1. Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, et al. Annual report to the nation on the status of cancer, 1975-2014, featuring survival. J Natl Cancer Inst. 2017; 109:djx030.
2. Wittekind C. Pathology of liver tumors. Zentralbl Chir. 2000; 125:587–591.
3. Reig M, Forner A, Rimola J, Ferrer-Fàbrega J, Burrel M, GarciaCriado Á, et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022; 76:681–693.
4. Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021; 18:293–313.
5. Brar G, Greten TF, Graubard BI, McNeel TS, Petrick JL, McGlynn KA, et al. Hepatocellular carcinoma survival by etiology: a SEERmedicare database analysis. Hepatol Commun. 2020; 4:1541–1551.
6. Goutté N, Sogni P, Bendersky N, Barbare JC, Falissard B, Farges O. Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country. J Hepatol. 2017; 66:537–544.
7. Trevisani F, Garuti F, Neri A. Alpha-fetoprotein for diagnosis, prognosis, and transplant selection. Semin Liver Dis. 2019; 39:163–177.
8. Ronot M, Chernyak V, Burgoyne A, Chang J, Jiang H, Bashir M, et al. Imaging to predict prognosis in hepatocellular carcinoma: current and future perspectives. Radiology. 2023; 307:e221429.
9. Gerlinger M, Rowan AJ, Horswell S, Math M, Larkin J, Endesfelder D, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366:883–892.
10. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016; 2:16018.
11. Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM. genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology. 2015; 149:1226–1239. e4.
12. Rebouissou S, Nault JC. Advances in molecular classification and precision oncology in hepatocellular carcinoma. J Hepatol. 2020; 72:215–229.
13. Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nat Rev Clin Oncol. 2018; 15:599–616.
14. Sangro B, Sarobe P, Hervás-Stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021; 18:525–543.
15. Couri T, Pillai A. Goals and targets for personalized therapy for HCC. Hepatol Int. 2019; 13:125–137.
16. Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell. 2017; 169:1327–1341. e23.
17. Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res. 2009; 69:7385–7392.
18. Boyault S, Rickman DS, de Reyniès A, Balabaud C, Rebouissou S, Jeannot E, et al. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 2007; 45:42–52.
19. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology. 2004; 40:667–676.
20. Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouzé E, Blanc JF, et al. Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol. 2017; 67:727–738.
21. Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, et al. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res. 2008; 68:6779–6788.
22. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021; 7:6.
23. Wang K, Lim HY, Shi S, Lee J, Deng S, Xie T, et al. Genomic landscape of copy number aberrations enables the identification of oncogenic drivers in hepatocellular carcinoma. Hepatology. 2013; 58:706–717.
24. Seehawer M, Heinzmann F, D’Artista L, Harbig J, Roux PF, Hoenicke L, et al. Necroptosis microenvironment directs lineage commitment in liver cancer. Nature. 2018; 562:69–75.
25. Villanueva A, Hoshida Y, Battiston C, Tovar V, Sia D, Alsinet C, et al. Combining clinical, pathology, and gene expression data to predict recurrence of hepatocellular carcinoma. Gastroenterology. 2011; 140:1501–1512.e2.
26. Nault JC, De Reyniès A, Villanueva A, Calderaro J, Rebouissou S, Couchy G, et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology. 2013; 145:176–187.
27. Llovet JM, Villanueva A, Lachenmayer A, Finn RS. Advances in targeted therapies for hepatocellular carcinoma in the genomic era. Nat Rev Clin Oncol. 2015; 12:408–424.
28. Hoshida Y, Toffanin S, Lachenmayer A, Villanueva A, Minguez B, Llovet JM. Molecular classification and novel targets in hepatocellular carcinoma: recent advancements. Semin Liver Dis. 2010; 30:35–51.
29. Villanueva A, Portela A, Sayols S, Battiston C, Hoshida Y, MéndezGonzález J, et al. DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma. Hepatology. 2015; 61:1945–1956.
30. Ziol M, Poté N, Amaddeo G, Laurent A, Nault JC, Oberti F, et al. Macrotrabecular-massive hepatocellular carcinoma: a distinctive histological subtype with clinical relevance. Hepatology. 2018; 68:103–112.
