier B, Ye P, Levin MK, Goldberg M, Burris H, Gay LM, Hoffman AD, Stephens PJ, Frampton GM, Lipson DM, Nguyen DM, Ganesan S, Park BH, Vahdat LT, Leyland-Jones B, Mughal TI, Pusztai L, O’Shaughnessy J, Miller VA, Ross JS, Ali SM (2017) Hybrid capture-based genomic profiling of circulating Tumor DNA from patients with estrogen receptor-positive metastatic breast Cancer. Ann Oncol 28(11):2866–2873. https://doi.org/10.1093/annonc/mdx490

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pan Y, Ji JS, Jin JG, Kuo WP, Kang H (2017) Cancer Liquid Biopsy: is it ready for clinic? IEEE Pulse 8(1):23–27. https://doi.org/10.1109/MPUL.2016.2630838

Article  PubMed  Google Scholar 

Moss J, Magenheim J, Neiman D, Zemmour H, Loyfer N, Korach A, Samet Y, Maoz M, Druid H, Arner P, Fu K-Y, Kiss E, Spalding KL, Landesberg G, Zick A, Grinshpun A, Shapiro AMJ, Grompe M, Wittenberg AD, Glaser B, Shemer R, Kaplan T, Dor Y (2018) Comprehensive Human cell-type methylation Atlas reveals Origins of circulating cell-free DNA in Health and Disease. Nat Commun 9(1):5068. https://doi.org/10.1038/s41467-018-07466-6

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lyu X, Tsui Y-M, Ho DW-H, Ng IO-L (2022) Liquid Biopsy using cell-free or circulating tumor DNA in the management of Hepatocellular Carcinoma. Cell Mol Gastroenterol Hepatol 13(6):1611–1624. https://doi.org/10.1016/j.jcmgh.2022.02.008

Article  CAS  PubMed  PubMed Central  Google Scholar 

Howell J, Atkinson SR, Pinato DJ, Knapp S, Ward C, Minisini R, Burlone ME, Leutner M, Pirisi M, Büttner R, Khan SA, Thursz M, Odenthal M, Sharma R (2019) Identification of mutations in circulating cell-free Tumour DNA as a Biomarker in Hepatocellular Carcinoma. Eur J Cancer 116:56–66. https://doi.org/10.1016/j.ejca.2019.04.014

Article  CAS  PubMed  Google Scholar 

Yan L, Chen Y, Zhou J, Zhao H, Zhang H, Wang G Diagnostic value of circulating cell-free DNA levels for Hepatocellular Carcinoma. International Journal of Infectious Diseases 2018, 67,92–97. https://doi.org/10.1016/j.ijid.2017.12.002

Xu H, Zhu X, Xu Z, Hu Y, Bo S, Xing T, Zhu K (2015) Non-invasive analysis of genomic Copy Number Variation in patients with Hepatocellular Carcinoma by Next Generation DNA sequencing. J Cancer 6(3):247–253. https://doi.org/10.7150/jca.10747

Article  PubMed  PubMed Central  Google Scholar 

Tao K, Bian Z, Zhang Q, Guo X, Yin C, Wang Y, Zhou K, Wan S, Shi M, Bao D, Yang C, Xing J (2020) Machine learning-based genome-wide interrogation of somatic Copy Number Aberrations in circulating Tumor DNA for early detection of Hepatocellular Carcinoma. EBioMedicine 56:102811. https://doi.org/10.1016/j.ebiom.2020.102811

Article  PubMed  PubMed Central  Google Scholar 

Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clément B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouzé E, Calvo F, Zucman-Rossi J (2012) Integrated Analysis of somatic mutations and Focal Copy-Number changes identifies key genes and pathways in Hepatocellular Carcinoma. Nat Genet 44(6):694–698. https://doi.org/10.1038/ng.2256

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaseb AO, Sánchez NS, Sen S, Kelley RK, Tan B, Bocobo AG, Lim KH, Abdel-Wahab R, Uemura M, Pestana RC, Qiao W, Xiao L, Morris J, Amin HM, Hassan MM, Rashid A, Banks KC, Lanman RB, Talasaz A, Mills-Shaw KR, George B, Haque A, Raghav KPS, Wolff RA, Yao JC, Meric-Bernstam F, Ikeda S, Kurzrock R (2019) Molecular profiling of Hepatocellular Carcinoma using circulating cell-free DNA. Clin Cancer Res 25(20):6107–6118. https://doi.org/10.1158/1078-0432.CCR-18-3341

Article  CAS  PubMed  PubMed Central  Google Scholar 

Totoki Y, Tatsuno K, Covington KR, Ueda H, Creighton CJ, Kato M, Tsuji S, Donehower LA, Slagle BL, Nakamura H, Yamamoto S, Shinbrot E, Hama N, Lehmkuhl M, Hosoda F, Arai Y, Walker K, Dahdouli M, Gotoh K, Nagae G, Gingras M-C, Muzny DM, Ojima H, Shimada K, Midorikawa Y, Goss JA, Cotton R, Hayashi A, Shibahara J, Ishikawa S, Guiteau J, Tanaka M, Urushidate T, Ohashi S, Okada N, Doddapaneni H, Wang M, Zhu Y, Dinh H, Okusaka T, Kokudo N, Kosuge T, Takayama T, Fukayama M, Gibbs RA, Wheeler DA, Aburatani H (2014) Shibata, T. Trans-Ancestry Mutational Landscape of Hepatocellular Carcinoma Genomes. Nat Genet 46(12):1267–1273. https://doi.org/10.1038/ng.3126