31. Jeon Y, Benedict M, Taddei T, Jain D, Zhang X. Macrotrabecular hepatocellular carcinoma: an aggressive subtype of hepatocellular carcinoma. Am J Surg Pathol. 2019; 43:943–948.
32. Calderaro J, Meunier L, Nguyen CT, Boubaya M, Caruso S, Luciani A, et al. ESM1 as a marker of macrotrabecular-massive hepatocellular carcinoma. Clin Cancer Res. 2019; 25:5859–5865.
33. Kumar D, Hafez O, Jain D, Zhang X. Can primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis? Hum Pathol. 2021; 113:39–46.
34. Mulé S, Galletto Pregliasco A, Tenenhaus A, Kharrat R, Amaddeo G, Baranes L, et al. Multiphase liver MRI for identifying the macrotrabecular-massive subtype of hepatocellular carcinoma. Radiology. 2020; 295:562–571.
35. Chen J, Xia C, Duan T, Cao L, Jiang H, Liu X, et al. Macrotrabecular-massive hepatocellular carcinoma: imaging identification and prediction based on gadoxetic acid-enhanced magnetic resonance imaging. Eur Radiol. 2021; 31:7696–7704.
36. Cannella R, Dioguardi Burgio M, Beaufrère A, Trapani L, Paradis V, Hobeika C, et al. Imaging features of histological subtypes of hepatocellular carcinoma: implication for LI-RADS. JHEP Rep. 2021; 3:100380.
37. Renne SL, Woo HY, Allegra S, Rudini N, Yano H, Donadon M, et al. Vessels encapsulating tumor clusters (VETC) is a powerful predictor of aggressive hepatocellular carcinoma. Hepatology. 2020; 71:183–195.
38. Loy LM, Low HM, Choi JY, Rhee H, Wong CF, Tan CH. Variant hepatocellular carcinoma subtypes according to the 2019 WHO classification: an imaging-focused review. AJR Am J Roentgenol. 2022; 219:212–223.
39. Chen J, Wu Z, Xia C, Jiang H, Liu X, Duan T, et al. Noninvasive prediction of HCC with progenitor phenotype based on gadoxetic acid-enhanced MRI. Eur Radiol. 2020; 30:1232–1242.
40. Choi SY, Kim SH, Park CK, Min JH, Lee JE, Choi YH, et al. Imaging features of gadoxetic acid-enhanced and diffusion-weighted MR imaging for identifying cytokeratin 19-positive hepatocellular carcinoma: a retrospective observational study. Radiology. 2018; 286:897–908.
41. Lachenmayer A, Alsinet C, Savic R, Cabellos L, Toffanin S, Hoshida Y, et al. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib. Clin Cancer Res. 2012; 18:4997–5007.
42. Salomao M, Yu WM, Brown RS Jr, Emond JC, Lefkowitch JH. 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.
43. Calderaro J, Ziol M, Paradis V, Zucman-Rossi J. Molecular and histological correlations in liver cancer. J Hepatol. 2019; 71:616–630.
44. Hwang YJ, Bae JS, Lee Y, Hur BY, Lee DH, Kim H. Classification of microvascular invasion of hepatocellular carcinoma: correlation with prognosis and magnetic resonance imaging. Clin Mol Hepatol. 2023; 29:733–746.
45. Liu G, Ma D, Wang H, Zhou J, Shen Z, Yang Y, et al. Three-dimensional multifrequency magnetic resonance elastography improves preoperative assessment of proliferative hepatocellular carcinoma. Insights Imaging. 2023; 14:89.
46. Hu H, Zheng Q, Huang Y, Huang XW, Lai ZC, Liu J, et al. A nonsmooth tumor margin on preoperative imaging assesses microvascular invasion of hepatocellular carcinoma: a systematic review and meta-analysis. Sci Rep. 2017; 7:15375.
47. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996; 334:693–699.
48. Zhuo JY, Lu D, Tan WY, Zheng SS, Shen YQ, Xu X. CK19-positive hepatocellular carcinoma is a characteristic subtype. J Cancer. 2020; 11:5069–5077.
49. Zhang L, Lin JB, Jia M, Zhang CC, Xu R, Guo L, et al. Clinical and imaging features preoperative evaluation of histological grade and microvascular infiltration of hepatocellular carcinoma. BMC Gastroenterol. 2022; 22:369.
50. Sumie S, Nakashima O, Okuda K, Kuromatsu R, Kawaguchi A, Nakano M, et al. The significance of classifying microvascular invasion in patients with hepatocellular carcinoma. Ann Surg Oncol. 2014; 21:1002–1009.
51. Chou CT, Chen RC, Lin WC, Ko CJ, Chen CB, Chen YL. Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation. AJR Am J Roentgenol. 2014; 203:W253–W259.
52. Fowler KJ, Burgoyne A, Fraum TJ, Hosseini M, Ichikawa S, Kim S, et al. Pathologic, molecular, and prognostic radiologic features of hepatocellular carcinoma. Radiographics. 2021; 41:1611–1631.
53. Reynolds AR, Furlan A, Fetzer DT, Sasatomi E, Borhani AA, Heller MT, et al. Infiltrative hepatocellular carcinoma: what radiologists need to know. Radiographics. 2015; 35:371–386.
54. An C, Kim MJ. Imaging features related with prognosis of hepatocellular carcinoma. Abdom Radiol (NY). 2019; 44:509–516.
55. Kim KA, Kim MJ, Jeon HM, Kim KS, Choi JS, Ahn SH, et al. Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodiumenhanced hepatobiliary phase images. J Magn Reson Imaging. 2012; 35:629–634.
56. Wu Y, Zhu M, Liu Y, Cao X, Zhang G, Yin L. Peritumoral imaging manifestations on Gd-EOB-DTPA-enhanced MRI for preoperative prediction of microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis. Front Oncol. 2022; 12:907076.
57. Chen S, Li K, Jiang J, Wang X, Chai Y, Zhang C, et al. Low expression of organic anion-transporting polypeptide 1B3 predicts a poor prognosis in hepatocellular carcinoma. World J Surg Oncol. 2020; 18:127.
58. Bae JS, Kim JH, Lee DH, Kim JH, Han JK. Hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with HCC: prognostic features before resection, ablation, or TACE. Eur Radiol. 2021; 31:3627–3637.
59. Zhang Y, Wei H, Song B. Magnetic resonance imaging for treatment response evaluation and prognostication of hepatocellular carcinoma after thermal ablation. Insights Imaging. 2023; 14:87.
60. Kang TW, Rhim H, Lee J, Song KD, Lee MW, Kim YS, et al. Magnetic resonance imaging with gadoxetic acid for local tumour progression after radiofrequency ablation in patients with hepatocellular carcinoma. Eur Radiol. 2016; 26:3437–3446.
61. Cucchetti A, Cescon M, Trevisani F, Pinna AD. Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients. World J Gastroenterol. 2012; 18:6398–6408.
62. Rong D, Liu W, Kuang S, Xie S, Chen Z, Chen F, et al. Preoperative prediction of pathologic grade of HCC on gadobenate dimeglumine-enhanced dynamic MRI. Eur Radiol. 2021; 31:7584–7593.
63. Hwang SH, Rhee H. Radiologic features of hepatocellular carcinoma related to prognosis. J Liver Cancer. 2023; 23:143–156.
64. Zhang J, Dong W, Li Y, Fu J, Jia N. Prediction of microvascular invasion in combined hepatocellular-cholangiocarcinoma based on preoperative contrast-enhanced CT and clinical data. Eur J Radiol. 2023; 163:110839.
65. Shan QY, Hu HT, Feng ST, Peng ZP, Chen SL, Zhou Q, et al. CTbased peritumoral radiomics signatures to predict early recurrence in hepatocellular carcinoma after curative tumor resection or ablation. Cancer Imaging. 2019; 19:11.
66. Choi JY, Lee JM, Sirlin CB. CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part II. Extracellular agents, hepatobiliary agents, and ancillary imaging features. Radiology. 2014; 273:30–50.
67. Li M, Xin Y, Fu S, Liu Z, Li Y, Hu B, et al. Corona enhancement and mosaic architecture for prognosis and selection between of liver resection versus transcatheter arterial chemoembolization in single hepatocellular carcinomas >5cm without extrahepatic metastases: an imaging-based retrospective study. Medicine (Baltimore). 2016; 95:e2458.