Article  CAS  PubMed  Google Scholar 

Qu C, Wang Y, Wang P, Chen K, Wang M, Zeng H, Lu J, Song Q, Diplas BH, Tan D, Fan C, Guo Q, Zhu Z, Yin H, Jiang L, Chen X, Zhao H, He H, Wang Y, Li G, Bi X, Zhao X, Chen T, Tang H, Lv C, Wang D, Chen W, Zhou J, Zhao H, Cai J, Wang X, Wang S, Yan H, Zeng Y-X, Cavenee WK, Jiao Y (2019) Detection of Early-Stage Hepatocellular Carcinoma in Asymptomatic HBsAg-Seropositive Individuals by Liquid Biopsy. Proc. Natl. Acad. Sci. U.S.A. 116 (13), 6308–6312. https://doi.org/10.1073/pnas.1819799116

Huang A, Zhang X, Zhou S-L, Cao Y, Huang X-W, Fan J, Yang X-R, Zhou J (2016) Plasma circulating Cell-Free DNA Integrity as a Promising Biomarker for diagnosis and surveillance in patients with Hepatocellular Carcinoma. J Cancer 7(13):1798–1803. https://doi.org/10.7150/jca.15618

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang P, Chan CWM, Chan KCA, Cheng SH, Wong J, Wong VW-S, Wong GLH, Chan SL, Mok TSK, Chan HLY, Lai PBS, Chiu RWK, Lo YMD (2015) Lengthening and Shortening of Plasma DNA in Hepatocellular Carcinoma Patients. Proc. Natl. Acad. Sci. U.S.A. 112 (11). https://doi.org/10.1073/pnas.1500076112

Meng Z, Ren Q, Zhong G, Li S, Chen Y, Wu W, Feng Y, Mao M, Zhang F, Long G (2021) Noninvasive detection of Hepatocellular Carcinoma with circulating Tumor DNA features and α-Fetoprotein. J Mol Diagn 23(9):1174–1184. https://doi.org/10.1016/j.jmoldx.2021.06.003

Article  CAS  PubMed  Google Scholar 

Jiang P, Sun K, Tong YK, Cheng SH, Cheng THT, Heung MMS, Wong J, Wong VWS, Chan HLY, Chan KCA, Lo YMD, Chiu RWK (2018) Preferred End Coordinates and Somatic Variants as Signatures of Circulating Tumor DNA Associated with Hepatocellular Carcinoma. Proc. Natl. Acad. Sci. U.S.A. 115 (46). https://doi.org/10.1073/pnas.1814616115

Jiang P, Sun K, Peng W, Cheng SH, Ni M, Yeung PC, Heung MMS, Xie T, Shang H, Zhou Z, Chan RWY, Wong J, Wong VWS, Poon LC, Leung TY, Lam WKJ, Chan JYK, Chan HLY, Chan KCA, Chiu RWK, Lo YM (2020) D. plasma DNA end-motif profiling as a fragmentomic marker in Cancer, pregnancy, and transplantation. Cancer Discov 10(5):664–673. https://doi.org/10.1158/2159-8290.CD-19-0622

Article  CAS  PubMed  Google Scholar 

Manel E Epigenetics in Cancer. N engl j med 2008, 12. https://doi.org/10.1056/NEJMra072067

Chatterjee R, Vinson C, CpG Methylation Recruits Sequence Specific Transcription Factors Essential for Tissue Specific Gene Expression (2012) Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1819(7):763–770. https://doi.org/10.1016/j.bbagrm.2012.02.014

Kisiel JB, Dukek BA, Kanipakam VSR, Ghoz R, Yab HM, Berger TC, Taylor CK, Foote WR, Giama PH, Onyirioha NH, Abdallah K, Burger MA, Slettedahl KN, Mahoney SW, Smyrk DW, Lewis TC, Giakoumopoulos JT, Allawi M, Lidgard HT, Roberts GP, Ahlquist LR (2019) D. A. Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation. Hepatology hep.30244. https://doi.org/10.1002/hep.30244

Xu R, Wei W, Krawczyk M, Wang W, Luo H, Flagg K, Yi S, Shi W, Quan Q, Li K, Zheng L, Zhang H, Caughey BA, Zhao Q, Hou J, Zhang R, Xu Y, Cai H, Li G, Hou R, Zhong Z, Lin D, Fu X, Zhu J, Duan Y, Yu M, Ying B, Zhang W, Wang J, Zhang E, Zhang C, Li O, Guo R, Carter H, Zhu J, Hao X, Zhang K (2017) Circulating Tumour DNA methylation markers for diagnosis and prognosis of Hepatocellular Carcinoma. Nat Mater 16(11):1155–1161. https://doi.org/10.1038/nmat4997

Article  CAS  PubMed  Google Scholar 

Luo B, Ma F, Liu H, Hu J, Rao L, Liu C, Jiang Y, Kuangzeng S, Lin X, Wang C, Lei Y, Si Z, Chen G, Zhou N, Liang C, Jiang F, Liu F, Dai W, Liu W, Gao Y, Li Z, Li X, Zhou G, Li B, Zhang Z, Nian W, Luo L, Liu X (2022) Cell-free DNA methylation markers for Differential diagnosis of Hepatocellular Carcinoma. BMC Med 20(1):8. https://doi.org/10.1186/s12916-021-02201-3

Article  CAS