68. Kitao A, Matsui O, Yoneda N, Kozaka K, Shinmura R, Koda W, et al. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging. Eur Radiol. 2011; 21:2056–2066.
69. Cho ES, Choi JY. MRI features of hepatocellular carcinoma related to biologic behavior. Korean J Radiol. 2015; 16:449–464.
70. Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Sanada J, et al. Hepatocellular carcinoma with β-catenin mutation: imaging and pathologic characteristics. Radiology. 2015; 275:708–717.
71. Fujita N, Nishie A, Asayama Y, Ishigami K, Ushijima Y, Kakihara D, et al. Hyperintense liver masses at hepatobiliary phase gadoxetic acid-enhanced MRI: imaging appearances and clinical importance. Radiographics. 2020; 40:72–94.
72. Ning BF, Ding J, Yin C, Zhong W, Wu K, Zeng X, et al. Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma. Cancer Res. 2010; 70:7640–7651.
73. Kim JY, Kim MJ, Kim KA, Jeong HT, Park YN. Hyperintense HCC on hepatobiliary phase images of gadoxetic acid-enhanced MRI: correlation with clinical and pathological features. Eur J Radiol. 2012; 81:3877–3882.
75. Hui CL, Mautone M. Patterns of enhancement in the hepatobiliary phase of gadoxetic acid-enhanced MRI. Br J Radiol. 2020; 93:20190989.
76. Park JH, Chung YE, Seo N, Choi JY, Park MS, Kim MJ. Hepatobiliary phase signal intensity: a potential method of diagnosing HCC with atypical imaging features among LR-M observations. PLoS One. 2021; 16:e0257308.
77. Li Y, Chen J, Weng S, Yan C, Ye R, Zhu Y, et al. Hepatobiliary phase hypointensity on gadobenate dimeglumine-enhanced magnetic resonance imaging may improve the diagnosis of hepatocellular carcinoma. Ann Transl Med. 2021; 9:55.
78. Braga FA, Torres US, Iared W, D Ippolito G. Does hypointense HCC in the hepatobiliary phase at gadoxetate-enhanced MRI predict recurrence after surgery? a systematic review and meta-analysis. Acad Radiol. 2023; 30:1298–1305.
79. Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Koda W, et al. Hypervascular hepatocellular carcinoma: correlation between biologic features and signal intensity on gadoxetic acid-enhanced MR images. Radiology. 2012; 265:780–789.
80. Jang YR, Lee KW, Kim H, Lee JM, Yi NJ, Suh KS. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma. Korean J Hepatobiliary Pancreat Surg. 2015; 19:167–172.
81. Shiomi M, Kamiya J, Nagino M, Uesaka K, Sano T, Hayakawa N, et al. Hepatocellular carcinoma with biliary tumor thrombi: aggressive operative approach after appropriate preoperative management. Surgery. 2001; 129:692–698.
82. Navadgi S, Chang CC, Bartlett A, McCall J, Pandanaboyana S. Systematic review and meta-analysis of outcomes after liver resection in patients with hepatocellular carcinoma (HCC) with and without bile duct thrombus. HPB (Oxford). 2016; 18:312–316.
83. Wu JY, Huang LM, Bai YN, Wu JY, Wei YG, Zhang ZB, et al. Imaging features of hepatocellular carcinoma with bile duct tumor thrombus: a multicenter study. Front Oncol. 2021; 11:723455.
84. Qin LX, Ma ZC, Wu ZQ, Fan J, Zhou XD, Sun HC, et al. Diagnosis and surgical treatments of hepatocellular carcinoma with tumor thrombosis in bile duct: experience of 34 patients. World J Gastroenterol. 2004; 10:1397–1401.
85. Zhou X, Wang J, Tang M, Huang M, Xu L, Peng Z, et al. Hepatocellular carcinoma with hilar bile duct tumor thrombus versus hilar cholangiocarcinoma on enhanced computed tomography: a diagnostic challenge. BMC Cancer. 2020; 20:54.
86. Jiang H, Wei J, Fu F, Wei H, Qin Y, Duan T, et al. Predicting microvascular invasion in hepatocellular carcinoma: a dualinstitution study on gadoxetate disodium-enhanced MRI. Liver Int. 2022; 42:1158–1172.
87. Choi BI, Lee GK, Kim ST, Han MC. Mosaic pattern of encapsulated hepatocellular carcinoma: correlation of magnetic resonance imaging and pathology. Gastrointest Radiol. 1990; 15:238–240.
88. Tohme S, Yazdani HO, Liu Y, Loughran P, van der Windt DJ, Huang H, et al. Hypoxia mediates mitochondrial biogenesis in hepatocellular carcinoma to promote tumor growth through HMGB1 and TLR9 interaction. Hepatology. 2017; 66:182–197.
89. Ling YH, Chen JW, Wen SH, Huang CY, Li P, Lu LH, et al. Tumor necrosis as a poor prognostic predictor on postoperative survival of patients with solitary small hepatocellular carcinoma. BMC Cancer. 2020; 20:607.
90. Wang Y, Zhang W, Ge H, Han X, Wu J, Sun X, et al. Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation. BMC Cancer. 2023; 23:86.
91. Wu ZJ, Xie YF, Chang X, Zhang L, Wu HY, Liu JB, et al. Type of necrosis influences prognosis in hepatocellular carcinoma after the first transarterial chemoembolization. Med Sci Monit. 2021; 27:e929884.
92. Hong SB, Choi SH, Kim SY, Shim JH, Lee SS, Byun JH, et al. MRI features for predicting microvascular invasion of hepatocellular carcinoma: a systematic review and meta-analysis. Liver Cancer. 2021; 10:94–106.
93. Mori Y, Tamai H, Shingaki N, Hayami S, Ueno M, Maeda Y, et al. Hypointense hepatocellular carcinomas on apparent diffusion coefficient mapping: pathological features and metastatic recurrence after hepatectomy. Hepatol Res. 2016; 46:634–641.
94. Chang WC, Chen RC, Chou CT, Lin CY, Yu CY, Liu CH, et al. Histological grade of hepatocellular carcinoma correlates with arterial enhancement on gadoxetic acid-enhanced and diffusion-weighted MR images. Abdom Imaging. 2014; 39:1202–1212.
95. Lee S, Kim SH, Hwang JA, Lee JE, Ha SY. Pre-operative ADC predicts early recurrence of HCC after curative resection. Eur Radiol. 2019; 29:1003–1012.
96. Feo F, Pascale RM. Multifocal hepatocellular carcinoma: intrahepatic metastasis or multicentric carcinogenesis? Ann Transl Med. 2015; 3:4.
97. Xie DY, Fan HK, Ren ZG, Fan J, Gao Q. Identifying clonal origin of multifocal hepatocellular carcinoma and its clinical implications. Clin Transl Gastroenterol. 2019; 10:e00006.
98. Yue YY, Zhou WL. Hepatic resection is associated with improved long-term survival compared to radio-frequency ablation in patients with multifocal hepatocellular carcinoma. Front Oncol. 2020; 10:110.
99. Risaliti M, Bartolini I, Campani C, Arena U, Xodo C, Adotti V, et al. Evaluating the best treatment for multifocal hepatocellular carcinoma: a propensity score-matched analysis. World J Gastroenterol. 2022; 28:3981–3993.
100. Min JH, Lee MW, Park HS, Lee DH, Park HJ, Lim S, et al. Interobserver variability and diagnostic performance of gadoxetic acidenhanced MRI for predicting microvascular invasion in hepatocellular carcinoma. Radiology. 2020; 297:573–581.
101. Yoneda N, Matsui O, Kobayashi S, Kitao A, Kozaka K, Inoue D, et al. Current status of imaging biomarkers predicting the biological nature of hepatocellular carcinoma. Jpn J Radiol. 2019; 37:191–208.
102. Ünal E, İdilman İS, Akata D, Özmen MN, Karçaaltıncaba M. Microvascular invasion in hepatocellular carcinoma. Diagn Interv Radiol. 2016; 22:125–132.
103. Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, et al. Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci. 2003; 94:851–857.